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Sample records for autologous stem cells

  1. Autologous stem cells for personalised medicine.

    PubMed

    Prasongchean, Weerapong; Ferretti, Patrizia

    2012-09-15

    Increasing understanding of stem cell biology, the ability to reprogramme differentiated cells to a pluripotent state and evidence of multipotency in certain adult somatic stem cells has opened the door to exciting therapeutic advances as well as a great deal of regulatory and ethical issues. Benefits will come from the possibility of modelling human diseases and develop individualised therapies, and from their use in transplantation and bioengineering. The use of autologous stem cells is highly desirable, as it avoids the problem of tissue rejection, and also reduces ethical and regulatory issues. Identification of the most appropriate cell sources for different potential applications, development of appropriate clinical grade methodologies and large scale well controlled clinical trials will be essential to assess safety and value of cell based therapies, which have been generating much hope, but are by and large not yet close to becoming standard clinical practice. We briefly discuss stem cells in the context of tissue repair and regenerative medicine, with a focus on individualised clinical approaches, and give examples of sources of autologous cells with potential for clinical intervention.

  2. Autologous hematopoietic stem cell transplantation for pediatric solid tumors.

    PubMed

    Hale, Gregory A

    2005-10-01

    While advances in the treatment of pediatric cancers have increased cure rates, children with metastatic or recurrent solid tumors have a dismal prognosis despite initial transient responses to therapy. Autologous hematopoietic stem cell transplantation takes advantage of the steep dose-response relationship observed with many chemotherapeutic agents. While clearly demonstrated to improve outcomes in patients with metastatic neuroblastoma, autologous hematopoietic stem cell transplantation is also frequently used to treat patients with other high-risk diseases such as Ewing sarcoma, osteosarcoma, rhabdomyosarcoma, Wilms' tumor, retinoblastoma, germ cell tumors, lymphomas and brain tumors. Most published experience consists of retrospective, single-arm studies; randomized clinical trials are lacking, due in part to the rarity of pediatric cancers treatable by autologous hematopoietic stem cell transplantation. These published literature demonstrate that autologous hematopoietic stem cell transplantation results in most cases in equivalent or superior outcomes when compared with conventional therapies. However, patient heterogeneity, patient selection, graft characteristics and processing and the varied conditioning regimens are additional factors to consider. Since the inception of autologous hematopoietic stem cell transplantation, regimen-related toxicity has markedly decreased and the vast majority of treatment failures are now due to disease recurrence. Prospective clinical trials are needed to identify specific high-risk patient populations, with randomization (when possible) to compare outcomes of patients undergoing autologous hematopoietic stem cell transplantation with those receiving standard therapy. In addition, investigators need to better define the role of autologous hematopoietic stem cell transplantation in these solid tumors, particularly in combination with other therapeutic modalities such as immunotherapy and novel cell processing methodologies.

  3. Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma without Cryopreservation

    PubMed Central

    Al-Anazi, Khalid Ahmed

    2012-01-01

    High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation is considered the standard of care for multiple myeloma patients who are eligible for transplantation. The process of autografting comprises the following steps: control of the primary disease by using a certain induction therapeutic protocol, mobilization of stem cells, collection of mobilized stem cells by apheresis, cryopreservation of the apheresis product, administration of high-dose pretransplant conditioning therapy, and finally infusion of the cryopreserved stem cells after thawing. However, in cancer centers that treat patients with multiple myeloma and have transplantation capabilities but lack or are in the process of acquiring cryopreservation facilities, alternatively noncryopreserved autologous stem cell therapy has been performed with remarkable success as the pretransplant conditioning therapy is usually brief. PMID:22693672

  4. Autologous Stem Cell Mobilization and Collection.

    PubMed

    Hsu, Yen-Michael S; Cushing, Melissa M

    2016-06-01

    Peripheral blood stem cell collection is an effective approach to obtain a hematopoietic graft for stem cell transplantation. Developing hematopoietic stem/progenitor cell (HSPC) mobilization methods and collection algorithms have improved efficiency, clinical outcomes, and cost effectiveness. Differences in mobilization mechanisms may change the HSPC content harvested and result in different engraftment kinetics and complications. Patient-specific factors can affect mobilization. Incorporating these factors in collection algorithms and improving assays for evaluating mobilization further extend the ability to obtain sufficient HSPCs for hematopoietic repopulation. Technological advance and innovations in leukapheresis have improved collection efficiency and reduced adverse effects. PMID:27112997

  5. Autologous hematopoietic stem cell transplantation in classical Hodgkin's lymphoma

    PubMed Central

    Cortez, Afonso José Pereira; Dulley, Frederico Luiz; Saboya, Rosaura; Mendrone Júnior, Alfredo; Amigo Filho, Ulisses; Coracin, Fabio Luiz; Buccheri, Valéria; Linardi, Camila da Cruz Gouveia; Ruiz, Milton Artur; Chamone, Dalton de Alencar Fischer

    2011-01-01

    Background Hodgkin's lymphoma has high rates of cure, but in 15% to 20% of general patients and between 35% and 40% of those in advanced stages, the disease will progress or will relapse after initial treatment. For this group, hematopoietic stem cell transplantation is considered one option of salvage therapy. Objectives To evaluate a group of 106 patients with Hodgkin's lymphoma, who suffered relapse or who were refractory to treatment, submitted to autologous hematopoietic stem cell transplantation in a single transplant center. Methods A retrospective study was performed with data collected from patient charts. The analysis involved 106 classical Hodgkin's lymphoma patients who were consecutively submitted to high-dose chemotherapy followed by autologous transplants in a single institution from April 1993 to December 2006. Results The overall survival rates of this population at five and ten years were 86% and 70%, respectively. The disease-free survival was approximately 60% at five years. Four patients died of procedure-related causes but relapse of classical Hodgkin's lymphoma after transplant was the most frequent cause of death. Univariate analysis shows that sensitivity to pre-transplant treatment and hemoglobin < 10 g/dL at diagnosis had an impact on patient survival. Unlike other studies, B-type symptoms did not seem to affect overall survival. Lactic dehydrogenase and serum albumin concentrations analyzed at diagnosis did not influence patient survival either. Conclusion Autologous hematopoietic stem cell transplantation is an effective treatment strategy for early and late relapse in classical Hodgkin's lymphoma for cases that were responsive to pre-transplant chemotherapy. Refractory to treatment is a sign of worse prognosis. Additionally, a hemoglobin concentration below 10 g/dL at diagnosis of Hodgkin's lymphoma has a negative impact on the survival of patients after transplant. As far as we know this relationship has not been previously reported

  6. Neurogenic Bladder Repair Using Autologous Mesenchymal Stem Cells.

    PubMed

    Mahajan, Pradeep V; Subramanian, Swetha; Danke, Amit; Kumar, Anand

    2016-01-01

    The normal function of the urinary bladder is to store and expel urine in a coordinated, controlled fashion, the activity of which is regulated by the central and peripheral nervous systems. Neurogenic bladder is a term applied to a malfunctioning urinary bladder due to neurologic dysfunction or insult emanating from internal or external trauma, disease, or injury. This report describes a case of neurogenic bladder following laminectomy procedure and long-standing diabetes mellitus with neuropathy treated with autologous cellular therapy. The differentiation potential and paracrine effects of mesenchymal stem cells on bladder function have been highlighted. PMID:27656308

  7. Neurogenic Bladder Repair Using Autologous Mesenchymal Stem Cells

    PubMed Central

    Kumar, Anand

    2016-01-01

    The normal function of the urinary bladder is to store and expel urine in a coordinated, controlled fashion, the activity of which is regulated by the central and peripheral nervous systems. Neurogenic bladder is a term applied to a malfunctioning urinary bladder due to neurologic dysfunction or insult emanating from internal or external trauma, disease, or injury. This report describes a case of neurogenic bladder following laminectomy procedure and long-standing diabetes mellitus with neuropathy treated with autologous cellular therapy. The differentiation potential and paracrine effects of mesenchymal stem cells on bladder function have been highlighted.

  8. Neurogenic Bladder Repair Using Autologous Mesenchymal Stem Cells

    PubMed Central

    Kumar, Anand

    2016-01-01

    The normal function of the urinary bladder is to store and expel urine in a coordinated, controlled fashion, the activity of which is regulated by the central and peripheral nervous systems. Neurogenic bladder is a term applied to a malfunctioning urinary bladder due to neurologic dysfunction or insult emanating from internal or external trauma, disease, or injury. This report describes a case of neurogenic bladder following laminectomy procedure and long-standing diabetes mellitus with neuropathy treated with autologous cellular therapy. The differentiation potential and paracrine effects of mesenchymal stem cells on bladder function have been highlighted. PMID:27656308

  9. SHIPi Enhances Autologous and Allogeneic Hematopoietic Stem Cell Transplantation

    PubMed Central

    Fernandes, Sandra; Brooks, Robert; Gumbleton, Matthew; Park, Mi-Young; Russo, Christopher M.; Howard, Kyle T.; Chisholm, John D.; Kerr, William G.

    2015-01-01

    Hematopoietic stem cell transplantation (HSCT) is a highly effective procedure enabling long-term survival for patients with hematologic malignancy or heritable defects. Although there has been a dramatic increase in the success rate of HSCT over the last two decades, HSCT can result in serious, sometimes untreatable disease due to toxic conditioning regimens and Graft-versus-Host-Disease. Studies utilizing germline knockout mice have discovered several candidate genes that could be targeted pharmacologically to create a more favorable environment for transplant success. SHIP1 deficiency permits improved engraftment of hematopoietic stem-progenitor cells (HS-PCs) and produces an immunosuppressive microenvironment ideal for incoming allogeneic grafts. The recent development of small molecule SHIP1 inhibitors has opened a different therapeutic approach by creating transient SHIP1-deficiency. Here we show that SHIP1 inhibition (SHIPi) mobilizes functional HS-PC, accelerates hematologic recovery, and enhances donor HS-PC engraftment in both allogeneic and autologous transplant settings. We also observed the expansion of key cell populations known to suppress host-reactive cells formed during engraftment. Therefore, SHIPi represents a non-toxic, new therapeutic that has significant potential to improve the success and safety of therapies that utilize autologous and allogeneic HSCT. PMID:26052545

  10. Persistent seropositivity for yellow fever in a previously vaccinated autologous hematopoietic stem cell transplantation recipient.

    PubMed

    Hayakawa, Kayoko; Takasaki, Tomohiko; Tsunemine, Hiroko; Kanagawa, Shuzo; Kutsuna, Satoshi; Takeshita, Nozomi; Mawatari, Momoko; Fujiya, Yoshihiro; Yamamoto, Kei; Ohmagari, Norio; Kato, Yasuyuki

    2015-08-01

    The duration of a protective level of yellow fever antibodies after autologous hematopoietic stem cell transplantation in a previously vaccinated person is unclear. The case of a patient who had previously been vaccinated for yellow fever and who remained seropositive for 22 months after autologous peripheral blood stem cell transplantation for malignant lymphoma is described herein.

  11. Cartilage Repair With Autologous Bone Marrow Mesenchymal Stem Cell Transplantation

    PubMed Central

    Yamasaki, Shinya; Mera, Hisashi; Itokazu, Maki; Hashimoto, Yusuke

    2014-01-01

    Clinical trials of various procedures, including bone marrow stimulation, mosaicplasty, and autologous chondrocyte implantation, have been explored to treat articular cartilage defects. However, all of them have some demerits. We focused on autologous culture-expanded bone marrow mesenchymal stem cells (BMSC), which can proliferate without losing their capacity for differentiation. First, we transplanted BMSC into the defective articular cartilage of rabbit and succeeded in regenerating osteochondral tissue. We then applied this transplantation in humans. Our previous reports showed that treatment with BMSC relieves the clinical symptoms of chondral defects in the knee and elbow joint. We investigated the efficacy of BMSC for osteoarthritic knee treated with high tibial osteotomy, by comparing 12 BMSC-transplanted patients with 12 cell-free patients. At 16-month follow-up, although the difference in clinical improvement between both groups was not significant, the arthroscopic and histological grading score was better in the cell-transplanted group. At the over 10-year follow-up, Hospital for Special Surgery knee scores improved to 76 and 73 in the BMSC-transplanted and cell-free groups, respectively, which were better than preoperative scores. Additionally, neither tumors nor infections were observed in all patients, and in the clinical study, we have never observed hypertrophy of repaired tissue, thereby guaranteeing the clinical safety of this therapy. Although we have never observed calcification above the tidemark in rabbit model and human histologically, the repair cartilage was not completely hyaline cartilage. To elucidate the optimum conditions for cell therapy, other stem cells, culture conditions, growth factors, and gene transfection methods should be explored. PMID:26069698

  12. First in Man: Sternal Reconstruction with Autologous Stem Cells.

    PubMed

    Khalpey, Zain; Marsh, Katherine M; Ferng, Alice; Riaz, Irbaz Bin; Hemphill, Courtney; Johnson, Kitsie; Oliva, Isabel; Friedman, Mark

    2015-01-01

    Sternal nonunion is associated with high morbidity and treated using rigid plate and screw fixation. This is the first reported example of successful sternal reconstruction using adipose-derived stromal vascular fraction (SVF) stem cells in addition to traditional techniques. Mesenchymal stem cells, one component of the SVF, play an important role in bone healing and were therefore used to promote remedial processes in a patient with sternal nonunion. A 3D printed model of the patient's sternum was used for preoperative planning of the plating. Intraoperatively, SVF was isolated using ultrasonic cavitation and previously planned sternal plating was completed. A total of 300 million cells were delivered via both local injection and intravenously before chest closure. The patient's pain dramatically decreased, commensurate with healed areas of nonunion by 3 months and maintained at 6 months postoperatively, supported by three-dimensional computed tomography imaging. Utilizing autologous stem cells from the SVF in conjunction with existing plating techniques may provide an optimal platform to stabilize the sternum and promote bone healing, although additional study is recommended.

  13. First in Man: Sternal Reconstruction with Autologous Stem Cells.

    PubMed

    Khalpey, Zain; Marsh, Katherine M; Ferng, Alice; Riaz, Irbaz Bin; Hemphill, Courtney; Johnson, Kitsie; Oliva, Isabel; Friedman, Mark

    2015-01-01

    Sternal nonunion is associated with high morbidity and treated using rigid plate and screw fixation. This is the first reported example of successful sternal reconstruction using adipose-derived stromal vascular fraction (SVF) stem cells in addition to traditional techniques. Mesenchymal stem cells, one component of the SVF, play an important role in bone healing and were therefore used to promote remedial processes in a patient with sternal nonunion. A 3D printed model of the patient's sternum was used for preoperative planning of the plating. Intraoperatively, SVF was isolated using ultrasonic cavitation and previously planned sternal plating was completed. A total of 300 million cells were delivered via both local injection and intravenously before chest closure. The patient's pain dramatically decreased, commensurate with healed areas of nonunion by 3 months and maintained at 6 months postoperatively, supported by three-dimensional computed tomography imaging. Utilizing autologous stem cells from the SVF in conjunction with existing plating techniques may provide an optimal platform to stabilize the sternum and promote bone healing, although additional study is recommended. PMID:25914951

  14. Autologous hematopoietic stem cell transplantation for autoimmune diseases.

    PubMed

    Gratwohl, A; Passweg, J; Bocelli-Tyndall, C; Fassas, A; van Laar, J M; Farge, D; Andolina, M; Arnold, R; Carreras, E; Finke, J; Kötter, I; Kozak, T; Lisukov, I; Löwenberg, B; Marmont, A; Moore, J; Saccardi, R; Snowden, J A; van den Hoogen, F; Wulffraat, N M; Zhao, X W; Tyndall, A

    2005-05-01

    Experimental data and early phase I/II studies suggest that high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT) can arrest progression of severe autoimmune diseases. We have evaluated the toxicity and disease response in 473 patients with severe autoimmune disease treated with autologous HSCT between 1995 and 2003, from 110 centers participating in the European Group for Blood and Marrow Transplantation (EBMT) autoimmune disease working party database. Survival, transplant-related mortality, treatment response and disease progression were assessed. In all, 420 patients (89%; 86+/-4% at 3 years, median follow-up 20 months) were alive, 53 (11%) had died from transplant-related mortality (N=31; 7+/-3% at 3 years) or disease progression (N=22; 9+/-4% at 3 years). Of 370 patients, 299 evaluable for response (81%) showed a treatment response, which was sustained in 213 (71% of responders). Response was associated with disease (P<0.001), was better in patients who received cyclophosphamide during mobilization (relative risk (RR)3.28 (1.57-6.83)) and was worse with increasing age (>40 years, RR0.29 (0.11-0.82)). Disease progression was associated with disease (P<0.001) and conditioning intensity (high intensity, RR1; intermediate intensity, RR1.81 (0.96-3.42)); low intensity, RR2.34 (1.074-5.11)). These data from the collective EBMT experience support the hypothesis that autologous HSCT can alter disease progression in severe autoimmune disease.

  15. Regeneration of the vocal fold using autologous mesenchymal stem cells.

    PubMed

    Kanemaru, Shin-Ichi; Nakamura, Tatsuo; Omori, Koichi; Kojima, Hisayoshi; Magrufov, Akhmar; Hiratsuka, Yasuyuki; Hirano, Shigeru; Ito, Juichi; Shimizu, Yasuhiko

    2003-11-01

    The aim of this study was to regenerate the injured vocal fold by means of selective cultured autologous mesenchymal stem cells (MSCs). Eight adult beagle dogs were used for this experiment. Selective incubation of MSCs from bone marrow was done. These MSCs were submitted to 3-dimensional incubation in 1% hydrochloric acid atelocollagen. Three-dimensional incubated MSCs were injected into the left vocal fold, and atelocollagen only was injected into the right vocal fold of the same dog as a control. Four days after injection, the posterior parts of the vocal folds were incised. The regeneration of the vocal fold was estimated by morphological and histologic evaluations. Our results showed that 3-dimensional incubated MSCs were useful in the regeneration of the injured vocal fold. This study shows that damaged tissues such as an injured vocal fold would be able to be regenerated by tissue engineering. PMID:14653358

  16. Autologous hematopoietic stem cell transplantation in autoimmune diseases.

    PubMed

    Annaloro, Claudio; Onida, Francesco; Lambertenghi Deliliers, Giorgio

    2009-12-01

    The term 'autoimmune diseases' encompasses a spectrum of diseases whose clinical manifestations and, possibly, biological features vary widely. The results of conventional treatment are considered unsatisfactory in aggressive forms, with subsets of patients having short life expectancies. Relying on wide experimental evidence and more feeble clinical data, some research groups have used autologous hematopoietic stem cell transplantation (HSCT) in the most disabling autoimmune diseases with the aim of resetting the patient's immune system. Immunoablative conditioning regimens are preferred over their myeloablative counterparts, and some form of in vivo and/or ex vivo T-cell depletion is generally adopted. Despite 15 years' experience, published controlled clinical trials are still lacking, with the evidence so far available coming from pilot studies and registry surveys. In multiple sclerosis, clinical improvement, or at least lasting disease stabilization, can be achieved in the majority of the patients; nevertheless, the worst results are observed in patients with progressive disease, where no benefit can be expected from conventional therapy. Concerning rheumatologic diseases, wide experience has been acquired in systemic sclerosis, with long-term improvements in cutaneous disease being frequently reported, although visceral involvement remains unchanged at best. Autografting has proved to be barely effective in rheumatoid arthritis and quite toxic in juvenile idiopathic arthritis, whereas it leads to clinical remission and the reversal of visceral impairment in the majority of patients with systemic lupus erythematosus. A promising indication is Crohn's disease, in which long-term endoscopic remission is frequently observed. Growing experience with autologous HCST in autoimmune diseases has progressively reduced concerns about transplant-related mortality and secondary myelodysplasia/leukemia. Therefore, a sustained complete remission seems to be within the

  17. Optimizing autologous cell grafts to improve stem cell gene therapy.

    PubMed

    Psatha, Nikoletta; Karponi, Garyfalia; Yannaki, Evangelia

    2016-07-01

    Over the past decade, stem cell gene therapy has achieved unprecedented curative outcomes for several genetic disorders. Despite the unequivocal success, clinical gene therapy still faces challenges. Genetically engineered hematopoietic stem cells are particularly vulnerable to attenuation of their repopulating capacity once exposed to culture conditions, ultimately leading to low engraftment levels posttransplant. This becomes of particular importance when transduction rates are low or/and competitive transplant conditions are generated by reduced-intensity conditioning in the absence of a selective advantage of the transduced over the unmodified cells. These limitations could partially be overcome by introducing megadoses of genetically modified CD34(+) cells into conditioned patients or by transplanting hematopoietic stem cells hematopoietic stem cells with high engrafting and repopulating potential. On the basis of the lessons gained from cord blood transplantation, we summarize the most promising approaches to date of increasing either the numbers of hematopoietic stem cells for transplantation or/and their engraftability, as a platform toward the optimization of engineered stem cell grafts. PMID:27106799

  18. Endocrinopathies after Allogeneic and Autologous Transplantation of Hematopoietic Stem Cells

    PubMed Central

    Muscogiuri, Giovanna; Palomba, Stefano; Serio, Bianca; Sessa, Mariarosaria; Giudice, Valentina; Ferrara, Idalucia; Tauchmanovà, Libuse; Colao, Annamaria; Selleri, Carmine

    2014-01-01

    Early and late endocrine disorders are among the most common complications in survivors after hematopoietic allogeneic- (allo-) and autologous- (auto-) stem cell transplant (HSCT). This review summarizes main endocrine disorders reported in literature and observed in our center as consequence of auto- and allo-HSCT and outlines current options for their management. Gonadal impairment has been found early in approximately two-thirds of auto- and allo-HSCT patients: 90–99% of women and 60–90% of men. Dysfunctions of the hypothalamus-pituitary-growth hormone/insulin growth factor-I axis, hypothalamus-pituitary-thyroid axis, and hypothalamus-pituitary-adrenal axis were documented as later complicances, occurring in about 10, 30, and 40–50% of transplanted patients, respectively. Moreover, overt or subclinical thyroid complications (including persistent low-T3 syndrome, chronic thyroiditis, subclinical hypo- or hyperthyroidism, and thyroid carcinoma), gonadal failure, and adrenal insufficiency may persist many years after HSCT. Our analysis further provides evidence that main recognized risk factors for endocrine complications after HSCT are the underlying disease, previous pretransplant therapies, the age at HSCT, gender, total body irradiation, posttransplant derangement of immune system, and in the allogeneic setting, the presence of graft-versus-host disease requiring prolonged steroid treatment. Early identification of endocrine complications can greatly improve the quality of life of long-term survivors after HSCT. PMID:24883377

  19. Endocrinopathies after allogeneic and autologous transplantation of hematopoietic stem cells.

    PubMed

    Orio, Francesco; Muscogiuri, Giovanna; Palomba, Stefano; Serio, Bianca; Sessa, Mariarosaria; Giudice, Valentina; Ferrara, Idalucia; Tauchmanovà, Libuse; Colao, Annamaria; Selleri, Carmine

    2014-01-01

    Early and late endocrine disorders are among the most common complications in survivors after hematopoietic allogeneic- (allo-) and autologous- (auto-) stem cell transplant (HSCT). This review summarizes main endocrine disorders reported in literature and observed in our center as consequence of auto- and allo-HSCT and outlines current options for their management. Gonadal impairment has been found early in approximately two-thirds of auto- and allo-HSCT patients: 90-99% of women and 60-90% of men. Dysfunctions of the hypothalamus-pituitary-growth hormone/insulin growth factor-I axis, hypothalamus-pituitary-thyroid axis, and hypothalamus-pituitary-adrenal axis were documented as later complicances, occurring in about 10, 30, and 40-50% of transplanted patients, respectively. Moreover, overt or subclinical thyroid complications (including persistent low-T3 syndrome, chronic thyroiditis, subclinical hypo- or hyperthyroidism, and thyroid carcinoma), gonadal failure, and adrenal insufficiency may persist many years after HSCT. Our analysis further provides evidence that main recognized risk factors for endocrine complications after HSCT are the underlying disease, previous pretransplant therapies, the age at HSCT, gender, total body irradiation, posttransplant derangement of immune system, and in the allogeneic setting, the presence of graft-versus-host disease requiring prolonged steroid treatment. Early identification of endocrine complications can greatly improve the quality of life of long-term survivors after HSCT. PMID:24883377

  20. The potential role of autologous stem cell transplantation in patients with systemic lupus erythematosus.

    PubMed

    Hahn, B H

    1997-05-01

    Transfer of disease by bone marrow cells has been described in experimental models of systemic lupus erythematosus (SLE). In one experiment, marrow ablation followed by transfer of T depleted allogeneic marrow resulted in prolonged survival of animals with SLE. Some experimental studies suggest a rationale for autologous stem cell transplantation indicating this intervention might "reset the thermostat" so that normal immunoregulation can control disease, while others indicate it might not be beneficial. The pros and cons of offering patients with SLE autologous hematopoietic stem cell transplantation are considered. A profile of the patient with SLE who might be considered as a candidate for autologous stem cell transplantation can be constructed by evaluating causes of death and factors that increase mortality. This profile includes life threatening disease, inadequate response to aggressive immunosuppressive therapy, and adequate function of all major organs so that risks associated with stem cell transplantation can be minimized.

  1. Post-transplant lymphoproliferative disorder after autologous peripheral stem cell transplantation in a pediatric patient.

    PubMed

    Lones, M A; Kirov, I; Said, J W; Shintaku, I P; Neudorf, S

    2000-11-01

    Post-transplant lymphoproliferative disorder (PTLD) is a complication of allogeneic bone marrow transplantation (BMT). Rare cases of PTLD after autologous BMT have been reported only in adults. This case report is the first to describe PTLD in a pediatric patient after autologous peripheral stem cell transplantation (PSCT). This 2-year-old male with stage IV neuroblastoma underwent autologous PSCT. The post-PSCT course was complicated by fever with hematochezia and a lung mass. On day 94 post PSCT, colonoscopy revealed an ulcer due to a PTLD, monomorphic type, B cell phenotype, associated with Epstein-Barr virus. Fine needle aspiration identified the lung mass as neuroblastoma. PTLD can occur in pediatric autologous PSCT recipients, and may occur more frequently in autologous grafts manipulated by T cell depletion or CD34+ cell selection.

  2. The Use of Autologous Mesenchymal Stem Cells for Cell Therapy of Patients with Amyotrophic Lateral Sclerosis in Belarus.

    PubMed

    Rushkevich, Yu N; Kosmacheva, S M; Zabrodets, G V; Ignatenko, S I; Goncharova, N V; Severin, I N; Likhachev, S A; Potapnev, M P

    2015-08-01

    We studied a new method of treatment of amyotrophic lateral sclerosis with autologous mesenchymal stem cells. Autologous mesenchymal stem cells were injected intravenously (intact cells) or via lumbar puncture (cells committed to neuronal differentiation). Evaluation of the results of cell therapy after 12-month follow-up revealed slowing down of the disease progression in 10 patients in comparison with the control group consisting of 15 patients. The cell therapy was safe for the patients.

  3. Lymphocyte subset recovery and outcome after autologous hematopoietic stem cell transplantation for plasma cell myeloma.

    PubMed

    Rueff, Jessica; Medinger, Michael; Heim, Dominik; Passweg, Jakob; Stern, Martin

    2014-06-01

    Rapid immune reconstitution--particularly of natural killer cells (NK cells)--after allogeneic hematopoietic stem cell transplantation (HSCT) is associated with protection from relapse. Whether such an association also exists after autologous stem cell transplantation is less clear. We retrospectively assessed lymphocyte subsets after autologous HSCT in 114 patients and correlated lymphocyte recovery with outcome. CD8 T cell and NK cell counts recovered rapidly to pretransplantation levels, whereas B cell and CD4 T cell recovery were delayed. Compared with patients with low NK cells (<100/uL), high NK cell count at 1 month after HSCT was associated with significantly prolonged progression-free survival: for NK cells 100 to 200/uL hazard ratio [HR], .33 (95% confidence interval [CI]; .16 to .80; P = .004); for NK cells > 200/μL HR, .27 (95% CI, .13 to .58; P = .001). No significant protective effects were associated with rapid recovery of any other lymphocyte subset. None influenced overall survival (OS) or time to next treatment. Early NK cell recovery is associated with better progression-free survival after autologous HSCT. The failure to detect an effect on OS might be due to the salvage strategies available to these patients.

  4. Untested, unproven, and unethical: the promotion and provision of autologous stem cell therapies in Australia.

    PubMed

    McLean, Alison K; Stewart, Cameron; Kerridge, Ian

    2015-01-01

    An increasing number of private clinics in Australia are marketing and providing autologous stem cell therapies to patients. Although advocates point to the importance of medical innovation and the primacy of patient choice, these arguments are unconvincing. First, it is a stark truth that these clinics are flourishing while the efficacy and safety of autologous stem cell therapies, outside of established indications for hematopioetic stem cell transplantation, are yet to be shown. Second, few of these therapies are offered within clinical trials. Third, patients with chronic and debilitating illnesses, who are often the ones who take up these therapies, incur significant financial burdens in the expectation of benefiting from these treatments. Finally, the provision of these stem cell therapies does not follow the established pathways for legitimate medical advancement. We argue that greater regulatory oversight and professional action are necessary to protect vulnerable patients and that at this time the provision of unproven stem cell therapies outside of clinical trials is unethical.

  5. Allogeneic and autologous mode of stem cell transplantation in regenerative medicine: which way to go?

    PubMed

    Mamidi, Murali Krishna; Dutta, Susmita; Bhonde, Ramesh; Das, Anjan Kumar; Pal, Rajarshi

    2014-12-01

    Stem cell transplantation is a generic term covering different techniques. However there is argument over the pros and cons of autologous and allogeneic transplants of mesenchymal stem cells (MSCs) for regenerative therapy. Given that the MSCs have already been proven to be safe in patients, we hypothesize that allogeneic transplantation could be more effective and cost-effective as compared to autologous transplantation specifically in older subjects who are the likely victims of degenerative diseases. This analysis is based on the scientific logic that allogeneic stem cells extracted in large numbers from young and healthy donors could be physiologically, metabolically and genetically more stable. Therefore stem cells from young donors may be expected to exhibit higher vigor in secreting trophic factors leading to activation of host tissue-specific stem cells and also be more efficient in remodeling the micro-environmental niche of damaged tissue.

  6. Differentiation within autologous fibrin scaffolds of porcine dermal cells with the mesenchymal stem cell phenotype

    SciTech Connect

    Puente, Pilar de la

    2013-02-01

    Porcine mesenchymal stem cells (pMSCs) are an attractive source of cells for tissue engineering because their properties are similar to those of human stem cells. pMSCs can be found in different tissues but their dermal origin has not been studied in depth. Additionally, MSCs differentiation in monolayer cultures requires subcultured cells, and these cells are at risk of dedifferentiation when implanting them into living tissue. Following this, we attempted to characterize the MSCs phenotype of porcine dermal cells and to evaluate their cellular proliferation and differentiation in autologous fibrin scaffolds (AFSs). Dermal biopsies and blood samples were obtained from 12 pigs. Dermal cells were characterized by flow cytometry. Frozen autologous plasma was used to prepare AFSs. pMSC differentiation was studied in standard structures (monolayers and pellets) and in AFSs. The pMSCs expressed the CD90 and CD29 markers of the mesenchymal lineage. AFSs afforded adipogenic, osteogenic and chondrogenic differentiation. The porcine dermis can be proposed to be a good source of MSCs with adequate proliferative capacity and a suitable expression of markers. The pMSCs also showed optimal proliferation and differentiation in AFSs, such that these might serve as a promising autologous and implantable material for use in tissue engineering. -- Highlights: ► Low fibrinogen concentration provides a suitable matrix for cell migration and differentiation. ► Autologous fibrin scaffolds is a promising technique in tissue engineering. ► Dermal cells are an easily accessible mesenchymal stem cell source. ► Fibrin scaffolds afforded adipogenic, osteogenic and chondrogenic differentiation.

  7. Membranous nephropathy in autologous hematopoietic stem cell transplant: autologous graft-versus-host disease or autoimmunity induction?

    PubMed Central

    Abudayyeh, Ala; Truong, Luan D.; Beck, Laurence H.; Weber, Donna M.; Rezvani, Katy; Abdelrahim, Maen

    2015-01-01

    With the increasing utility of hematopoietic stem cell transplantation (SCT) as a treatment for cancer and noncancerous disorders, more challenges and complications associated with SCT have emerged. Renal injury immediately after transplant is common and well understood, but long-term renal injury is becoming more evident. Chronic graft-versus-host disease (GVHD) is a known long-term complication of SCT, and membranous nephropathy (MN) is emerging as the most common cause of SCT-associated glomerular pathology. In this case report, we present a patient who developed features of anti-PLA2R antibody-negative MN following autologous SCT. The renal injury responded well to steroids and further response to rituximab therapy was noted, suggesting antibody-mediated autoimmune glomerular disease. We also present a review of the literature on autologous GVHD and the role of T and B cells in induction of autoimmunity by SCT. PMID:26251713

  8. Differentiation within autologous fibrin scaffolds of porcine dermal cells with the mesenchymal stem cell phenotype.

    PubMed

    de la Puente, Pilar; Ludeña, Dolores; López, Marta; Ramos, Jennifer; Iglesias, Javier

    2013-02-01

    Porcine mesenchymal stem cells (pMSCs) are an attractive source of cells for tissue engineering because their properties are similar to those of human stem cells. pMSCs can be found in different tissues but their dermal origin has not been studied in depth. Additionally, MSCs differentiation in monolayer cultures requires subcultured cells, and these cells are at risk of dedifferentiation when implanting them into living tissue. Following this, we attempted to characterize the MSCs phenotype of porcine dermal cells and to evaluate their cellular proliferation and differentiation in autologous fibrin scaffolds (AFSs). Dermal biopsies and blood samples were obtained from 12 pigs. Dermal cells were characterized by flow cytometry. Frozen autologous plasma was used to prepare AFSs. pMSC differentiation was studied in standard structures (monolayers and pellets) and in AFSs. The pMSCs expressed the CD90 and CD29 markers of the mesenchymal lineage. AFSs afforded adipogenic, osteogenic and chondrogenic differentiation. The porcine dermis can be proposed to be a good source of MSCs with adequate proliferative capacity and a suitable expression of markers. The pMSCs also showed optimal proliferation and differentiation in AFSs, such that these might serve as a promising autologous and implantable material for use in tissue engineering.

  9. Spontaneous bilateral kidney rupture during autologous stem cell transplantation in a patient affected by amyloidosis

    PubMed Central

    Ferrannini, Michele; Vischini, Gisella; De Angelis, Gottardo; Giannakakis, Konstantinos; Arcese, William

    2011-01-01

    Kidney spontaneous rupture is not a recognized complication neither for amyloidosis nor of autologous stem cell transplantation (ASCT). A 46-year-old white woman, affected by nephrotic syndrome, was diagnosed as AL amyloidosis by renal biopsy. We report the singular case of a bilateral spontaneous kidney rupture during ASCT for AL with renal rescue. PMID:25984105

  10. Oversight for clinical uses of autologous adult stem cells: lessons from international regulations.

    PubMed

    Lysaght, Tamra; Kerridge, Ian; Sipp, Douglas; Porter, Gerard; Capps, Benjamin J

    2013-12-01

    Autologous adult stem cells (ASCs) are being administered by physicians for indications that have not been demonstrated as safe and effective in formal clinical trials. Examination of regulatory frameworks across five countries suggests that balancing the demands of research with clinical freedom has created structural weaknesses that are being exploited.

  11. Regeneration of Cartilage in Human Knee Osteoarthritis with Autologous Adipose Tissue-Derived Stem Cells and Autologous Extracellular Matrix.

    PubMed

    Pak, Jaewoo; Lee, Jung Hun; Park, Kwang Seung; Jeong, Byeong Chul; Lee, Sang Hee

    2016-01-01

    This clinical case series demonstrates that percutaneous injections of autologous adipose tissue-derived stem cells (ADSCs) and homogenized extracellular matrix (ECM) in the form of adipose stromal vascular fraction (SVF), along with hyaluronic acid (HA) and platelet-rich plasma (PRP) activated by calcium chloride, could regenerate cartilage-like tissue in human knee osteoarthritis (OA) patients. Autologous lipoaspirates were obtained from adipose tissue of the abdominal origin. Afterward, the lipoaspirates were minced to homogenize the ECM. These homogenized lipoaspirates were then mixed with collagenase and incubated. The resulting mixture of ADSCs and ECM in the form of SVF was injected, along with HA and PRP activated by calcium chloride, into knees of three Korean patients with OA. The same affected knees were reinjected weekly with additional PRP activated by calcium chloride for 3 weeks. Pretreatment and post-treatment magnetic resonance imaging (MRI) data, functional rating index, range of motion (ROM), and pain score data were then analyzed. All patients' MRI data showed cartilage-like tissue regeneration. Along with MRI evidence, the measured physical therapy outcomes in terms of ROM, subjective pain, and functional status were all improved. This study demonstrates that percutaneous injection of ADSCs with ECM contained in autologous adipose SVF, in conjunction with HA and PRP activated by calcium chloride, is a safe and potentially effective minimally invasive therapy for OA of human knees. PMID:27588219

  12. Regeneration of Cartilage in Human Knee Osteoarthritis with Autologous Adipose Tissue-Derived Stem Cells and Autologous Extracellular Matrix

    PubMed Central

    Pak, Jaewoo; Lee, Jung Hun; Park, Kwang Seung; Jeong, Byeong Chul; Lee, Sang Hee

    2016-01-01

    Abstract This clinical case series demonstrates that percutaneous injections of autologous adipose tissue-derived stem cells (ADSCs) and homogenized extracellular matrix (ECM) in the form of adipose stromal vascular fraction (SVF), along with hyaluronic acid (HA) and platelet-rich plasma (PRP) activated by calcium chloride, could regenerate cartilage-like tissue in human knee osteoarthritis (OA) patients. Autologous lipoaspirates were obtained from adipose tissue of the abdominal origin. Afterward, the lipoaspirates were minced to homogenize the ECM. These homogenized lipoaspirates were then mixed with collagenase and incubated. The resulting mixture of ADSCs and ECM in the form of SVF was injected, along with HA and PRP activated by calcium chloride, into knees of three Korean patients with OA. The same affected knees were reinjected weekly with additional PRP activated by calcium chloride for 3 weeks. Pretreatment and post-treatment magnetic resonance imaging (MRI) data, functional rating index, range of motion (ROM), and pain score data were then analyzed. All patients' MRI data showed cartilage-like tissue regeneration. Along with MRI evidence, the measured physical therapy outcomes in terms of ROM, subjective pain, and functional status were all improved. This study demonstrates that percutaneous injection of ADSCs with ECM contained in autologous adipose SVF, in conjunction with HA and PRP activated by calcium chloride, is a safe and potentially effective minimally invasive therapy for OA of human knees. PMID:27588219

  13. Autologous stem cell transplantation versus alternative allogeneic donor transplants in adult acute leukemias.

    PubMed

    Claude Gorin, Norbert

    2016-04-01

    The availability of alternative sources of stem cells including most recently T-replete haploidentical marrow or peripheral blood, and the increasing use of reduced-intensity conditioning (RIC), renders feasible an allogeneic transplant to almost all patients with acute leukemia up to 70 years of age. Autologous stem cell transplantation (ASCT) for consolidation of complete remission (CR), however, offers in some circumstances an alternative option. Although associated with a higher relapse rate, autologous transplant benefits from a lower non-relapse mortality, the absence of graft-versus-host disease (GVHD), and a better quality of life for long-term survivors. The recent use of intravenous busulfan (IVBU) with high-dose melphalan, better monitoring of minimal residual disease (MRD), and maintenance therapy post autografting bring new interest. Few retrospective studies compared the outcome following alternative donor versus autologous transplants for remission consolidation. Genoidentical and phenoidentical allogeneic stem cell transplantations are undisputed gold standards, but there are no data showing the superiority of alternative allogeneic donor over autologous transplantation, at the time of undetectable MRD, in patients with good- and intermediate-1 risk acute myelocytic leukemia (AML) in first complete remission (CR1), acute promyelocytic leukemia in second complete remission (CR2), and Philadelphia chromosome-positive (Ph(+)) acute lymphocytic leukemia (ALL). PMID:27000734

  14. Autologous stem cell transplantation versus alternative allogeneic donor transplants in adult acute leukemias.

    PubMed

    Claude Gorin, Norbert

    2016-04-01

    The availability of alternative sources of stem cells including most recently T-replete haploidentical marrow or peripheral blood, and the increasing use of reduced-intensity conditioning (RIC), renders feasible an allogeneic transplant to almost all patients with acute leukemia up to 70 years of age. Autologous stem cell transplantation (ASCT) for consolidation of complete remission (CR), however, offers in some circumstances an alternative option. Although associated with a higher relapse rate, autologous transplant benefits from a lower non-relapse mortality, the absence of graft-versus-host disease (GVHD), and a better quality of life for long-term survivors. The recent use of intravenous busulfan (IVBU) with high-dose melphalan, better monitoring of minimal residual disease (MRD), and maintenance therapy post autografting bring new interest. Few retrospective studies compared the outcome following alternative donor versus autologous transplants for remission consolidation. Genoidentical and phenoidentical allogeneic stem cell transplantations are undisputed gold standards, but there are no data showing the superiority of alternative allogeneic donor over autologous transplantation, at the time of undetectable MRD, in patients with good- and intermediate-1 risk acute myelocytic leukemia (AML) in first complete remission (CR1), acute promyelocytic leukemia in second complete remission (CR2), and Philadelphia chromosome-positive (Ph(+)) acute lymphocytic leukemia (ALL).

  15. Autologous transplant: microbial contamination of hematopoietic stem cell products.

    PubMed

    Almeida, Igor Dullius; Schmalfuss, Tissiana; Röhsig, Liane Marise; Goldani, Luciano Zubaran

    2012-01-01

    Hematopoietic progenitor cells from peripheral blood (HPCPB) are commonly used for autologous and allogenic transplants in patients with most various onco-hematological diseases, and despite the utilization of sterile techniques during collection and processing of these products, bacterial contamination can occur. This study aimed to investigate the microbial contamination of HPCPB products. Microbial cultures of 837 HPCPB products between the year 2000 and 2009 were retrospectively analyzed to determine the incidence of culture positivity and identify the main organisms that cause contamination. The microbiological studies were performed with an automated system (BacT/Alert(®) bioMérieux Corporate). Thirty-six (4.3%) of 837 microbial cultures were contaminated. Coagulase-negative Staphylococcus was the most frequent bacteria isolated from HPCPB products (20 [56%] of the 36 positive microbial cultures). Considering the 36 contaminated samples, 22 HPCPB products were infused and 14 discarded. Pre- and post-infusion antibiotic therapy of the patients transfused with contaminated products was established based on the isolated microorganism and its antibiogram. Microbial contamination rate of HPCPB products was low. Clinically significant outcomes after infusion of contaminated HPCPB products were not observed. PMID:22846122

  16. [Monomorphic post-transplant T-lymphoproliferative disorder after autologous stem cell transplantation for multiple myeloma].

    PubMed

    Ishikawa, Tetsuya; Shimizu, Hiroaki; Takei, Toshifumi; Koya, Hiroko; Iriuchishima, Hirono; Hosiho, Takumi; Hirato, Junko; Kojima, Masaru; Handa, Hiroshi; Nojima, Yoshihisa; Murakami, Hirokazu

    2016-01-01

    We report a rare case of T cell type monomorphic post-transplant lymphoproliferative disorders (PTLD) after autologous stem cell transplantation. A 53-year-old man with multiple myeloma received autologous stem cell transplantation and achieved a very good partial response. Nine months later, he developed a high fever and consciousness disturbance, and had multiple swollen lymph nodes and a high titer of Epstein-Barr (EB) virus DNA in his peripheral blood. Neither CT nor MRI of the brain revealed any abnormalities. Cerebrospinal fluid contained no malignant cells, but the EB virus DNA titer was high. Lymph node biopsy revealed T cell type monomorphic PTLD. Soon after high-dose treatment with methotrexate and cytosine arabinoside, the high fever and consciousness disturbance subsided, and the lymph node swelling and EB virus DNA disappeared. Given the efficacy of chemotherapy in this case, we concluded that the consciousness disturbance had been induced by central nervous system involvement of monomorphic PTLD. PMID:26861102

  17. [Monomorphic post-transplant T-lymphoproliferative disorder after autologous stem cell transplantation for multiple myeloma].

    PubMed

    Ishikawa, Tetsuya; Shimizu, Hiroaki; Takei, Toshifumi; Koya, Hiroko; Iriuchishima, Hirono; Hosiho, Takumi; Hirato, Junko; Kojima, Masaru; Handa, Hiroshi; Nojima, Yoshihisa; Murakami, Hirokazu

    2016-01-01

    We report a rare case of T cell type monomorphic post-transplant lymphoproliferative disorders (PTLD) after autologous stem cell transplantation. A 53-year-old man with multiple myeloma received autologous stem cell transplantation and achieved a very good partial response. Nine months later, he developed a high fever and consciousness disturbance, and had multiple swollen lymph nodes and a high titer of Epstein-Barr (EB) virus DNA in his peripheral blood. Neither CT nor MRI of the brain revealed any abnormalities. Cerebrospinal fluid contained no malignant cells, but the EB virus DNA titer was high. Lymph node biopsy revealed T cell type monomorphic PTLD. Soon after high-dose treatment with methotrexate and cytosine arabinoside, the high fever and consciousness disturbance subsided, and the lymph node swelling and EB virus DNA disappeared. Given the efficacy of chemotherapy in this case, we concluded that the consciousness disturbance had been induced by central nervous system involvement of monomorphic PTLD.

  18. Autologous Hematopoietic Stem Cell Transplantation-10 Years of Data From a Developing Country.

    PubMed

    Ali, Natasha; Adil, Salman Naseem; Shaikh, Mohammad Usman

    2015-08-01

    Intensive chemotherapy followed by autologous stem cell transplantation is the treatment of choice for patients with hematological malignancies. The objective of the present study was to evaluate the outcomes of patients with mainly lymphoma and multiple myeloma after autologous stem cell transplant. The pretransplant workup consisted of the complete blood count, an evaluation of the liver, kidney, lung, and infectious profile, chest radiographs, and a dental review. For lymphoma, all patients who achieved at least a 25% reduction in the disease after salvage therapy were included in the study. Mobilization was done with cyclophosphamide, followed by granulocyte colony-stimulating factor, 300 µg twice daily. The conditioning regimens included BEAM (carmustine, etoposide, cytarabine, melphalan) and high-dose melphalan. A total of 206 transplants were performed from April 2004 to December 2014. Of these, 137 were allogeneic transplants and 69 were autologous. Of the patients receiving an autologous transplant, 49 were male and 20 were female. Of the 69 patients, 26 underwent transplantation for Hodgkin's lymphoma, 23 for non-Hodgkin's lymphoma, and 15 for multiple myeloma and 4 and 1 for Ewing's sarcoma and neuroblastoma, respectively. The median age ± SD was 34 ± 13.1 years (range, 4-64). A mean of 4.7 × 10⁸ ± 1.7 mononuclear cells per kilogram were infused. The median time to white blood cell recovery was 18.2 ± 5.34 days. Transplant-related mortality occurred in 10 patients. After a median follow-up period of 104 months, the overall survival rate was 86%. High-dose chemotherapy, followed by autologous stem cell transplant, is an effective treatment option for patients with hematological malignancies, allowing further consolidation of response.

  19. Human transgene-free amniotic-fluid-derived induced pluripotent stem cells for autologous cell therapy.

    PubMed

    Jiang, Guihua; Di Bernardo, Julie; Maiden, Michael M; Villa-Diaz, Luis G; Mabrouk, Omar S; Krebsbach, Paul H; O'Shea, K Sue; Kunisaki, Shaun M

    2014-11-01

    The establishment of a reliable prenatal source of autologous, transgene-free progenitor cells has enormous potential in the development of regenerative-medicine-based therapies for infants born with devastating birth defects. Here, we show that a largely CD117-negative population of human amniotic fluid mesenchymal stromal cells (AF-MSCs) obtained from fetuses with or without prenatally diagnosed anomalies are readily abundant and have limited baseline differentiation potential when compared with bone-marrow-derived MSCs and other somatic cell types. Nonetheless, the AF-MSCs could be easily reprogrammed into induced pluripotent stem cells (iPSCs) using nonintegrating Sendai viral vectors encoding for OCT4, SOX2, KLF4, and cMYC. The iPSCs were virtually indistinguishable from human embryonic stem cells in multiple assays and could be used to generate a relatively homogeneous population of neural progenitors, expressing PAX6, SOX2, SOX3, Musashi-1, and PSA-NCAM, for potential use in neurologic diseases. Further, these neural progenitors showed engraftment potential in vivo and were capable of differentiating into mature neurons and astrocytes in vitro. This study demonstrates the usefulness of AF-MSCs as an excellent source for the generation of human transgene-free iPSCs ideally suited for autologous perinatal regenerative medicine applications. PMID:25014361

  20. Autologous transplantation of amniotic fluid-derived mesenchymal stem cells into sheep fetuses.

    PubMed

    Shaw, S W Steven; Bollini, Sveva; Nader, Khalil Abi; Gastaldello, Annalisa; Gastadello, Annalisa; Mehta, Vedanta; Filppi, Elisa; Cananzi, Mara; Gaspar, H Bobby; Qasim, Waseem; De Coppi, Paolo; David, Anna L

    2011-01-01

    Long-term engraftment and phenotype correction has been difficult to achieve in humans after in utero stem cell transplantation mainly because of allogeneic rejection. Autologous cells could be obtained during gestation from the amniotic fluid with minimal risk for the fetus and the mother. Using a sheep model, we explored the possibility of using amniotic fluid mesenchymal stem cells (AFMSCs) for autologous in utero stem cell/gene therapy. We collected amniotic fluid (AF) under ultrasound-guided amniocentesis in early gestation pregnant sheep (n = 9, 58 days of gestation, term = 145 days). AFMSCs were isolated and expanded in all sampled fetal sheep. Those cells were transduced using an HIV vector encoding enhanced green fluorescent protein (GFP) with 63.2% (range 38.3-96.2%) transduction efficiency rate. After expansion, transduced AFMSCs were injected into the peritoneal cavity of each donor fetal sheep at 76 days under ultrasound guidance. One ewe miscarried twin fetuses after amniocentesis. Intraperitoneal injection was successful in the remaining 7 fetal sheep giving a 78% survival for the full procedure. Tissues were sampled at postmortem examination 2 weeks later. PCR analysis detected GFP-positive cells in fetal tissues including liver, heart, placenta, membrane, umbilical cord, adrenal gland, and muscle. GFP protein was detected in these tissues by Western blotting and further confirmed by cytofluorimetric and immunofluorescence analyses. This is the first demonstration of autologous stem cell transplantation in the fetus using AFMSCs. Autologous cells derived from AF showed widespread organ migration and could offer an alternative way to ameliorate prenatal congenital disease.

  1. Multiple Myeloma Relapse Following Autologous Stem Cell Transplant Presenting With Diffuse Pulmonary Nodules

    PubMed Central

    Sumrall, Bradley; Diethelm, Lisa; Brown, Archie

    2013-01-01

    Background Multiple myeloma is a common disease, accounting for about 10% of hematologic malignancies in the United States. For eligible patients, the treatment of choice includes induction therapy (usually involving newer biologic agents) followed by autologous stem cell transplant; however, this treatment is generally not considered curative, and relapses usually occur. However, extramedullary relapse is an uncommon presentation, and relapses that involve the lungs have only rarely been described. Case Report We report the case of a patient who underwent an autologous stem cell transplant for multiple myeloma and subsequently relapsed with diffuse pulmonary nodules. She then had a rapid clinical and serologic response following initiation of salvage therapy. Conclusion This case is remarkable for both the radiographic appearance of the pulmonary involvement, as well as the rapid resolution of these findings after 2 cycles of treatment with bortezomib, dexamethasone, and lenalidomide. PMID:24358007

  2. Noncultured Autologous Adipose-Derived Stem Cells Therapy for Chronic Radiation Injury

    PubMed Central

    Akita, Sadanori; Akino, Kozo; Hirano, Akiyoshi; Ohtsuru, Akira; Yamashita, Shunichi

    2010-01-01

    Increasing concern on chronic radiation injuries should be treated properly for life-saving improvement of wound management and quality of life. Recently, regenerative surgical modalities should be attempted with the use of noncultured autologous adipose-derived stem cells (ADSCs) with temporal artificial dermis impregnated and sprayed with local angiogenic factor such as basic fibroblast growth factor, and secondary reconstruction can be a candidate for demarcation and saving the donor morbidity. Autologous adipose-derived stem cells, together with angiogenic and mitogenic factor of basic fibroblast growth factor and an artificial dermis, were applied over the excised irradiated skin defect and tested for Patients who were uneventfully healed with minimal donor-site morbidity, which lasts more than 1.5 years. PMID:21151652

  3. Fractionated stem cell infusions for patients with plasma cell myeloma undergoing autologous hematopoietic cell transplantation.

    PubMed

    Landau, Heather; Wood, Kevin; Chung, David J; Koehne, Guenther; Lendvai, Nikoletta; Hassoun, Hani; Lesokhin, Alexander; Hoover, Elizabeth; Zheng, Junting; Devlin, Sean M; Giralt, Sergio

    2016-08-01

    We conducted a phase II trial investigating the impact of fractionated hematopoietic cell infusions on engraftment kinetics and symptom burden in patients with plasma cell myeloma (PCM) undergoing autologous hematopoietic cell transplant (AHCT). We hypothesized that multiple hematopoietic cell infusions would reduce duration of neutropenia and enhance immune recovery resulting in a better tolerated procedure. Twenty-six patients received high-dose melphalan followed by multiple cell infusions (Days 0, +2, +4, +6) and were compared to PCM patients (N = 77) who received high-dose melphalan and a single infusion (Day 0) (concurrent control group). The primary endpoint was number of days with ANC <500K/mcL. Symptom burden was assessed using the MSK-modified MD Anderson Symptom Inventory. Median duration of neutropenia was similar in study (4 days, range 3-5) and control patients (4 days, range 3-9) (p = 0.654). There was no significant difference in the number of red cell or platelet transfusions, days of fever, diarrhea, antibiotics, number of documented infections, or length of admission. Symptom burden surveys showed that AHCT was well-tolerated in both study and control patients. We conclude that fractionated stem cell infusions following high-dose melphalan do not enhance engraftment kinetics or significantly alter patients' clinical course following AHCT in PCM.

  4. The graft of autologous adipose-derived stem cells in the corneal stromal after mechanic damage.

    PubMed

    Ma, Xiao-Yun; Bao, Hui-Jing; Cui, Lei; Zou, Jun

    2013-01-01

    This study was designed to explore the feasibility of using autologous rabbit adipose derived stem cells (rASCs) as seed cells and polylactic-co-glycolic acid (PLGA) as a scaffold for repairing corneal stromal defects. rASCs isolated from rabbit nape adipose tissue were expanded and seeded on a PLGA scaffold to fabricate cell-scaffold constructs. After 1 week of cultivation in vitro, the cell-scaffold complexes were transplanted into corneal stromal defects in rabbits. In vivo, the autologous rASCs-PLGA constructed corneal stroma gradually became transparent without corneal neovascularization after 12 weeks. Hematoxylin and eosin staining and transmission electron microscopy examination revealed that their histological structure and collagen fibril distribution at 24 weeks after implantation were similar to native counterparts. As to the defect treated with PLGA alone, the stromal defects remained. And scar tissue was observed in the untreated-group. The implanted autologous ASCs survived up to 24 weeks post-transplantation and differentiated into functional keratocytes, as assessed by the expression of aldehyde-3-dehydrogenase1A1 (ALDH1A1) and cornea-specific proteoglycan keratocan. Our results revealed that autologous rASCs could be one of the cell sources for corneal stromal restoration in diseased corneas or for tissue engineering of a corneal equivalent.

  5. Bone marrow concentrate for autologous transplantation in minipigs. Characterization and osteogenic potential of mesenchymal stem cells.

    PubMed

    Herten, M; Grassmann, J P; Sager, M; Benga, L; Fischer, J C; Jäger, M; Betsch, M; Wild, M; Hakimi, M; Jungbluth, P

    2013-01-01

    Autologous bone marrow plays an increasing role in the treatment of bone, cartilage and tendon healing disorders. Cell-based therapies display promising results in the support of local regeneration, especially therapies using intra-operative one-step treatments with autologous progenitor cells. In the present study, bone marrow-derived cells were concentrated in a point-of-care device and investigated for their mesenchymal stem cell (MSC) characteristics and their osteogenic potential. Bone marrow was harvested from the iliac crest of 16 minipigs. The mononucleated cells (MNC) were concentrated by gradient density centrifugation, cultivated, characterized by flow cytometry and stimulated into osteoblasts, adipocytes, and chondrocytes. Cell differentiation was investigated by histological and immunohistological staining of relevant lineage markers. The proliferation capacity was determined via colony forming units of fibroblast and of osteogenic alkaline-phosphatase-positive-cells. The MNC could be enriched 3.5-fold in nucleated cell concentrate in comparison to bone marrow. Flow cytometry analysis revealed a positive signal for the MSC markers. Cells could be differentiated into the three lines confirming the MSC character. The cellular osteogenic potential correlated significantly with the percentage of newly formed bone in vivo in a porcine metaphyseal long-bone defect model. This study demonstrates that bone marrow concentrate from minipigs display cells with MSC character and their osteogenic differentiation potential can be used for osseous defect repair in autologous transplantations.

  6. Safety Concern between Autologous Fat Graft, Mesenchymal Stem Cell and Osteosarcoma Recurrence

    PubMed Central

    Perrot, Pierre; Rousseau, Julie; Bouffaut, Anne-Laure; Rédini, Françoise; Cassagnau, Elisabeth; Deschaseaux, Frédéric; Heymann, Marie-Françoise; Heymann, Dominique; Duteille, Franck; Trichet, Valérie; Gouin, François

    2010-01-01

    Background Osteosarcoma is the most common malignant primary bone tumour in young adult treated by neo adjuvant chemotherapy, surgical tumor removal and adjuvant multidrug chemotherapy. For correction of soft tissue defect consecutive to surgery and/or tumor treatment, autologous fat graft has been proposed in plastic and reconstructive surgery. Principal Findings We report here a case of a late local recurrence of osteosarcoma which occurred 13 years after the initial pathology and 18 months after a lipofilling procedure. Because such recurrence was highly unexpected, we investigated the possible relationship of tumor growth with fat injections and with mesenchymal stem/stromal cell like cells which are largely found in fatty tissue. Results obtained in osteosarcoma pre-clinical models show that fat grafts or progenitor cells promoted tumor growth. Significance These observations and results raise the question of whether autologous fat grafting is a safe reconstructive procedure in a known post neoplasic context. PMID:20544017

  7. A question of ethics: selling autologous stem cell therapies flaunts professional standards.

    PubMed

    Munsie, Megan; Hyun, Insoo

    2014-11-01

    The idea that the body's own stem cells could act as a repair kit for many conditions, including cardiac repair, underpins regenerative medicine. While progress is being made, with hundreds of clinical trials underway to evaluate possible autologous cell-based therapies, some patients and physicians are not prepared to wait and are pursuing treatments without evidence that the proposed treatments are effective, or even safe. This article explores the inherent tension between patients, practitioners and the need to regulate the development and commercialization of new cellular therapies--even when the cells come from the patient.

  8. Novel therapy for type 1 diabetes: autologous hematopoietic stem cell transplantation.

    PubMed

    Li, Lirong; Gu, Weiqiong; Zhu, Dalong

    2012-12-01

    Type 1 diabetes is characterized pathologically by autoimmune insulitis-related islet β-cell destruction. Although intensive insulin therapy for patients with type 1 diabetes can correct hyperglycemia, this therapy does not prevent all diabetes-related complications. Recent studies have shown that autologous hematopoietic stem cell transplantation (HSCT) is a promising new approach for the treatment of type 1 diabetes by reconstitution of immunotolerance and preservation of islet β-cell function. Herein we discuss the therapeutic efficacy and potential mechanisms underlying the action of HSCT and other perspectives in the clinical management of type 1 diabetes.

  9. Reengineering autologous bone grafts with the stem cell activator WNT3A.

    PubMed

    Jing, Wei; Smith, Andrew A; Liu, Bo; Li, Jingtao; Hunter, Daniel J; Dhamdhere, Girija; Salmon, Benjamin; Jiang, Jie; Cheng, Du; Johnson, Chelsey A; Chen, Serafine; Lee, Katherine; Singh, Gurpreet; Helms, Jill A

    2015-04-01

    Autologous bone grafting represents the standard of care for treating bone defects but this biomaterial is unreliable in older patients. The efficacy of an autograft can be traced back to multipotent stem cells residing within the bone graft. Aging attenuates the viability and function of these stem cells, leading to inconsistent rates of bony union. We show that age-related changes in autograft efficacy are caused by a loss in endogenous Wnt signaling. Blocking this endogenous Wnt signal using Dkk1 abrogates autograft efficacy whereas providing a Wnt signal in the form of liposome-reconstituted WNT3A protein (L-WNT3A) restores bone forming potential to autografts from aged animals. The bioengineered autograft exhibits significantly better survival in the hosting site. Mesenchymal and skeletal stem cell populations in the autograft are activated by L-WNT3A and mitotic activity and osteogenic differentiation are significantly enhanced. In a spinal fusion model, aged autografts treated with L-WNT3A demonstrate superior bone forming capacity compared to the standard of care. Thus, a brief incubation in L-WNT3A reliably improves autologous bone grafting efficacy, which has the potential to significantly improve patient care in the elderly.

  10. Reengineering autologous bone grafts with the stem cell activator WNT3A.

    PubMed

    Jing, Wei; Smith, Andrew A; Liu, Bo; Li, Jingtao; Hunter, Daniel J; Dhamdhere, Girija; Salmon, Benjamin; Jiang, Jie; Cheng, Du; Johnson, Chelsey A; Chen, Serafine; Lee, Katherine; Singh, Gurpreet; Helms, Jill A

    2015-04-01

    Autologous bone grafting represents the standard of care for treating bone defects but this biomaterial is unreliable in older patients. The efficacy of an autograft can be traced back to multipotent stem cells residing within the bone graft. Aging attenuates the viability and function of these stem cells, leading to inconsistent rates of bony union. We show that age-related changes in autograft efficacy are caused by a loss in endogenous Wnt signaling. Blocking this endogenous Wnt signal using Dkk1 abrogates autograft efficacy whereas providing a Wnt signal in the form of liposome-reconstituted WNT3A protein (L-WNT3A) restores bone forming potential to autografts from aged animals. The bioengineered autograft exhibits significantly better survival in the hosting site. Mesenchymal and skeletal stem cell populations in the autograft are activated by L-WNT3A and mitotic activity and osteogenic differentiation are significantly enhanced. In a spinal fusion model, aged autografts treated with L-WNT3A demonstrate superior bone forming capacity compared to the standard of care. Thus, a brief incubation in L-WNT3A reliably improves autologous bone grafting efficacy, which has the potential to significantly improve patient care in the elderly. PMID:25682158

  11. Infusion of autologous retrodifferentiated stem cells into patients with beta-thalassemia.

    PubMed

    Abuljadayel, Ilham Saleh; Quereshi, Huma; Ahsan, Tasnim; Rizvi, Shakil; Ahmed, Tamseela; Khan, Sabiha Mirza; Akhtar, Jawaid; Dhoot, Ghazi

    2006-01-01

    Beta-thalassemia is a genetic, red blood cell disorder affecting the beta-globin chain of the adult hemoglobin gene. This results in excess accumulation of unpaired alpha-chain gene products leading to reduced red blood cell life span and the development of severe anemia. Current treatment of this disease involves regular blood transfusion and adjunct chelation therapy to lower blood transfusion-induced iron overload. Fetal hemoglobin switching agents have been proposed to treat genetic blood disorders, such as sickle cell anemia and beta-thalassemia, in an effort to compensate for the dysfunctional form of the beta-globin chain in adult hemoglobin. The rationale behind this approach is to pair the excess normal alpha-globin chain with the alternative fetal gamma-chain to promote red blood cell survival and ameliorate the anemia. Reprogramming of differentiation in intact, mature, adult white blood cells in response to inclusion of monoclonal antibody CR3/43 has been described. This form of retrograde development has been termed "retrodifferentiation", with the ability to re-express a variety of stem cell markers in a heterogeneous population of white blood cells. This form of reprogramming, or reontogeny, to a more pluripotent stem cell state ought to recapitulate early hematopoiesis and facilitate expression of a fetal and/or adult program of hemoglobin synthesis or regeneration on infusion and subsequent redifferentiation. Herein, the outcome of infusion of autologous retrodifferentiated stem cells (RSC) into 21 patients with beta-thalassemia is described. Over 6 months, Infusion of 3-h autologous RSC subjected to hematopoietic-conducive conditions into patients with beta-thalassemia reduced mean blood transfusion requirement, increased mean fetal hemoglobin synthesis, and significantly lowered mean serum ferritin. This was always accompanied by an increase in mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin

  12. [Outcomes of using autologous peripheral-blood stem cells in patients with chronic lower arterial insufficiency].

    PubMed

    Maksimov, A V; Kiiasov, A P; Plotnikov, M V; Maianskaia, S D; Shamsutdinova, I I; Gazizov, I M; Mavlikeev, M O

    2011-01-01

    Presented herein are the outcomes of using autologous peripheral blood stem cells (SCs) in patients with stage II В lower limb chronic obliterating diseases (according to A.V. Pokrovsky's classification). Autologous SCs had previously been stimulated by means of the recombinant granulocytic colony stimulating factor (G-CSF) for five days. On day six, we performed mobilization of the peripheral blood stem cells on the MSC+ unit by means of leukopheresis followed by intramuscular administration of half of the obtained dose into the affected extremity. The mean number of the transplanted mononuclears amounted to 6.73 ± 2.2 x 10(9) cells, with the number of CD34+ cells averaging 2.94 ± 2.312 x 10(7). Assessing the therapeutic outcomes at 3 and 6 months of follow-up showed a statistically significant increase in the ankle-brachial pressure index (ABPI) [being at baseline 0.59 ± 0.04, at 3 months - 0.66 ± 0.04 (P=0.001), and after 6 months - 0.73 ± .08 (P=0.035)], accompanied and followed by improved measures of the treadmill test, with the pain-free walking distance at baseline equalling 102.2 ± 11.55 m, after 3 months - 129 ± 11.13 m (P<0.001), and after 6 months - 140 ± 13.11 m=0.021 vs baseline). The findings of the immunohistochemical study confirmed the development of neoangiogenesis in the skeletal muscle and a 25 percent increase in the capillary-network density following administration of autologous stem cells into the muscle. The method of transplanting peripheral-blood autologous stem cells for treatment of patients presenting with distal forms of chronic obliterating insufficiency of the lower limbs proved safe and efficient. The findings obtained during this study made it possible to recommend extending the indications for its application at the expense of patients with critical ischaemia. PMID:21983456

  13. T-cell-replete haploidentical transplantation versus autologous stem cell transplantation in adult acute leukemia: a matched pair analysis.

    PubMed

    Gorin, Norbert-Claude; Labopin, Myriam; Piemontese, Simona; Arcese, William; Santarone, Stella; Huang, He; Meloni, Giovanna; Ferrara, Felicetto; Beelen, Dietrich; Sanz, Miguel; Bacigalupo, Andrea; Ciceri, Fabio; Mailhol, Audrey; Nagler, Arnon; Mohty, Mohamad

    2015-04-01

    Adult patients with acute leukemia in need of a transplant but without a genoidentical donor are usually considered upfront for transplantation with stem cells from any other allogeneic source, rather than autologous stem cell transplantation. We used data from the European Society for Blood and Marrow Transplantation and performed a matched pair analysis on 188 T-cell-replete haploidentical and 356 autologous transplants done from January 2007 to December 2012, using age, diagnosis, disease status, cytogenetics, and interval from diagnosis to transplant as matching factors. "Haploidentical expert" centers were defined as having reported more than five haploidentical transplants for acute leukemia (median value for the study period). The median follow-up was 28 months. Multivariate analyses, including type of transplant categorized into three classes ("haploidentical regular", "haploidentical expert" and autologous), conditioning intensity (reduced intensity versus myeloablative conditioning) and the random effect taking into account associations related to matching, showed that non-relapse mortality was higher following haploidentical transplants in expert (HR: 4.7; P=0.00004) and regular (HR: 8.98; P<10(-5)) centers. Relapse incidence for haploidentical transplants was lower in expert centers (HR:0.39; P=0.0003) but in regular centers was similar to that for autologous transplants. Leukemia-free survival and overall survival rates were higher following autologous transplantation than haploidentical transplants in regular centers (HR: 1.63; P=0.008 and HR: 2.31; P=0.0002 respectively) but similar to those following haploidentical transplants in expert centers. We conclude that autologous stem cell transplantation should presently be considered as a possible alternative to haploidentical transplantation in regular centers that have not developed a specific expert program. PMID:25637051

  14. T-cell-replete haploidentical transplantation versus autologous stem cell transplantation in adult acute leukemia: a matched pair analysis.

    PubMed

    Gorin, Norbert-Claude; Labopin, Myriam; Piemontese, Simona; Arcese, William; Santarone, Stella; Huang, He; Meloni, Giovanna; Ferrara, Felicetto; Beelen, Dietrich; Sanz, Miguel; Bacigalupo, Andrea; Ciceri, Fabio; Mailhol, Audrey; Nagler, Arnon; Mohty, Mohamad

    2015-04-01

    Adult patients with acute leukemia in need of a transplant but without a genoidentical donor are usually considered upfront for transplantation with stem cells from any other allogeneic source, rather than autologous stem cell transplantation. We used data from the European Society for Blood and Marrow Transplantation and performed a matched pair analysis on 188 T-cell-replete haploidentical and 356 autologous transplants done from January 2007 to December 2012, using age, diagnosis, disease status, cytogenetics, and interval from diagnosis to transplant as matching factors. "Haploidentical expert" centers were defined as having reported more than five haploidentical transplants for acute leukemia (median value for the study period). The median follow-up was 28 months. Multivariate analyses, including type of transplant categorized into three classes ("haploidentical regular", "haploidentical expert" and autologous), conditioning intensity (reduced intensity versus myeloablative conditioning) and the random effect taking into account associations related to matching, showed that non-relapse mortality was higher following haploidentical transplants in expert (HR: 4.7; P=0.00004) and regular (HR: 8.98; P<10(-5)) centers. Relapse incidence for haploidentical transplants was lower in expert centers (HR:0.39; P=0.0003) but in regular centers was similar to that for autologous transplants. Leukemia-free survival and overall survival rates were higher following autologous transplantation than haploidentical transplants in regular centers (HR: 1.63; P=0.008 and HR: 2.31; P=0.0002 respectively) but similar to those following haploidentical transplants in expert centers. We conclude that autologous stem cell transplantation should presently be considered as a possible alternative to haploidentical transplantation in regular centers that have not developed a specific expert program.

  15. Transient global amnesia associated with the infusion of DMSO-cryopreserved autologous peripheral blood stem cells.

    PubMed

    Otrock, Zaher K; Beydoun, Ahmad; Barada, Wissam M; Masroujeh, Rami; Hourani, Rola; Bazarbachi, Ali

    2008-03-01

    Dimethylsulfoxide (DMSO) is a solvent commonly used for the cryopreservation of autologous peripheral blood stem cells (APBSC). Side effects upon infusion of DMSO-cryopreserved APBSC mainly consist of nausea, emesis, chills, rigors, and cardiovascular events, such as bradyarrhythmia or hypotension. We report the case of a patient who received DMSO-cryopreserved APBSC after myeloablative chemotherapy for a relapsing lymphoma. The patient developed a rare reaction during the infusion manifesting as transient global amnesia. The clinical course during the reaction is described and an explanation of the possible causes is discussed. This observation underlines the need for an adequate DMSO depletion to limit neurotoxicity or other adverse manifestations. PMID:18310533

  16. The Role of Autologous and Allogeneic Hematopoietic Stem Cell Transplantation for Hodgkin Lymphoma

    PubMed Central

    Holmberg, Leona; Maloney, David G.

    2011-01-01

    Patients with Hodgkin lymphoma are usually cured by primary therapy using chemotherapy alone or combined modality therapy with external beam radiation. Patients who do not experience a complete remission or those who experience relapse may by salvaged by high-dose therapy and autologous hematopoietic stem cell transplantation (ASCT). Success of this approach is largely dependent on the tumor being sensitive to salvage chemotherapy before transplant. More studies are showing the predictive value of functional imaging in this setting. Allogeneic hematopoietic stem cell transplantation has greater risk of nonrelapse mortality and is generally reserved for patients who experience relapse post-ASCT, but may provide long-term survival for some patients through graft-versus-tumor immune effects. PMID:21917627

  17. Autologous Stem Cell Transplant Recipients Tolerate Haploidentical Related-Donor Natural Killer Cell Enriched Infusions

    PubMed Central

    Klingemann, Hans; Grodman, Carrie; Cutler, Elliott; Duque, Marvin; Kadidlo, Diane; Klein, Andreas K.; Sprague, Kellie A.; Miller, Kenneth B.; Comenzo, Raymond L.; Kewalramani, Tarun; Yu, Neng; Van Etten, Richard A.; McKenna, David H.

    2012-01-01

    BACKGROUND In the setting of allogeneic stem cell transplantation (alloSCT), infusing natural killer (NK) cells from a major histocompatibility complex (MHC) mismatched donor can mediate an anti-leukemic effect. Graft versus tumor (GvT) effect following autologous stem cell transplantation (ASCT) may result in less disease relapse. STUDY DESIGN AND METHODS We performed a phase I clinical trial to assess the safety and feasibility of infusing distantly processed donor NK enriched mononuclear cell (NK-MC) infusions from a MHC haplotype mismatched (haploidentical) donor to patients who recently underwent ASCT for a hematologic malignancy. On day 1, peripheral blood mononuclear cells (MC) were obtained by steady-state leukapheresis and sent from Boston to the Production Assistance for Cellular Therapies (PACT) facility at the University of Minnesota, where immunomagnetic depletion of CD3 cells was performed on day 2. NK-MC product were then returned to Boston on day 2 for infusion on day 3. Toxicity, cellular product characteristics and logistic events were monitored. RESULTS At a median of 90 days (range, 49–191) following ASCT, thirteen patients were treated with escalating doses of NK-MC per kg from 105 to 2 ×107. Adverse effects included grade 2 rigors and muscle aches, but no grade 3 or 4 events, and no GvHD or marrow suppression. One air courier delay occurred. NK-MC products were viable with cytotoxic activity after transport. CONCLUSION CD3-depleted, MHC mismatched allogeneic NK-MC infusions can be safely and feasibly administered to patients after ASCT following distant processing and transport, justifying further development of this approach. PMID:22738379

  18. Autologous Adipose Stem Cells in Treatment of Female Stress Urinary Incontinence: Results of a Pilot Study

    PubMed Central

    Sartoneva, Reetta; Haimi, Suvi; Mannerström, Bettina; Tomás, Eija; Miettinen, Susanna; Nieminen, Kari

    2014-01-01

    The purpose of our study was to find out whether transurethral injections of autologous adipose stem cells (ASCs) are an effective and a safe treatment for female stress urinary incontinence (SUI). We treated five SUI patients with ASCs combined with bovine collagen gel and saline. Prior to the treatment, the ASCs were isolated from subcutaneous fat and expanded for 3 weeks in a good manufacturing practice-level laboratory. The mixture of ASCs and collagen was injected transurethrally via cystoscope. Additionally, viability, multipotency, and surface marker profile of ASCs were analyzed in vitro. We followed up with patients 3, 6, and 12 months after the injections. The primary endpoint was a cough test to measure objectively the effect of the treatment. Validated questionnaires were used to determine the subjective cure rate. After 6 months, 1 of 5 patients displayed a negative cough test with full bladder filled with 500 ml of saline. At 1 year, the cough test was negative with three patients; two of them were satisfied with the treatment and did not wish further treatment for SUI. Validated questionnaires showed some subjective improvement in all five patients. This is the first study describing the use of autologous ASCs in combination with collagen gel for female SUI treatments. Thus far, the treatment with autologous ASCs has proven safe and well tolerated. However, the feasibility and efficacy of the treatment were not optimal; therefore, additional research is needed to develop SUI injection therapies. PMID:24985079

  19. Autologous Transplantation of Bone Marrow Adult Stem Cells for the Treatment of Idiopathic Dilated Cardiomyopathy

    PubMed Central

    Westphal, Ricardo João; Bueno, Ronaldo Rocha Loures; Galvão, Paulo Bezerra de Araújo; Zanis Neto, José; Souza, Juliano Mendes; Guérios, Ênio Eduardo; Senegaglia, Alexandra Cristina; Brofman, Paulo Roberto; Pasquini, Ricardo; da Cunha, Claudio Leinig Pereira

    2014-01-01

    Background Morbimortality in patients with dilated idiopathic cardiomyopathy is high, even under optimal medical treatment. Autologous infusion of bone marrow adult stem cells has shown promising preliminary results in these patients. Objective Determine the effectiveness of autologous transplantation of bone marrow adult stem cells on systolic and diastolic left ventricular function, and on the degree of mitral regurgitation in patients with dilated idiopathic cardiomyopathy in functional classes NYHA II and III. Methods We administered 4,54 x 108 ± 0,89 x 108 bone marrow adult stem cells into the coronary arteries of 24 patients with dilated idiopathic cardiomyopathy in functional classes NYHA II and III. Changes in functional class, systolic and diastolic left ventricular function and degree of mitral regurgitation were assessed after 3 months, 6 months and 1 year. Results During follow-up, six patients (25%) improved functional class and eight (33.3%) kept stable. Left ventricular ejection fraction improved 8.9%, 9.7% e 13.6%, after 3, 6 and 12 months (p = 0.024; 0.017 and 0.018), respectively. There were no significant changes neither in diastolic left ventricular function nor in mitral regurgitation degree. A combined cardiac resynchronization and implantable cardioversion defibrillation was implanted in two patients (8.3%). Four patients (16.6%) had sudden death and four patients died due to terminal cardiac failure. Average survival of these eight patients was 2.6 years. Conclusion Intracoronary infusion of bone marrow adult stem cells was associated with an improvement or stabilization of functional class and an improvement in left ventricular ejection fraction, suggesting the efficacy of this intervention. There were no significant changes neither in left ventricular diastolic function nor in the degree of mitral regurgitation. PMID:25590932

  20. Human autologous mesenchymal stem cells with extracorporeal shock wave therapy for nonunion of long bones

    PubMed Central

    Zhai, Lei; Ma, Xin-Long; Jiang, Chuan; Zhang, Bo; Liu, Shui-Tao; Xing, Geng-Yan

    2016-01-01

    Background: Currently, the available treatments for long bone nonunion (LBN) are removing of focus of infection, bone marrow transplantation as well as Ilizarov methods etc. Due to a high percentage of failures, the treatments are complex and debated. To develop an effective method for the treatment of LBN, we explored the use of human autologous bone mesenchymal stems cells (hBMSCs) along with extracorporeal shock wave therapy (ESWT). Materials and Methods: Sixty three patients of LBN were subjected to ESWT treatment and were divided into hBMSCs transplantation group (Group A, 32 cases) and simple ESWT treatment group (Group B, 31 cases). Results: The patients were evaluated for 12 months after treatment. In Group A, 14 patients were healed and 13 showed an improvement, with fracture healing rate 84.4%. In Group B, eight patients were healed and 13 showed an improvement, with fracture healing rate 67.7%. The healing rates of the two groups exhibited a significant difference (P < 0.05). There was no significant difference for the callus formation after 3 months treatment (P > 0.05). However, the callus formation in Group A was significantly higher than that in the Group B after treatment for 6, 9, and 12 months (P < 0.05). Conclusion: Autologous bone mesenchymal stems cell transplantation with ESWT can effectively promote the healing of long bone nonunions. PMID:27746499

  1. How we manage autologous stem cell transplantation for patients with multiple myeloma

    PubMed Central

    Dingli, David

    2014-01-01

    An estimated 22 350 patients had multiple myeloma diagnosed in 2013, representing 1.3% of all new cancers; 10 710 deaths are projected, representing 1.8% of cancer deaths. Approximately 0.7% of US men and women will have a myeloma diagnosis in their lifetime, and with advances in therapy, 77 600 US patients are living with myeloma. The 5-year survival rate was 25.6% in 1989 and was 44.9% in 2005. The median age at diagnosis is 69 years, with 62.4% of patients aged 65 or older at diagnosis. Median age at death is 75 years. The rate of new myeloma cases has been rising 0.7% per year during the past decade. The most common indication for autologous stem cell transplantation in the United States is multiple myeloma, and this article is designed to provide the specifics of organizing a transplant program for multiple myeloma. We review the data justifying use of stem cell transplantation as initial management in myeloma patients. We provide selection criteria that minimize the risks of transplantation. Specific guidelines on mobilization and supportive care through the transplant course, as done at Mayo Clinic, are given. A review of the data on tandem vs sequential autologous transplants is provided. PMID:24973360

  2. Resetting the immune system with immunoablation and autologous haematopoietic stem cell transplantation in autoimmune diseases.

    PubMed

    Alexander, Tobias; Arnold, Renate; Hiepe, Falk; Radbruch, Andreas

    2016-01-01

    Over the past 20 years, immunoablation followed by transplantation of autologous haematopoietic stem cells (ASCT) has emerged as a promising treatment option for patients with severe forms of autoimmune diseases (ADs) that insufficiently respond to standard immunosuppressive or novel biologic treatment. Meanwhile, mechanistic studies have provided the proof-of-concept that the long-term, treatment-free remissions achieved by ASCT are associated with the eradication of the autoreactive immunologic memory and a fundamental reconfiguration of the immune system. The latter comprises regeneration of naive B cells and a stable thymic reactivation with re-emergence of thymic-derived naive T cells, including Foxp3+ regulatory T cells, with new antigen receptors, i.e. immune reset. In this article, we discuss mechanistic studies that investigated how such immune renewal after ASCT may rewire a faulty immune system in ADs into a self-tolerant state, to induce long-term remissions. PMID:27586805

  3. Treatment of severe post-traumatic bone defects with autologous stem cells loaded on allogeneic scaffolds.

    PubMed

    Vulcano, Ettore; Murena, Luigi; Cherubino, Paolo; Falvo, Daniele A; Rossi, Antonio; Baj, Andreina; Toniolo, Antonio

    2012-12-01

    Mesenchymal stem cells may differentiate into angiogenic and osteoprogenitor cells. The effectiveness of autologous pluripotent mesenchymal cells for treating bone defects has not been investigated in humans. We present a case series to evaluate the rationale of using nucleated cells from autologous bone marrow aspirates in the treatment of severe bone defects that failed to respond to traditional treatments. Ten adult patients (mean age, 49.6-years-old) with severe bone defects were included in this study. Lower limb bone defects were >or=5 cm3 in size, and upper limb defects .or=2 cm3. Before surgery, patients were tested for antibodies to common pathogens. Treatment consisted of bone allogeneic scaffold enriched with bone marrow nucleated cells harvested from the iliac crest and concentrated using an FDA-approved device. Postsurgery clinical and radiographic follow-up was performed at 1, 3, 6, and 12 months. To assess viability, morphology, and immunophenotype, bone marrow nucleated cells were cultured in vitro, tested for sterility, and assayed for the possible replication of adventitious (contaminating) viruses. In 9 of 10 patients, both clinical and radiographic healing of the bone defect along with bone graft integration were observed (mean time, 5.6 months); one patient failed to respond. No post-operative complications were observed. Bone marrow nucleated cells were enriched 4.49-fold by a single concentration step, and these enriched cells were free of microbial contamination. The immunophenotype of adherent cells was compatible with that of mesenchymal stem cells. We detected the replication of Epstein-Barr virus in 2/10 bone marrow cell cultures tested. Hepatitis B virus, cytomegalovirus, parvovirus B19, and endogenous retrovirus HERV-K replication were not detected. Overall, 470 to 1,150 million nucleated cells were grafted into each patient. This case series, with a mean follow-up of almost 2 years, demonstrates that an allogeneic bone scaffold

  4. Outcome after autologous stem cell transplantation for multiple myeloma in patients with preceding plasma cell disorders.

    PubMed

    Kumar, Shaji K; Dingli, David; Lacy, Martha Q; Dispenzieri, Angela; Hayman, Suzanne R; Buadi, Francis K; Rajkumar, S Vincent; Litzow, Mark R; Gertz, Morie A

    2008-04-01

    A third of patients with multiple myeloma (MM) have a preceding diagnosis of plasma cell proliferative disorder (PCPD), mostly monoclonal gammopathy of undetermined significance (MGUS), smoldering MM (SMM) or plasmacytoma. While autologous stem cell transplantation (SCT) improves survival in MM, it is not clear if patients with preceding PCPD have a different outcome. We identified 151 patients with preceding PCPD from among 804 patients undergoing SCT, and their outcomes were compared. The response rates, including complete responses, were similar between the groups. Patients with a preceding diagnosis of MGUS had longer time to progression (TTP; 27.5 months vs. 17.2 months, P = 0.01), and longer overall survival (OS) from transplant (80.2 months vs. 48.3 months, P = 0.03) compared to those with de novo myeloma. However no differences were seen among those with a preceding diagnosis of SMM or plasmacytoma in terms of TTP or OS from transplant when compared to those with de novo myeloma. Multivariate analysis indicated that the presence of MGUS prior to myeloma was prognostic for post-transplant relapse independent of other known risk factors. Patients with pre-existing MGUS prior to myeloma diagnosis have a better outcome following HDT, reflecting more indolent disease and a favourable biology than those presenting with de novo myeloma. PMID:18318761

  5. Therapeutic Efficacy of Fresh, Autologous Mesenchymal Stem Cells for Severe Refractory Gingivostomatitis in Cats

    PubMed Central

    Mills-Ko, Emily; Verstraete, Frank J.M.; Kol, Amir; Walker, Naomi J.; Badgley, Megan R.; Fazel, Nasim; Murphy, William J.; Vapniarsky, Natalia; Borjesson, Dori L.

    2016-01-01

    Mesenchymal stem cells (MSCs) are a promising therapy for immune-mediated and inflammatory disorders, because of their potent immunomodulatory properties. In this study, we investigated the use of fresh, autologous, adipose-derived MSCs (ASCs) for feline chronic gingivostomatitis (FCGS), a chronic, debilitating, idiopathic, oral mucosal inflammatory disease. Nine cats with refractory FCGS were enrolled in this pilot study. Each cat received 2 intravenous injections of 20 million autologous ASCs, 1 month apart. Oral biopsies were taken before and at 6 months after the first ASC injection. Blood immune cell subsets, serum protein, and cytokine levels were measured at 0, 1, 3, and 6 months after treatment to assess immunomodulatory effects. Seven of the 9 cats completed the study. Five cats responded to treatment by either complete clinical remission (n = 3) or substantial clinical improvement (n = 2). Two cats were nonresponders. Cats that responded to treatment also exhibited systemic immunomodulation demonstrated by decreased numbers of circulating CD8+ T cells, a normalization of the CD4/CD8 ratio, decreased neutrophil counts, and interferon-γ and interleukin (IL)-1β concentration, and a temporary increase in serum IL-6 and tumor necrosis factor-α concentration. No clinical recurrence has occurred following complete clinical remission (follow-up of 6–24 months). In this study, cats with <15% cytotoxic CD8 T cells with low expression of CD8 (CD8lo) cells were 100% responsive to ASC therapy, whereas cats with >15% CD8lo cells were nonresponders. The relative absence of CD8lo cells may be a biomarker to predict response to ASC therapy, and may shed light on pathogenesis of FCGS and mechanisms by which ASCs decrease oral inflammation and affect T-cell phenotype. Significance This study is the first to demonstrate the safety and efficacy of fresh, autologous, adipose-derived stem cell systemic therapy for a naturally occurring, chronic inflammatory disease in cats

  6. Bone reconstruction of large defects using bone marrow derived autologous stem cells.

    PubMed

    Lucarelli, Enrico; Donati, Davide; Cenacchi, Annarita; Fornasari, Pier Maria

    2004-04-01

    Bone is a tissue that has the ability to heal itself when fractured. Occasionally, a critical defect can be formed when part of the bone is lost or excised, in this case the bone fails to heal and requires bone reconstruction to prevent a non-union defect. Autogenous cancellous bone is the current gold standard treatment in bone loss. Because the amount of autogenous cancellous bone that can be harvested is limited, the expanding need for bone reconstruction is paired by the growth of interest in the discipline of tissue engineering. Labs worldwide are working to provide the right carrier and the right set of cells that, once retransplanted, will ensure bone repair. Several investigators have focused their attention on a subset of autologous non-hematopoietic stem/progenitor cells contained in the adult bone marrow stroma, referred to as stromal stem cells (SSC), as the appropriate cells to be transplanted. The use of autologous cells is facilitated by less stringent ethical and regulatory issues and does not require the patient to be immunologically suppressed. In pre-clinical and clinical protocols of critical defects in which SSC are employed, two approaches are mainly used: in the first, SSC are derived from bone marrow and directly introduced at the lesion site, in the second, SSC are derived from several sites and are expanded ex vivo before being implanted. Both approaches, equally correct in principle, will have to demonstrate, with definitive evidence of their efficacy, their capability of solving a critical clinical problem such as non-union. In this report we outline the difficulties of working with SSC.

  7. Myeloid/Microglial Driven Autologous Hematopoietic Stem Cell Gene Therapy Corrects a Neuronopathic Lysosomal Disease

    PubMed Central

    Sergijenko, Ana; Langford-Smith, Alexander; Liao, Ai Y; Pickford, Claire E; McDermott, John; Nowinski, Gabriel; Langford-Smith, Kia J; Merry, Catherine LR; Jones, Simon A; Wraith, J Edmond; Wynn, Robert F; Wilkinson, Fiona L; Bigger, Brian W

    2013-01-01

    Mucopolysaccharidosis type IIIA (MPSIIIA) is a lysosomal storage disorder caused by mutations in N-sulfoglucosamine sulfohydrolase (SGSH), resulting in heparan sulfate (HS) accumulation and progressive neurodegeneration. There are no treatments. We previously demonstrated improved neuropathology in MPSIIIA mice using lentiviral vectors (LVs) overexpressing SGSH in wild-type (WT) hematopoietic stem cell (HSC) transplants (HSCTs), achieved via donor monocyte/microglial engraftment in the brain. However, neurological disease was not corrected using LVs in autologous MPSIIIA HSCTs. To improve brain expression via monocyte/microglial specificity, LVs expressing enhanced green fluorescent protein (eGFP) under ubiquitous phosphoglycerate kinase (PGK) or myeloid-specific promoters were compared in transplanted HSCs. LV-CD11b-GFP gave significantly higher monocyte/B-cell eGFP expression than LV-PGK-GFP or LV-CD18-GFP after 6 months. Subsequently, autologous MPSIIIA HSCs were transduced with either LV-PGK-coSGSH or LV-CD11b-coSGSH vectors expressing codon-optimized SGSH and transplanted into MPSIIIA mice. Eight months after HSCT, LV-PGK-coSGSH vectors produced bone marrow SGSH (576% normal activity) similar to LV-CD11b-coSGSH (473%), but LV-CD11b-coSGSH had significantly higher brain expression (11 versus 7%), demonstrating improved brain specificity. LV-CD11b-coSGSH normalized MPSIIIA behavior, brain HS, GM2 ganglioside, and neuroinflammation to WT levels, whereas LV-PGK-coSGSH partly corrected neuropathology but not behavior. We demonstrate compelling evidence of neurological disease correction using autologous myeloid driven lentiviral-HSC gene therapy in MPSIIIA mice. PMID:23748415

  8. EXERCISE in pediatric autologous stem cell transplant patients: a randomized controlled trial protocol

    PubMed Central

    2012-01-01

    Background Hematopoietic stem cell transplantation is an intensive therapy used to improve survivorship and cure various oncologic diseases. However, this therapy is associated with high mortality rates and numerous negative side-effects. The recovery of the immune system is a special concern and plays a key role in the success of this treatment. In healthy populations it is known that exercise plays an important role in immune system regulation, but little is known about the role of exercise in the hematological and immunological recovery of children undergoing hematopoietic stem cell transplant. The primary objective of this randomized-controlled trial (RCT) is to study the effect of an exercise program (in- and outpatient) on immune cell recovery in patients undergoing an autologous stem cell transplantation. The secondary objective is to determine if an exercise intervention diminishes the usual deterioration in quality of life, physical fitness, and the acquisition of a sedentary lifestyle. Methods This RCT has received approval from The Conjoint Health Research Ethics Board (CHREB) of the University of Calgary (Ethics ID # E-24476). Twenty-four participants treated for a malignancy with autologous stem cell transplant (5 to 18 years) in the Alberta Children’s Hospital will be randomly assigned to an exercise or control group. The exercise group will participate in a two-phase exercise intervention (in- and outpatient) from hospitalization until 10 weeks after discharge. The exercise program includes strength, flexibility and aerobic exercise. During the inpatient phase this program will be performed 5 times/week and will be supervised. The outpatient phase will combine a supervised session with two home-based exercise sessions with the use of the Wii device. The control group will follow the standard protocol without any specific exercise program. A range of outcomes, including quantitative and functional recovery of immune system, cytokine levels in

  9. Plerixafor for autologous stem-cell mobilization and transplantation for patients in Ontario

    PubMed Central

    Kouroukis, C.T.; Varela, N.P.; Bredeson, C.; Kuruvilla, J.; Xenocostas, A.

    2016-01-01

    Background High-dose chemotherapy with autologous stem-cell transplantation (asct) is an accepted part of standard therapy for patients with hematologic malignancies. Usually, stem-cell mobilization uses granulocyte colony–stimulating factor (g-csf); however, some patients are not able to be mobilized with chemotherapy and g-csf, and such patients could be at higher risk of failing mobilization. Plerixafor is a novel mobilization agent that is absorbed quickly after subcutaneous injection and, at the recommended dose of 0.24 mg/kg, provides a sustained increase in circulating CD34+ cells for 10–18 hours. The main purpose of the present report was to evaluate the most current evidence on the efficacy of plerixafor in enhancing hematopoietic stem-cell mobilization and collection before asct for patients in Ontario so as to make recommendations for clinical practice and to assist Cancer Care Ontario in decision-making with respect to this intervention. Methods The medline and embase databases were systematically searched for evidence from January 1996 to March 2015, and the best available evidence was used to draft recommendations relevant to the efficacy of plerixafor in enhancing hematopoietic stem-cell mobilization and collection before asct. Final approval of this practice guideline report was obtained from both the Stem Cell Transplant Steering Committee and the Report Approval Panel of the Program in Evidence-Based Care. Recommendations These recommendations apply to adult patients considered for asct: ■ Adding plerixafor to g-csf is an option for initial mobilization in patients with non-Hodgkin lymphoma or multiple myeloma who are eligible for asct when chemotherapy cannot be used and only g-csf mobilization is available.■ For patients with a low peripheral blood CD34+ cell count (for example, <10/μL) at the time of anticipated stem-cell harvesting, or with an inadequate first-day apheresis collection, it is recommended that plerixafor be added to the

  10. Autologous stem cell transplantation in the treatment of refractory rheumatoid arthritis.

    PubMed Central

    Kim, Ki Chan; Lee, In Hong; Choi, Jung Hye; Oh, Mee Ran; Ahn, Myung Ju; Kim, Seong Yoon

    2002-01-01

    The concept of using high-dose immunosuppressive treatment (HDIT) with autologous stem cell transplantation (ASCT) to treat patients with refractory rheumatoid arthritis has been provided by animal studies and anecdotal case reports. Over the past five years, an increasing number of patients with refractory rheumatoid arthritis have received HDIT with ASCT as an adjunct to intense immunosuppression. Here, we present a case of refractory rheumatoid arthritis in a 54-yr-old woman using HDIT with ASCT. Peripheral blood stem cells were mobilized with cyclophosphamide (4 g/m(2)) followed by G-CSF (5 microg/kg/day). Leukapheresis continued daily until the number of harvested progenitor cells reached 2 x 10(6) CD34+ cells/kg after CliniMax CD34+ positive selection. For HDIT, high-dose cyclophosphamide (total dose 200 mg/kg) and antithymocyte globulin (total dose 90 mg/kg) were administered and CD34+ cells were infused 24 hr after HDIT. The patient tolerated the treatment well but experienced an episode of neutropenic fever. She achieved an early dramatic improvement of joint symptoms during therapy. Fifty percent of improvement of rheumatoid arthritis by the American College of Rheumatology (ACR 50) preliminary definition was fulfilled during the 6 months following ASCT. Although further long-term follow-up is required, the patient's activity of arthritis has been stable since receiving HDIT with ASCT. PMID:11850603

  11. High-dose chemotherapy with autologous stem cell rescue in the outpatient setting.

    PubMed

    Dix, S P; Geller, R B

    2000-02-01

    Intensive outpatient care is rapidly becoming the primary mode of care for selected patients undergoing high-dose chemotherapy with autologous peripheral blood stem cell (PBSC) transplantation. Although the traditional inpatient model of care may still be necessary for high-risk patients, published data suggest that outpatient care is safe and feasible during or after administration of high-dose chemotherapy and autologous PBSC transplant. Blood and marrow transplant (BMT) centers have developed programs to provide more outpatient care under three basic models: an early discharge model, a delayed admission model, and a comprehensive, or total, outpatient model. This review will describe these models of care and address the elements necessary for the development of an outpatient BMT program, including patient selection, staff development, and patient and caregiver education. Available supportive care strategies to facilitate outpatient care will also be highlighted. Clinical outcome data and pharmacoeconomic analyses evaluating various outpatient BMT programs, as well as limited quality-of-life evaluations, will be reviewed.

  12. Bone regeneration in sheep using acropora coral, a natural resorbable scaffold, and autologous mesenchymal stem cells.

    PubMed

    Manassero, Mathieu; Viateau, Véronique; Deschepper, Mickael; Oudina, Karim; Logeart-Avramoglou, Delphine; Petite, Hervé; Bensidhoum, Morad

    2013-07-01

    Tissue constructs containing mesenchymal stem cells (MSC) are an appealing strategy for repairing massive segmental bone defects. However, their therapeutic effectiveness does not match that of autologous bone grafts; among the complicating reasons, the scaffold resorbability has been identified as a critical feature for achieving bone regeneration. In the present study, the osteogenic potential of constructs obtained by expanding autologous MSC onto granules of Acropora coral, a natural fully-resorbable scaffold, was investigated. MSC adhered and proliferated well in vitro after 1 week. When implanted in vivo into long-bone, critical-size defects in sheep (n=5), these constructs exhibited a two-fold increase in bone formation 6 months postimplantation compared to Acropora scaffolds alone (n=5). Interestingly, osteogenesis, mediated by MSC, within these constructs was found continuous not only with the bony stumps, but also at the core of the implants. Scaffold resorption was almost complete at 6 months, leading to full bone regeneration in one animal. Acropora coral appear to be an appealing scaffold for bone tissue engineering because it supported in vitro MSC adhesion and proliferation. Moreover, these results provided evidence that MSC could promote bone regeneration in sheep when loaded one a natural fully resorbable scaffold.

  13. Autologous haematopoietic stem cell transplantation for secondary progressive multiple sclerosis: an exploratory cost-effectiveness analysis.

    PubMed

    Tappenden, P; Saccardi, R; Confavreux, C; Sharrack, B; Muraro, P A; Mancardi, G L; Kozak, T; Farge-Bancel, D; Madan, J; Rafia, R; Akehurst, R; Snowden, J

    2010-06-01

    Treatment options for secondary progressive multiple sclerosis (SPMS) are limited. Mitoxantrone is routinely used to stabilize disease progression; however, evolving evidence suggests clinical benefit from intensive treatment with autologous haematopoietic stem cell transplantation (HSCT). Given differences in cost and outcomes, preliminary cost-effectiveness studies are warranted if this approach is to be developed for more widespread application in SPMS. We developed a decision-analytic Markov model to explore the potential cost-effectiveness of autologous HSCT versus mitoxantrone in SPMS, using patient-level data from registry sources. The model evaluates the lifetime costs and health outcomes associated with disability progression and relapse. Sensitivity analyses were undertaken to examine the uncertainty surrounding cost-effectiveness outcomes. In the absence of randomised controlled trial (RCT) evidence, conditions for comparative analysis were not ideal. Under optimistic assumptions, HSCT is estimated to cost below pound3000 per quality adjusted life year gained. However, when a strict 6-month sustained progression rule is adopted, HSCT may be less effective and more expensive than mitoxantrone. The model results were sensitive to reducing procedural costs and HSCT-related mortality. We conclude that HSCT could potentially achieve an acceptable level of cost-effectiveness. However, caution should be exercised as large, high-quality RCTs comparing HSCT versus mitoxantrone are necessary to validate these findings.

  14. Update on the Role of Autologous Hematopoietic Stem Cell Transplantation in Follicular Lymphoma

    PubMed Central

    Cabrero, Mónica; Redondo, Alba; Martin, Alejandro; Caballero, Dolores

    2012-01-01

    Follicular lymphoma (FL) remains incurable despite advances in new strategies of treatment, including monoclonal antibodies (MoAb). Except for early stages, FL is characterized by responses to treatments and systematic relapses. The main objective in this disease is to achieve a better progression free survival (PFS) and to increase overall survival (OS), mainly in young patients. In order to improve the results of conventional chemotherapy, autologous stem cell transplant (ASCT) is a feasible treatment in these patients. In this moment, ASCT is not recommended as first line treatment, except for transformed FL, but is a good strategy as salvage therapy with an improved PFS and OS. New drugs have been introduced to enhance responses of ASCT, but nowadays they are not part of conventional conditioning regimen. PMID:23205262

  15. Autologous stem cell transplantation in mantle cell lymphoma: a report from the SFGM-TC.

    PubMed

    Touzeau, Cyrille; Leux, Christophe; Bouabdallah, Reda; Roussel, Murielle; Delarue, Richard; Bouabdallah, Krimo; Thieblemont, Catherine; Cacheux, Victoria; Cartron, Guillaume; Compain, Laetitia; Gyan, Emmanuel; Morschhauser, Franck; Casasnovas, Olivier; Moles, Marie-Pierre; Michallet, Anne-Sophie; Gressin, Remy; Damaj, Gandhi; Rose, Christian; Sirvent, Anne; Hermine, Olivier; Mohty, Mohamad; Milpied, Noel; Le Gouill, Steven

    2014-02-01

    Autologous stem cell transplantation (ASCT) is considered as an attractive treatment option for young mantle cell lymphoma (MCL) patients. This retrospective SFGM-TC study analyzed the outcome of 500 MCL patients treated with ASCT and investigated parameters that may modify the outcome of patients who proceeded to ASCT upfront (n = 396). For all patients, median age at ASCT was 56 years (range, 26-71). Median follow-up was 34 months. Three-year progression free survival (PFS) and overall survival (OS) were 63.5 % [95 % CI, 58.7-68.6 %] and 79.5 % [95 % CI, 75.3-83.4 %], respectively. Median time from ASCT to relapse was 22 months (range, 0-136 m). For patients transplanted upfront and in multivariate analysis, age (HR = 2 [1.2-3.4], p = .01, and HR = 2.3 [1.2-4.5], p = .01), disease status at time of ASCT (HR = 1.7 [1.1-2.6], p = .01 and HR = 1.8 [1.1-3.1], p = .03), and use of rituximab (HR = 0.5 [0.3-0.8], p = .002 and HR = 0.5 [0.3-0.9], p = .01) were statistically predictive for both PFS and OS. Also, first line treatment including anthracycline and high-dose cytarabine followed by ASCT conditioned with TAM improved PFS. To conclude, this study suggests that ASCT in MCL can provide a high response rate but may not be sufficient to cure MCL even when ASCT is performed upfront, highlighting the need for innovative approaches before ASCT, aiming to increase complete response rate, and after ASCT, to maintain response. PMID:23949376

  16. Autologous stem cell transplantation in mantle cell lymphoma: a report from the SFGM-TC.

    PubMed

    Touzeau, Cyrille; Leux, Christophe; Bouabdallah, Reda; Roussel, Murielle; Delarue, Richard; Bouabdallah, Krimo; Thieblemont, Catherine; Cacheux, Victoria; Cartron, Guillaume; Compain, Laetitia; Gyan, Emmanuel; Morschhauser, Franck; Casasnovas, Olivier; Moles, Marie-Pierre; Michallet, Anne-Sophie; Gressin, Remy; Damaj, Gandhi; Rose, Christian; Sirvent, Anne; Hermine, Olivier; Mohty, Mohamad; Milpied, Noel; Le Gouill, Steven

    2014-02-01

    Autologous stem cell transplantation (ASCT) is considered as an attractive treatment option for young mantle cell lymphoma (MCL) patients. This retrospective SFGM-TC study analyzed the outcome of 500 MCL patients treated with ASCT and investigated parameters that may modify the outcome of patients who proceeded to ASCT upfront (n=396). For all patients, median age at ASCT was 56 years (range, 26-71). Median follow-up was 34 months. Three-year progression free survival (PFS) and overall survival (OS)were 63.5% [95 % CI, 58.7–68.6 %] and 79.5 % [95 % CI, 75.3–83.4 %], respectively. Median time from ASCT to relapse was 22 months (range, 0–136 m). For patients transplanted upfront and in multivariate analysis, age (HR=2 [1.2–3.4], p=.01, and HR=2.3 [1.2–4.5], p=.01), disease status at time of ASCT (HR=1.7 [1.1–2.6], p=.01 and HR=1.8 [1.1–3.1], p=.03), and use of rituximab (HR=0.5 [0.3–0.8], p=.002 and HR=0.5 [0.3–0.9], p=.01) were statistically predictive for both PFS and OS. Also, first line treatment including anthracycline and high-dose cytarabine followed by ASCT conditioned with TAM improved PFS. To conclude, this study suggests that ASCT in MCL can provide a high response rate but may not be sufficient to cure MCL even when ASCT is performed upfront, highlighting the need for innovative approaches before ASCT, aiming to increase complete response rate, and after ASCT, to maintain response. PMID:24563925

  17. Autologous stem cell transplantation for the treatment of neuroblastoma in Korea.

    PubMed

    Ryu, Kyung Ha; Ahn, Hyo Seop; Koo, Hong Hoe; Kook, Hoon; Kim, Moon Kyu; Kim, Hack Ki; Ghim, Thad; Moon, Hyung Nam; Seo, Jong Jin; Sung, Ki Woong; Shin, Hee Young; Yoo, Eun Sun; Lyu, Chuhl Joo; Lee, Young Ho; Lee, Hahng; Cho, Bin; Cho, Hyun Sang; Choi, Hyung Soo; Hah, Jeong Ok; Hwang, Tai Ju

    2003-04-01

    Autologous stem cell transplantation (ASCT) for the treatment of high-risk neuroblastoma (NBL) is an accepted method for restoring bone marrow depression after high dose chemotherapy. We retrospectively analyzed eighty eight cases of NBL that underwent ASCT following marrow ablative therapy at 12 transplant centers of the Korean Society of Pediatric Hematology-Oncology between January 1996 and September 2000. Seventy nine children were of stage IV NBL and 9 were of stage III with N-myc amplification. Various cytoreductive regimens were used. However, the main regimen was 'CEM' consisting of carboplatin, etoposide and melphalan, and this was used in 66 patients. Total body irradiation was also added in 36 patients for myeloablation. To reduce tumor cell contamination, stem cell infusions after CD34+ cell selection were performed in 16 patients. Post-transplantation therapies included the second transplantation in 18 patients, interleukin2 therapy in 45, 13-cis retinoic acid in 40, 131-meta-iodobenzylguanidine in 4, conventional chemotherapy in 11, and local radiotherapy in 8. Twenty two patients died, sixty six patients are surviving 1 to 46 months after ASCT (median followup duration, 14.5 months). Although the follow-up period was short and the number of patients small, we believe that ASCT might improve the survival rate in high-risk NBL.

  18. The mobilization of autologous bone marrow stem cells in the treatment of heart failure with Chinese medicine.

    PubMed

    Yao, Kui-Wu; Zhang, Liang-Deng; Wang, Jie

    2011-11-01

    Heart failure (HF) is a severe heart disease. The use of autologous bone marrow stem cells (BMCs) mobilization in the treatment of HF has been a hot topic to research both in Western medicine and Chinese medicine (CM). There are many clinical trials and experiments on study of BMCs mobilization for HF therapy, including integrative medicine. The effect of BMCs mobilization is favorable for cardiac repair, while some advantages of CM support the advanced study of its application in BMCs mobilization to treat HF. In addition, with mechanisms of autologous BMCs mobilization for the treatment of HF that will be revealed in the future, especially stem cells niches, integrative medicine would play an important role in this clinical thought of therapy model gradually. Simultaneously, CM should adapt the new approaches of stem cells progresses on HF treatment as holding characteristics of itself.

  19. Regenerative repair of damaged meniscus with autologous adipose tissue-derived stem cells.

    PubMed

    Pak, Jaewoo; Lee, Jung Hun; Lee, Sang Hee

    2014-01-01

    Mesenchymal stem cells (MSCs) are defined as pluripotent cells found in numerous human tissues, including bone marrow and adipose tissue. Such MSCs, isolated from bone marrow and adipose tissue, have been shown to differentiate into bone and cartilage, along with other types of tissues. Therefore, MSCs represent a promising new therapy in regenerative medicine. The initial treatment of meniscus tear of the knee is managed conservatively with nonsteroidal anti-inflammatory drugs and physical therapy. When such conservative treatment fails, an arthroscopic resection of the meniscus is necessary. However, the major drawback of the meniscectomy is an early onset of osteoarthritis. Therefore, an effective and noninvasive treatment for patients with continuous knee pain due to damaged meniscus has been sought. Here, we present a review, highlighting the possible regenerative mechanisms of damaged meniscus with MSCs (especially adipose tissue-derived stem cells (ASCs)), along with a case of successful repair of torn meniscus with significant reduction of knee pain by percutaneous injection of autologous ASCs into an adult human knee.

  20. Combined transplantation of autologous hematopoietic stem cells and allogenic mesenchymal stem cells increases T regulatory cells in systemic lupus erythematosus with refractory lupus nephritis and leukopenia.

    PubMed

    Wang, Q; Qian, S; Li, J; Che, N; Gu, L; Wang, Q; Liu, Y; Mei, H

    2015-10-01

    Autologous hematopoietic stem cell (HSC) and mesenchymal stem cell (MSC) transplantation is currently being evaluated as a novel treatment for autoimmune diseases, such as systemic lupus erythematosus (SLE). Here we report a case of autologous HSC transplantation combined with MSCs in a 25-year-old severe SLE patient with multiple life-threatening complications and refractory to conventional cyclophosphamide (CYC) therapy. After being pretreated with CYC, fludarabine and antithymocyte globulin, the patient was transplanted with autologous CD34+HSCs and MSCs by intravenous infusion. Hematopoietic regeneration was observed on day 12 thereafter. After HSC and MSC transplantation, the patient's clinical symptoms caused by SLE were remitted, and the SLEDAI score decreased. Moreover, CD4+CD25+FoxP3+Treg cells increased in peripheral blood mononuclear cells (PBMCs) after transplantation. This result suggests that the combined transplantation of HSCs and MSCs may reset the adaptive immune system to re-establish self-tolerance in SLE. A 36-month follow-up showed that the clinical symptoms remained in remission. Although a longer follow-up is required for assessing the long-term efficacy, our present results suggest that the combined transplantation of HSCs and MSCs may be a novel and effective therapy for refractory SLE.

  1. The Mutual Interactions between Mesenchymal Stem Cells and Myoblasts in an Autologous Co-Culture Model

    PubMed Central

    Szczepanska, Izabela; Zarychta-Wisniewska, Weronika; Pajak, Beata; Bojarczuk, Kamil; Dybowski, Bartosz; Paczek, Leszek

    2016-01-01

    Both myoblasts and mesenchymal stem cells (MSC) take part in the muscle tissue regeneration and have been used as experimental cellular therapy in muscular disorders treatment. It is possible that co-transplantation approach could improve the efficacy of this treatment. However, the relations between those two cell types are not clearly defined. The aim of this study was to determine the reciprocal interactions between myoblasts and MSC in vitro in terms of the features important for the muscle regeneration process. Primary caprine muscle-derived cells (MDC) and bone marrow-derived MSC were analysed in autologous settings. We found that MSC contribute to myotubes formation by fusion with MDC when co-cultured directly, but do not acquire myogenic phenotype if exposed to MDC-derived soluble factors only. Experiments with exposure to hydrogen peroxide showed that MSC are significantly more resistant to oxidative stress than MDC, but a direct co-culture with MSC does not diminish the cytotoxic effect of H2O2 on MDC. Cell migration assay demonstrated that MSC possess significantly greater migration ability than MDC which is further enhanced by MDC-derived soluble factors, whereas the opposite effect was not found. MSC-derived soluble factors significantly enhanced the proliferation of MDC, whereas MDC inhibited the division rate of MSC. To conclude, presented results suggest that myogenic precursors and MSC support each other during muscle regeneration and therefore myoblasts-MSC co-transplantation could be an attractive approach in the treatment of muscular disorders. PMID:27551730

  2. The Mutual Interactions between Mesenchymal Stem Cells and Myoblasts in an Autologous Co-Culture Model.

    PubMed

    Kulesza, Agnieszka; Burdzinska, Anna; Szczepanska, Izabela; Zarychta-Wisniewska, Weronika; Pajak, Beata; Bojarczuk, Kamil; Dybowski, Bartosz; Paczek, Leszek

    2016-01-01

    Both myoblasts and mesenchymal stem cells (MSC) take part in the muscle tissue regeneration and have been used as experimental cellular therapy in muscular disorders treatment. It is possible that co-transplantation approach could improve the efficacy of this treatment. However, the relations between those two cell types are not clearly defined. The aim of this study was to determine the reciprocal interactions between myoblasts and MSC in vitro in terms of the features important for the muscle regeneration process. Primary caprine muscle-derived cells (MDC) and bone marrow-derived MSC were analysed in autologous settings. We found that MSC contribute to myotubes formation by fusion with MDC when co-cultured directly, but do not acquire myogenic phenotype if exposed to MDC-derived soluble factors only. Experiments with exposure to hydrogen peroxide showed that MSC are significantly more resistant to oxidative stress than MDC, but a direct co-culture with MSC does not diminish the cytotoxic effect of H2O2 on MDC. Cell migration assay demonstrated that MSC possess significantly greater migration ability than MDC which is further enhanced by MDC-derived soluble factors, whereas the opposite effect was not found. MSC-derived soluble factors significantly enhanced the proliferation of MDC, whereas MDC inhibited the division rate of MSC. To conclude, presented results suggest that myogenic precursors and MSC support each other during muscle regeneration and therefore myoblasts-MSC co-transplantation could be an attractive approach in the treatment of muscular disorders. PMID:27551730

  3. Autologous stem cell transplantation aids autoimmune patients by functional renewal and TCR diversification of regulatory T cells.

    PubMed

    Delemarre, Eveline M; van den Broek, Theo; Mijnheer, Gerdien; Meerding, Jenny; Wehrens, Ellen J; Olek, Sven; Boes, Marianne; van Herwijnen, Martijn J C; Broere, Femke; van Royen, Annet; Wulffraat, Nico M; Prakken, Berent J; Spierings, Eric; van Wijk, Femke

    2016-01-01

    Autologous hematopoietic stem cell transplantation (HSCT) is increasingly considered for patients with severe autoimmune diseases whose prognosis is poor with standard treatments. Regulatory T cells (Tregs) are thought to be important for disease remission after HSCT. However, eliciting the role of donor and host Tregs in autologous HSCT is not possible in humans due to the autologous nature of the intervention. Therefore, we investigated their role during immune reconstitution and re-establishment of immune tolerance and their therapeutic potential following congenic bone marrow transplantation (BMT) in a proteoglycan-induced arthritis (PGIA) mouse model. In addition, we determined Treg T-cell receptor (TCR) CDR3 diversity before and after HSCT in patients with juvenile idiopathic arthritis and juvenile dermatomyositis. In the PGIA BMT model, after an initial predominance of host Tregs, graft-derived Tregs started dominating and displayed a more stable phenotype with better suppressive capacity. Patient samples revealed a striking lack of diversity of the Treg repertoire before HSCT. This ameliorated after HSCT, confirming reset of the Treg compartment following HSCT. In the mouse model, a therapeutic approach was initiated by infusing extra Foxp3(GFP+) Tregs during BMT. Infusion of Foxp3(GFP+) Tregs did not elicit additional clinical improvement but conversely delayed reconstitution of the graft-derived T-cell compartment. These data indicate that HSCT-mediated amelioration of autoimmune disease involves renewal of the Treg pool. In addition, infusion of extra Tregs during BMT results in a delayed reconstitution of T-cell compartments. Therefore, Treg therapy may hamper development of long-term tolerance and should be approached with caution in the clinical autologous setting. PMID:26480932

  4. Successful second autologous peripheral blood stem cell transplantation conditioned with total body irradiation for progressive neuroblastoma after recurrence.

    PubMed

    Morimoto, Tsuyoshi; Matsufuji, Hiroshi; Yokomori, Kinji; Hosoya, Ryohta

    2006-12-01

    A girl with recurrent neuroblastoma was successfully treated with second autologous stem cell transplantation (SCT) conditioned with total body irradiation (TBI). This patient was diagnosed as stage IV neuroblastoma at the age of 18 months. Pathological finding was stroma-poor unfavorable histology and amplification of MYCN gene was extremely high (153 copies). In spite of autologous SCT with non-TBI regimen in the status of disease-free, neuroblastoma relapsed at the primary site 6 months later. Second autologous SCT conditioned with TBI and melphalan was performed although the tumor was progressive. Over 3 years after second SCT, she has been well with no evidence of further recurrence of neuroblastoma, but she was complicated with permanent atrophy of left kidney. TBI might be effective for relapsed neuroblastoma who previously received SCT with non-TBI regimen.

  5. Current Role of Autologous and Allogeneic Stem Cell Transplantation for Relapsed and Refractory Hodgkin Lymphoma

    PubMed Central

    Castagna, Luca; Carlo-Stella, Carmelo; Mazza, Rita; Santoro, Armando

    2015-01-01

    Classical Hodgkin lymphoma (cHL) is a relatively rare disease, with approximately 9,200 estimated new cases and 1,200 estimated deaths per year in the United States. First-line chemo-radiotherapy leads to cure rates approaching 80% in patients with advanced-stage disease. However, 25 to 30% of these patients are not cured with chemotherapy alone (i.e., the ABVD regimen) and show either primary refractoriness to chemotherapy, early disease relapse or late disease relapse. Second-line salvage high-dose chemotherapy (HDC) and autologous stem cell transplantation (SCT) have an established role in the management of refractory/relapsed cHL, leading to durable responses in approximately 50% of relapsed patients and a minority of refractory patients. However, due to the poor responses to second-line salvage chemotherapy and dismal long-term disease control of primary refractory and early relapsed patients, their treatment represents an unmet medical need. Allogeneic SCT represents, by far, the only strategy with a curative potential for these patients; however, as discussed in this review, it’s role in cHL remains controversial. Despite a general consensus that early relapsed and primary refractory patients represent a clinical challenge requiring effective treatments to achieve long-term disease control, there has been no consensus on the optimal therapy that should be offered to these patients. This review will briefly discuss the clinical results and the main issues regarding autologous SCT as well as the current role of allogeneic SCT. PMID:25745542

  6. Reconstruction of Beagle Hemi-Mandibular Defects with Allogenic Mandibular Scaffolds and Autologous Mesenchymal Stem Cells

    PubMed Central

    Luo, JinChao; Liu, HuaWei; Hu, Min; Yue, Wen

    2014-01-01

    Objective Massive bone allografts are frequently used in orthopedic reconstructive surgery, but carry a high failure rate of approximately 25%. We tested whether treatment of graft with mesenchymal stem cells (MSCs) can increase the integration of massive allografts (hemi-mandible) in a large animal model. Methods Thirty beagle dogs received surgical left-sided hemi-mandibular defects, and then divided into two equal groups. Bony defects of the control group were reconstructed using allografts only. Those of the experimental group were reconstructed using allogenic mandibular scaffold-loaded autologous MSCs. Beagles from each group were killed at4 (n = 4), 12 (n = 4), 24 (n = 4) or 48 weeks (n = 3) postoperatively. CT and micro-CT scans, histological analyses and the bone mineral density (BMD) of transplants were used to evaluate defect reconstruction outcomes. Results Gross and CT examinations showed that the autologous bone grafts had healed in both groups. At 48 weeks, the allogenic mandibular scaffolds of the experimental group had been completely replaced by new bone, which has a smaller surface area to that of the original allogenic scaffold, whereas the scaffold in control dogs remained the same size as the original allogenic scaffold throughout. At 12 weeks, the BMD of the experimental group was significantly higher than the control group (p<0.05), and all micro-architectural parameters were significantly different between groups (p<0.05). Histological analyses showed almost all transplanted allogeneic bone was replaced by new bone, principally fibrous ossification, in the experimental group, which differed from the control group where little new bone formed. Conclusions Our study demonstrated the feasibility of MSC-loaded allogenic mandibular scaffolds for the reconstruction of hemi-mandibular defects. Further studies are needed to test whether these results can be surpassed by the use of allogenic mandibular scaffolds loaded with a

  7. A retrospective study of autologous stem cell mobilization to guide an immediate salvage protocol using plerixafor for patients who mobilize stem cells poorly.

    PubMed

    Hay, Annette Elizabeth; Lawrie, Alastair; Robinson, Nicolas; Dong, Bin; Culligan, Dominic J

    2013-10-01

    The addition of plerixafor to G-CSF decreases the risk of failed stem cell collection, but at considerable extra cost. Using a logistic regression model based on 354 autologous mobilizations, we have identified a local minimum peripheral blood CD34 count at which the probability of a successful collection is 50%. This seems an appropriate CD34 count at which to add immediate salvage plerixafor.

  8. Phase 1 Trial of Autologous Bone Marrow Stem Cell Transplantation in Patients with Spinal Cord Injury

    PubMed Central

    Kakabadze, Zurab; Mardaleishvili, Konstantine; Chutkerashvili, Gocha; Chelishvili, Irakli; Harders, Albrecht; Loladze, George; Shatirishvili, Gocha; Kipshidze, Nodar; Chakhunashvili, David; Chutkerashvili, Konstantine

    2016-01-01

    Introduction. A total of 18 patients, with complete motor deficits and paraplegia caused by thoracic and lumbar spine trauma without muscle atrophy or psychiatric problems, were included into this study. Materials and Methods. The bone marrow was aspirated from the anterior iliac crest under local anesthesia and the mononuclear fraction was isolated by density gradient method. At least 750 million mononuclear-enriched cells, suspended in 2 mL of saline, were infused intrathecally. Results and Discussion. The study reports demonstrated improvement of motor and sensory functions of various degrees observed in 9 of the 18 (50%) cases after bone marrow stem cell transplantation. Measured by the American Spinal Injury Association (ASIA) scale, 7 (78%) out of the 9 patients observed an improvement by one grade, while two cases (22%) saw an improvement by two grades. However, there were no cases in which the condition was improved by three grades. Conclusions. Analysis of subsequent treatment results indicated that the transplantation of mononuclear-enriched autologous BMSCs is a feasible and safe technique. However, successful application of the BMSCs in the clinical practice is associated with the necessity of executing more detailed examinations to evaluate the effect of BMSCs on the patients with spinal cord injury. PMID:27433165

  9. Steroids prevent engraftment syndrome after autologous hematopoietic stem cell transplantation without increasing the risk of infection.

    PubMed

    Mossad, S; Kalaycio, M; Sobecks, R; Pohlman, B; Andresen, S; Avery, R; Rybicki, L; Jarvis, J; Bolwell, B

    2005-02-01

    Engraftment syndrome (ES) following autologous hematopoietic stem cell transplantation (AHSCT) is characterized by fever and rash. In January 2002, we instituted steroid prophylaxis for ES from day +4 to +14. This study was conducted to assess whether this practice increased the risk of infection. In total, 194 consecutive patients were reviewed, 111 did not receive steroid prophylaxis (group A), and 83 did (group B). Initial antimicrobial prophylaxis was the same in both groups. There were no significant differences between groups in age, gender, race, prior radiation therapy, number of prior chemotherapy regimens, disease status at transplant, mobilization regimen, days of leukopheresis, CD34(+) cell dose, and days to platelet and neutrophil engraftment. Group B had significantly fewer patients with non-Hodgkin's lymphoma and multiple myeloma, shorter median duration from diagnosis to transplant, lower risk of ES, and shorter mean length of hospital stay. The incidence of early and late microbiologically confirmed infections was not significantly different between groups. Types of infections and types of organisms identified were similar in both groups. Hospital readmission rates were similar in both groups. Steroid prophylaxis significantly decreases the risk of ES following AHSCT, and is associated with shortened hospitalization, without increasing risk of infection. PMID:15640827

  10. High-dose immunosuppressive therapy and autologous peripheral blood stem cell transplantation for severe multiple sclerosis

    PubMed Central

    Nash, Richard A.; Bowen, James D.; McSweeney, Peter A.; Pavletic, Steven Z.; Maravilla, Kenneth R.; Park, Man-soo; Storek, Jan; Sullivan, Keith M.; Al-Omaishi, Jinan; Corboy, John R.; DiPersio, John; Georges, George E.; Gooley, Theodore A.; Holmberg, Leona A.; LeMaistre, C. Fred; Ryan, Kate; Openshaw, Harry; Sunderhaus, Julie; Storb, Rainer; Zunt, Joseph; Kraft, George H.

    2010-01-01

    There were 26 patients enrolled in a pilot study of high-dose immunosuppressive therapy (HDIT) for severe multiple sclerosis (MS). Median baseline expanded disability status scale (EDSS) was 7.0 (range, 5.0–8.0). HDIT consisted of total body irradiation, cyclophosphamide, and antithymocyte globulin (ATG) and was followed by transplantation of autologous, granulocyte colony-stimulating factor (G-CSF)-mobilized CD34-selected stem cells. Regimen-related toxicities were mild. Because of bladder dysfunction, there were 8 infectious events of the lower urinary tract. One patient died from Epstein-Barr virus (ESV)-related posttransplantation lymphoproliferative disorder (PTLD) associated with a change from horse-derived to rabbit-derived ATG in the HDIT regimen. An engraftment syndrome characterized by noninfectious fever with or without rash developed in 13 of the first 18 patients and was associated in some cases with transient worsening of neurologic symptoms. There were 2 significant adverse neurologic events that occurred, including a flare of MS during mobilization and an episode of irreversible neurologic deterioration after HDIT associated with fever. With a median follow-up of 24 (range, 3–36) months, the Kaplan-Meier estimate of progression (≥ 1.0 point EDSS) at 3 years was 27%. Of 12 patients who had oligoclonal bands in the cerebrospinal fluid at baseline, 9 had persistence after HDIT. After HDIT, 4 patients developed new enhancing lesions on magnetic resonance imaging of the brain. The estimate of survival at 3 years was 91%. Important clinical issues in the use of HDIT and stem cell transplantation for MS were identified; however, modifications of the initial approaches appear to reduce treatment risks. This was a heterogeneous high-risk group, and a phase 3 study is planned to fully assess efficacy. PMID:12763935

  11. Tbo-Filgrastim versus Filgrastim during Mobilization and Neutrophil Engraftment for Autologous Stem Cell Transplantation.

    PubMed

    Elayan, Mohammed M; Horowitz, Justin G; Magraner, Jose M; Shaughnessy, Paul J; Bachier, Carlos

    2015-11-01

    There are limited data available supporting the use of the recombinant granulocyte colony-stimulating factor (G-CSF), tbo-filgrastim, rather than traditionally used filgrastim to mobilize peripheral blood stem cells (PBSC) or to accelerate engraftment after autologous stem cell transplantation (ASCT). We sought to compare the efficacy and cost of tbo-filgrastim to filgrastim in these settings. Patients diagnosed with lymphoma or plasma cell disorders undergoing G-CSF mobilization, with or without plerixafor, were included in this retrospective analysis. The primary outcome was total collected CD34(+) cells/kg. Secondary mobilization endpoints included peripheral CD34(+) cells/μL on days 4 and 5 of mobilization, adjunctive use of plerixafor, CD34(+) cells/kg collected on day 5, number of collection days and volumes processed, number of collections reaching 5 million CD34(+) cells/kg, and percent reaching target collection goal in 1 day. Secondary engraftment endpoints included time to neutrophil and platelet engraftment, number of blood product transfusions required before engraftment, events of febrile neutropenia, and length of stay. A total of 185 patients were included in the final analysis. Patients receiving filgrastim (n = 86) collected a median of 5.56 × 10(6) CD34(+) cells/kg, compared with a median of 5.85 × 10(6) CD34(+) cells/kg in the tbo-filgrastim group (n = 99; P = .58). There were no statistically significant differences in all secondary endpoints with the exception of apheresis volumes processed (tbo-filgrastim, 17.0 liters versus filgrastim, 19.7 liters; P < .01) and mean platelet transfusions (tbo-filgrastim, 1.7 units versus filgrastim, 1.4 units; P = .04). In conclusion, tbo-filgrastim demonstrated similar CD34(+) yield compared with filgrastim in mobilization and post-transplantation settings, with no clinically meaningful differences in secondary efficacy and safety endpoints. Furthermore, tbo-filgrastim utilization was associated

  12. Tbo-Filgrastim versus Filgrastim during Mobilization and Neutrophil Engraftment for Autologous Stem Cell Transplantation.

    PubMed

    Elayan, Mohammed M; Horowitz, Justin G; Magraner, Jose M; Shaughnessy, Paul J; Bachier, Carlos

    2015-11-01

    There are limited data available supporting the use of the recombinant granulocyte colony-stimulating factor (G-CSF), tbo-filgrastim, rather than traditionally used filgrastim to mobilize peripheral blood stem cells (PBSC) or to accelerate engraftment after autologous stem cell transplantation (ASCT). We sought to compare the efficacy and cost of tbo-filgrastim to filgrastim in these settings. Patients diagnosed with lymphoma or plasma cell disorders undergoing G-CSF mobilization, with or without plerixafor, were included in this retrospective analysis. The primary outcome was total collected CD34(+) cells/kg. Secondary mobilization endpoints included peripheral CD34(+) cells/μL on days 4 and 5 of mobilization, adjunctive use of plerixafor, CD34(+) cells/kg collected on day 5, number of collection days and volumes processed, number of collections reaching 5 million CD34(+) cells/kg, and percent reaching target collection goal in 1 day. Secondary engraftment endpoints included time to neutrophil and platelet engraftment, number of blood product transfusions required before engraftment, events of febrile neutropenia, and length of stay. A total of 185 patients were included in the final analysis. Patients receiving filgrastim (n = 86) collected a median of 5.56 × 10(6) CD34(+) cells/kg, compared with a median of 5.85 × 10(6) CD34(+) cells/kg in the tbo-filgrastim group (n = 99; P = .58). There were no statistically significant differences in all secondary endpoints with the exception of apheresis volumes processed (tbo-filgrastim, 17.0 liters versus filgrastim, 19.7 liters; P < .01) and mean platelet transfusions (tbo-filgrastim, 1.7 units versus filgrastim, 1.4 units; P = .04). In conclusion, tbo-filgrastim demonstrated similar CD34(+) yield compared with filgrastim in mobilization and post-transplantation settings, with no clinically meaningful differences in secondary efficacy and safety endpoints. Furthermore, tbo-filgrastim utilization was associated

  13. High-Dose Therapy and Autologous Stem Cell Transplantation for Chemoresistant Hodgkin Lymphoma: The Seattle Experience

    PubMed Central

    Gopal, Ajay K; Metcalfe, Tracee L; Gooley, Ted A; Pagel, John M; Petersdorf, Stephen H; Bensinger, William I; Holmberg, Leona; Maloney, David G; Press, Oliver W

    2009-01-01

    Background High-dose therapy (HDT) with autologous stem cell transplantation (ASCT) is the standard treatment for patients with chemosensitive relapsed/refractory Hodgkin lymphoma (HL), but this therapy is commonly denied to patients with resistant disease. We explored the utility of HDT and ASCT for chemoresistant HL since there are few established therapies for these patients. Patients and Methods Sixty-four chemoresistant HL patients underwent HDT followed by ASCT at our center. Baseline characteristics included: median age = 35 years (range, 14–59 yrs), stage III/IV = 49 (77%), nodular sclerosis histology = 51 (80%), and prior radiation = 32 (50%). Twenty-six patients (41%) received total body irradiation (TBI)-based regimens and 38 (59%) underwent non-TBI conditioning. Results The estimated 5-year overall survival (OS) and progression-free survival (PFS) were 31% and 17%, respectively, (median follow-up = 4.2 years). Multivariable analysis only identified year of transplant as independently associated with improved OS (p=.008) and PFS (p=.04), with patients transplanted in later years having better outcome. The probabilities of 3-year PFS for patients transplanted between 1986–1989, 1990–July 1993, August 1993–1999, and 2000–2005 were 9%, 21%, 33%, and 31%, respectively. Conclusions These data suggest that HDT and ASCT may result in prolonged remissions and survival for a subset of chemoresistant HL pts, with improved outcomes in patients transplanted more recently. PMID:18623377

  14. Current Status of Autologous Stem Cell Transplantation in Relapsed and Refractory Hodgkin's Lymphoma

    PubMed Central

    Colpo, Anna; Hochberg, Ephraim

    2012-01-01

    Despite the relatively high long-term disease-free survival (DFS) rate for patients with Hodgkin lymphoma (HL) with modern combination chemotherapy or combined modality regimens, ∼20% of patients die from progressive or relapsed disease. The standard treatment for relapsed and primary refractory HL is salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT), which has shown a 5-year progression-free survival rate of ∼50%–60%. Recent developments in a number of diagnostic and therapeutic modalities have begun to improve these results. Functional imaging, refinement of clinical prognostic factors, and development of novel biomarkers have improved the predictive algorithms, allowing better patient selection and timing for ASCT. In addition, these algorithms have begun to identify a group of patients who are candidates for more aggressive treatment beyond standard ASCT. Novel salvage regimens may potentially improve the rate of complete remission prior to ASCT, and the use of maintenance therapy after ASCT has become a subject of current investigation. We present a summary of developments in each of these areas. PMID:22210089

  15. High-dose consolidation therapy with autologous stem cell rescue in stage IV breast cancer.

    PubMed

    Williams, S F; Mick, R; Desser, R; Golick, J; Beschorner, J; Bitran, J D

    1989-12-01

    We designed a phase II study to determine whether induction chemotherapy (CT) consisting of leucovorin, vincristine, methotrexate, doxorubicin, and cyclophosphamide (LOMAC) followed by high-dose intensification chemotherapy (ICT) with cyclophosphamide, thiotepa, and autologous stem cell rescue (ASCR) could increase the complete response (CR) rate and survival in women with stage IV breast cancer. Twenty-nine women were enrolled on study; 16 patients had received prior adjuvant chemotherapy and no patient had received chemotherapy for stage IV disease. Two patients were found to be ineligible and excluded from further analysis. Of the 27 patients treated, four (15%) obtained a CR and 15 (56%) a partial response (PR) after LOMAC induction, for an overall response rate of 70%. Of the 22 patients treated with ICT, 12 patients had a CR, and nine were in PR after induction and converted to CR after ICT. The toxicities included nausea/vomiting, mucositis, diarrhea, dermatitis, alopecia, and infections secondary to neutropenia. The 1-year survival is 60%; the median has not yet been reached. The time to treatment failure for patients on study is 10 months. The treatment approach of ICT and ASCR following induction chemotherapy can lead to an improved CR rate in stage IV breast cancer. How this increased CR rate leads to a prolonged disease-free survival requires further follow-up.

  16. High-dose chemotherapy with autologous stem cell rescue in children with nephroblastoma.

    PubMed

    Kremens, B; Gruhn, B; Klingebiel, T; Hasan, C; Laws, H-J; Koscielniak, E; Hero, B; Selle, B; Niemeyer, C; Finckenstein, F G; Schulz, A; Wawer, A; Zintl, F; Graf, N

    2002-12-01

    Children with Wilms tumor who have a particular risk of failure at relapse or at primary diagnosis were treated with high-dose chemotherapy (HDC) and autologous peripheral blood stem cell rescue in order to improve their probability of survival. From April 1992 to December 1998, 23 evaluable patients received HDC within the German Cooperative Wilms Tumor Studies. Nineteen were given melphalan, etoposide and carboplatin (MEC); the others received different regimens. The dose of carboplatin was adjusted according to renal function. Indications for HDC were high-risk relapse in 20 patients, bone metastases in two patients and no response in one patient. Fourteen of 23 patients are alive after a median observation time of 41 months, 11 of 14 in continuous complete remission, three in CR after relapse post HDC. The estimated survival and event-free survival for these patients are 60.9% and 48.2%. Twelve children relapsed after HDC; nine of them died within 12 months and three are surviving from 20 to 33 months after relapse. The main toxicities were hematologic, mucositis and renal (tubular dysfunction; intermittent hemodialysis in one patient). There were no toxic deaths. About half of the children suffering from Wilms tumor with very unfavorable prognostic factors survive disease-free after HDC for over 3 years. Besides hematological toxicity, mucositis and infections, renal function is at risk during HDC. With dose adjustment on glomerular filtration rate, however, no permanent renal failure was observed. PMID:12476282

  17. Clinical Application of Autologous Adipose Stem Cells in Patients with Multiple Sclerosis: Preliminary Results

    PubMed Central

    Stepien, Adam; Dabrowska, Natalia L.; Maciagowska, Marzena; Zolocinska, Aleksandra; Mazur, Slawomir; Frankowska, Emilia; Kidzinski, Rafał

    2016-01-01

    The clinical outcome of autologous adipose stem cell (ASC) treatment of patients with multiple sclerosis (MS) was investigated following one year of observation. Methods. The clinical and MRI outcomes of 16 ASC-treated patients with RRMS and SPMS are reported after a one-year follow-up period. Results. At 18 months of follow-up, some patients showed “enticing” improvements on some exploratory efficacy measures, although a significant benefit was not observed for any measure across the entire group. Neither the progression of disability nor relapses were observed in any cases. In four patients, we found new gadolinium+ (Gd+) lesions on MRI. Our results indicate that ASC therapy is safe and does not produce any substantial side effects. Disease progression-free survival (PFS) of 18 months was seen in all patients with RRMS and SPMS. In these patients, EDSS scores did not progress above baseline scores. Gd-enhancing lesions were observed in two cases with RRMS, but these patients did not exhibit changes in EDSS score. Conclusion. Intrathecal treatment with ASCs is an attractive form of therapy for patients with MS but should be reserved for cases with aggressive disease progression, for cases that are still in the inflammatory phase, and for the malignant form. PMID:27761060

  18. Fertility in premenopausal women post autologous stem cell transplant with BEAM conditioning.

    PubMed

    Lasica, Masa; Taylor, Emma; Bhattacharyya, Puja; Bennett, Ashwini; Cooke, Rachel E; Stern, Catharyn; Agresta, Franca; Ayton, Rosemary; Grigg, Andrew

    2016-10-01

    There is currently minimal data on fertility outcomes in premenopausal women undergoing autologous stem cell transplant (ASCT) with carmustine, etoposide, cytarabine and melphalan (BEAM) conditioning. A retrospective analysis of fertility outcomes in premenopausal females aged between 18 and 40 yr who underwent BEAM/ASCT for lymphoma between 1995 and 2011 was performed at four transplant centres. Of 41 premenopausal women who underwent BEAM conditioning, 25 met the inclusion criteria with the main exclusion criterion being inadequate documentation. Eighteen had Hodgkin lymphoma, and seven had non-Hodgkin lymphoma. Median number of chemotherapy regimens pretransplant was 2 (1-3). Seventeen women (68%) with a median age at transplant of 25 yr (range 17-33) recovered their menses. The comparative group without recovery was older with a median age of 34 yr (range 20-40) (P = 0.007). Ten patients, with a median age at transplant of 22 yr (range 17-30), had 15 naturally conceived pregnancies. Chemotherapy regimens and lymphoma type did not obviously influence the incidence of menses recovery or conception. The incidence of recovery of menses and fertility in premenopausal women undergoing BEAM/ASCT for lymphoma is substantial. Younger age at transplant correlates with superior fertility outcomes.

  19. Juvenile Swine Surgical Alveolar Cleft Model to Test Novel Autologous Stem Cell Therapies

    PubMed Central

    Caballero, Montserrat; Morse, Justin C.; Halevi, Alexandra E.; Emodi, Omri; Pharaon, Michael R.; Wood, Jeyhan S.

    2015-01-01

    Reconstruction of craniofacial congenital bone defects has historically relied on autologous bone grafts. Engineered bone using mesenchymal stem cells from the umbilical cord on electrospun nanomicrofiber scaffolds offers an alternative to current treatments. This preclinical study presents the development of a juvenile swine model with a surgically created maxillary cleft defect for future testing of tissue-engineered implants for bone generation. Five-week-old pigs (n=6) underwent surgically created maxillary (alveolar) defects to determine critical-sized defect and the quality of treatment outcomes with rib, iliac crest cancellous bone, and tissue-engineered scaffolds. Pigs were sacrificed at 1 month. Computed tomography scans were obtained at days 0 and 30, at the time of euthanasia. Histological evaluation was performed on newly formed bone within the surgical defect. A 1 cm surgically created defect healed with no treatment, the 2 cm defect did not heal. A subsequently created 1.7 cm defect, physiologically similar to a congenitally occurring alveolar cleft in humans, from the central incisor to the canine, similarly did not heal. Rib graft treatment did not incorporate into adjacent normal bone; cancellous bone and the tissue-engineered graft healed the critical-sized defect. This work establishes a juvenile swine alveolar cleft model with critical-sized defect approaching 1.7 cm. Both cancellous bone and tissue engineered graft generated bridging bone formation in the surgically created alveolar cleft defect. PMID:25837453

  20. Acupoint Injection of Autologous Stromal Vascular Fraction and Allogeneic Adipose-Derived Stem Cells to Treat Hip Dysplasia in Dogs

    PubMed Central

    Marx, Camila; Silveira, Maiele Dornelles; Selbach, Isabel; da Silva, Ariel Silveira; Braga, Luisa Maria Gomes de Macedo; Camassola, Melissa; Nardi, Nance Beyer

    2014-01-01

    Stem cells isolated from adipose tissue show great therapeutic potential in veterinary medicine, but some points such as the use of fresh or cultured cells and route of administration need better knowledge. This study aimed to evaluate the effect of autologous stromal vascular fraction (SVF, n = 4) or allogeneic cultured adipose-derived stem cells (ASCs, n = 5) injected into acupuncture points in dogs with hip dysplasia and weak response to drug therapy. Canine ASCs have proliferation and differentiation potential similar to ASCs from other species. After the first week of treatment, clinical evaluation showed marked improvement compared with baseline results in all patients treated with autologous SVF and three of the dogs treated with allogeneic ASCs. On days 15 and 30, all dogs showed improvement in range of motion, lameness at trot, and pain on manipulation of the joints, except for one ASC-treated patient. Positive results were more clearly seen in the SVF-treated group. These results show that autologous SVF or allogeneic ASCs can be safely used in acupoint injection for treating hip dysplasia in dogs and represent an important therapeutic alternative for this type of pathology. Further studies are necessary to assess a possible advantage of SVF cells in treating joint diseases. PMID:25180040

  1. Trichoderma species fungemia after high-dose chemotherapy and autologous stem cell transplantation: a case report.

    PubMed

    Festuccia, M; Giaccone, L; Gay, F; Brunello, L; Maffini, E; Ferrando, F; Talamo, E; Boccadoro, M; Serra, R; Barbui, A; Bruno, B

    2014-08-01

    We present a case of Trichoderma fungemia with pulmonary involvement in a multiple myeloma patient, who was severely immunocompromised and heavily treated with high-dose melphalan, and underwent autologous hematopoietic cell transplantation. This is the first report, to our knowledge, of proven Trichoderma fungemia, defined by published criteria, successfully treated with voriconazole.

  2. Autologous tissue patch rich in stem cells created in the subcutaneous tissue

    PubMed Central

    Garcia-Gomez, Ignacio; Gudehithlu, Krishnamurthy P; Arruda, Jose A L; Singh, Ashok K

    2015-01-01

    AIM: To investigate whether we could create natural autologous tissue patches in the subcutaneous space for organ repair. METHODS: We implanted the following three types of inert foreign bodies in the subcutaneous tissue of rats to produce autologous tissue patches of different geometries: (1) a large-sized polyvinyl tube (L = 25 mm, internal diameter = 7 mm) sealed at both ends by heat application for obtaining a large flat piece of tissue patch for organ repair; (2) a fine polyvinyl tubing (L = 25 mm, internal diameter = 3 mm) for creating cylindrically shaped grafts for vascular or nerve repair; and (3) a slurry of polydextran particle gel for inducing a bladder-like tissue. Implantation of inert materials was carried out by making a small incision on one or either side of the thoracic-lumbar region of rats. Subcutaneous pockets were created by blunt dissection around the incision into which the inert bodies were inserted (1 or 2 per rat). The incisions were closed with silk sutures, and the animals were allowed to recover. In case of the polydextran gel slurry 5 mL of the slurry was injected in the subcutaneous space using an 18 gauge needle. After implanting the foreign bodies a newly regenerated encapsulating tissue developed around the foreign bodies. The tissues were harvested after 4-42 d of implantation and studied by gross examination, histology, and histochemistry for organization, vascularity, and presence of mesenchymal stem cells (MSCs) (CD271+CD34+ cells). RESULTS: Implanting a large cylindrically shaped polyvinyl tube resulted in a large flat sheet of tissue that could be tailored to a specific size and shape for use as a tissue patch for repairing large organs. Implanting a smaller sized polyvinyl tube yielded a cylindrical tissue that could be useful for repairing nerves and blood vessels. This type of patch could be obtained in different lengths by varying the length of the implanted tube. Implanting a suspension of inert polydextran suspension

  3. Autologous mesenchymal stem cell therapy in progressive multiple sclerosis: an open label study.

    PubMed

    Bonab, Mandana Mohyeddin; Sahraian, Mohammad Ali; Aghsaie, Aida; Karvigh, Sanaz Ahmadi; Hosseinian, Seyed Massoud; Nikbin, Behrouz; Lotfi, Jamshid; Khorramnia, Saeideh; Motamed, Mohammad Reza; Togha, Mansoureh; Harirchian, Mohammad Hossien; Moghadam, Nahid Beladi; Alikhani, Katayoun; Yadegari, Samira; Jafarian, Sirous; Gheini, Mohammad Reza

    2012-11-01

    Despite updating knowledge and a growing number of medications for multiple sclerosis (MS), no definite treatment is available yet for patients suffering from progressive forms of the disease. Autologous bone marrow derived mesenchymal stem cell (BM-MSC) transplantation is a promising method proposed as a therapy for MS. Although the safety of these cells has been confirmed in hematological, cardiac and inflammatory diseases, its efficacy in MS treatment is still under study. Patients with progressive MS (expanded disability status scale score: 4.0 -6.50) unresponsive to conventional treatments were recruited for this study. Twenty-five patients [f/m: 19/6, mean age: 34.7±7] received a single intrathecal injection of ex-vivo expanded MSCs (mean dose: 29.5×10(6) cells). We observed their therapeutic response for 12 months. Associated short-term adverse events of injection consisted of transient low-grade fever, nausea /vomiting, weakness in the lower limbs and headache. No major delayed adverse effect was reported. 3 patients left the study for personal reasons. The mean (SD) expanded disability status scale (EDSS) score of 22 patients changed from 6.1 (0.6) to 6.3 (0.4). Clinical course of the disease (measured by EDSS) improved in 4, deteriorated in 6 and had no change in 12 patients. In MRI evaluation, 15 patients showed no change, whereas 6 patients showed new T2 or gadolinium enhanced lesions (1 lost to follow-up). It seems that MSC therapy can improve/stabilize the course of the disease in progressive MS in the first year after injection with no serious adverse effects. Repeating the study with a larger sample size, booster injections and longer follow-up using a controlled study design is advised. PMID:23061813

  4. Autologous platelet-rich plasma: a biological supplement to enhance adipose-derived mesenchymal stem cell expansion.

    PubMed

    Atashi, Fatemeh; Jaconi, Marisa E E; Pittet-Cuénod, Brigitte; Modarressi, Ali

    2015-03-01

    Currently the use of non-autologous cell culture media (e.g., animal-derived or allogeneic serum) for clinical applications of mesenchymal stem cells (MSCs) is criticized by regulatory agencies. Autologous platelet-rich plasma (PRP) is proposed as a safer alternative medium supplement for adipose-derived mesenchymal stem cells (AT-MSC) culture. To study its efficiency on cell proliferation, AT-MSCs were cultured for 10 days in media supplemented with different concentrations of autologous non-activated PRP (nPRP) or thrombin-activated PRP (tPRP) (1-60%). AT-MSC proliferation, cell phenotype, multipotency capacity, and chromosome stability were assessed and compared to AT-MSCs expanded in a classical medium supplemented with 10% of fetal bovine serum (FBS). Culture media supplemented with nPRP showed dose-dependent higher AT-MSC proliferation than did FBS or tPRP. Twenty percent nPRP was the most effective concentration to promote cell proliferation. This condition increased 13.9 times greater AT-MSC number in comparison to culture with FBS, without changing the AT-MSC phenotype, differentiation capacity, and chromosome status. We concluded that 20% autologous nPRP is a safe, efficient, and cost-effective supplement for AT-MSC expansion. It should be considered as an alternative to FBS or other nonautologous blood derivatives. It could serve as a potent substitute for the validation of future clinical protocols as it respects good manufacturing practices and regulatory agencies' standards. PMID:25025830

  5. Autologous Platelet-Rich Plasma: A Biological Supplement to Enhance Adipose-Derived Mesenchymal Stem Cell Expansion

    PubMed Central

    Atashi, Fatemeh; Jaconi, Marisa E.E.; Pittet-Cuénod, Brigitte

    2015-01-01

    Currently the use of non-autologous cell culture media (e.g., animal-derived or allogeneic serum) for clinical applications of mesenchymal stem cells (MSCs) is criticized by regulatory agencies. Autologous platelet-rich plasma (PRP) is proposed as a safer alternative medium supplement for adipose-derived mesenchymal stem cells (AT-MSC) culture. To study its efficiency on cell proliferation, AT-MSCs were cultured for 10 days in media supplemented with different concentrations of autologous non-activated PRP (nPRP) or thrombin-activated PRP (tPRP) (1–60%). AT-MSC proliferation, cell phenotype, multipotency capacity, and chromosome stability were assessed and compared to AT-MSCs expanded in a classical medium supplemented with 10% of fetal bovine serum (FBS). Culture media supplemented with nPRP showed dose-dependent higher AT-MSC proliferation than did FBS or tPRP. Twenty percent nPRP was the most effective concentration to promote cell proliferation. This condition increased 13.9 times greater AT-MSC number in comparison to culture with FBS, without changing the AT-MSC phenotype, differentiation capacity, and chromosome status. We concluded that 20% autologous nPRP is a safe, efficient, and cost-effective supplement for AT-MSC expansion. It should be considered as an alternative to FBS or other nonautologous blood derivatives. It could serve as a potent substitute for the validation of future clinical protocols as it respects good manufacturing practices and regulatory agencies' standards. PMID:25025830

  6. Concise Review: Human Dermis as an Autologous Source of Stem Cells for Tissue Engineering and Regenerative Medicine

    PubMed Central

    Vapniarsky, Natalia; Arzi, Boaz; Hu, Jerry C.; Nolta, Jan A.

    2015-01-01

    The exciting potential for regenerating organs from autologous stem cells is on the near horizon, and adult dermis stem cells (DSCs) are particularly appealing because of the ease and relative minimal invasiveness of skin collection. A substantial number of reports have described DSCs and their potential for regenerating tissues from mesenchymal, ectodermal, and endodermal lineages; however, the exact niches of these stem cells in various skin types and their antigenic surface makeup are not yet clearly defined. The multilineage potential of DSCs appears to be similar, despite great variability in isolation and in vitro propagation methods. Despite this great potential, only limited amounts of tissues and clinical applications for organ regeneration have been developed from DSCs. This review summarizes the literature on DSCs regarding their niches and the specific markers they express. The concept of the niches and the differentiation capacity of cells residing in them along particular lineages is discussed. Furthermore, the advantages and disadvantages of widely used methods to demonstrate lineage differentiation are considered. In addition, safety considerations and the most recent advancements in the field of tissue engineering and regeneration using DSCs are discussed. This review concludes with thoughts on how to prospectively approach engineering of tissues and organ regeneration using DSCs. Our expectation is that implementation of the major points highlighted in this review will lead to major advancements in the fields of regenerative medicine and tissue engineering. Significance Autologous dermis-derived stem cells are generating great excitement and efforts in the field of regenerative medicine and tissue engineering. The substantial impact of this review lies in its critical coverage of the available literature and in providing insight regarding niches, characteristics, and isolation methods of stem cells derived from the human dermis. Furthermore, it

  7. A population-based cohort study of late mortality in adult autologous hematopoietic stem cell transplant recipients in Australia.

    PubMed

    Ashton, Lesley J; Le Marsney, Renate E; Dodds, Anthony J; Nivison-Smith, Ian; Wilcox, Leonie; O'Brien, Tracey A; Vajdic, Claire M

    2014-07-01

    We assessed overall and cause-specific mortality and risk factors for late mortality in a nation-wide population-based cohort of 4547 adult cancer patients who survived 2 or more years after receiving an autologous hematopoietic stem cell transplantation (HSCT) in Australia between 1992 and 2005. Deaths after HSCT were identified from the Australasian Bone Marrow Transplant Recipient Registry and through data linkage with the National Death Index. Overall, the survival probability was 56% at 10 years from HSCT, ranging from 34% for patients with multiple myeloma to 90% for patients with testicular cancer. Mortality rates moved closer to rates observed in the age- and sex-matched Australian general population over time but remained significantly increased 11 or more years from HSCT (standardized mortality ratio, 5.9). Although the proportion of deaths from nonrelapse causes increased over time, relapse remained the most frequent cause of death for all diagnoses, 10 or more years after autologous HSCT. Our findings show that prevention of disease recurrence remains 1 of the greatest challenges for autologous HSCT recipients, while the increasing rates of nonrelapse deaths due to the emergence of second cancers, circulatory diseases, and respiratory diseases highlight the long-term health issues faced by adult survivors of autologous HSCT. PMID:24631736

  8. The Role of Autologous Stem Cell Transplantation in the Treatment of Diffuse Large B-Cell Lymphoma

    PubMed Central

    Gunnellini, Marco; Emili, Rita; Coaccioli, Stefano; Liberati, Anna Marina

    2012-01-01

    Diffuse large B-cell non-Hodgkin's lymphoma (DLBCL) accounting for approximately 30% of new lymphoma diagnoses in adult patients. Complete remissions (CRs) can be achieved in 45% to 55% of patients and cure in approximately 30–35% with anthracycline-containing combination chemotherapy. The ageadjusted IPI (aaIPI) has been widely employed, particularly to “tailor” more intensive therapy such as high-dose therapy (HDT) with autologous hemopoietic stem cell rescue (ASCT). IPI, however, has failed to reliably predict response to specific therapies. A subgroup of young patients with poor prognosis exists. To clarify the role of HDT/ASCT combined with rituximab in the front line therapy a longer follow-up and randomized studies are needed. The benefit of HDT/ASCT for refractory or relapsed DLBCL is restricted to patients with immunochemosensitive disease. Currently, clinical and biological research is focused to improve the curability of this setting of patients, mainly young. PMID:22312366

  9. Very small embryonic-like stem cells with maximum regenerative potential get discarded during cord blood banking and bone marrow processing for autologous stem cell therapy.

    PubMed

    Bhartiya, Deepa; Shaikh, Ambreen; Nagvenkar, Punam; Kasiviswanathan, Sandhya; Pethe, Prasad; Pawani, Harsha; Mohanty, Sujata; Rao, S G Ananda; Zaveri, Kusum; Hinduja, Indira

    2012-01-01

    Very small embryonic-like stem cells (VSELs) are possibly lost during cord blood banking and bone marrow (BM) processing for autologus stem cell therapy mainly because of their small size. The present study was conducted on human umbilical cord blood (UCB, n=6) and discarded red blood cells (RBC) fraction obtained after separation of mononuclear cells from human BM (n=6), to test this hypothesis. The results show that VSELs, which are pluripotent stem cells with maximum regenerative potential, settle along with the RBCs during Ficoll-Hypaque density separation. These cells are very small in size (3-5 μm), have high nucleo-cytoplasmic ratio, and express nuclear Oct-4, cell surface protein SSEA-4, and other pluripotent markers such as Nanog, Sox-2, Rex-1, and Tert as indicated by immunolocalization and quantitative polymerase chain reaction (Q-PCR) studies. Interestingly, a distinct population of slightly larger, round hematopoietic stem cells (HSCs) with cytoplasmic Oct-4 were detected in the "buffy" coat, which usually gets banked or used during autologus stem cell therapy. Immunohistochemical studies on the umbilical cord tissue (UCT) sections (n=3) showed the presence of nuclear Oct-4-positive VSELs and many fibroblast-like mesenchymal stem cells (MSCs) with cytoplasmic Oct-4. These VSELs with nuclear Oct-4, detected in UCB, UCT, and discarded RBC fraction obtained after BM processing, may persist throughout life, maintain tissue homeostasis, and undergo asymmetric cell division to self-renew as well as produce larger progenitor stem cells, viz. HSCs or MSCs, which follow differentiation trajectories depending on the somatic niche. Hence, it can be concluded that the true stem cells in adult body tissues are the VSELs, whereas the HSCs and MSCs are actually progenitor stem cells that arise by asymmetric cell division of VSELs. The results of the present study may help explain low efficacy reported during adult autologous stem cell trials, wherein unknowingly

  10. Importance of Achieving Stringent Complete Response After Autologous Stem-Cell Transplantation in Multiple Myeloma

    PubMed Central

    Kapoor, Prashant; Kumar, Shaji K.; Dispenzieri, Angela; Lacy, Martha Q.; Buadi, Francis; Dingli, David; Russell, Stephen J.; Hayman, Suzanne R.; Witzig, Thomas E.; Lust, John A.; Leung, Nelson; Lin, Yi; Zeldenrust, Steven R.; McCurdy, Arleigh; Greipp, Philip R.; Kyle, Robert A.; Rajkumar, S. Vincent; Gertz, Morie A.

    2013-01-01

    Purpose To study the impact of achieving stringent complete response (sCR), an increasingly attainable goal, after autologous stem-cell transplantation (ASCT) in patients with multiple myeloma (MM). Patients and Methods Maximal response rates were determined in 445 consecutive patients who underwent ASCT within 12 months of diagnosis of MM. The patients achieving varying degrees of complete response (CR) are the focus of our study. Results One hundred and nine patients (25%) achieved sCR after ASCT. The median overall survival (OS) rate from the time of transplantation for patients attaining sCR was not reached (NR), in contrast to those patients achieving conventional complete response (CR; n = 37; OS, 81 months) or near CR (nCR; n = 91; OS, 60 months; P < .001). Five-year OS rates were 80%, 53%, and 47% for sCR, CR, and nCR, respectively. The median time to progression (TTP) from ASCT of patients achieving sCR was significantly longer (50 months) than TTP of patients achieving CR or nCR (20 months and 19 months, respectively). On multivariable analysis, post-ASCT response of sCR was an independent prognostic factor for survival (hazard ratio, 0.44; 95% CI, 0.25 to 0.80; versus CR; P = .008), in addition to proliferation rate, pre-ASCT cytogenetics, and performance status. OS rates of patients attaining sCR continued to remain superior at 2-year landmark (median, NR v 70 months for conventional CR group; P = .007). Conclusion Improved long-term outcome is seen after ASCT with achievement of sCR when compared with lesser degrees of responses. Myeloma trials reporting the response rates should identify patients achieving sCR and CR separately, owing to markedly disparate outcomes of the two categories. PMID:24248686

  11. Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Atypical Teratoid/Rhabdoid Tumor

    PubMed Central

    Sung, Ki Woong; Lim, Do Hoon; Yi, Eun Sang; Choi, Young Bae; Lee, Ji Won; Yoo, Keon Hee; Koo, Hong Hoe; Kim, Ji Hye; Suh, Yeon-Lim; Joung, Yoo Sook; Shin, Hyung Jin

    2016-01-01

    Purpose We prospectively evaluated the effectiveness of tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) in improving the survival of patients with atypical teratoid/rhabdoid tumors while reducing the risks of late adverse effects from radiotherapy (RT). Materials and Methods For young children (< 3 years old), tandem HDCT/auto-SCT was administered after six cycles of induction chemotherapy. RT was deferred until after 3 years of age unless the tumor showed relapse or progression. For older patients (> 3 years old), RT including reduced-dose craniospinal RT (23.4 or 30.6 Gy) was administered either after two cycles of induction chemotherapy or after surgery, and tandem HDCT/auto-SCT was administered after six cycles of induction chemotherapy. Results A total of 13 patients (five young and eight older) were enrolled from November 2004 to June 2012. Eight patients, including all five young patients, had metastatic disease at diagnosis. Six patients (four young and two older) experienced progression before initiation of RT, and seven were able to proceed to HDCT/auto-SCT without progression during induction treatment. Three of six patients who experienced progression during induction treatment underwent HDCT/auto-SCT as salvage treatment. All five young patients died from disease progression. However, four of the eight older patients remain progression-freewith a median follow-up period of 64 months (range, 39 to 108 months). Treatment-related late toxicities were acceptable. Conclusion The required dose of craniospinal RT might be reduced in older patients if the intensity of chemotherapy is increased. However, early administration of RT should be considered to prevent early progression in young patients. PMID:27034140

  12. Autologous preconditioned mesenchymal stem cell sheets improve left ventricular function in a rabbit old myocardial infarction model

    PubMed Central

    Tanaka, Yuya; Shirasawa, Bungo; Takeuchi, Yuriko; Kawamura, Daichi; Nakamura, Tamami; Samura, Makoto; Nishimoto, Arata; Ueno, Koji; Morikage, Noriyasu; Hosoyama, Tohru; Hamano, Kimikazu

    2016-01-01

    Mesenchymal stem cells (MSCs) constitute one of the most powerful tools for therapeutic angiogenesis in infarcted hearts. However, conventional MSC transplantation approaches result in insufficient therapeutic effects due to poor retention of graft cells in severe ischemic diseases. Cell sheet technology has been developed as a new method to prolong graft cell retention even in ischemic tissue. Recently, we demonstrated that hypoxic pretreatment enhances the therapeutic efficacy of cell sheet implantation in infarcted mouse hearts. In this study, we investigated whether hypoxic pretreatment activates the therapeutic functions of bone marrow-derived MSC (BM-MSC) sheets and improves cardiac function in rabbit infarcted hearts following autologous transplantation. Production of vascular endothelial growth factor (VEGF) was increased in BM-MSC monolayer sheets and it peaked at 48 h under hypoxic culture conditions (2% O2). To examine in vivo effects, preconditioned autologous BM-MSC sheets were implanted into a rabbit old myocardial infarction model. Implantation of preconditioned BM-MSC sheets accelerated angiogenesis in the peri-infarcted area and decreased the infarcted area, leading to improvement of the left ventricular function of the infarcted heart. Importantly, the therapeutic efficacy of the preconditioned BM-MSC sheets was higher than that of standardly cultured sheets. Thus, implantation of autologous preconditioned BM-MSC sheets is a feasible approach for enhancing therapeutic angiogenesis in chronically infarcted hearts. PMID:27347329

  13. Scaffold-Based Delivery of Autologous Mesenchymal Stem Cells for Mandibular Distraction Osteogenesis: Preliminary Studies in a Porcine Model

    PubMed Central

    Sun, Zongyang; Tee, Boon Ching; Kennedy, Kelly S.; Kennedy, Patrick M.; Kim, Do-Gyoon; Mallery, Susan R.; Fields, Henry W.

    2013-01-01

    Purpose Bone regeneration through distraction osteogenesis (DO) is promising but remarkably slow. To accelerate it, autologous mesenchymal stem cells have been directly injected to the distraction site in a few recent studies. Compared to direct injection, a scaffold-based method can provide earlier cell delivery with potentially better controlled cell distribution and retention. This pilot project investigated a scaffold-based cell-delivery approach in a porcine mandibular DO model. Materials and Methods Eleven adolescent domestic pigs were used for two major sets of studies. The in-vitro set established methodologies to: aspirate bone marrow from the tibia; isolate, characterize and expand bone marrow-derived mesenchymal stem cells (BM-MSCs); enhance BM-MSC osteogenic differentiation using FGF-2; and confirm cell integration with a gelatin-based Gelfoam scaffold. The in-vivo set transplanted autologous stem cells into the mandibular distraction sites using Gelfoam scaffolds; completed a standard DO-course and assessed bone regeneration by macroscopic, radiographic and histological methods. Repeated-measure ANOVAs and t-tests were used for statistical analyses. Results From aspirated bone marrow, multi-potent, heterogeneous BM-MSCs purified from hematopoietic stem cell contamination were obtained. FGF-2 significantly enhanced pig BM-MSC osteogenic differentiation and proliferation, with 5 ng/ml determined as the optimal dosage. Pig BM-MSCs integrated readily with Gelfoam and maintained viability and proliferative ability. After integration with Gelfoam scaffolds, 2.4–5.8×107 autologous BM-MSCs (undifferentiated or differentiated) were transplanted to each experimental DO site. Among 8 evaluable DO sites included in the final analyses, the experimental DO sites demonstrated less interfragmentary mobility, more advanced gap obliteration, higher mineral content and faster mineral apposition than the control sites, and all transplanted scaffolds were completely

  14. Technologies enabling autologous neural stem cell-based therapies for neurodegenerative disease and injury

    NASA Astrophysics Data System (ADS)

    Bakhru, Sasha H.

    The intrinsic abilities of mammalian neural stem cells (NSCs) to self-renew, migrate over large distances, and give rise to all primary neural cell types of the brain offer unprecedented opportunity for cell-based treatment of neurodegenerative diseases and injuries. This thesis discusses development of technologies in support of autologous NSC-based therapies, encompassing harvest of brain tissue biopsies from living human patients; isolation of NSCs from harvested tissue; efficient culture and expansion of NSCs in 3D polymeric microcapsule culture systems; optimization of microcapsules as carriers for efficient in vivo delivery of NSCs; genetic engineering of NSCs for drug-induced, enzymatic release of transplanted NSCs from microcapsules; genetic engineering for drug-induced differentiation of NSCs into specific therapeutic cell types; and synthesis of chitosan/iron-oxide nanoparticles for labeling of NSCs and in vivo tracking by cellular MRI. Sub-millimeter scale tissue samples were harvested endoscopically from subventricular zone regions of living patient brains, secondary to neurosurgical procedures including endoscopic third ventriculostomy and ventriculoperitoneal shunt placement. On average, 12,000 +/- 3,000 NSCs were isolated per mm 3 of subventricular zone tissue, successfully demonstrated in 26 of 28 patients, ranging in age from one month to 68 years. In order to achieve efficient expansion of isolated NSCs to clinically relevant numbers (e.g. hundreds of thousands of cells in Parkinson's disease and tens of millions of cells in multiple sclerosis), an extracellular matrix-inspired, microcapsule-based culture platform was developed. Initial culture experiments with murine NSCs yielded unprecedented expansion folds of 30x in 5 days, from initially minute NSC populations (154 +/- 15 NSCs per 450 mum diameter capsule). Within 7 days, NSCs expanded as almost perfectly homogenous populations, with 94.9% +/- 4.1% of cultured cells staining positive for

  15. Patients' perception of health-related quality of life during the first year after autologous and allogeneic stem cell transplantation.

    PubMed

    Andersson, I; Ahlberg, K; Stockelberg, D; Persson, L-O

    2011-05-01

    Little attention has been paid to examine health-related quality of life (HRQoL) the first year post-transplant, despite that this period is crucial for returning to normal life and functioning and to prevent delayed psychosocial adjustment. The purpose of the present study was to describe HRQoL after autologous versus allogeneic stem cell transplantations during the first year post-transplant. The allogeneic group was further divided into two groups: allogeneic stem cell transplantation after reduced intensive conditioning and allogeneic stem cell transplantation after myeloablative conditioning. All together 202 patients were enrolled in the study. HRQoL was assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the treatment-specific module High-Dose Chemotherapy (HDC-19). The questionnaires were filled out at six occasions (from inclusion to 12 months after transplantation). The reduced intensive conditioning group seemed to recover in the same way as the autologous group and these two groups were closer in their scoring compared with the myeloablative conditioning group. One month after the transplantation there were no significant differences in change scores between the autologous and reduced intensive conditioning group, and 1 year after the transplantation levels of symptoms and functioning were back to baseline or better. The myeloablative conditioning group, who perceived more symptoms and lower levels of functioning during the whole period, was still impaired in 10 out of 29 scales 1 year after the transplantation and no significant improvements compared with baseline were observed for this group.

  16. The Use Of Laser Irradiation To Stimulate Adipose Derived Stem Cell Proliferation And Differentiation For Use In Autologous Grafts

    NASA Astrophysics Data System (ADS)

    Abrahamse, Heidi

    2009-09-01

    Stem cells are characterized by the qualities of self-renewal, long term viability, and the ability to differentiate into various cell types. Historically, stem cells have been isolated from the inner cell mass of blastocysts and harvesting these cells resulted in the death of the embryo leading to religious, political and ethical issues. The identification and subsequent isolation of adult stem cells from bone marrow stroma have been welcomed as an alternate source for stem cells. The clinical use of Mesenchymal Stem Cells (MSCs) presented problems such as limited cell number, pain and morbidity upon isolation. Adipose tissue is derived from the mesenchyme, is easily isolated, a reliable source of stem cells and able to differentiate into different cell types including smooth muscle. Over the past few years, the identification and characterization of stem cells has led the potential use of these cells as a promising alternative to cell replacement therapy. Smooth muscle is a major component of human tissues and is essential for the normal functioning of many different organs. Low intensity laser irradiation has been shown to increase viability, protein expression and migration of stem cells in vitro, and to stimulate proliferation of various types of stem cells. In addition, the use of laser irradiation to stimulate differentiation in the absence of growth factors has also been demonstrated in normal human neural progenitor cells (NHNPCs) in vitro where NHNPCs are not only capable of being sustained by light in the absence of growth factors, but that they are also able to differentiate normally as assessed by neurite formation. Our work has focused on the ability of laser irradiation to proliferate adipose derived stem cells (ADSCs), maintain ADSC character and increase the rate and maintenance of differentiation of ADSCs into smooth muscle and skin fibroblast cells. Current studies are also investigating the effect of different irradiation wavelengths and

  17. Autologous stem cell transplantation in chronic myeloid leukemia: a single center experience.

    PubMed

    Pigneux, A; Faberes, C; Boiron, J M; Mahon, F X; Cony-Makhoul, P; Agape, P; Lounici, A; Bernard, P; Bilhou-Nabera, C; Bouzgarrou, R; Marit, G; Reiffers, J

    1999-08-01

    Between 1980 and 1996, we transplanted 72 patients with CML using blood stem cells collected at diagnosis before treatment and without any mobilization. The median age of patients at diagnosis was 47.5 years (range 20.5-59.5). The median numbers of nucleated cells and CFU-GM transplanted were 10 x 10(8)/kg and 97 x 10(4)/kg, respectively. The median duration to reach more than 0.5 x 10(9)/l neutrophils and 50 x 10(9)/l platelets was 12 (range 5-19) and 11 days (range 0-79), respectively. Twenty patients (group I) were transplanted in chronic phase either for resistance to IFN (14 patients) (group IA) or because the Sokal index was more than 1.2 (six patients) (group IB). All those patients had preparative regimen with busulfan (4 mg/kg/day x 4) and melphalan (140 mg/m2). They were treated with recombinant alpha-interferon (IFN) after transplant. The cumulative incidence of major cytogenetic response (MCR) at 12 months was 25 +/- 21% (95% CI), the 5-year survival was 75 +/- 42% (95% CI). These results (observed in patients with bad prognosis factors) are similar to those usually observed in CML patients treated by IFN, whatever the Sokal risk. Thus autologous transplantation is able to reproduce for poor prognosis patients the results observed in standard risk patients treated with IFN. This suggests that it could prolong survival. Fifty-two other patients (group II) were transplanted for CML in transformation (accelerated phase = 32; blast crisis = 20) after a preparative regimen containing either total body irradiation (TBI) or busulfan. The median survival was short (10.4 months) and only 21 patients survived more than 1 year. The survival was longer for patients transplanted in accelerated phase (vs blast crisis), those who were due to receive a double transplant (vs single) (34 patients), those who were treated with IFN after transplant (vs hydroxyurea) and for the patients who obtained a complete hematologic response.

  18. Potential new strategies for the treatment of ovarian infertility and degenerative diseases with autologous ovarian stem cells.

    PubMed

    Bukovsky, Antonin; Copas, Pleas; Virant-Klun, Irma

    2006-04-01

    The 50-year-old and currently prevailing view that all oocytes in adult human ovaries persist from the fetal period of life is controversial as it clashes with Darwinian evolutionary theory. Studies of oogenesis and follicular renewal in adult human ovaries, and of the role of hormonal signals and third-party cells (tissue macrophages and T cells), could all be helpful in providing better understanding of the causes of ovarian infertility, its prevention and potential therapy. In addition, the authors recently reported differentiation of distinct cell types and the production of new eggs in cultures derived from premenopausal and postmenopausal human ovaries. It is possible that fertilisation of such eggs will open up new opportunities for providing genetically related children to infertile women for whom conventional in vitro fertilisation has failed. As ovarian stem cells appear to represent a new type of totipotent adult stem cell, they could also be utilised for autologous stem cell therapy of degenerative diseases, without any involvement of allogeneic embryonic stem cells and somatic cell nuclear transfer.

  19. Isolation, expansion and neural differentiation of stem cells from human plucked hair: a further step towards autologous nerve recovery.

    PubMed

    Gho, Coen G; Schomann, Timo; de Groot, Simon C; Frijns, Johan H M; Rivolta, Marcelo N; Neumann, Martino H A; Huisman, Margriet A

    2016-10-01

    Stem cells from the adult hair follicle bulge can differentiate into neurons and glia, which is advantageous for the development of an autologous cell-based therapy for neurological diseases. Consequently, bulge stem cells from plucked hair may increase opportunities for personalized neuroregenerative therapy. Hairs were plucked from the scalps of healthy donors, and the bulges were cultured without prior tissue treatment. Shortly after outgrowth from the bulge, cellular protein expression was established immunohistochemically. The doubling time was calculated upon expansion, and the viability of expanded, cryopreserved cells was assessed after shear stress. The neuroglial differentiation potential was assessed from cryopreserved cells. Shortly after outgrowth, the cells were immunopositive for nestin, SLUG, AP-2α and SOX9, and negative for SOX10. Each bulge yielded approximately 1 × 10(4) cells after three passages. Doubling time was 3.3 (±1.5) days. Cellular viability did not differ significantly from control cells after shear stress. The cells expressed class III β-tubulin (TUBB3) and synapsin-1 after 3 weeks of neuronal differentiation. Glial differentiation yielded KROX20- and MPZ-immunopositive cells after 2 weeks. We demonstrated that human hair follicle bulge-derived stem cells can be cultivated easily, expanded efficiently and kept frozen until needed. After cryopreservation, the cells were viable and displayed both neuronal and glial differentiation potential.

  20. Autologous bone marrow stem cell transplantation for the treatment of postoperative hand infection with a skin defect in diabetes mellitus: A case report.

    PubMed

    Liu, Yihong; Liu, Yuchen; Wang, Pujie; Tian, Haoming; Ai, Jianzhong; Liu, Yangbo; Zhou, Yi; Liu, Zhongwen; Guo, Wenjun; Yang, Shenke

    2014-06-01

    Among stem cells, autologous mesenchymal stem cells (MSCs) are ideal for transplantation by virtue of limited rejection reactions and marked proliferative ability. This study presents a novel method by which MSCs were harvested from the bone marrow of a patient who presented with severe post-traumatic infection and a non-healing skin defect in the hand, secondary to uncontrolled diabetes mellitus (DM). An autologous MSC suspension was injected into the persistent skin defect after stabilizing the blood glucose level and appropriate infection control. During the course of a regular 18-month postoperative follow-up, the patient exhibited immediate recovery with no transplant-associated complications, as well as no evidence of tumorigenicity. Thus, transplantation of autologous MSCs may play a role in the clinical application of stem cells, particularly for treatment of skin defects following surgery in cases of DM and for those caused by various other traumas.

  1. Scaffold-free Three-dimensional Graft From Autologous Adipose-derived Stem Cells for Large Bone Defect Reconstruction

    PubMed Central

    Dufrane, Denis; Docquier, Pierre-Louis; Delloye, Christian; Poirel, Hélène A.; André, Wivine; Aouassar, Najima

    2015-01-01

    Abstract Long bone nonunion in the context of congenital pseudarthrosis or carcinologic resection (with intercalary bone allograft implantation) is one of the most challenging pathologies in pediatric orthopedics. Autologous cancellous bone remains the gold standard in this context of long bone nonunion reconstruction, but with several clinical limitations. We then assessed the feasibility and safety of human autologous scaffold-free osteogenic 3-dimensional (3D) graft (derived from autologous adipose-derived stem cells [ASCs]) to cure a bone nonunion in extreme clinical and pathophysiological conditions. Human ASCs (obtained from subcutaneous adipose tissue of 6 patients and expanded up to passage 4) were incubated in osteogenic media and supplemented with demineralized bone matrix to obtain the scaffold-free 3D osteogenic structure as confirmed in vitro by histomorphometry for osteogenesis and mineralization. The 3D “bone-like” structure was finally transplanted for 3 patients with bone tumor and 3 patients with bone pseudarthrosis (2 congenital, 1 acquired) to assess the clinical feasibility, safety, and efficacy. Although minor clones with structural aberrations (aneuploidies, such as tri or tetraploidies or clonal trisomy 7 in 6%–20% of cells) were detected in the undifferentiated ASCs at passage 4, the osteogenic differentiation significantly reduced these clonal anomalies. The final osteogenic product was stable, did not rupture with forceps manipulation, did not induce donor site morbidity, and was easily implanted directly into the bone defect. No acute (<3 mo) side effects, such as impaired wound healing, pain, inflammatory reaction, and infection, or long-term side effects, such as tumor development, were associated with the graft up to 4 years after transplantation. We report for the first time that autologous ASC can be fully differentiated into a 3D osteogenic-like implant without any scaffold. We demonstrated that this engineered tissue can

  2. Human Induced Pluripotent Stem Cells Are Targets for Allogeneic and Autologous Natural Killer (NK) Cells and Killing Is Partly Mediated by the Activating NK Receptor DNAM-1

    PubMed Central

    Monecke, Sebastian; Cyganek, Lukas; Elsner, Leslie; Hübscher, Daniela; Walter, Lutz; Streckfuss-Bömeke, Katrin; Guan, Kaomei; Dressel, Ralf

    2015-01-01

    Human induced pluripotent stem cells (hiPSCs) could be used to generate autologous cells for therapeutic purposes, which are expected to be tolerated by the recipient. However, iPSC-derived grafts are at risk of giving rise to teratomas in the host, if residuals of tumorigenic cells are not rejected by the recipient. We have analyzed the susceptibility of hiPSC lines to allogeneic and autologous natural killer (NK) cells. IL-2-activated, in contrast to resting NK cells killed hiPSC lines efficiently (P=1.69x10-39). Notably, the specific lysis of the individual hiPSC lines by IL-2-activated NK cells was significantly different (P=1.72x10-6) and ranged between 46 % and 64 % in 51Cr-release assays when compared to K562 cells. The hiPSC lines were killed by both allogeneic and autologous NK cells although autologous NK cells were less efficient (P=8.63x10-6). Killing was partly dependent on the activating NK receptor DNAM-1 (P=8.22x10-7). The DNAM-1 ligands CD112 and CD155 as well as the NKG2D ligands MICA and MICB were expressed on the hiPSC lines. Low amounts of human leukocyte antigen (HLA) class I proteins, which serve as ligands for inhibitory and activating NK receptors were also detected. Thus, the susceptibility to NK cell killing appears to constitute a common feature of hiPSCs. Therefore, NK cells might reduce the risk of teratoma formation even after autologous transplantations of pluripotent stem cell-derived grafts that contain traces of pluripotent cells. PMID:25950680

  3. Autologous mesenchymal stem cell therapy for progressive supranuclear palsy: translation into a phase I controlled, randomized clinical study

    PubMed Central

    2014-01-01

    Background Progressive Supranuclear Palsy (PSP) is a sporadic and progressive neurodegenerative disease which belongs to the family of tauopathies and involves both cortical and subcortical structures. No effective therapy is to date available. Methods/design Autologous bone marrow (BM) mesenchymal stem cells (MSC) from patients affected by different type of parkinsonisms have shown their ability to improve the dopaminergic function in preclinical and clinical models. It is also possible to isolate and expand MSC from the BM of PSP patients with the same proliferation rate and immuphenotypic profile as MSC from healthy donors. BM MSC can be efficiently delivered to the affected brain regions of PSP patients where they can exert their beneficial effects through different mechanisms including the secretion of neurotrophic factors. Here we propose a randomized, placebo-controlled, double-blind phase I clinical trial in patients affected by PSP with MSC delivered via intra-arterial injection. Discussion To our knowledge, this is the first clinical trial to be applied in a no-option parkinsonism that aims to test the safety and to exploit the properties of autologous mesenchymal stem cells in reducing disease progression. The study has been designed to test the safety of this “first-in-man” approach and to preliminarily explore its efficacy by excluding the placebo effect. Trial registration NCT01824121 PMID:24438512

  4. Use of Autologous Mesenchymal Stem Cells Derived from Bone Marrow for the Treatment of Naturally Injured Spinal Cord in Dogs

    PubMed Central

    Penha, Euler Moraes; Meira, Cássio Santana; Guimarães, Elisalva Teixeira; Mendonça, Marcus Vinícius Pinheiro; Gravely, Faye Alice; Pinheiro, Cláudia Maria Bahia; Pinheiro, Taiana Maria Bahia; Barrouin-Melo, Stella Maria; Ribeiro-dos-Santos, Ricardo; Soares, Milena Botelho Pereira

    2014-01-01

    The use of stem cells in injury repair has been extensively investigated. Here, we examined the therapeutic effects of autologous bone marrow mesenchymal stem cells (MSC) transplantation in four dogs with natural traumatic spinal cord injuries. MSC were cultured in vitro, and proliferation rate and cell viability were evaluated. Cell suspensions were prepared and surgically administered into the spinal cord. The animals were clinically evaluated and examined by nuclear magnetic resonance. Ten days after the surgical procedure and MSC transplantation, we observed a progressive recovery of the panniculus reflex and diminished superficial and deep pain response, although there were still low proprioceptive reflexes in addition to a hyperreflex in the ataxic hind limb movement responses. Each dog demonstrated an improvement in these gains over time. Conscious reflex recovery occurred simultaneously with moderate improvement in intestine and urinary bladder functions in two of the four dogs. By the 18th month of clinical monitoring, we observed a remarkable clinical amelioration accompanied by improved movement, in three of the four dogs. However, no clinical gain was associated with alterations in magnetic resonance imaging. Our results indicate that MSC are potential candidates for the stem cell therapy following spinal cord injury. PMID:24723956

  5. Effect of autologous platelet-rich plasma on the chondrogenic differentiation of rabbit adipose-derived stem cells in vitro

    PubMed Central

    TANG, XIAO-BO; DONG, PEI-LONG; WANG, JIAN; ZHOU, HAI-YANG; ZHANG, HAI-XIANG; WANG, SHAN-ZHENG

    2015-01-01

    This study aimed to isolate rabbit adipose-derived stem cells (ADSCs) and explore the potential of platelet-rich plasma (PRP) in the chondrogenic differentiation of ADSCs, thereby potentially providing a new approach for the repair and regeneration of cartilage injury. Rabbit ADSCs were isolated and characterized by induction towards adipogenic, osteogenic and chondrogenic lineages in vitro. The isolated ADSCs were also cultured with or without 10% PRP. Immunofluorescence staining, toluidine blue staining and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to detect type II collagen (Col II) and aggrecan (AGC) expression. Col II immunofluorescence staining and toluidine blue staining indicated that following induction by autologous PRP, ADSCs manifested Col II and AGC expression. The expression of Col II and AGC mRNA was significantly upregulated in the PRP-treated cells when compared with that in control cells. Autologous PRP produced by laboratory centrifugation was able to promote the chondrogenic differentiation of rabbit ADSCs in vitro. PMID:26622340

  6. Salvage chemotherapy and autologous stem cell transplant in primary refractory diffuse large B-cell lymphoma: outcomes and prognostic factors.

    PubMed

    Telio, David; Fernandes, Kim; Ma, Clement; Tsang, Richard; Keating, Armand; Crump, Michael; Kuruvilla, John

    2012-05-01

    Patients with primary refractory diffuse large B-cell lymphoma (REF DLBCL: progression on or within 3 months of completion of primary therapy) sensitive to salvage chemotherapy undergo autologous stem cell transplant (ASCT). We conducted a retrospective review of 111 patients with REF DLBCL treated between 1999 and 2007. Primary treatment consisted of cyclophosphamide, adriamycin, vincristine and prednisone (CHOP; 66%) and rituximab with CHOP (R-CHOP; 33%); 14% received involved field radiation. The response rate (RR) to first salvage chemotherapy was 23% (RR by regimen: dexamethasone, cytosine arabinoside and cisplatin [DHAP] 15%, etoposide, Solu-Medrol, cytosine arabinoside and cisplatin [ESHAP] 36%, and gemcitabine, dexamethasone and cisplatin [GDP] 45%); 25% (n = 28) of patients underwent ASCT. With a median follow-up of 5.9 months (range 1-94), the median progression-free and overall survival from primary treatment failure was 3 and 10 months, respectively. Outcomes in patients with REF DLBCL after CHOP or R-CHOP appear equally poor. Second-generation platinum-containing regimens (ESHAP, GDP) may be superior to DHAP in this setting. Novel, prospectively evaluated treatment approaches should be pursued in REF DLBCL. PMID:22136378

  7. Effect of remission status and induction chemotherapy regimen on outcome of autologous stem cell transplantation for mantle cell lymphoma.

    PubMed

    Till, Brian G; Gooley, Theodore A; Crawford, Nathan; Gopal, Ajay K; Maloney, David G; Petersdorf, Stephen H; Pagel, John M; Holmberg, Leona; Bensinger, William; Press, Oliver W

    2008-06-01

    We analysed the outcomes of autologous stem cell transplantation (ASCT) following high-dose therapy with respect to remission status at the time of transplantation and induction regimen used in 56 consecutive patients with mantle cell lymphoma (MCL). Twenty-one patients received induction chemotherapy with HyperCVAD with or without rituximab (+/-R) followed by ASCT in first complete or partial remission (CR1/PR1), 15 received CHOP (+/-R) followed by ASCT in CR1/PR1 and 20 received ASCT following disease progression. Estimates of overall and progression-free survival (PFS) at 3 years among patients transplanted in CR1/PR1 were 93% and 63% compared with 46% and 36% for patients transplanted with relapsed/refractory disease, respectively. The hazard of mortality among patients transplanted with relapsed/refractory disease was 6.09 times that of patients transplanted in CR1/PR1 (P = 0.006). Patients in the CHOP (+/-R) group had a higher risk of failure for PFS compared with patients in the HyperCVAD (+/-R) group, though the difference did not reach statistical significance (hazard ratio 3.67, P = 0.11). These results suggest that ASCT in CR1/PR1 leads to improved survival outcomes for patients with MCL compared to ASCT with relapsed/refractory disease, and a HyperCVAD (+/-R) induction regimen may be associated with an improved PFS among patients transplanted in CR1/PR1. PMID:18452065

  8. Pretransplantation Minimal Residual Disease Predicts Survival in Patients with Mantle Cell Lymphoma Undergoing Autologous Stem Cell Transplantation in Complete Remission.

    PubMed

    Cowan, Andrew J; Stevenson, Philip A; Cassaday, Ryan D; Graf, Solomon A; Fromm, Jonathan R; Wu, David; Holmberg, Leona A; Till, Brian G; Chauncey, Thomas R; Smith, Stephen D; Philip, Mary; Orozco, Johnnie J; Shustov, Andrei R; Green, Damian J; Libby, Edward N; Bensinger, William I; Shadman, Mazyar; Maloney, David G; Press, Oliver W; Gopal, Ajay K

    2016-02-01

    Autologous stem cell transplantation (ASCT) is standard therapy for mantle cell lymphoma (MCL) in remission after induction chemotherapy, with the best results for patients in complete remission (CR). We hypothesized that evaluation of minimal residual disease (MRD) before ASCT could further stratify outcomes for these patients. Patients with MCL who underwent ASCT in clinical CR between 1996 and 2011 with pretransplantation MRD testing were eligible. Presence of a clonal IgH rearrangement, t(11; 14) by PCR or positive flow cytometry from blood or bone marrow, was considered positive. An adjusted proportional hazards model for associations with progression-free (PFS) and overall survival (OS) was performed. Of 75 MCL patients in CR, 8 (11%) were MRD positive. MRD positivity was associated with shorter OS and PFS. The median OS for MRD-negative patients was not reached, with 82% survival at 5 years, whereas for the MRD-positive patients, median OS was 3.01 years (hazard ratio [HR], 4.04; P = .009), with a median follow-up of 5.1 years. The median PFS for MRD-negative patients was not reached with 75% PFS at 5 years, whereas for MRD-positive patients, it was 2.38 years (HR, 3.69; P = .002). MRD positivity is independently associated with poor outcomes after ASCT for MCL patients in CR.

  9. Brazilian experience using high dose sequential chemotherapy followed by autologous hematopoietic stem cell transplantation for malignant lymphomas

    PubMed Central

    Duarte, Bruno Kosa Lino; Miranda, Eliana Cristina Martins; Nucci, Marcio; Vigorito, Afonso Celso; Penteado, Francisco José; Marques Jr, José Francisco Comenalli; Oliveira-Duarte, Gislaine Borba; Lorand-Metze, Irene Gyongyver Heidemarie; Pagnano, Katia Borgia; Delamain, Marcia Torresan; Baldissera, Renata; Valente, Isabella Salvetti; de Souza, Carmino Antonio

    2011-01-01

    Objective To evaluate the use of high-dose sequential chemotherapy in a Brazilian population. Methods High-dose cyclophosphamide followed by autologous hematopoietic stem cell transplantation is an effective and feasible therapy for refractory/relapsed lymphomas; this regimen has never before been evaluated in a Brazilian population. All patients (106 with high-grade non-Hodgkin lymphoma and 77 with Hodgkin's lymphoma) submitted to this treatment between 1998 and 2006 were analyzed. Chemotherapy consisted of the sequential administration of high-dose cyclophosphamide (4 or 7 g/m2) and granulocyte-colony stimulating factor (300 µg/day), followed by peripheral blood progenitor cell harvesting, administration of etoposide (2g/m2) and methotrexate (8 g/m2 only for Hodgkin's lymphoma) and autologous hematopoietic stem cell transplantation. Results At diagnosis, non-Hodgkin lymphoma patients had a median age of 45 (range: 8-65) years old, 78% had diffuse large B-cell lymphoma and 83% had stage III/IV disease. The Hodgkin's lymphoma patients had a median age of 23 (range: 7-68) years old, 64.9% had the nodular sclerosis subtype and 65% had stage III/IV disease. Nine Hodgkin's lymphoma patients (13%) and 10 (9%) non-Hodgkin lymphoma patients had some kind of cardiac toxicity. The overall survival, disease-free survival and progression-free survival in Hodgkin's lymphoma were 29%, 59% and 26%, respectively. In non-Hodgkin lymphoma, these values were 40%, 49% and 31%, respectively. High-dose cyclophosphamide-related mortality was 10% for Hodgkin's lymphoma and 5% for non-Hodgkin lymphoma patients. High-dose cyclophosphamide dosing had no impact on toxicity or survival for both groups. Conclusions Despite a greater prevalence of poor prognostic factors, our results are comparable to the literature. The incidence of secondary neoplasias is noteworthy. Our study suggests that this approach is efficient and feasible, regardless of toxicity-related mortality. PMID:23049359

  10. Autologous transplantation of peripheral blood stem cells as an effective therapeutic approach for severe arteriosclerosis obliterans of lower extremities.

    PubMed

    Huang, Ping Ping; Li, Shan Zhu; Han, Ming Zhe; Xiao, Zhi Jian; Yang, Ren Chi; Qiu, Lu Gui; Han, Zhong Chao

    2004-03-01

    Treatment of severe arteriosclerosis obliterans of lower extremities (ASOLE) remains a clinical challenge. To develop a more effective approach, we evaluated the clinical efficacy of autologous transplantation of mobilized peripheral blood stem cells (PBSCs) in 5 patients with ASOLE. The patients received recombinant human granulocyte colony-stimulating factor (rhG-CSF, 600 micro g/day) for 5 consecutive days. On day 5, PBSCs were collected, sorted from blood circulation of patients, and then intramuscularly injected into their ischemic lower limbs. A significant improvement of clinical manifestations including severe pain, skin temperature and ulcer, was observed, without obvious adverse effect. The patient's limb was successfully saved. Satisfactory remission was obtained 3 months after transplantation as shown by significant improvement in ankle-brachial pressure index (ABI), blood flow in personal vascular laboratory (PVL), laser Doppler blood perfusion, and the angio-graphic scores. Our data suggest for the first time that autologous transplantation of mobilized PBSCs provides a practical, safe, and effective method of treatment for lower limb ischemia.

  11. Repeated autologous bone marrow-derived mesenchymal stem cell injections improve radiation-induced proctitis in pigs.

    PubMed

    Linard, Christine; Busson, Elodie; Holler, Valerie; Strup-Perrot, Carine; Lacave-Lapalun, Jean-Victor; Lhomme, Bruno; Prat, Marie; Devauchelle, Patrick; Sabourin, Jean-Christophe; Simon, Jean-Marc; Bonneau, Michel; Lataillade, Jean-Jacques; Benderitter, Marc

    2013-11-01

    The management of proctitis in patients who have undergone very-high-dose conformal radiotherapy is extremely challenging. The fibrosis-necrosis, fistulae, and hemorrhage induced by pelvic overirradiation have an impact on morbidity. Augmenting tissue repair by the use of mesenchymal stem cells (MSCs) may be an important advance in treating radiation-induced toxicity. Using a preclinical pig model, we investigated the effect of autologous bone marrow-derived MSCs on high-dose radiation-induced proctitis. Irradiated pigs received repeated intravenous administrations of autologous bone marrow-derived MSCs. Immunostaining and real-time polymerase chain reaction analysis were used to assess the MSCs' effect on inflammation, extracellular matrix remodeling, and angiogenesis, in radiation-induced anorectal and colon damages. In humans, as in pigs, rectal overexposure induces mucosal damage (crypt depletion, macrophage infiltration, and fibrosis). In a pig model, repeated administrations of MSCs controlled systemic inflammation, reduced in situ both expression of inflammatory cytokines and macrophage recruitment, and augmented interleukin-10 expression in rectal mucosa. MSC injections limited radiation-induced fibrosis by reducing collagen deposition and expression of col1a2/col3a1 and transforming growth factor-β/connective tissue growth factor, and by modifying the matrix metalloproteinase/TIMP balance. In a pig model of proctitis, repeated injections of MSCs effectively reduced inflammation and fibrosis. This treatment represents a promising therapy for radiation-induced severe rectal damage. PMID:24068742

  12. [EBV-associated B-cell lymphoproliferative disorder of the elderly successfully treated with autologous peripheral blood stem cell transplantation and locoregional radiotherapy].

    PubMed

    Sugino, Noriko; Nakamura, Chishiho; Fujii, Sumie; Matsui, Yusuke; Kaneko, Hitomi; Watanabe, Mitsumasa; Miura, Yasuo; Wakasa, Tomoko; Tsudo, Mitsuru

    2011-03-01

    Age-related EBV-associated B-cell lymphoproliferative disorder is a highly aggressive lymphoma, and a standard therapy for this disease has not yet been established. A 58-year-old male was admitted to our hospital because of fever and lymphadenopathy across the whole body. Neck lymph node biopsy showed hemorrhagic and geographic necrosis with Hodgkin-like large cells against a background of small lymphocytes. The large cells were positive for CD30 and EBER. The patient was diagnosed as having age-related EBV-associated B-cell lymphoproliferative disorder. Although there was no response to CHOP therapy, he obtained partial response after 3 courses of DeVIC therapy. Because his lymphoma was highly aggressive and chemotherapy-resistant, he underwent autologous stem cell transplantation with a conditioning regimen including ranimustine, etoposide, cytarabine, and melphalan. After stem cell transplantation and subsequent radiotherapy to the residual lesion, the patient achieved complete remission. This is the first report of successful autologous stem cell transplantation for a patient with age-related EBV-associated B-cell lymphoproliferative disorder. PMID:21471700

  13. The Impact of the German Tissue Act on the Manufacturing of Autologous and Allogeneic Stem Cell Preparations.

    PubMed

    Schlenke, Peter; Tapernon, Karin; Ahlke, Christoph; Mertens, Alexandra; Sibrowski, Walter

    2008-01-01

    SUMMARY: Cellular therapeutic agents considerably contribute to the optimal treatment of patients with hematological malignancies such as leukemia or nonhematological disorders. Over the last 50 years especially the transplantation of autologous and allogeneic stem cells from different sources after high-dose or myeloablative chemotherapy became a well-established standard therapy that cures or alleviates the symptoms in more than 50,000 patients/year worldwide. In the near future, the current progress in fundamental research on stem cells and immunobiology will allow for the clinical implementation of novel advanced cellular therapies, including gene therapeutic options. The European and German legislation have realized the need of international regulations for improved standardization and harmonization of stem cell transplants, associated cell-therapeutic agents as well as various tissue-engineered preparations in the emerging field of regenerative medicine. The Tissue Directive 2004/23/EC, issued and ratified by the European Parliament in March 2004, and its national transition into the German Tissue Act which came into force in July 2007 define the quality and safety standards for the donation, procurement, testing, processing, preservation, storage, and distribution of human tissues and cells. These standards are of high relevance to ensure the efficient prevention of the transmission of viral and nonviral infectious pathogens and to achieve the same safeguards as in the population's blood supply. This review discusses the pros and cons of the new legislation and argues for keeping the administrative and regulative demands in reasonable limits and for offering innovative approaches of cellular therapies to the European citizens.

  14. The Role of Autologous and Allogeneic Stem Cell Transplantation in Follicular Lymphoma in The New Drugs Era.

    PubMed

    Maura, Francesco; Farina, Lucia; Corradini, Paolo

    2016-01-01

    Follicular lymphoma (FL) is the second most common histotype of non-Hodgkin's lymphoma, and it is generally characterized by a heterogeneous clinical course. Despite recent therapeutic and diagnostic improvements, a significant fraction of FL patients still relapsed. In younger and/or fit FL relapsed patients bone marrow transplant (BMT) has represented the main salvage therapy for many years. Thanks to the ability of high-dose chemotherapy to overcome the lymphoma resistance and refractoriness, autologous stem cell transplantation (ASCT) can achieve a high complete remission rate (CR) and favorable outcome regarding progression-free survival (PFS) and overall survival (OS). Allogeneic stem cell transplantation (alloSCT) combines the high dose chemotherapy effect together with the immune reaction of the donor immune system against lymphoma, the so-called 'graft versus lymphoma' (GVL) effect. Considering the generally higher transplant-related mortality (TRM), alloSCT is mostly indicated for FL relapsed after ASCT. During the last years, there have been a great spread of novel effective and feasible drugs Although these and future novel drugs will probably change our current approach to FL, the OS post-BMT (ASCT and alloSCT) has never been reproduced by any novel combination. In this scenario, it is important to correctly evaluate the disease status, the relapse risk and the comorbidity profile of the relapsed FL patients in order to provide the best salvage therapy and eventually transplant consolidation. PMID:27648208

  15. The Role of Autologous and Allogeneic Stem Cell Transplantation in Follicular Lymphoma in The New Drugs Era

    PubMed Central

    Maura, Francesco; Farina, Lucia; Corradini, Paolo

    2016-01-01

    Follicular lymphoma (FL) is the second most common histotype of non-Hodgkin’s lymphoma, and it is generally characterized by a heterogeneous clinical course. Despite recent therapeutic and diagnostic improvements, a significant fraction of FL patients still relapsed. In younger and/or fit FL relapsed patients bone marrow transplant (BMT) has represented the main salvage therapy for many years. Thanks to the ability of high-dose chemotherapy to overcome the lymphoma resistance and refractoriness, autologous stem cell transplantation (ASCT) can achieve a high complete remission rate (CR) and favorable outcome regarding progression-free survival (PFS) and overall survival (OS). Allogeneic stem cell transplantation (alloSCT) combines the high dose chemotherapy effect together with the immune reaction of the donor immune system against lymphoma, the so-called ‘graft versus lymphoma’ (GVL) effect. Considering the generally higher transplant-related mortality (TRM), alloSCT is mostly indicated for FL relapsed after ASCT. During the last years, there have been a great spread of novel effective and feasible drugs Although these and future novel drugs will probably change our current approach to FL, the OS post-BMT (ASCT and alloSCT) has never been reproduced by any novel combination. In this scenario, it is important to correctly evaluate the disease status, the relapse risk and the comorbidity profile of the relapsed FL patients in order to provide the best salvage therapy and eventually transplant consolidation. PMID:27648208

  16. The Role of Autologous and Allogeneic Stem Cell Transplantation in Follicular Lymphoma in The New Drugs Era

    PubMed Central

    Maura, Francesco; Farina, Lucia; Corradini, Paolo

    2016-01-01

    Follicular lymphoma (FL) is the second most common histotype of non-Hodgkin’s lymphoma, and it is generally characterized by a heterogeneous clinical course. Despite recent therapeutic and diagnostic improvements, a significant fraction of FL patients still relapsed. In younger and/or fit FL relapsed patients bone marrow transplant (BMT) has represented the main salvage therapy for many years. Thanks to the ability of high-dose chemotherapy to overcome the lymphoma resistance and refractoriness, autologous stem cell transplantation (ASCT) can achieve a high complete remission rate (CR) and favorable outcome regarding progression-free survival (PFS) and overall survival (OS). Allogeneic stem cell transplantation (alloSCT) combines the high dose chemotherapy effect together with the immune reaction of the donor immune system against lymphoma, the so-called ‘graft versus lymphoma’ (GVL) effect. Considering the generally higher transplant-related mortality (TRM), alloSCT is mostly indicated for FL relapsed after ASCT. During the last years, there have been a great spread of novel effective and feasible drugs Although these and future novel drugs will probably change our current approach to FL, the OS post-BMT (ASCT and alloSCT) has never been reproduced by any novel combination. In this scenario, it is important to correctly evaluate the disease status, the relapse risk and the comorbidity profile of the relapsed FL patients in order to provide the best salvage therapy and eventually transplant consolidation.

  17. Autologous peripheral blood stem cell transplantation in tumor-stage mycosis fungoides: predictors of disease-free survival.

    PubMed

    Russell-Jones, R; Child, F; Olavarria, E; Whittaker, S; Spittle, M; Apperley, J

    2001-09-01

    Nine patients with mycosis fungoides (age range 27-67) underwent autologous peripheral blood stem cell transplantation (PBSCT). All patients had tumor-stage disease, and four had lymph node involvement. Eight patients exhibited a peripheral blood T cell clone using PCR/SSCP analysis of the TCR gamma gene, six prior to harvest and two at the time of harvest. Mobilization of CD34+ stem cells was achieved with etoposide and G-CSF. Harvested cells were positively selected for CD34. After negative selection for CD4 and CD8, only two samples became PCR negative. Conditioning prior to reinfusion of stem cells was achieved with various combinations of total skin electron beam (TSEB), total body irradiation (TBI), and chemotherapy, depending upon the patient's prior exposure to radiotherapy. One patient failed to engraft and died of candidal septicemia 15 days posttransplant. The other eight patients achieved complete remission, but this was short-lived in four (median disease-free survival [DFS] = 2 months) and prolonged in three (median DFS 11 months). Those with a short DFS were distinguished by rapid tumor onset prior to transplant but not by stage at transplant. Loss of a detectable T cell clone after manipulation of the harvest did not discriminate between the two groups, but rapid relapsers had been subjected to a greater degree of T cell depletion, possibly indicating a compromised cytotoxic response post-PBSCT. The median survival of the cohort is four years from tumor onset, 15 months from PBSCT, and 27 months from the date a peripheral blood clone was first detected in the presence of tumor-stage disease. Rapid relapse was associated with poor overall survival. Our data demonstrate the value of PBSCT for inducing remission in tumor-stage mycosis fungoides. Reinfusion of neoplastic cells could be avoided by harvesting stem cells at an earlier stage in the disease process, preferably before a T cell clone is detectable in the peripheral blood. Alternatively T cell

  18. Incidence Of Supraventricular Arrhythmias During Autologous Peripheral Blood Stem Cell Transplantation

    PubMed Central

    Singla, Abhishek; Hogan, William J.; Ansell, Stephen M.; Buadi, Francis K.; Dingli, David; Dispenzieri, Angela; Gastineau, Dennis A.; Gertz, Morie A.; Hayman, Suzanne R.; Inwards, David J.; Johnston, Patrick B.; Lacy, Martha Q.; Litzow, Mark R.; Micallef, Ivana N.; Porrata, Luis F.; Kumar, Shaji K.

    2013-01-01

    Arrhythmias, especially supraventricular arrhythmias, often complicate the clinical course during autologous hematopoietic cell transplantation (AHCT). We undertook this study to determine the incidence and risk factors for cardiac arrhythmias during AHCT. The study included 983 patients who underwent AHCT between August 2006 and December 2010 at a single institution, and in whom all the relevant medical records were available for review. The median age was 58 years (range; 19–77); 61% were male. AHCT was done for plasma cell disorders in 58% patients and for lymphoma or leukemia in the remaining. Overall, 92 (9.4%) patients developed a supraventricular tachyarrhythmia at a median of 9 days post transplant (range; 0, 18) and with a median duration of <1 day (range; <1 to 17 days). Atrial fibrillation (AF) was the most common and seen in 71 (7%) patients, followed by atrial flutter and supraventricular tachycardia in 12 (1%) and 8 (1%) patients respectively. In multivariate analysis, age > 63 years, presence of premature supraventricular complexes or Atrio-ventricular conduction delay on pre-transplant ECG, and history of any prior arrhythmia increased the risk of arrhythmia. Development of arrhythmia resulted in longer outpatient follow up after AHCT, with the median follow-up for those developing an arrhythmia of 22 days compared with 19 days for the rest; P < 0.001. In conclusion, 9% of patients undergoing ASCT develop supraventricular arrhythmias post transplant and this risk is elevated among the older patients, those with a prior history of arrhythmias, and those with pre-transplant ECG abnormalities. PMID:23747600

  19. Dose escalation of the hypoxic cell sensitizer etanidazole combined with ifosfamide, carboplatin, etoposide, and autologous hematopoietic stem cell support.

    PubMed

    Elias, A D; Wheeler, C; Ayash, L J; Schwartz, G; Ibrahim, J; Mills, L; McCauley, M; Coleman, N; Warren, D; Schnipper, L; Antman, K H; Teicher, B A; Frei, E

    1998-06-01

    Multiple mechanisms of drug resistance contribute to treatment failure. Although high-dose therapy attempts to overwhelm these defenses pharmacologically, this approach is only successful in a fraction of treated patients. Many drug resistance mechanisms are shared between malignant and normal cells, but the expression of various drug resistance mechanisms associated with hypoxia is largely confined to tumor tissue. Thus, reversal of this mechanism is likely to provide a therapeutic advantage to the host. This study was designed to define the dose-limiting toxicities and maximum tolerated dose of etanidazole when it is given concurrently with high-dose ifosfamide, carboplatin, and etoposide (ICE), with hematopoietic stem cell support. The maximum tolerated doses of high-dose ICE were administered concurrently with dose escalations of etanidazole, a hypoxic cell sensitizer. All agents were given by 96-h continuous i.v. infusion beginning on day -7. Mesna uroprotection was provided. Autologous marrow and cytokine mobilized peripheral blood progenitor cells were reinfused on day 0. Granulocyte colony-stimulating factor was administered following reinfusion until the granulocytes recovered to > 1000/microliter. Fifty-five adults with advanced malignancies were enrolled in cohorts of five to nine patients. Four dose levels of etanidazole between 3 and 5.5 g/m2/day (12, 16, 20, and 22 g/m2 total doses) and two doses of carboplatin (1600 and 1800 mg/m2 total doses) were evaluated. Seven patients died of organ toxicity (13%); two each from veno-occlusive disease of liver and sepsis; and one each from sudden death, renal failure, and refractory thrombocytopenic hemorrhage. Five deaths occurred at the top dose level. One additional patient suffered a witnessed cardiorespiratory arrest from ventricular fibrillation and was resuscitated. Dose-dependent and largely reversible peripheral neuropathy was observed consisting of two syndromes: severe cramping myalgic/neuralgic pain

  20. Successful treatment with autologous peripheral blood stem cell transplantation for acquired immunodeficiency syndrome (AIDS)-related malignant lymphoma.

    PubMed

    NAGAI, Yuya; MORI, Minako; INOUE, Daichi; KIMURA, Takaharu; SHIMOJI, Sonoko; TOGAMI, Katsuhiro; TABATA, Sumie; MATSUSHITA, Akiko; NAGAI, Kenichi; Imai, Yukihiro; Takafuta, Toshiro; Takahashi, Takayuki

    2009-11-01

    A 62-year-old man was diagnosed with human immunodeficiency virus (HIV) infection while suffering from recurrent herpes zoster infection. Laboratory examination revealed CD4(+) lymphocyte count 16 cells/mul and HIV loading 150,000 copies/ml at presentation. In addition, he had multiple lymph node swelling. Histologic diagnosis of a biopsied lymph node was diffuse, large, B cell-type malignant lymphoma. The karyotype of the lymphoma cells was t(8;14)(q24;q32), which was confirmed by G-banding and fluorescent in situ hybridization. Positron emission tomography (PET)-combined CT scanning revealed systemic extranodal tumors involving the gastrointestinal tract, pancreas, and bone marrow. The clinical stage of the lymphoma was IVB and the international prognosis index was categorized as high. Complete remission (CR) of the lymphoma was obtained after 2 courses of CHOP (cyclophosphamide, adriamycin, vincristine, prednisolone) chemotherapy and 4 subsequent courses of rituximab-combined CHOP (R-CHOP). Highly active antiretroviral therapy (HAART) was started at the initiation of CHOP. Because of the poor prognosis of AIDS-related lymphoma, he received autologous peripheral blood stem cell transplantation with the MEAM protocol (ranimustine, etoposide, cytarabine, melphalan) as a conditioning procedure without a severe infectious episode. He remains in CR 24 months after the transplantation. PMID:20009441

  1. [Clinical efficacy of autologous mesenclyme multipotential stem cells transplantation in the liver cirrhosis and portal hypertension treatment].

    PubMed

    2014-09-01

    In 14 patients with cirrhosis and portal hypertention autologous mesenclyme multipotential stem cells (AMMSC) transplanation was performed in portal vein (I group, n=7) and common trunk of the hepatic artery (II group, n=6). Duration of pathological processes since diagnosis is 1-8 years (3,7±2,4 years). The initial severity was evaluated by a set of child-Pugh score: Class A - 6 (42,9%), Class B - 8 (57,1%). Cell cultures indentication and characteristics consistent with International Society of cell technology guidanes (ISCT) since 2006.   The treatment results and patients survival were determined in period 2 month - 5 years according Kaplan-Meir survival curve analysis. Morphology of liver bioptats also was performed.   It was shown that AMMSC transplantation generally positivly affects on the morpho-functional dynamics and basic hepatic syndromes. Aterial perivascular zone is the most optimal for transplantation in terms of migration, engraftment and differentiation of cells in comparison with portal field, as evidenced by the transition of some patients from class B to class A by child-Pugh score. PMID:25341236

  2. Bone tissue engineering using polyetherketoneketone scaffolds combined with autologous mesenchymal stem cells in a sheep calvarial defect model.

    PubMed

    Adamzyk, Carina; Kachel, Paul; Hoss, Mareike; Gremse, Felix; Modabber, Ali; Hölzle, Frank; Tolba, Rene; Neuss, Sabine; Lethaus, Bernd

    2016-08-01

    Polyetherketoneketone (PEKK) a high performance thermoplastic polymer that is FDA-approved for cranio- and maxillo-facial as well as spineal surgery. We studied the viability, growth and osteogenic differentiation of bone marrow-derived human and sheep mesenchymal stem cells (MSC) in combination with a 3D scaffold made of PEKK using different cell-based assays. To investigate if autologous MSC, either undifferentiated or osteogenically pre-differentiated, augmented bone formation after implantation, we implanted cell-seeded 3D PEKK scaffolds into calvarial defects in sheep for 12 weeks. The volume and quality of newly formed bone were investigated using micro-computer tomography (micro-CT) and histological stainings. Our results show that the 3D PEKK scaffolds were cyto- and bio-compatible. They allowed for adherence, growth and osteogenic differentiation of human and ovine MSC. However, bone healing seemed unaffected by whether the scaffolds were seeded with MSC. Considerable amounts of newly formed bone were found in all PEKK treated groups, but a fibrous capsule was formed around the implants regardless of cell seeding with MSC. PMID:27328894

  3. Clinical-scale laser-based scanning and processing of live cells: selective photothermal killing of fluorescent tumor targets for autologous stem cell transplantation

    NASA Astrophysics Data System (ADS)

    Koller, Manfred R.; Hanania, Elie G.; Eisfeld, Timothy; O'Neal, Robert A.; Khovananth, Kevin M.; Palsson, Bernhard O.

    2001-04-01

    High-dose chemotherapy, followed by autologous hematopoietic stem cell (HSC) transplantation, is widely used for the treatment of cancer. However, contaminating tumor cells within HSC harvests continue to be of major concern since re-infused tumor cells have proven to contribute to disease relapse. Many tumor purging methods have been evaluated, but all leave detectable tumor cells in the transplant and result in significant loss of HSCs. These shortcomings cause engraftment delays and compromise the therapeutic value of purging. A novel approach integrating automated scanning cytometry, image analysis, and selective laser-induced killing of labeled cells within a cell mixture is described here. Non-Hodgkin's lymphoma (NHL) cells were spiked into cell mixtures, and fluorochrome-conjugated antibodies were used to label tumor cells within the mixture. Cells were then allowed to settle on a surface, and as the surface was scanned with a fluorescence excitation source, a laser pulse was fired at every detected tumor cell using high-speed beam steering mirrors. Tumor cells were selectively killed with little effect on adjacent non-target cells, demonstrating the feasibility of this automated cell processing approach. This technology has many potential research and clinical applications, one example of which is tumor cell purging for autologous HSC transplantation.

  4. A Novel Biopsy Method for Isolating Neural Stem Cells from the Subventricular Zone of the Adult Rat Brain for Autologous Transplantation in CNS Injuries.

    PubMed

    Aligholi, Hadi; Hassanzadeh, Gholamreza; Gorji, Ali; Azari, Hassan

    2016-01-01

    Despite all attempts the problem of regeneration in damaged central nervous system (CNS) has remained challenging due to its cellular complexity and highly organized and sophisticated connections. In this regard, stem cell therapy might serve as a viable therapeutic approach aiming either to support the damaged tissue and hence to reduce the subsequent neurological dysfunctions and impairments or to replace the lost cells and re-establish damaged circuitries. Adult neural stem/progenitor cells (NS/PCs) are one of the outstanding cell sources that can be isolated from the subventricular zone (SVZ) of the lateral ventricles. These cells can differentiate into neurons, astrocytes, and oligodendrocytes. Implanting autologous NS/PCs will greatly benefit the patients by avoiding immune rejection after implantation, better survival, and integration with the host tissue. Developing safe and efficient methods in small animal models will provide us with the opportunity to optimize procedures required to achieve successful human autologous NS/PC transplantation in near future. In this chapter, a highly controlled and safe biopsy method for harvesting stem cell containing tissue from the SVZ of adult rat brain is introduced. Then, isolation and expansion of NS/PCs from harvested specimen as well as the techniques to verify proliferation and differentiation capacity of the resulting NS/PCs are discussed. Finally, a method for assessing the biopsy lesion volume in the brain is described. This safe biopsy method in rat provides a unique tool to study autologous NS/PC transplantation in different CNS injury models. PMID:27604747

  5. Involved Field Radiation After Autologous Stem Cell Transplant for Diffuse Large B-Cell Lymphoma in the Rituximab Era

    SciTech Connect

    Biswas, Tithi; Dhakal, Sughosh; Chen Rui; Hyrien, Ollivier; Bernstein, Steven; Friedberg, Jonathan W.; Fisher, Richard I.; Liesveld, Jane; Phillips, Gordon; Constine, Louis S.

    2010-05-01

    Purpose: For patients with recurrent or refractory large B-cell non-Hodgkin's lymphoma, high-dose chemotherapy and autologous stem cell transplant (ASCT) is the treatment of choice. We evaluated the role of involved field radiation therapy (IFRT) post-ASCT for patients initially induced with cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) or, more recently, rituximab-CHOP (R-CHOP). Materials and Methods: Between May 1992 and April 2005, 176 patients underwent ASCT for recurrent or refractory large B-cell non-Hodgkin's lymphoma; 164 patients were evaluable for endpoint analysis. Fifty percent of the CHOP group (n = 131), and 39% of the R-CHOP group (n = 33), received IFRT. Follow-up from the time of transplant was a median/mean of 1.7/3 years (range, 0.03-13 years). Results: The 5-year overall survival (OS) and disease-specific survival (DSS) improved with IFRT in both the R-CHOP (p = 0.006 and 0.02, respectively) and CHOP (p = 0.02 and p = 0.04, respectively) groups. IFRT was associated with a 10% (p = 0.17) reduction in local failure, alone or with a distant site. On univariate analysis, IFRT was associated with superior OS (hazard ratio [HR] = 0.50 [95% CI 0.32, 0.78]; p = 0.002) and DSS (HR = 0.53 [95% CI 0.33, 0.86]; p = 0.009). Presence of B symptoms was adverse (p = 0.03). On multivariate analysis, only IFRT was associated with significant improvement in OS (HR = 0.35 [0.18, 0.68]; p = 0.002) and DSS (HR = 0.39 [95% CI 0.18, 0.84]; p = 0.01). Conclusions: Recognizing that positive and negative patient selection bias exists for the use of IFRT post-ASCT, patients initially treated with CHOP or R-CHOP and who undergo ASCT for recurrent or refractory disease may benefit from subsequent IFRT presumably due to enhanced local control that can translate into a survival advantage.

  6. Long-Term Effects of Autologous Bone Marrow Stem Cell Treatment in Acute Myocardial Infarction: Factors That May Influence Outcomes

    PubMed Central

    Clifford, David M.; Fisher, Sheila A.; Brunskill, Susan J.; Doree, Carolyn; Mathur, Anthony; Clarke, Mike J.; Watt, Suzanne M.; Martin-Rendon, Enca

    2012-01-01

    Aims To investigate whether there are important sources of heterogeneity between the findings of different clinical trials which administer autologous stem cell treatment for acute myocardial infarction (AMI) and to evaluate what factors may influence the long-term effects of this treatment. Methods and Results MEDLINE (1950-January 2011), EMBASE (1974-January 2011), CENTRAL (The Cochrane Library 2011, Issue 1), CINAHL (1982-January 2011), and ongoing trials registers were searched for randomised trials of bone marrow stem cells as treatment for AMI. Hand-searching was used to screen recent, relevant conference proceedings (2005–2010/11). Meta-analyses were conducted using random-effects models and heterogeneity between subgroups was assessed using chi-squared tests. Planned analyses included length of follow-up, timing of cell infusion and dose, patient selection, small trial size effect, methodological quality, loss of follow-up and date of publication. Thirty-three trials with a total of 1,765 participants were included. There was no evidence of bias due to publication or time-lag, methodological quality of included studies, participant drop-out, duration of follow-up or date of the first disclosure of results. However, in long-term follow-ups the treatment seemed more effective when administered at doses greater than 108 cells and to patients with more severe heart dysfunction. Conclusions Evaluation of heterogeneity between trials has not identified significant sources of bias in this study. However, clinical differences between trials are likely to exist which should be considered when undertaking future trials. PMID:22655042

  7. Outcomes and costs of autologous stem cell mobilization with chemotherapy plus G-CSF versus G-CSF alone

    PubMed Central

    Sung, Anthony D.; Grima, Daniel T.; Bernard, Lisa M.; Brown, Stephen; Carrum, George; Holmberg, Leona; Horwitz, Mitchell E.; Liesveld, Jane L.; Kanda, Junya; McClune, Brian; Shaughnessy, Paul; Tricot, Guido J.; Chao, Nelson J.

    2013-01-01

    Chemotherapy plus granulocyte colony stimulating factor (G-CSF) (C+G) and G-CSF alone are two of the most common methods of mobilizing CD34+ cells for autologous hematopoietic stem cell transplantation (AHSCT). In order to compare and determine real-world outcomes and costs of these strategies, we performed a retrospective study of 226 consecutive patients at 11 medical centers (64 lymphoma, 162 multiple myeloma), of whom 55% and 66% received C+G. Patients with C+G collected more CD34+ cells/day than G-CSF alone (lymphoma: average 5.51x106 cells/kg on day 1 vs. 2.92x106 cells/kg, p=0.0231; myeloma: 4.16x106 cells/kg vs. 3.69x106 cells/kg, p<0.00001) and required fewer days of apheresis (lymphoma: average 2.11 days vs. 2.96, p=0.012; myeloma: 2.02 vs. 2.83 days, p=0.0015), though nearly all patients ultimately reached the goal of 2x106 cells/kg. With the exception of higher rates of febrile neutropenia in myeloma patients with C+G (17% vs. 2%, p<0.05), toxicities and other outcomes were similar. Mobilization with C+G cost significantly more (lymphoma: median $10,300 vs. $7,300, p<0.0001; myeloma: $8,800 vs. $5,600, p<0.0001), though re-mobilization adds $6,700 for drugs alone. Our results suggest that while both C+G and G-CSF alone are effective mobilization strategies, C+G may be more cost-effective for patients at high risk of insufficient mobilization. PMID:23749109

  8. Detection of Minimal Residual Disease by Flow Cytometry for Patients with Multiple Myeloma Submitted to Autologous Hematopoietic Stem Cell Transplantation

    PubMed Central

    Dal Bó, Suzane; Pezzi, Annelise; Amorin, Bruna; Valim, Vanessa; Isabel Bittencourt, Rosane; Silla, Lucia

    2013-01-01

    The treatment strategy in multiple myeloma (MM) is to get complete remission followed by high-dose chemotherapy and autologous Hematopoietic Stem Cell Transplantation (HSCT). Neoplastic Plasma Cells (NPCs) are CD45−/dim, CD38+high, CD138+, CD19−, and  CD56+high in most cases. The description of this immunophenotype is of major importance as it leads to the correct identification of minimal residual disease (MRD). Samples from 44 Patients were analyzed prospectively in this study. We analyzed if the presence of MRD at three months after HSCT was predictive of relapse or death. There were 40 evaluable patients of whom 16/40 patients had MRD at three moths after HSCT and there were none in cytological relapse. The mean overall survival (OS) was 34 months and disease-free survival (RFS) was 28 months after HSCT. There was no significant difference in the log rank analysis comparing OS and the presence of MRD (P = 0,611) and RFS (P = 0,3106). Here, we demonstrate that three color flow cytometry (FCM) is more sensitive for MDR evaluation than cytological analyzes. However, based in our data we can not affirm that MRD is a good predictor of MM relapse or death. In conclusion, our results could be attributed to a short followup, small sample size, and over most to the inability of a three-color FCM to detect the NPC population. PMID:23864957

  9. Successful treatment of POEMS syndrome with bortezomib and dexamethasone, combined with radiotherapy, and followed by autologous stem cell transplantation.

    PubMed

    Ishii, Yoshimi; Yamazaki, Etsuko; Ishiyama, Yasufumi; Yamamoto, Eri; Hattori, Yukako; Hagihara, Maki; Tomita, Naoto; Ishigatsubo, Yoshiaki

    2013-12-01

    POEMS syndrome is a monoclonal plasma cell disorder characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes. High-dose therapy (HDT) and autologous stem cell transplantation (ASCT) are an effective therapy, but optimal treatment options are still under debate. Bortezomib is an important agent for the treatment of patients with multiple myeloma and has recently been reported as efficacious in the treatment of patients with POEMS syndrome. We present a case of POEMS syndrome in a 33-year-old woman, who was successfully treated with BorDex (bortezomib and dexamethasone) combined with radiotherapy, and followed by ASCT. She was diagnosed with POEMS syndrome with a localized plasmacytoma of bone 5 months after her initial symptoms of heart failure. Her Eastern Cooperative Oncology Group (ECOG) performance status was 4. She was first administered BorDex therapy, which was subsequently combined with radiotherapy. Her general condition including heart failure dramatically improved after four cycles of BorDex therapy and radiation, resulting in partial response. After chemoradiotherapy, HDT and ASCT were performed. After treatment, she was able to walk unassisted and her plasma endothelial growth factor (VEGF) level decreased. She did not experience neurotoxicity induced by bortezomib. Bortezomib was well tolerated and we suggest that BorDex therapy followed by HDT and ASCT may be an effective therapy for POEMS syndrome. PMID:24166587

  10. Successful treatment of POEMS syndrome with bortezomib and dexamethasone, combined with radiotherapy, and followed by autologous stem cell transplantation.

    PubMed

    Ishii, Yoshimi; Yamazaki, Etsuko; Ishiyama, Yasufumi; Yamamoto, Eri; Hattori, Yukako; Hagihara, Maki; Tomita, Naoto; Ishigatsubo, Yoshiaki

    2013-12-01

    POEMS syndrome is a monoclonal plasma cell disorder characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes. High-dose therapy (HDT) and autologous stem cell transplantation (ASCT) are an effective therapy, but optimal treatment options are still under debate. Bortezomib is an important agent for the treatment of patients with multiple myeloma and has recently been reported as efficacious in the treatment of patients with POEMS syndrome. We present a case of POEMS syndrome in a 33-year-old woman, who was successfully treated with BorDex (bortezomib and dexamethasone) combined with radiotherapy, and followed by ASCT. She was diagnosed with POEMS syndrome with a localized plasmacytoma of bone 5 months after her initial symptoms of heart failure. Her Eastern Cooperative Oncology Group (ECOG) performance status was 4. She was first administered BorDex therapy, which was subsequently combined with radiotherapy. Her general condition including heart failure dramatically improved after four cycles of BorDex therapy and radiation, resulting in partial response. After chemoradiotherapy, HDT and ASCT were performed. After treatment, she was able to walk unassisted and her plasma endothelial growth factor (VEGF) level decreased. She did not experience neurotoxicity induced by bortezomib. Bortezomib was well tolerated and we suggest that BorDex therapy followed by HDT and ASCT may be an effective therapy for POEMS syndrome.

  11. Tantalum coating of porous carbon scaffold supplemented with autologous bone marrow stromal stem cells for bone regeneration in vitro and in vivo.

    PubMed

    Wei, Xiaowei; Zhao, Dewei; Wang, Benjie; Wang, Wei; Kang, Kai; Xie, Hui; Liu, Baoyi; Zhang, Xiuzhi; Zhang, Jinsong; Yang, Zhenming

    2016-03-01

    Porous tantalum metal with low elastic modulus is similar to cancellous bone. Reticulated vitreous carbon (RVC) can provide three-dimensional pore structure and serves as the ideal scaffold of tantalum coating. In this study, the biocompatibility of domestic porous tantalum was first successfully tested with bone marrow stromal stem cells (BMSCs) in vitro and for bone tissue repair in vivo. We evaluated cytotoxicity of RVC scaffold and tantalum coating using BMSCs. The morphology, adhesion, and proliferation of BMSCs were observed via laser scanning confocal microscope and scanning electron microscopy. In addition, porous tantalum rods with or without autologous BMSCs were implanted on hind legs in dogs, respectively. The osteogenic potential was observed by hard tissue slice examination. At three weeks and six weeks following implantation, new osteoblasts and new bone were observed at the tantalum-host bone interface and pores. At 12 weeks postporous tantalum with autologous BMSCs implantation, regenerated trabecular equivalent to mature bone was found in the pore of tantalum rods. Our results suggested that domestic porous tantalum had excellent biocompatibility and could promote new bone formation in vivo. Meanwhile, the osteogenesis of porous tantalum associated with autologous BMSCs was more excellent than only tantalum implantation. Future clinical studies are warranted to verify the clinical efficacy of combined implantation of this domestic porous tantalum associated with autologous BMSCs implantation and compare their efficacy with conventional autologous bone grafting carrying blood vessel in patients needing bone repairing.

  12. Tantalum coating of porous carbon scaffold supplemented with autologous bone marrow stromal stem cells for bone regeneration in vitro and in vivo

    PubMed Central

    Wei, Xiaowei; Wang, Benjie; Wang, Wei; Kang, Kai; Xie, Hui; Liu, Baoyi; Zhang, Xiuzhi; Zhang, Jinsong; Yang, Zhenming

    2016-01-01

    Porous tantalum metal with low elastic modulus is similar to cancellous bone. Reticulated vitreous carbon (RVC) can provide three-dimensional pore structure and serves as the ideal scaffold of tantalum coating. In this study, the biocompatibility of domestic porous tantalum was first successfully tested with bone marrow stromal stem cells (BMSCs) in vitro and for bone tissue repair in vivo. We evaluated cytotoxicity of RVC scaffold and tantalum coating using BMSCs. The morphology, adhesion, and proliferation of BMSCs were observed via laser scanning confocal microscope and scanning electron microscopy. In addition, porous tantalum rods with or without autologous BMSCs were implanted on hind legs in dogs, respectively. The osteogenic potential was observed by hard tissue slice examination. At three weeks and six weeks following implantation, new osteoblasts and new bone were observed at the tantalum–host bone interface and pores. At 12 weeks postporous tantalum with autologous BMSCs implantation, regenerated trabecular equivalent to mature bone was found in the pore of tantalum rods. Our results suggested that domestic porous tantalum had excellent biocompatibility and could promote new bone formation in vivo. Meanwhile, the osteogenesis of porous tantalum associated with autologous BMSCs was more excellent than only tantalum implantation. Future clinical studies are warranted to verify the clinical efficacy of combined implantation of this domestic porous tantalum associated with autologous BMSCs implantation and compare their efficacy with conventional autologous bone grafting carrying blood vessel in patients needing bone repairing. PMID:26843518

  13. Tantalum coating of porous carbon scaffold supplemented with autologous bone marrow stromal stem cells for bone regeneration in vitro and in vivo.

    PubMed

    Wei, Xiaowei; Zhao, Dewei; Wang, Benjie; Wang, Wei; Kang, Kai; Xie, Hui; Liu, Baoyi; Zhang, Xiuzhi; Zhang, Jinsong; Yang, Zhenming

    2016-03-01

    Porous tantalum metal with low elastic modulus is similar to cancellous bone. Reticulated vitreous carbon (RVC) can provide three-dimensional pore structure and serves as the ideal scaffold of tantalum coating. In this study, the biocompatibility of domestic porous tantalum was first successfully tested with bone marrow stromal stem cells (BMSCs) in vitro and for bone tissue repair in vivo. We evaluated cytotoxicity of RVC scaffold and tantalum coating using BMSCs. The morphology, adhesion, and proliferation of BMSCs were observed via laser scanning confocal microscope and scanning electron microscopy. In addition, porous tantalum rods with or without autologous BMSCs were implanted on hind legs in dogs, respectively. The osteogenic potential was observed by hard tissue slice examination. At three weeks and six weeks following implantation, new osteoblasts and new bone were observed at the tantalum-host bone interface and pores. At 12 weeks postporous tantalum with autologous BMSCs implantation, regenerated trabecular equivalent to mature bone was found in the pore of tantalum rods. Our results suggested that domestic porous tantalum had excellent biocompatibility and could promote new bone formation in vivo. Meanwhile, the osteogenesis of porous tantalum associated with autologous BMSCs was more excellent than only tantalum implantation. Future clinical studies are warranted to verify the clinical efficacy of combined implantation of this domestic porous tantalum associated with autologous BMSCs implantation and compare their efficacy with conventional autologous bone grafting carrying blood vessel in patients needing bone repairing. PMID:26843518

  14. Successful Chemotherapy Following Autologous Stem Cell Transplantation in Multiple Myeloma and Multi-organ Dysfunction with Infiltration of Eosinophils: A Case Report.

    PubMed

    Lee, Ho Sup; Park, Lee Chun; Shin, Seong Hoon; Lee, Sang Uk; Chang, Hee Kyung; Huh, Bang; Jung, Gyoo Sik; Kim, Mi Hyang; Kim, Yang Soo

    2011-09-01

    Eosinophils are derived from hematopoietic stem cells. Peripheral blood eosinophilia is defined as an absolute eosinophil count of ≥0.5×10(9)/L. Eosinophilia is classified into primary or clonal eosinophilia, secondary eosinophilia, and idiopathic categories including idiopathic hypereosinophilic syndrome. Both hematopoietic and solid neoplasms may be associated with peripheral blood eosinophilia, but multiple myeloma is rarely associated with eosinophilia. We now report the case of a 31-year-old man with multiple myeloma associated with marked eosinophilia who developed multiple organ dysfunction with infiltration of eosinophils. He recovered after treatment with chemotherapy followed by autologous stem cell transplantation.

  15. Antibody responses to tetanus toxoid and Haemophilus influenzae type b conjugate vaccines following autologous peripheral blood stem cell transplantation (PBSCT).

    PubMed

    Chan, C Y; Molrine, D C; Antin, J H; Wheeler, C; Guinan, E C; Weinstein, H J; Phillips, N R; McGarigle, C; Harvey, S; Schnipper, C; Ambrosino, D M

    1997-07-01

    Accelerated granulocyte and platelet recovery following peripheral blood stem cell transplantation (PBSCT) are well documented. We hypothesize that functional immunity may also be enhanced in PBSCT and performed a phase II trial of immunizations in patients with lymphoma undergoing autologous transplantation with peripheral blood stem cells or bone marrow. Seventeen BMT and 10 PBSCT recipients were immunized at 3, 6, 12, and 24-months post-transplantation with Haemophilus influenzae type b (HIB)-conjugate and tetanus toxoid (TT) vaccines. IgG anti-HIB and anti-TT antibody concentrations were measured and compared between the two groups. Geometric mean IgG anti-HIB antibody concentrations were significantly higher for PBSCT recipients compared to BMT recipients at 24 months post-transplantation (11.3 micrograms/ml vs 0.93 microgram/ml, P = 0.051) and following the 24 month immunization (66.2 micrograms/ml vs 1.30 micrograms/ml, P = 0.006). Similar results were noted for IgG anti-TT antibody with significantly higher geometric mean antibody concentrations in the PBSCT group at 24 months post-transplantation (182 micrograms/ml vs 21.6 micrograms/ml, P = 0.039). Protective levels of total anti-HIB antibody were achieved earlier in PBSCT recipients compared with those of BMT recipients. PBSCT recipients had higher antigen-specific antibody concentrations following HIB and TT immunizations. These results suggest enhanced recovery of humoral immunity in PBSCT recipients and earlier protection against HIB with immunization.

  16. Infusing CD19-directed T cells to augment disease control in patients undergoing autologous hematopoietic stem-cell transplantation for advanced B-lymphoid malignancies.

    PubMed

    Kebriaei, Partow; Huls, Helen; Jena, Bipulendu; Munsell, Mark; Jackson, Rineka; Lee, Dean A; Hackett, Perry B; Rondon, Gabriela; Shpall, Elizabeth; Champlin, Richard E; Cooper, Laurence J N

    2012-05-01

    Limited curative treatment options exist for patients with advanced B-lymphoid malignancies, and new therapeutic approaches are needed to augment the efficacy of hematopoietic stem-cell transplantation (HSCT). Cellular therapies, such as adoptive transfer of T cells that are being evaluated to target malignant disease, use mechanisms independent of chemo- and radiotherapy with nonoverlapping toxicities. Gene therapy is employed to generate tumor-specific T cells, as specificity can be redirected through enforced expression of a chimeric antigen receptor (CAR) to achieve antigen recognition based on the specificity of a monoclonal antibody. By combining cell and gene therapies, we have opened a new Phase I protocol at the MD Anderson Cancer Center (Houston, TX) to examine the safety and feasibility of administering autologous genetically modified T cells expressing a CD19-specific CAR (capable of signaling through chimeric CD28 and CD3-ζ) into patients with high-risk B-lymphoid malignancies undergoing autologous HSCT. The T cells are genetically modified by nonviral gene transfer of the Sleeping Beauty system and CAR(+) T cells selectively propagated in a CAR-dependent manner on designer artificial antigen-presenting cells. The results of this study will lay the foundation for future protocols including CAR(+) T-cell infusions derived from allogeneic sources. PMID:22107246

  17. Infusing CD19-Directed T Cells to Augment Disease Control in Patients Undergoing Autologous Hematopoietic Stem-Cell Transplantation for Advanced B-Lymphoid Malignancies

    PubMed Central

    Kebriaei, Partow; Huls, Helen; Jena, Bipulendu; Munsell, Mark; Jackson, Rineka; Lee, Dean A.; Hackett, Perry B.; Rondon, Gabriela; Shpall, Elizabeth; Champlin, Richard E.

    2012-01-01

    Abstract Limited curative treatment options exist for patients with advanced B-lymphoid malignancies, and new therapeutic approaches are needed to augment the efficacy of hematopoietic stem-cell transplantation (HSCT). Cellular therapies, such as adoptive transfer of T cells that are being evaluated to target malignant disease, use mechanisms independent of chemo- and radiotherapy with nonoverlapping toxicities. Gene therapy is employed to generate tumor-specific T cells, as specificity can be redirected through enforced expression of a chimeric antigen receptor (CAR) to achieve antigen recognition based on the specificity of a monoclonal antibody. By combining cell and gene therapies, we have opened a new Phase I protocol at the MD Anderson Cancer Center (Houston, TX) to examine the safety and feasibility of administering autologous genetically modified T cells expressing a CD19-specific CAR (capable of signaling through chimeric CD28 and CD3-ζ) into patients with high-risk B-lymphoid malignancies undergoing autologous HSCT. The T cells are genetically modified by nonviral gene transfer of the Sleeping Beauty system and CAR+ T cells selectively propagated in a CAR-dependent manner on designer artificial antigen-presenting cells. The results of this study will lay the foundation for future protocols including CAR+ T-cell infusions derived from allogeneic sources. PMID:22107246

  18. Outcomes for Patients Who Fail High Dose Chemoradiotherapy and Autologous Stem Cell Rescue for Relapsed and Primary Refractory Hodgkin Lymphoma

    PubMed Central

    Moskowitz, Alison J; Perales, Miguel-Angel; Kewalramani, Tarun; Yahalom, Joachim; Castro-Malaspina, Hugo; Zhang, Zhigang; Vanak, Jill; Zelenetz, Andrew D; Moskowitz, Craig H

    2012-01-01

    Most patients with Hodgkin lymphoma (HL) are cured with first and second-line treatment; however for those who fail high dose chemoradiotherapy with autologous stem cell transplant (HDT-ASCT), outcome is unknown. This report is an analysis of patients with relapsed and primary refractory HL who were treated with HDT-ASCT and failed due to progression of disease (POD). Two hundred and two patients received HDT-ASCT at Memorial Sloan Kettering Cancer Center for relapsed or refractory HL between December 1994 and December 2005 and 71 failed due to POD. The median survival following HDT-ASCT failure was 25 months. Only 16 (23%) of the 71 patients are currently alive, 9 of whom are in remission. Multivariate analysis revealed two factors associated with poor outcome: relapse within 6 months of HDT-ASCT and primary refractory disease. The only factor associated with improved survival was the ability to receive a second transplant, in particular, reduced intensity allogeneic transplant (RIT). Novel therapies are needed for patients who fail HDT-ASCT, particularly those with primary refractory disease and those who relapse within 6 months of HDT-ASCT. Future studies should focus on prospectively evaluating RIT following HDT-ASCT failure in patients with remission duration from HDT-ASCT of greater than 6 months. PMID:19438504

  19. Early Results of Clinical Application of Autologous Whole Bone Marrow Stem Cell Transplantation for Critical Limb Ischemia with Buerger's Disease.

    PubMed

    Heo, Seon-Hee; Park, Yoong-Seok; Kang, Eun-Suk; Park, Kwang-Bo; Do, Young-Soo; Kang, Kyung-Sun; Kim, Dong-Ik

    2016-01-01

    Our goal was to evaluate early results of the clinical application of autologous whole bone marrow stem cell transplantation (AWBMSCT) for critical limb ischemia (CLI) in patients with Buerger's disease. We retrospectively analyzed the data of 58 limbs of 37 patients (mean age, 43.0 years; range, 28-63 years; male, 91.9%) with Buerger's disease with CLI who were treated with AWBMSCT from March 2013 to December 2014. We analyzed Rutherford category, pain score, pain-free walking time (PFWT), total walking time (TWT), ankle brachial pressure index (ABPI), and toe brachial pressure index (TBPI), and investigated wound healing and occurrence of unplanned amputations. The mean follow-up duration was 11.9 ± 7.2 months (range, 0.9-23.9 months) and 100%, 72.4%, and 74.1% of patients were available to follow-up 1, 3 and 6 months after AWBMST, respectively. At 6 months, patients demonstrated significant improvements in Rutherford category (P < 0.0001), pain score (P < 0.0001), PFWT (P < 0.0001) and TBPI (P < 0.0001). ABPI was increased compared to baseline, but the difference was not significant. A total of 76.5% ischemic wounds achieved complete or improved healing. AWBMSCT is a safe and effective alternative or adjunctive treatment modality to achieve clinical improvement in patients with CLI. PMID:26791280

  20. Patterns of Relapse and Progression in Multiple Myeloma Patients after Autologous Stem Cell Transplantation: Implications for Patients’ Monitoring After Transplantation

    PubMed Central

    Zamarin, Dmitriy; Giralt, Sergio; Landau, Heather; Lendvai, Nikoletta; Lesokhin, Alex; Chung, David; Koehne, Guenther; Chimento, Danielle; Devlin, Sean M.; Riedel, Elyn; Bhutani, Manisha; Babu, Dilip; Hassoun, Hani

    2013-01-01

    Autologous stem cell transplantation (ASCT) is widely used in first-line treatment of multiple myeloma (MM). However, most patients eventually have relapse or progression of disease (R/POD). While precise knowledge of R/POD patterns would be important to generate evidence-based surveillance recommendations after ASCT, such data is limited in the literature, especially after introduction of the free light chain assay (FLCA). This retrospective study examined the patterns of R/POD after first-line ASCT in 273 patients, using established criteria. At time of R/POD, only 2% of patients had no associated serologic evidence of R/POD. Eighty five percent had asymptomatic R/POD first detected by serologic testing, while 15% had symptomatic R/POD with aggressive disease, early R/POD, and short survival, with poor cytogenetics and younger age identified as risk factors. While occult skeletal lesions were found in 40% of asymptomatic patients tested following serologic R/POD, yearly skeletal surveys and urine testing were poor at heralding R/POD. We found a consistent association between paraprotein types at diagnosis and R/POD allowing informed recommendations for appropriate serologic monitoring and propose a new needed criterion using FLCA for patients relapsing by FLC only. Our findings provide important evidence-based recommendations that strengthen current monitoring guidelines after first-line ASCT in MM. PMID:22890289

  1. Hepatitis B virus reactivation in patients with multiple myeloma receiving bortezomib-containing regimens followed by autologous stem cell transplant.

    PubMed

    Li, Juan; Huang, Beihui; Li, Ying; Zheng, Dong; Zhou, Zhenhai; Liu, Junru

    2015-06-01

    To investigate hepatitis B virus (HBV) reactivation and survival in patients with multiple myeloma (MM) receiving bortezomib-containing regimens, we analyzed 139 patients with MM receiving bortezomib-containing regimens in our hospital. Twenty-seven/139 patients were hepatitis B surface antigen positive (HBsAg+) with nine having DNA levels > 500 IU/mL, including four > 1000 IU/mL. All but five HBsAg+ patients were treated with lamivudine or entecavir before chemotherapy until at least 6 months after chemotherapy or autologous stem cell transplant (ASCT). HBV reactivation occurred in six HBsAg+ patients and two HBsAg- patients, including six who received ASCT. Overall survival and progression-free survival of HBsAg- patients were significantly longer than for HBsAg+ patients (both p < 0.01). From these results, we confirmed that the incidence of HBV reactivation was notable in patients with MM receiving bortezomib-containing regimens, especially those who underwent ASCT. HBsAg+ patients with MM had a poorer prognosis than HBsAg- patients. Prophylactic treatment should be prescribed to all patients with HBsAg+ MM for a minimum duration of 12 months.

  2. Transplantation of Autologous Bone Marrow Mesenchymal Stem Cells with Platelet-Rich Plasma Accelerate Distraction Osteogenesis in A Canine Model

    PubMed Central

    Dehghan, Mohammad Mehdi; Baghaban Eslaminejad, Mohamadreza; Motallebizadeh, Nader; Ashrafi Halan, Javad; Tagiyar, Leila; Soroori, Sarang; Nikmahzar, Agbibi; Pedram, Mirsepehr; Shahverdi, Abdolhossein; Kazemi Mehrjerdi, Hossein; Izadi, Sadra

    2015-01-01

    Objective Distraction osteogenesis (DO) is a surgical procedure used to generate large volumes of new bone for limb lengthening. Materials and Methods In this animal experimental study, a 30% lengthening of the left tibia (mean distraction distance: 60.8 mm) was performed in ten adult male dogs by callus distraction after osteotomy and application of an Ilizarov fixator. Distraction was started on postoperative day seven with a distraction rate of 0.5 mm twice per day and carried out at a rate of 1.5 mm per day until the end of the study. Autologous bone marrow mesenchymal stem cells (BM-MSCs) and platelet-rich plasma (PRP) as the treatment group (n=5) or PRP alone (control group, n=5) were injected into the distracted callus at the middle and end of the distraction period. At the end of the consolidation period, the dogs were sacrificed after which computerized tomography (CT) and histomorphometric evaluations were performed. Results Radiographic evaluationsrevealed that the amount and quality of callus formations were significantly higher in the treatment group (P<0.05). As measured by CT scan, the healing parametersin dogs of the treatment group were significantly greater (P<0.05). New bone formation in the treatment group was significantly higher (P<0.05). Conclusion The present study showed that the transplantation of BM-MSCs positively affects early bony consolidation in DO. The use of MSCs might allow a shortened period of consolidation and therefore permit earlier device removal. PMID:26199903

  3. Clostridium difficile infection after adult autologous stem cell transplantation: A multicenter study of epidemiology and risk factors

    PubMed Central

    Dufresne, Simon F.; Hanna, David B.; Labbé, Annie-Claude; Treadway, Suzanne B.; Neofytos, Dionissios; Bélanger, Sylvie; Huff, Carol Ann; Laverdière, Michel; Marr, Kieren A.

    2013-01-01

    We sought to describe the epidemiology of Clostridium difficile infection (CDI) among adult recipients of autologous hematopoietic stem cell transplantation (auto HSCT) within the first year after HSCT in centers with variable epidemiology of hyper-toxigenic strains. A multicenter, retrospective nested case-control study was conducted among 873 auto HSCT recipients at Johns Hopkins Hospital (JHH, Baltimore, MD) and Hôpital Maisonneuve-Rosemont (HMR, Montreal, Canada) between 1/2003-12/2008. Despite center differences in the prevalence of NAP-1 strains over the time period (21-43% JHH; 80-84% HMR), the 1-year incidence of CDI was similar (6.2% JHH; 5.7% HMR). The median time to infection was 11 days (interquartile range [IQR] 1 to 27). In case control analysis, the following were predictors for CDI: grade 2 or higher mucositis (odds ratio [OR]: 3.00, P=0.02) and receipt of a 4th generation cephalosporin (OR: 2.76, P=0.04). Mucositis was the strongest predictor of risk for CDI in multivariate analysis (adjusted OR [AOR]: 2.77; P=0.03). CDI is a common and early complication of auto HSCT. Treatment-related gastrointestinal mucosal damage, in addition to the potentially modifiable risk of antimicrobial exposure, influence risk for CDI early post-auto HSCT. PMID:23916741

  4. The role of upfront autologous stem cell transplantation in high-risk younger patients with primary central nervous system lymphoma.

    PubMed

    Cho, Hyunsoo; Chang, Jong Hee; Kim, Yu Ri; Kim, Soo-Jeong; Chung, Haerim; Park, Hyunsung; Lee, Jung Yeon; Jang, Ji Eun; Kim, Yundeok; Kim, Se Hoon; Yang, Woo Ick; Suh, Chang-Ok; Cheong, June-Won; Min, Yoo Hong; Kim, Jin Seok

    2016-08-01

    Upfront autologous stem cell transplantation (ASCT) has shown favourable outcome in patients with primary central nervous system lymphoma (PCNSL), but the role of risk-adapted upfront ASCT consolidation has not been evaluated in PCNSL. As PCNSL patients with the International Extranodal Lymphoma Study Group (IELSG) prognostic score ≥2 or those who did not achieve complete response after two courses of induction chemotherapy (non-CR1) have shown inferior outcomes, we retrospectively analysed the role of upfront ASCT in 66 high-risk (IELSG ≥2 and/or non-CR1) younger (age <65 years) immunocompetent PCNSL patients who achieved at least partial response after initial high-dose methotrexate-based chemotherapy. Nineteen patients who received upfront ASCT exhibited significantly better overall survival (OS, P = 0·021) and progression-free survival (PFS, P = 0·005) compared to 47 patients who did not. In univariate and multivariate analyses, upfront ASCT was associated with better OS (P = 0·037 and P = 0·025, respectively) and PFS (P = 0·009 and P = 0·007, respectively). In a propensity score-matched cohort (n = 36), patients who received upfront ASCT also showed better outcome (P = 0·037 for OS, P = 0·001 for PFS). Our results suggest that upfront ASCT consolidation might be especially beneficial for high-risk PCNSL patients.

  5. Autologous Stem Cell Transplant Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoma

    ClinicalTrials.gov

    2016-02-23

    Prolymphocytic Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Childhood Hodgkin Lymphoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hodgkin Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma; T-Cell Chronic Lymphocytic Leukemia; T-Cell Prolymphocytic Leukemia

  6. Favorable outcomes in elderly patients undergoing high-dose therapy and autologous stem cell transplantation for non-Hodgkin lymphoma.

    PubMed

    Dahi, Parastoo B; Tamari, Roni; Devlin, Sean M; Maloy, Molly; Bhatt, Valkal; Scordo, Michael; Goldberg, Jenna; Zelenetz, Andrew D; Hamlin, Paul A; Matasar, Matthew J; Maragulia, Jocelyn; Giralt, Sergio A; Perales, Miguel-Angel; Moskowitz, Craig H; Sauter, Craig S

    2014-12-01

    High-dose therapy and autologous stem cell transplantation (HDT-ASCT) can offer potential long-term remission or cure in patients with non-Hodgkin lymphoma (NHL). Limited experience is available on the safety and efficacy of HDT-ASCT in elderly patients. This is a single-center, retrospective study examining outcomes of HDT-ASCT for 202 NHL patients, ages 60 years and older, between January 2001 and December 2012. Overall survival (OS) and progression-free survival (PFS) were analyzed according to age at HDT-ASCT, hematopoietic cell transplantation comorbidity index (HCT-CI), NHL histology, and remission status at the time of HDT-ASCT. The median age was 65 years (range, 60 to 74) and the majority had either diffuse large B cell lymphoma (n = 73, 37%) or mantle cell lymphoma (n = 69, 34%). One hundred and fifteen patients (57%) had high HCT-CI scores at the time of HDT-ASCT. With a median follow-up of 3.6 years (range, 4 to 11.9 years) for survivors, PFS and OS at 3 years were 60% (95% confidence interval [CI], 53% to 68%) and 73% (95% CI, 67% to 80%), respectively. Transplantation-related mortality (TRM) was 4% both at 100 days and at 1 year after HDT-ASCT. Age and HCT-CI score were not associated with OS or PFS, and high HCT-CI did not correlate with TRM. Seven patients (4%) developed secondary myelodysplastic syndrome or acute myeloid leukemia at a median of 35 months (range, 6 to 48) after HDT-ASCT. In this single-center cohort of elderly patients with NHL undergoing HDT-ASCT, this intervention was proven tolerable and effective, with results similar to those of historic controls in younger patients. Our data suggest that age alone should not preclude HDT-ASCT in elderly patients.

  7. Neurotrophic Factor-Secreting Autologous Muscle Stem Cell Therapy for the Treatment of Laryngeal Denervation Injury

    PubMed Central

    Halum, Stacey L.; McRae, Bryan; Bijangi-Vishehsaraei, Khadijeh; Hiatt, Kelly

    2012-01-01

    Objectives To determine if the spontaneous reinnervation that characteristically ensues after recurrent laryngeal nerve (RLN) injury could be selectively promoted and directed to certain laryngeal muscles with the use of neurotrophic factor (NF)-secreting muscle stem cell (MSC) vectors while antagonistic reinnervation is inhibited with vincristine (VNC). Study Design Basic science investigations involving primary cell cultures, gene cloning/transfer, and animal experiments. Methods (i.) MSC survival assays were used to test multiple individual NFs in vitro. (ii.) Motoneuron outgrowth assays assessed the trophic effects of identified NF on cranial nerve X-derived (CNX) motoneurons in vitro. (iii.) Therapeutic NF was cloned into a lentiviral vector, and MSCs were tranduced to secrete NF. 60 rats underwent left RLN transection injury, and at 3 weeks received injections of either MSCs (n=24), MSCs secreting NF (n=24), or saline (n=12) into the left thyroarytenoid muscle complex (TA); half of the animals in the MSC groups simultaneously received left posterior cricoarytenoid (PCA) injections of vincristine (VNC) while half the animals received saline. Results (i.) Ciliary-derived neurotrophic factor (CNTF) had the greatest survival-promoting effect on MSCs in culture. (ii.) Addition of CNTF (50 ng/mL) to CN X motoneuron cultures resulted in enhanced neurite outgrowth and branching. (iii.) In the animal model, the injected MSCs fused with the denervated myofibers, immunohistochemistry demonstrated enhanced reinnervation based on motor endplate to nerve contact, and RT-PCR confirmed stable CNTF expression at longest follow-up (4 months) in the CNTF-secreting MSC treated groups. Conclusions MSC therapy may have a future role in selectively promoting and directing laryngeal reinnervation after RLN injury. Level of evidence: NA PMID:22965802

  8. Autologous Bone Marrow-Derived Mesenchymal Stem Cells Modulate Molecular Markers of Inflammation in Dogs with Cruciate Ligament Rupture.

    PubMed

    Muir, Peter; Hans, Eric C; Racette, Molly; Volstad, Nicola; Sample, Susannah J; Heaton, Caitlin; Holzman, Gerianne; Schaefer, Susan L; Bloom, Debra D; Bleedorn, Jason A; Hao, Zhengling; Amene, Ermias; Suresh, M; Hematti, Peiman

    2016-01-01

    Mid-substance rupture of the canine cranial cruciate ligament rupture (CR) and associated stifle osteoarthritis (OA) is an important veterinary health problem. CR causes stifle joint instability and contralateral CR often develops. The dog is an important model for human anterior cruciate ligament (ACL) rupture, where rupture of graft repair or the contralateral ACL is also common. This suggests that both genetic and environmental factors may increase ligament rupture risk. We investigated use of bone marrow-derived mesenchymal stem cells (BM-MSCs) to reduce systemic and stifle joint inflammatory responses in dogs with CR. Twelve dogs with unilateral CR and contralateral stable partial CR were enrolled prospectively. BM-MSCs were collected during surgical treatment of the unstable CR stifle and culture-expanded. BM-MSCs were subsequently injected at a dose of 2x106 BM-MSCs/kg intravenously and 5x106 BM-MSCs by intra-articular injection of the partial CR stifle. Blood (entry, 4 and 8 weeks) and stifle synovial fluid (entry and 8 weeks) were obtained after BM-MSC injection. No adverse events after BM-MSC treatment were detected. Circulating CD8+ T lymphocytes were lower after BM-MSC injection. Serum C-reactive protein (CRP) was decreased at 4 weeks and serum CXCL8 was increased at 8 weeks. Synovial CRP in the complete CR stifle was decreased at 8 weeks. Synovial IFNγ was also lower in both stifles after BM-MSC injection. Synovial/serum CRP ratio at diagnosis in the partial CR stifle was significantly correlated with development of a second CR. Systemic and intra-articular injection of autologous BM-MSCs in dogs with partial CR suppresses systemic and stifle joint inflammation, including CRP concentrations. Intra-articular injection of autologous BM-MSCs had profound effects on the correlation and conditional dependencies of cytokines using causal networks. Such treatment effects could ameliorate risk of a second CR by modifying the stifle joint inflammatory response

  9. Autologous Bone Marrow-Derived Mesenchymal Stem Cells Modulate Molecular Markers of Inflammation in Dogs with Cruciate Ligament Rupture

    PubMed Central

    Muir, Peter; Hans, Eric C.; Racette, Molly; Volstad, Nicola; Sample, Susannah J.; Heaton, Caitlin; Holzman, Gerianne; Schaefer, Susan L.; Bloom, Debra D.; Bleedorn, Jason A.; Hao, Zhengling; Amene, Ermias; Suresh, M.; Hematti, Peiman

    2016-01-01

    Mid-substance rupture of the canine cranial cruciate ligament rupture (CR) and associated stifle osteoarthritis (OA) is an important veterinary health problem. CR causes stifle joint instability and contralateral CR often develops. The dog is an important model for human anterior cruciate ligament (ACL) rupture, where rupture of graft repair or the contralateral ACL is also common. This suggests that both genetic and environmental factors may increase ligament rupture risk. We investigated use of bone marrow-derived mesenchymal stem cells (BM-MSCs) to reduce systemic and stifle joint inflammatory responses in dogs with CR. Twelve dogs with unilateral CR and contralateral stable partial CR were enrolled prospectively. BM-MSCs were collected during surgical treatment of the unstable CR stifle and culture-expanded. BM-MSCs were subsequently injected at a dose of 2x106 BM-MSCs/kg intravenously and 5x106 BM-MSCs by intra-articular injection of the partial CR stifle. Blood (entry, 4 and 8 weeks) and stifle synovial fluid (entry and 8 weeks) were obtained after BM-MSC injection. No adverse events after BM-MSC treatment were detected. Circulating CD8+ T lymphocytes were lower after BM-MSC injection. Serum C-reactive protein (CRP) was decreased at 4 weeks and serum CXCL8 was increased at 8 weeks. Synovial CRP in the complete CR stifle was decreased at 8 weeks. Synovial IFNγ was also lower in both stifles after BM-MSC injection. Synovial/serum CRP ratio at diagnosis in the partial CR stifle was significantly correlated with development of a second CR. Systemic and intra-articular injection of autologous BM-MSCs in dogs with partial CR suppresses systemic and stifle joint inflammation, including CRP concentrations. Intra-articular injection of autologous BM-MSCs had profound effects on the correlation and conditional dependencies of cytokines using causal networks. Such treatment effects could ameliorate risk of a second CR by modifying the stifle joint inflammatory response

  10. Immunotherapy with low-dose recombinant interleukin 2 after high-dose chemotherapy and autologous stem cell transplantation in neuroblastoma.

    PubMed

    Pession, A; Prete, A; Locatelli, F; Pierinelli, S; Pession, A L; Maccario, R; Magrini, E; De Bernardi, B; Paolucci, P; Paolucci, G

    1998-08-01

    The purpose of this study was to evaluate in a phase I-II trial whether low doses of recombinant human interleukin 2 (rHuIL-2) over a prolonged period of time are safe and effective in eradicating or controlling minimal residual disease in children with neuroblastoma given high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT). From January 1992 to July 1996, 17 consecutive patients, with either stage IV or relapsed neuroblastoma, were enrolled. Patients received rHuIL-2 after a median time interval (min-max) of 105 days (56-153) after HDCT and ASCT. The protocol consisted of 2 'priming' courses of rHuIL-2 at escalating doses administered intravenously at 72-h intervals, followed by 'maintenance' with 11 monthly and six bimonthly boosting 5-day courses administered subcutaneously on an outpatient basis. At April 1997, 7 out of the 17 patients had completed the treatment schedule, four had discontinued treatment because of toxicity and four because of relapse; the remaining two patients are still on treatment, having completed 15 courses. Expansion of T lymphocytes, together with an increase in both natural killer cells and in activated T lymphocytes was evidenced. After a median (min-max) follow-up time of 30 (16-64) months, 12 out of 17 patients are alive and well. Two patients relapsed and died 14 and 35 months after transplant. Three patients are alive after having relapsed at 41, 21 and 13 months. The actuarial 2-year event-free survival and overall survival are 67% and 92% respectively. Intermittent administration of low doses of rHuIL-2 given for a long period of time is well tolerated and seems capable of controlling minimal residual disease after HDCT and ASCT in children with high-risk neuroblastoma.

  11. Autologous adipose tissue-derived stem cells treatment demonstrated favorable and sustainable therapeutic effect for Crohn's fistula.

    PubMed

    Lee, Woo Yong; Park, Kyu Joo; Cho, Yong Beom; Yoon, Sang Nam; Song, Kee Ho; Kim, Do Sun; Jung, Sang Hun; Kim, Mihyung; Yoo, Hee-Won; Kim, Inok; Ha, Hunjoo; Yu, Chang Sik

    2013-11-01

    Fistula is a representative devastating complication in Crohn's patients due to refractory to conventional therapy and high recurrence. In our phase I clinical trial, adipose tissue-derived stem cells (ASCs) demonstrated their safety and therapeutic potential for healing fistulae associated with Crohn's disease. This study was carried out to evaluate the efficacy and safety of ASCs in patients with Crohn's fistulae. In this phase II study, forty-three patients were treated with ASCs. The amount of ASCs was proportioned to fistula size and fistula tract was filled with ASCs in combination with fibrin glue after intralesional injection of ASCs. Patients without complete closure of fistula at 8 weeks received a second injection of ASCs containing 1.5 times more cells than the first injection. Fistula healing at week 8 after final dose injection and its sustainability for 1-year were evaluated. Healing was defined as a complete closure of external opening without any sign of drainage and inflammation. A modified per-protocol analysis showed that complete fistula healing was observed in 27/33 patients (82%) by 8 weeks after ASC injection. Of 27 patients with fistula healing, 26 patients completed additional observation study for 1-year and 23 patients (88%) sustained complete closure. There were no adverse events related to ASC administration. ASC treatment for patients with Crohn's fistulae was well tolerated, with a favorable therapeutic outcome. Furthermore, complete closure was well sustained. These results strongly suggest that autologous ASC could be a novel treatment option for the Crohn's fistula with high-risk of recurrence.

  12. Single or tandem autologous stem-cell transplantation for first-relapsed or refractory Hodgkin lymphoma: 10-year follow-up of the prospective H96 trial by the LYSA/SFGM-TC study group

    PubMed Central

    Sibon, David; Morschhauser, Franck; Resche-Rigon, Matthieu; Ghez, David; Dupuis, Jehan; Marçais, Ambroise; Deau-Fischer, Bénédicte; Bouabdallah, Reda; Sebban, Catherine; Salles, Gilles; Brice, Pauline

    2016-01-01

    We assessed the long-term results of autologous stem-cell transplantation for patients with first-relapsed or refractory Hodgkin lymphoma included in the prospective Lymphoma Study Association/Société Française de Greffe de Moelle H96 trial. This large multicenter phase II trial evaluated a risk-adapted strategy with single or tandem autologous stem-cell transplantation for 245 Hodgkin lymphoma patients. Poor-risk patients (n=150) had primary refractory Hodgkin lymphoma (n=77) or ≥2 risk factors at first relapse (n=73) and were eligible for tandem autologous stem-cell transplantation. Intermediate-risk patients (n=95) had one risk factor at first relapse and were eligible for single autologous stem-cell transplantation. With a median follow-up of 10.3 years, 10-year freedom from second failure and overall survival rates were, respectively: 64% (95% CI, 54% to 74%) and 70% (95% CI, 61% to 80%) for the intermediate-risk group, and 41% (95% CI, 33% to 49%) and 47% (95% CI, 39% to 55%) for the poor-risk group. Considering only patients who did not relapse after completing autologous stem-cell transplantation, the 15-year cumulative incidences of second primary malignancies were 24% for the 70 intermediate-risk patients and 2% for the 75 poor-risk ones. With long-term follow-up, the risk-adapted strategy remains appropriate. Tandem autologous stem-cell transplantation can still be considered an option for poor-risk patients, but integration of positron-emission tomography findings and new drugs may help to refine the need for a second autologous stem-cell transplant and possibly improve outcomes of patients with first-relapsed or refractory Hodgkin lymphoma. PMID:26721893

  13. Clinical protocol. Purging of autologous stem cell sources with bcl-x(s) adenovirus for women undergoing high-dose chemotherapy for stage IV breast carcinoma.

    PubMed

    Ayash, L J; Clarke, M; Adams, P; Ferrara, J; Ratanatharathorn, V; Reynolds, C; Roessler, B; Silver, S; Strawderman, M; Uberti, J; Wicha, M

    2001-11-01

    High-dose chemotherapy (HDCT) and autologous bone marrow transplantation (BMT) is frequently used to treat patients with metastatic cancer including breast cancer and neuroblastoma. However, the bone marrow of such patients is often contaminated with tumor cells. Recently, we have found that a recombinant adenovirus vector that contains a bcl-x, minigene (a dominant negative inhibitor of the bcl-2 family), called the bcl-x(s) adenovirus, is lethal to cancer cells derived from epithelial tissues, but not to normal human hematopoietic cells. To determine the mechanism, by which this virus spares normal hematopoietic cells, we isolated normal mouse hematopoietic stem cells and infected them with an adenovirus that contains a beta-galactosidase minigene. Such cells do not express beta-galactosidase, indicating that hematopoietic stem cells do not express transgene encoded by adenovirus vectors based upon the RSV-AD5 vector system. When breast cancer cells mixed with hematopoietic cells were infected with the bcl-x(s) adenovirus, cancer cells were selectively killed by the suicide adenoviruses. Hematopoietic cells exposed to the suicide vectors were able to reconstitute the bone marrow of mice exposed to lethal doses of y-irradiation. These studies suggest that adenovirus suicide vectors may provide a simple and effective method to selectively eliminate cancer cells derived from epithelial tissue that contaminate bone marrow to be used for autologous BMT. We therefore propose to initiate a phase I clinical trial to test the safety of this virus in women with breast cancer undergoing high does chemotherapy and autologous BMT.

  14. Autologous Peripheral Blood Stem Cell Transplantation Improves Portal Hemodynamics in Patients with Hepatitis B Virus-related Decompensated Cirrhosis

    PubMed Central

    Deng, Qinzhi; Cai, Ting; Zhang, Shun; Hu, Airong; Zhang, Xingfen; Wang, Yinyin; Huang, Jianrong

    2015-01-01

    Background: Chronic hepatitis B virus (HBV) infection may eventually lead to decompensated liver cirrhosis, which is a terminal illness. Objectives: The aim of this study was to investigate the therapeutic efficacy of autologous peripheral blood stem cell (APBSC) transplantation to improve portal vein hemodynamics in patients with HBV-related decompensated cirrhosis. Patients and Methods: This prospective study included 68 hospitalized patients who were diagnosed with HBV-related decompensated cirrhosis. These patients were divided into two groups: the transplantation group included 33 patients, while the control group included 35. Both groups received conventional medical treatment simultaneously, and APBSC transplantation was performed on the patients in the transplantation group. We evaluated the effects of APBSC transplantation on postoperative liver function using the following indices: total bilirubin, serum prothrombin and albumin, spleen size, and portal vein hemodynamics. Postoperatively, all of the patients were followed up at 24, 36, and 48 weeks. Results: The transplantation group had no serious reactions. Compared with the control group, albumin and prothrombin activity in the transplantation group was significantly improved at 24, 36, and 48 weeks after the procedure, and spleen length and portal vein diameter were substantially reduced at 48 weeks. The velocity of peak portal vein blood flow and mean maximum portal vein blood flow were greatly increased in the APBSC transplantation group at 36 and 48 weeks, respectively; however, there was also decreased portal vein diameter, which reduced portal vein pressure in patients with HBV-related decompensated cirrhosis. Conclusions: APBSC transplantation greatly benefits HBV-linked decompensated cirrhosis patients and should be recommended in clinical practice. PMID:26977164

  15. In vivo cytokine responses to interleukin-2 immunotherapy after autologous stem cell transplantation in children with solid tumors.

    PubMed

    Bönig, H; Laws, H J; Wundes, A; Verheyen, J; Hannen, M; Kim, Y M; Banning, U; Nürnberger, W; Körholz, D

    2000-07-01

    The potent immunostimulatory cytokine interleukin-2 (IL-2) has been extensively investigated for its potential to induce anti-tumor immunity in a number of tumor models. Only recently the complex interplay of mutually suppressive or supportive cytokines of the IL-2-induced network of cytokines has been better characterized. The aim of this study was to assess which of these in vitro findings are reproducible in vivo in recipients of stem cell transplants (SCT), since in these patients long- lasting impairments in cytokine inducibility have been described. We have therefore studied the kinetics of putative modulators and mediators of IL-2-induced immune activation, namely IL-1beta, IL-4, IL-5, IL-10, IL-12, soluble Fas ligand (sFasL), and GM-CSF during IL-2 therapy. All patients were children or adolescents suffering from solid tumors with poor prognosis who received three 5-day courses of high-dose intravenous IL-2 as an adjuvant to their radio-chemotherapy and autologous SCT. While IL-1beta, IL-4 and IL-12 were not, and sFasL was only mildly affected by the IL-2 therapy, we observed a consistent and early rise of IL-10, IL-5, and GM-CSF. These increases were rapidly reversible after discontinuation of IL-2 therapy. The inducibility of IL-10, IL-5 and GM-CSF was more pronounced with increasing time from the SCT, and in the third cycle reached an order of magnitude as in high-dose IL-2 patients without SCT. Together with the abundant in vitro data, these findings may help devise a combination immunotherapy permitting stronger anti-tumor effects, but lesser adverse effects.

  16. Incidence, risk factors, and outcome of bacteremia following autologous hematopoietic stem cell transplantation in 720 adult patients.

    PubMed

    Piñana, José Luis; Montesinos, Pau; Martino, Rodrigo; Vazquez, Lourdes; Rovira, Montserrat; López, Javier; Batlle, Montserrat; Figuera, Ángela; Barba, Pere; Lahuerta, Juan José; Debén, Guillermo; Perez-Lopez, Cristina; García, Raimundo; Rosique, Pedro; Lavilla, Esperanza; Gascón, Adriana; Martínez-Cuadrón, David; Sanz, Miguel Ángel

    2014-02-01

    Bacteremia is the most frequent infectious complication during neutropenia in patients receiving autologous hematopoietic stem cell transplantation (ASCT). The objective of this study was to analyze the incidence, characteristics, risk factors, and outcome of bacteremia during the early period after ASCT. A total of 720 patients undergoing ASCT in two observational prospective consecutive multicenter studies of the Programa Español para el Tratamiento de las Hemopatías group were analyzed. Bacteremia occurred in 20 % of patients. Coagulase-negative Staphylococcus was the most frequent (66 %) among the gram-positive agents and Escherichia coli (49 %) among the gram-negative agents. Multivariate analysis showed that the length of neutropenia <1 × 10(9)/L (more than 9 days) [relative risk (RR) of 2.6, p < 0.001] was the sole risk factor for overall bacteremia. We identified the length of neutropenia <1 × 10(9)/L (more than 9 days) (RR 4.98, p < 0.001) and the use of prophylactic fluoroquinolones (RR 0.46, p < 0.01) as specific risk factors for gram-negative bacteremia. Risk factors for gram-positive bacteremia were the use of total parenteral nutrition (RR 1.92, p < 0.01) and deep neutropenia (<0.1 × 10(9)/L), with duration over 5 days (RR 1.67, p < 0.027). Bacteremia showed an increased morbidity with no impact on neither overall nor infectious related mortality. The identification of such risk factors may be helpful to implement prophylactic and therapeutic risk-adapted strategies to reduce the incidence of bacteremia in ASCT. PMID:23995612

  17. Autologous Stem-Cell Transplantation Without Hematopoietic Support for the Treatment of Hematologic Malignancies in Jehovah's Witnesses

    PubMed Central

    Ford, Patricia A.; Grant, Shakira J.; Mick, Rosemarie; Keck, Gina

    2015-01-01

    Purpose Autologous stem-cell transplantation (ASCT) has shown to provide curative benefit in patients with relapsed lymphoma and multiple myeloma (MM), often requiring hematopoietic support until marrow engraftment. Because of Jehovah's Witnesses' (JW) refusal of blood products, treatment challenges arise. This study represents 125 JWs with lymphoma (n = 55), MM (n = 68), or amyloidosis (n = 2), treated with high-dose chemotherapy (HDC) and ASCT without transfusions. Patients and Methods Priming with intravenous iron and erythropoietin occurred to increase hemoglobin (Hb) pretransplantation. Cytokine mobilization of stem-cells was used. Delay to HDC was done to allow Hb and platelets to approach 11 g/dL and 100 × 103/μL, respectively. Patients with MM received a standard dose of melphalan 200 mg/m2, with dose reduction for severe kidney dysfunction. Patients with lymphoma received carmustine 300 mg/m2, cyclophosphamide 1,500 mg/m2 on days 2 through 5 (total 6 g/m2), and etoposide 700 mg/m2 per day on days 2 through 4 (total 2,100 mg/m2). Post-transplantation, a combination of granulocyte colony-stimulating factor, erythropoietin, aminocaproic acid, and phytonadione was administered. Results There were two major and 15 minor bleeding complications, none occurring at platelets less than 5.0 × 103/μL, with six (4.8%) treatment-related mortalities. The median decrease in Hb was 5.0 g/dL, with median Hb nadir of 7.0 g/dL. The median number of days with platelet count less than 10 × 103/μL was 3, with median platelet nadir of 5.0 × 103/μL. Cardiac complications occurred in 40 patients (32%). Conclusion ASCT can safely be performed without transfusion support. A platelet transfusion trigger of ≤ 5 × 103/μL may be appropriate in select patients. Pharmacotherapy and cardiac monitoring are effective in the management of cardiac complications. PMID:25870085

  18. Treatment of aggressive multiple myeloma by high-dose chemotherapy and total body irradiation followed by blood stem cells autologous graft

    SciTech Connect

    Fermand, J.P.; Levy, Y.; Gerota, J.; Benbunan, M.; Cosset, J.M.; Castaigne, S.; Seligmann, M.; Brouet, J.C.

    1989-01-01

    Eight patients with stage III aggressive multiple myeloma, refractory to current chemotherapy in six cases, were treated by high-dose chemotherapy (nitrosourea, etoposide, and melphalan) (HDC) and total body irradiation (TBI), followed by autografting with blood stem cells. These cells were previously collected by leukapheresis performed during hematologic recovery following cytotoxic drug-induced bone marrow aplasia. Seven patients were alive 9 to 17 months after HDC-TBI and graft. One died at day 40 from cerebral bleeding. All living patients achieved a 90% or greater reduction in tumor mass. In two cases, a complete remission (CR) has persisted at a follow-up of 15 and 16 months. Three patients have been well and off therapy with stable minimal residual disease (RD) since 10, 11, and 17 months, respectively. A patient in apparent CR and another with RD have relapsed 9 to 12 months posttreatment. Autologous blood-derived hematopoietic stem cells induced successful and sustained engraftment in all living patients. These results, although still preliminary, indicate that HDC and TBI, followed by blood stem cells autograft, which has both practical and theoretical interest over allogeneic or autologous bone marrow transplantation, deserve consideration in selected patients with multiple myeloma.

  19. Muscle derived stem cell contains the potential to enhance long term retention as well as an aesthetic outcome of autologous fat grafting.

    PubMed

    Han, Duanyang; Ma, Zhiqiang; Zhang, Peipei; Yang, Jenny F; Zhang, Yingbo; Yang, Daping; Liu, Jianyu

    2011-06-01

    Autologous fat graft has been mentioned as a prospective source of soft-tissue filler for decades. It gives a natural consistency, is easy and safe to harvest, exhibits no hypersensitivity or foreign body reactions, and is readily available. However, the traditional fat grafting has its limitations in long term process, such as partial necrosis, loss of volume, and internal calcification. They all compromise the functional and aesthetic outcome of this procedure. In recent studies, the best results were obtained by transplanting fat tissue inside muscle, thus benefiting from its better blood supply. Muscle-derived stem cells have recently emerged as a promising source of multipotent cells which give rise to muscle fibers within muscular environment. Previous studies have also proved that muscle-derived stem cells are capable of releasing various kinds of angiogenesis agents, such as VEGF, HGF, and FGF. These cytokines are known to promote revascularization. Based on the foregoing facts, we postulate that co-transplant of autologous fat and muscle derived stem cells may enhance the long term retention and aesthetic outcome of fat grafting. PMID:21419577

  20. Repair of large full-thickness cartilage defect by activating endogenous peripheral blood stem cells and autologous periosteum flap transplantation combined with patellofemoral realignment.

    PubMed

    Fu, Wei-Li; Ao, Ying-Fang; Ke, Xiao-Yan; Zheng, Zhuo-Zhao; Gong, Xi; Jiang, Dong; Yu, Jia-Kuo

    2014-03-01

    Minimal-invasive procedure and one-step surgery offer autologous mesenchymal stem cells derived from peripheral blood (PB-MSCs) a promising prospective in the field of cartilage regeneration. We report a case of a 19-year-old male athlete of kickboxing with ICRS grade IV chondral lesions at the 60° region of lateral femoral trochlea, which was repaired by activating endogenous PB-MSCs plus autologous periosteum flap transplantation combined with correcting the patellofemoral malalignment. After a 7.5 year follow-up, the result showed that the patient returned to competitive kickboxing. Second-look under arthroscopy showed a smooth surface at 8 months postoperation. The IKDC 2000 subjective score, Lysholm score and Tegner score were 95, 98 and 9 respectively at the final follow up. CT and MRI evaluations showed a significant improvement compared with those of pre-operation.

  1. sb203580 preconditioning recharges matrix-expanded human adult stem cells for chondrogenesis in an inflammatory environment – a feasible approach for autologous stem cell based osteoarthritic cartilage repair

    PubMed Central

    Zhang, Ying; Pizzute, Tyler; Li, Jingting; He, Fan; Pei, Ming

    2015-01-01

    Autologous stem cells are a promising cell source for cartilage regeneration; however, cell replicative senescence and joint posttraumatic inflammation provide challenges to bring this treatment modality to fruition. In this study, we hypothesized that preconditioning with p38 MAPK inhibitor (sb203580) would recharge decellularized extracellular matrix (dECM) expanded human synovium-derived stem cell (hSDSC) chondrogenesis in an inflammatory environment. We found that preconditioning with sb203580 greatly enhanced dECM expanded hSDSC proliferation and chondrogenic potential while supplementation with sb203580 in an induction medium dramatically retarded hSDSC chondrogenic differentiation, even for dECM expanded cells. We also found that sb203580 preconditioning enhanced matrix-expanded hSDSC chondrogenic capacity even in an interleukin-1 (IL-1) induced inflammatory environment. Non-detectable expression of HLA-DR in the hSDSCs grown on allogeneic dECM indicates the feasibility of commercial preparation of these dECMs from healthy, young donors for patients who need autologous transplantation. Our study indicated that p38 MAPK inhibitor has a distinctive priming effect on dECM mediated stem cell cartilage regeneration. Combined rejuvenation with sb203580 and dECM expansion can precondition hSDSCs’ resurfacing capacity for osteoarthritic patients with cartilage defects. PMID:26122165

  2. Impact of Prophylactic Levofloxacin on Rates of Bloodstream Infection and Fever in Neutropenic Patients with Multiple Myeloma Undergoing Autologous Hematopoietic Stem Cell Transplantation

    PubMed Central

    Satlin, Michael J.; Vardhana, Santosh; Soave, Rosemary; Shore, Tsiporah B.; Mark, Tomer M.; Jacobs, Samantha E.; Walsh, Thomas J.; Gergis, Usama

    2015-01-01

    Few studies have evaluated the role of antibacterial prophylaxis during neutropenia in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation (HSCT). At our center, levofloxacin prophylaxis was initiated in June 2006 in patients with myeloma who were undergoing autologous HSCT. We compared the incidence of bloodstream infection (BSI) and fever and neutropenia (FN) within 30 days of transplantation before (January 2003 - May 2006) and after (June 2006 - April 2010) the initiation of levofloxacin prophylaxis in patients undergoing autologous HSCT for myeloma. We also compared rates of BSI and FN during the same time periods in autologous HSCT recipients with lymphoma who did not receive antibacterial prophylaxis during either time period. After the initiation of levofloxacin prophylaxis, the BSI rate decreased from 41.2% (49/119) to 14.7% (23/156) and the rate of FN decreased from 91.6% to 60.9% in patients with myeloma (P < 0.001, for each). In contrast, rates of BSI (43.1% vs. 47.3%; P = 0.50) and FN (98.8% vs. 97.1%; P = 0.63) did not change in patients with lymphoma. Levofloxacin prophylaxis was independently associated with decreased odds of BSI (odds ratio [OR] 0.27; 95% confidence interval [CI] 0.14–0.51; P < 0.001) and FN (OR 0.18, 95% CI 0.09–0.36; P < 0.001) in multivariate analysis. Patients with myeloma had a non-significant increase in the risk of BSI due to levofloxacin-resistant Enterobacteriaceae (5% vs. 1%, P = 0.08) and Clostridium difficile infection (7% vs. 3%, P = 0.12) after the initiation of levofloxacin prophylaxis, but did not have higher rates of BSI due to other resistant bacteria. Levofloxacin prophylaxis is associated with decreased risk of BSI and FN in patients with myeloma undergoing autologous HSCT. PMID:26150022

  3. Effect of activated autologous platelet-rich plasma on proliferation and osteogenic differentiation of human adipose-derived stem cells in vitro

    PubMed Central

    Xu, Fang-Tian; Li, Hong-Mian; Yin, Qing-Shui; Liang, Zhi-Jie; Huang, Min-Hong; Chi, Guang-Yi; Huang, Lu; Liu, Da-Lie; Nan, Hua

    2015-01-01

    To investigate whether activated autologous platelet-rich plasma (PRP) can promote proliferation and osteogenic differentiation of human adipose-derived stem cells (hASCs) in vitro. hASCs were isolated from lipo-aspirates, and characterized by specific cell markers and multilineage differentiation capacity after culturing to the 3rd passage. PRP was collected and activated from human peripheral blood of the same patient. Cultured hASCs were treated with normal osteogenic inductive media alone (group A, control) or osteogenic inductive media plus 5%, 10%, 20%, 40%PRP (group B, C, D, E, respectively). Cell proliferation was assessed by CCK-8 assay. mRNA expression of osteogenic marker genes including alkaline phosphatase (ALP), osteopontin (OPN), osteocalcin (OCN) and core binding factor alpha 1 (Cbfa1) were determined by Real-Time Quantitative PCR Analysis (qPCR). Data revealed that different concentrations of activated autologous PRP significantly promoted hASCs growth in the proliferation phase compared to the without PRP group and resulted in a dose-response relationship. At 7-d and 14-d time point of the osteogenic induced stage, ALP activity in PRP groups gradually increased with the increasing of concentrations of PRP and showed that dose-response relationship. At 21-d time point of the osteogenic induced stage, PRP groups make much more mineralization and mRNA relative expression of ALP, OPN, OCN and Cbfa1 than that without PRP groups and show that dose-response relationship. This study indicated that different concentrations of activated autologous PRP can promote cell proliferation at earlier stage and promote osteogenic differentiation at later stage of hASCs in vitro. Moreover, it displayed a dose-dependent effect of activated autologous PRP on cell proliferation and osteogenic differentiation of hASCs in vitro. PMID:25901195

  4. T-cell depletion and autologous stem cell transplantation in the management of tumour stage mycosis fungoides with peripheral blood involvement.

    PubMed

    Olavarria, E; Child, F; Woolford, A; Whittaker, S J; Davis, J G; McDonald, C; Chilcott, S; Spittle, M; Grieve, R J; Stewart, S; Apperley, J F; Russell-Jones, R

    2001-09-01

    Nine patients with tumour stage mycosis fungoides (MF) have been entered into a pilot study of T-cell depletion and autologous stem cell transplantation (SCT). Eight patients had detectable rearrangements of the T-cell receptor (TCR) gamma-gene demonstrated by polymerase chain reaction (PCR)/single-stranded conformation polymorphism (SSCP) in the peripheral blood. The median age was 47 years and the median duration of disease before SCT was 61 months; Peripheral blood progenitor cells were mobilized using high-dose etoposide (1.6 g/m2) and granulocyte colony-stimulating factor (G-CSF). The apheresis products underwent rigorous T-cell depletion with immunomagnetic methods. Double CD34-positive and CD4/CD8-negative selection achieved a median reduction of 3.89 log of T cells. All nine patients have been transplanted. Conditioning included carmustine (BCNU), etoposide and melphalan (BEM) in seven patients and total body irradiation plus etoposide or melphalan in two. Eight patients engrafted promptly and one patient died of septicaemia. All survivors entered complete remission. Seven patients have relapsed at a median of 7 months (2-14) post SCT. However, most patients have relapsed into a less aggressive stage, which has responded to conventional therapy. Four out of seven evaluable patients had detectable TCR rearrangements in the T-cell depleted graft. A T-cell clone was also detected in the peripheral blood before relapse in four cases. Autologous SCT is feasible, safe and can result in complete remission in a significant proportion of patients with tumour stage mycosis fungoides. Despite a short relapse-free survival, most patients achieved good disease control at the time of relapse.

  5. Autologous Peripheral Blood Stem Cell Transplantation in Patients With Life Threatening Autoimmune Diseases

    ClinicalTrials.gov

    2005-06-23

    Purpura, Schoenlein-Henoch; Graft Versus Host Disease; Anemia, Hemolytic, Autoimmune; Rheumatoid Arthritis; Churg-Strauss Syndrome; Hypersensitivity Vasculitis; Wegener's Granulomatosis; Systemic Lupus Erythematosus; Giant Cell Arteritis; Pure Red Cell Aplasia; Juvenile Rheumatoid Arthritis; Polyarteritis Nodosa; Autoimmune Thrombocytopenic Purpura; Takayasu Arteritis

  6. A case of disseminated histoplasmosis following autologous stem cell transplantation for Hodgkin's lymphoma: an initial misdiagnosis with a false-positive serum galactomannan assay.

    PubMed

    Jones, O; Cleveland, K O; Gelfand, M S

    2009-06-01

    Systemic histoplasmosis is uncommonly reported in patients who have undergone bone marrow or solid organ transplantation. Diagnosis of systemic histoplasmosis in recipients of transplants may be hampered by lack of consideration of this infection in the differential diagnosis and may be confounded by conflicting information from other testing performed to evaluate for opportunistic infections in this population. We report successful treatment of a case of disseminated histoplasmosis in a patient with Hodgkin's lymphoma who had undergone autologous stem cell transplantation. The diagnosis was delayed by the finding of a positive serum galactomannan assay. PMID:19302274

  7. The Fate and Distribution of Autologous Bone Marrow Mesenchymal Stem Cells with Intra-Arterial Infusion in Osteonecrosis of the Femoral Head in Dogs

    PubMed Central

    Jin, Hongting; Xu, Taotao; Chen, Qiqing; Wu, Chengliang; Wang, Pinger; Mao, Qiang; Zhang, Shanxing; Shen, Jiayi; Tong, Peijian

    2016-01-01

    This study aimed to investigate if autologous bone marrow mesenchymal stem cells (MSCs) could treat osteonecrosis of the femoral head (ONFH) and what the fate and distribution of the cells are in dogs. Twelve Beagle dogs were randomly divided into two groups: MSCs group and SHAM operated group. After three weeks, dogs in MSCs group and SHAM operated group were intra-arterially injected with autologous MSCs and 0.9% normal saline, respectively. Eight weeks after treatment, the necrotic volume of the femoral heads was significantly reduced in MSCs group. Moreover, the trabecular bone volume was increased and the empty lacunae rate was decreased in MSCs group. In addition, the BrdU-positive MSCs were unevenly distributed in femoral heads and various vital organs. But no obvious abnormalities were observed. Furthermore, most of BrdU-positive MSCs in necrotic region expressed osteocalcin in MSCs group and a few expressed peroxisome proliferator-activated receptor-γ (PPAR-γ). Taken together, these data indicated that intra-arterially infused MSCs could migrate into the necrotic field of femoral heads and differentiate into osteoblasts, thus improving the necrosis of femoral heads. It suggests that intra-arterial infusion of autologous MSCs might be a feasible and relatively safe method for the treatment of femoral head necrosis. PMID:26779265

  8. Hybrid approach of ventricular assist device and autologous bone marrow stem cells implantation in end-stage ischemic heart failure enhances myocardial reperfusion

    PubMed Central

    2011-01-01

    We challenge the hypothesis of enhanced myocardial reperfusion after implanting a left ventricular assist device together with bone marrow mononuclear stem cells in patients with end-stage ischemic cardiomyopathy. Irreversible myocardial loss observed in ischemic cardiomyopathy leads to progressive cardiac remodelling and dysfunction through a complex neurohormonal cascade. New generation assist devices promote myocardial recovery only in patients with dilated or peripartum cardiomyopathy. In the setting of diffuse myocardial ischemia not amenable to revascularization, native myocardial recovery has not been observed after implantation of an assist device as destination therapy. The hybrid approach of implanting autologous bone marrow stem cells during assist device implantation may eventually improve native cardiac function, which may be associated with a better prognosis eventually ameliorating the need for subsequent heart transplantation. The aforementioned hypothesis has to be tested with well-designed prospective multicentre studies. PMID:21247486

  9. Role of Salvage Radiation Therapy for Patients With Relapsed or Refractory Hodgkin Lymphoma Who Failed Autologous Stem Cell Transplant

    SciTech Connect

    Goda, Jayant S.; Massey, Christine; Kuruvilla, John; Gospodarowicz, Mary K.; Wells, Woodrow; Hodgson, David C.; Sun, Alexander; Keating, Armand; Crump, Michael; Tsang, Richard W.

    2012-11-01

    Purpose: To analyze, through chart review, the efficacy of salvage radiation therapy (sRT) for relapsed or progressive Hodgkin lymphoma (HL) patients who failed autologous stem cell transplant (ASCT). Patients and Methods: Among 347 patients with recurrent/refractory HL who received ASCT from 1986-2006, 163 had post-ASCT progression or relapse. Of these, 56 received sRT and form the basis of this report. Median age at sRT was 30 years (range, 17-59 years). Disease was confined to lymph nodes in 27 patients, whereas 24 had both nodal and extranodal disease. Salvage radiation therapy alone was given in 34 patients (61%), and sRT plus chemotherapy was given in 22 (39%). Median interval from ASCT to sRT was 0.8 years (range, 0.1-5.6 years). The median dose was 35 Gy (range, 8-40.3 Gy). The sRT technique was extended-field in 14 patients (25%) and involved-field in 42 (75%). Results: The median follow-up from sRT was 31.3 months (range, 0.2-205.5 months). Overall response rate was 84% (complete response: 36%; partial response: 48%). The median overall survival was 40.8 months (95% confidence interval, 34.2-56.3 months). The 5-year overall survival was 29% (95% confidence interval, 14%-44%). The 2-year progression-free survival (PFS) was 16%; the 2-year local PFS was 65%, whereas the 2-year systemic PFS was 17%. The 1-year PFS was higher in patients in whom all diseased sites were irradiated (49%) compared with those in whom only the symptomatic site was treated (22%, P=.07). Among 20 alive patients, 5 were disease free (at 6.4, 6.8, 7.4, 7.9, and 17.1 years). Conclusion: For patients with HL who fail ASCT, a selective use of RT provides a durable local control rate of 65% at 2 years and should be considered as part of the standard management plan for the palliation of incurable HL. Occasionally irradiation of truly localized disease can lead to long-term survival.

  10. Hepatitis B virus infection status is an independent risk factor for multiple myeloma patients after autologous hematopoietic stem cell transplantation.

    PubMed

    Li, Juan; Liu, Junru; Huang, Beihui; Zheng, Dong; Chen, Mei; Zhou, Zhenhai; Xu, Duorong; Zou, Waiyi

    2013-06-01

    The purposes of this study were to evaluate the infection by hepatitis B virus (HBV) and its impact on survival and to provide a clinical reference for monitoring and treating HBV during and after autologous hematopoietic stem cell transplantation (ASCT) in patients with multiple myeloma (MM). A retrospective analysis of HBV infections was performed in 70 MM patients who received a sequential bortezomib-containing induction therapy and ASCT in our department from June 2006 to February 2012. Among the 70 patients in our study, 11 cases (15.7 %) were hepatitis B surface antigen positive (HBsAg+), and 23 cases (33.3 %) were hepatitis B core antibody positive (HBcAb+). Eight cases were HBsAg, hepatitis B e antibody (HBeAb), and HBcAb positive, while one case was HBsAg, hepatitis B e antigen (HBeAg), and HBcAb positive. The median follow-up times for the HBsAg+ group and the HBsAg-negative (HBsAg-) group were 27.0 (7.6-85.2) months and 28.7 (7.1-111.0) months, respectively. The 1-year, 2-year, and 3-year overall survival rates of the HBsAg+ group were 90.9, 80.8, and 34.6 %, respectively, and the median survival time was 31.2 months (95 % CI, 24.8-37.6). The 1-year, 2-year, and 3-year overall survival rates of the HBsAg- group were 98.2, 94, and 84.6 %, respectively, while the median survival time was not yet available. There was a statistically significant difference (p=0.008) in the overall survival rate between the two groups. By Cox regression analysis, we found that the HBsAg+ status was a prognostic factor, which could independently influence the overall survival rate for ASCT. In conclusion, the HBsAg+ status is an independent risk factor for patients with MM receiving ASCT. The application of standard antiviral treatment might help to overcome this risk factor. PMID:23436046

  11. Utilizing muscle-derived stem cells to enhance long-term retention and aesthetic outcome of autologous fat grafting: pilot study in mice.

    PubMed

    Ma, Zhiqiang; Han, Duanyang; Zhang, Peipei; Yang, Jenny F; Wang, Yiqiang; Zhang, Yingbo; Yang, Daping; Liu, Jianyu

    2012-02-01

    Autologous fat grafting has been regarded as the ideal soft tissue filler for more than a century. Low long-term retention rate and unpredictability limit it from widespread clinical practice. Many theories for this have been proposed: lack of sufficient blood supply and subsequent necrosis is the most accepted. In this pilot study, we showed both macroscopically and microscopically the viability of muscle-derived stem cells (MDSCs) cotransplanted with fat placed intramuscularly for 3 months. MRI scanning showed a stronger fat signal in the MDSC-treated group than that of the control group. Moreover, histological evaluation exhibited well-preserved and intact fat cells in the MDSC-treated group. In contrast, the control group showed extensive fibrosis and fat graft loss. Furthermore, the MDSC-treated group possessed almost threefold greater capillary density than the control group. We conclude that cotransplantation of muscle-derived stem cells and autologous fat tissue improves the long-term survival of intramuscular fat transplants by promoting neovascularization. PMID:21607534

  12. Technological progress and challenges towards cGMP manufacturing of human pluripotent stem cells based therapeutic products for allogeneic and autologous cell therapies.

    PubMed

    Abbasalizadeh, Saeed; Baharvand, Hossein

    2013-12-01

    Recent technological advances in the generation, characterization, and bioprocessing of human pluripotent stem cells (hPSCs) have created new hope for their use as a source for production of cell-based therapeutic products. To date, a few clinical trials that have used therapeutic cells derived from hESCs have been approved by the Food and Drug Administration (FDA), but numerous new hPSC-based cell therapy products are under various stages of development in cell therapy-specialized companies and their future market is estimated to be very promising. However, the multitude of critical challenges regarding different aspects of hPSC-based therapeutic product manufacturing and their therapies have made progress for the introduction of new products and clinical applications very slow. These challenges include scientific, technological, clinical, policy, and financial aspects. The technological aspects of manufacturing hPSC-based therapeutic products for allogeneic and autologous cell therapies according to good manufacturing practice (cGMP) quality requirements is one of the most important challenging and emerging topics in the development of new hPSCs for clinical use. In this review, we describe main critical challenges and highlight a series of technological advances in all aspects of hPSC-based therapeutic product manufacturing including clinical grade cell line development, large-scale banking, upstream processing, downstream processing, and quality assessment of final cell therapeutic products that have brought hPSCs closer to clinical application and commercial cGMP manufacturing.

  13. Scaffold-free Three-dimensional Graft From Autologous Adipose-derived Stem Cells for Large Bone Defect Reconstruction: Clinical Proof of Concept.

    PubMed

    Dufrane, Denis; Docquier, Pierre-Louis; Delloye, Christian; Poirel, Hélène A; André, Wivine; Aouassar, Najima

    2015-12-01

    Long bone nonunion in the context of congenital pseudarthrosis or carcinologic resection (with intercalary bone allograft implantation) is one of the most challenging pathologies in pediatric orthopedics. Autologous cancellous bone remains the gold standard in this context of long bone nonunion reconstruction, but with several clinical limitations. We then assessed the feasibility and safety of human autologous scaffold-free osteogenic 3-dimensional (3D) graft (derived from autologous adipose-derived stem cells [ASCs]) to cure a bone nonunion in extreme clinical and pathophysiological conditions. Human ASCs (obtained from subcutaneous adipose tissue of 6 patients and expanded up to passage 4) were incubated in osteogenic media and supplemented with demineralized bone matrix to obtain the scaffold-free 3D osteogenic structure as confirmed in vitro by histomorphometry for osteogenesis and mineralization. The 3D "bone-like" structure was finally transplanted for 3 patients with bone tumor and 3 patients with bone pseudarthrosis (2 congenital, 1 acquired) to assess the clinical feasibility, safety, and efficacy. Although minor clones with structural aberrations (aneuploidies, such as tri or tetraploidies or clonal trisomy 7 in 6%-20% of cells) were detected in the undifferentiated ASCs at passage 4, the osteogenic differentiation significantly reduced these clonal anomalies. The final osteogenic product was stable, did not rupture with forceps manipulation, did not induce donor site morbidity, and was easily implanted directly into the bone defect. No acute (<3 mo) side effects, such as impaired wound healing, pain, inflammatory reaction, and infection, or long-term side effects, such as tumor development, were associated with the graft up to 4 years after transplantation. We report for the first time that autologous ASC can be fully differentiated into a 3D osteogenic-like implant without any scaffold. We demonstrated that this engineered tissue can safely promote

  14. The Influence of Autologous Bone Marrow Stem Cell Transplantation on Matrix Metalloproteinases in Patients Treated for Acute ST-Elevation Myocardial Infarction

    PubMed Central

    Furenes, Eline Bredal; Opstad, Trine Baur; Solheim, Svein; Lunde, Ketil; Arnesen, Harald; Seljeflot, Ingebjørg

    2014-01-01

    Background. Matrix metalloproteinase-9 (MMP-9), regulated by tissue inhibitor of metalloproteinase-9 (TIMP-1) and the extracellular matrix metalloproteinase inducer (EMMPRIN), contributes to plaque instability. Autologous stem cells from bone marrow (mBMC) treatment are suggested to reduce myocardial damage; however, limited data exists on the influence of mBMC on MMPs. Aim. We investigated the influence of mBMC on circulating levels of MMP-9, TIMP-1, and EMMPRIN at different time points in patients included in the randomized Autologous Stem-Cell Transplantation in Acute Myocardial Infarction (ASTAMI) trial (n = 100). Gene expression analyses were additionally performed. Results. After 2-3 weeks we observed a more pronounced increase in MMP-9 levels in the mBMC group, compared to controls (P = 0.030), whereas EMMPRIN levels were reduced from baseline to 2-3 weeks and 3 months in both groups (P < 0.0001). Gene expression of both MMP-9 and EMMPRIN was reduced from baseline to 3 months. MMP-9 and EMMPRIN were significantly correlated to myocardial injury (CK: P = 0.005 and P < 0.001, resp.) and infarct size (SPECT: P = 0.018 and P = 0.008, resp.). Conclusion. The results indicate that the regulation of metalloproteinases is important during AMI, however, limited influenced by mBMC. PMID:25294955

  15. In vitro fabrication of autologous living tissue-engineered vascular grafts based on prenatally harvested ovine amniotic fluid-derived stem cells.

    PubMed

    Weber, Benedikt; Kehl, Debora; Bleul, Ulrich; Behr, Luc; Sammut, Sébastien; Frese, Laura; Ksiazek, Agnieszka; Achermann, Josef; Stranzinger, Gerald; Robert, Jérôme; Sanders, Bart; Sidler, Michele; Brokopp, Chad E; Proulx, Steven T; Frauenfelder, Thomas; Schoenauer, Roman; Emmert, Maximilian Y; Falk, Volkmar; Hoerstrup, Simon P

    2016-01-01

    Amniotic fluid cells (AFCs) have been proposed as a valuable source for tissue engineering and regenerative medicine. However, before clinical implementation, rigorous evaluation of this cell source in clinically relevant animal models accepted by regulatory authorities is indispensable. Today, the ovine model represents one of the most accepted preclinical animal models, in particular for cardiovascular applications. Here, we investigate the isolation and use of autologous ovine AFCs as cell source for cardiovascular tissue engineering applications. Fetal fluids were aspirated in vivo from pregnant ewes (n = 9) and from explanted uteri post mortem at different gestational ages (n = 91). Amniotic non-allantoic fluid nature was evaluated biochemically and in vivo samples were compared with post mortem reference samples. Isolated cells revealed an immunohistochemical phenotype similar to ovine bone marrow-derived mesenchymal stem cells (MSCs) and showed expression of stem cell factors described for embryonic stem cells, such as NANOG and STAT-3. Isolated ovine amniotic fluid-derived MSCs were screened for numeric chromosomal aberrations and successfully differentiated into several mesodermal phenotypes. Myofibroblastic ovine AFC lineages were then successfully used for the in vitro fabrication of small- and large-diameter tissue-engineered vascular grafts (n = 10) and cardiovascular patches (n = 34), laying the foundation for the use of this relevant pre-clinical in vivo assessment model for future amniotic fluid cell-based therapeutic applications.

  16. Posterolateral spinal fusion with nano-hydroxyapatite-collagen/PLA composite and autologous adipose-derived mesenchymal stem cells in a rabbit model.

    PubMed

    Tang, Zi-Bin; Cao, Jun-Kai; Wen, Ning; Wang, Hai-Bin; Zhang, Zhong-Wen; Liu, Zhi-Qiang; Zhou, Jin; Duan, Cui-Mi; Cui, Fu-Zhai; Wang, Chang-Yong

    2012-04-01

    Spinal fusion is routinely performed to treat low back pain caused by degeneration of intervertebral discs. An autologous bone graft derived from the iliac crest is the standard procedure used for spinal fusion. However, several shortcomings, including pseudarthrosis, pain and the need for blood transfusion are known to be associated with the procedure. Our study analysed the effectiveness of a new mineralized collagen matrix, nano-hydroxyapatite-collagen-polylactic acid (nHAC-PLA), combined with autologous adipose-derived mesenchymal stem cells (ADMSCs) as a graft material for posterolateral spinal fusion in a rabbit model. Forty rabbits were randomly divided into four groups: autologous iliac crest bone group (ACB), nHAC-PLA composite group (nHAC-PLA), autologous iliac crest bone mixed with nHAC-PLA composite group (ACB + nHAC-PLA), and nHAC-PLA composite combined with ADMSCs (ADMSCs + nHAC-PLA). The viability and the proliferation of the ADMSCs seeded on the scaffolds were evaluated by live/dead kit and MTT assay in vitro, respectively. Lumbar posterolateral fusions were assessed by manual palpation, radiographical and histological procedures, mechanical strength and scanning electronic microscopy (SEM) in 10 weeks of observation. The results showed that the rate of fusion was significantly higher in the ACB and ADMSCs + nHAC-PLA groups than that in the nHAC-PLA and ACB + nHAC-PLA groups. It was not significantly higher in the ACB group than in the ADMSCs + nHAC-PLA group. From microstructural analysis of the samples using histological staining methods, there was more new bone-like tissue formation in the ACB and ADMSCs + nHAC-PLA groups than that in the other two groups at the 10th postoperative week. Our study demonstrated the effective impact of nHAC-PLA combined with ADMSCs in rabbit posterolateral spinal fusion.

  17. The use of autologous neurogenically-induced bone marrow-derived mesenchymal stem cells for the treatment of paraplegic dogs without nociception due to spinal trauma

    PubMed Central

    BESALTI, Omer; AKTAS, Zeynep; CAN, Pinar; AKPINAR, Eylul; ELCIN, Ayse Eser; ELCIN, Yasar Murat

    2016-01-01

    The aim of this study was to investigate the effects of percutaneous transplanted autologous neurogenically-induced bone marrow-derived mesenchymal stem cells (NIBM-MSCs) in paraplegic dogs without deep pain perception (DPP) secondary to external spinal trauma. Thirteen client owned dogs that had failed in improvement neurologically at least 42 days after conservative management, decompression and decompression-stabilization were included in the study. Each dog received two doses of autologous 5.0 × 106 NIBM-MSCs suspension, which were positive to 2′,3′-Cyclic-nucleotide-3′-phosphodiesterase (CNPase) and Microtubule-associated protein 2 (MAP-2), as well as to Glial fibrillary acidic protein (GFAP) and beta III tubulin. The cells were injected into the spinal cord through the hemilaminectomy or laminectomy defects percutaneously with 21 days interval for 2 times. The results were evaluated using Texas Spinal Cord Injury Scale (TSCIS), somatosensory evoked potentials (SEP) and motor evoked potentials (MEP) at the admission time, cell transplantation procedures and during 2, 5, 7 and 12th months after the second cell transplantation. Improvement after cell transplantation in gait, nociception, proprioception, SEP and MEP results was observed in just 2 cases, and only gait score improvement was seen in 6 cases, and no improvement was recorded in 5 cases. All progresses were observed until 2nd month after the second cell transplantation, however, there was no improvement after this period. In conclusion, percutaneous transplantation of autologous NIBM-MSCs is a promising candidate modality for cases with spinal cord injury after spinal trauma and poor prognosis. PMID:27301583

  18. [Expression of adhesion molecules on CD34+ cells of BM and PB stem cell samples during high-dose chemotherapy combined with transplantation of autologous PB stem cells].

    PubMed

    Liu, Peng; Han, Xiao-Hong; Shi, Yuan-Kai; He, Xiao-Hui; Yang, Cheng; Ai, Bin

    2004-12-01

    This study was aimed to investigate the expressions of adhesion molecules such as CD54, CD49d and CD62L by CD34(+) cells sampled from different stages of bone marrow (BM) and peripheral blood (PB) before/after G-CSF mobilization and after transplantation through the direct labeling with three colour-immunofluorescence and flow cytometry, and to explore the differences in expression of adhesion molecules on CD34(+) cells from different origins and their clinical significance. Mononuclear cells collected from BM and PB before mobilization, after collection of stem cells and hematopoietic recostruction of BM at the end of transplantation were marked with CD54-FITC, CD49d-FITC and CD62L-FITC separately, as well as CD34-PE and CD45PerCE. 3-color fluorescene analysis was carried out by FACS. The expression differences of CD34(+) and adhesion molecules between BM and APBSC were compared. The results showed that expression differences of CD54, CD49d and cd62Lon CD34(+) cells belore mobilization, after collection and reconstraction of transplantation were not statiscally significant, the difference of CD54, CD49d and CD62L on CD34(+) between 1st and 2nd collections of hematopoietic stem cells also were not statiscally significant. In the collected APBSC, the expression level of CD34(+) CD49d(+) was significantly lower than those in BM before mobilization (P = 0.001). It is concluded that the method of chemotherapy combined with G-CSF mobilization can down-regulate CD49d expression in BM CD34(+) cells, thus can mobilize and move theirs into peripheral blood. After the reconstitution by transplantation, the expression of CD49d on CD34(+) cells tends to normal, the clinical significance needs to be elucidated by accumulation of much more cases.

  19. Guided bone regeneration in pig calvarial bone defects using autologous mesenchymal stem/progenitor cells - a comparison of different tissue sources.

    PubMed

    Stockmann, Philipp; Park, Jung; von Wilmowsky, Cornelius; Nkenke, Emeka; Felszeghy, Endre; Dehner, Jan-Friedrich; Schmitt, Christian; Tudor, Christian; Schlegel, Karl Andreas

    2012-06-01

    Due to donor side morbidity and the absence of osteogenic properties in bone substitutes, there is a growing need for an alternative to traditional bone grafting within the scope of tissue engineering. This animal study was conducted to compare the in vivo osteogenic potential of adipose-derived (AD), periosteum-derived (PD) and bone marrow-derived (BM) mesenchymal stem/progenitor cells (MSC). Autologous mesenchymal stem/progenitor cells of named tissue origin were induced into osteogenic differentiation following in vitro cell expansion. Ex vivo cultivated cells were seeded on a collagen scaffold and subsequently added to freshly created monocortical calvarial bone defects in 21 domestic pigs. Pure collagen scaffold served as a control defect. The animals were sacrificed at specific time points and de novo bone formation was quantitatively analyzed by histomorphometry. Bone volume/total defect volume (BV/TV) and the mineralization rate of newly formed bone were compared among the groups. In the early stages of wound healing, up to 30 days, the test defects did not show better bone regeneration than those in the control defect, but the bone healing process in the test defects was accelerated in the later stage compared to those in the control defect. All the test defects showed complete osseous healing after 90 days compared to those in the control defect. During the observation period, no significant differences in BV/TV and mineralization of newly formed bone among the test defects were observed. Irrespective of the tissue sources of MSC, the speed and pattern of osseous healing after cell transplantations into monocortical bone defects were comparable. Our results indicate that the efficiency of autologous AD-MSC, PD-MSC and BM-MSC transplantation following ex vivo cell expansion is not significantly different for the guided regeneration of bone defects.

  20. Guided bone regeneration in pig calvarial bone defects using autologous mesenchymal stem/progenitor cells - a comparison of different tissue sources.

    PubMed

    Stockmann, Philipp; Park, Jung; von Wilmowsky, Cornelius; Nkenke, Emeka; Felszeghy, Endre; Dehner, Jan-Friedrich; Schmitt, Christian; Tudor, Christian; Schlegel, Karl Andreas

    2012-06-01

    Due to donor side morbidity and the absence of osteogenic properties in bone substitutes, there is a growing need for an alternative to traditional bone grafting within the scope of tissue engineering. This animal study was conducted to compare the in vivo osteogenic potential of adipose-derived (AD), periosteum-derived (PD) and bone marrow-derived (BM) mesenchymal stem/progenitor cells (MSC). Autologous mesenchymal stem/progenitor cells of named tissue origin were induced into osteogenic differentiation following in vitro cell expansion. Ex vivo cultivated cells were seeded on a collagen scaffold and subsequently added to freshly created monocortical calvarial bone defects in 21 domestic pigs. Pure collagen scaffold served as a control defect. The animals were sacrificed at specific time points and de novo bone formation was quantitatively analyzed by histomorphometry. Bone volume/total defect volume (BV/TV) and the mineralization rate of newly formed bone were compared among the groups. In the early stages of wound healing, up to 30 days, the test defects did not show better bone regeneration than those in the control defect, but the bone healing process in the test defects was accelerated in the later stage compared to those in the control defect. All the test defects showed complete osseous healing after 90 days compared to those in the control defect. During the observation period, no significant differences in BV/TV and mineralization of newly formed bone among the test defects were observed. Irrespective of the tissue sources of MSC, the speed and pattern of osseous healing after cell transplantations into monocortical bone defects were comparable. Our results indicate that the efficiency of autologous AD-MSC, PD-MSC and BM-MSC transplantation following ex vivo cell expansion is not significantly different for the guided regeneration of bone defects. PMID:21723141

  1. Autologous serum improves bone formation in a primary stable silica-embedded nanohydroxyapatite bone substitute in combination with mesenchymal stem cells and rhBMP-2 in the sheep model

    PubMed Central

    Boos, Anja M; Weigand, Annika; Deschler, Gloria; Gerber, Thomas; Arkudas, Andreas; Kneser, Ulrich; Horch, Raymund E; Beier, Justus P

    2014-01-01

    New therapeutic strategies are required for critical size bone defects, because the gold standard of transplanting autologous bone from an unharmed area of the body often leads to several severe side effects and disadvantages for the patient. For years, tissue engineering approaches have been seeking a stable, axially vascularized transplantable bone replacement suitable for transplantation into the recipient bed with pre-existing insufficient conditions. For this reason, the arteriovenous loop model was developed and various bone substitutes have been vascularized. However, it has not been possible thus far to engineer a primary stable and axially vascularized transplantable bone substitute. For that purpose, a primary stable silica-embedded nanohydroxyapatite (HA) bone substitute in combination with blood, bone marrow, expanded, or directly retransplanted mesenchymal stem cells, recombinant human bone morphogenetic protein 2 (rhBMP-2), and different carrier materials (fibrin, cell culture medium, autologous serum) was tested subcutaneously for 4 or 12 weeks in the sheep model. Autologous serum lead to an early matrix change during degradation of the bone substitute and formation of new bone tissue. The best results were achieved in the group combining mesenchymal stem cells expanded with 60 μg/mL rhBMP-2 in autologous serum. Better ingrowth of fibrovascular tissue could be detected in the autologous serum group compared with the control (fibrin). Osteoclastic activity indicating an active bone remodeling process was observed after 4 weeks, particularly in the group with autologous serum and after 12 weeks in every experimental group. This study clearly demonstrates the positive effects of autologous serum in combination with mesenchymal stem cells and rhBMP-2 on bone formation in a primary stable silica-embedded nano-HA bone grafting material in the sheep model. In further experiments, the results will be transferred to the sheep arteriovenous loop model in

  2. Clinical efficacy and safety of autologous stem cell transplantation for patients with ST-segment elevation myocardial infarction

    PubMed Central

    Li, Rong; Li, Xiao-Ming; Chen, Jun-Rong

    2016-01-01

    Purpose The purpose of this study is to evaluate the therapeutic efficacy and safety of stem cells for the treatment of patients with ST-segment elevation myocardial infarction (STEMI). Materials and methods We performed a systematic review and meta-analysis of relevant published clinical studies. A computerized search was conducted for randomized controlled trials of stem cell therapy for STEMI. Results Twenty-eight randomized controlled trials with a total of 1,938 STEMI patients were included in the present meta-analysis. Stem cell therapy resulted in an improvement in long-term (12 months) left ventricular ejection fraction of 3.15% (95% confidence interval 1.01–5.29, P<0.01). The 3-month to 4-month, 6-month, and 12-month left ventricular end-systolic volume showed favorable results in the stem cell therapy group compared with the control group (P≤0.05). Significant decrease was also observed in left ventricular end-diastolic volume after 3-month to 4-month and 12-month follow-up compared with controls (P<0.05). Wall mean score index was reduced significantly in stem cell therapy group when compared with the control group at 6-month and 12-month follow-up (P=0.01). Moreover, our analysis showed a significant change of 12-month infarct size decrease in STEMI patients treated with stem cells compared with controls (P<0.01). In addition, no significant difference was found between treatment group and control in adverse reactions (P>0.05). Conclusion Overall, stem cell therapy is efficacious in the treatment of patients with STEMI, with low rates of adverse events compared with control group patients. PMID:27536122

  3. Impact of the use of autologous stem cell transplantation at first relapse both in naïve and previously rituximab exposed follicular lymphoma patients treated in the GELA/GOELAMS FL2000 study

    PubMed Central

    Le Gouill, Steven; De Guibert, Sophie; Planche, Lucie; Brice, Pauline; Dupuis, Jehan; Cartron, Guillaume; Van Hoof, Achiel; Casasnovas, Olivier; Gyan, Emmanuel; Tilly, Hervé; Fruchart, Christophe; Deconinck, Eric; Fitoussi, Olivier; Gastaud, Lauris; Delwail, Vincent; Gabarre, Jean; Gressin, Rémy; Blanc, Michel; Foussard, Charles; Salles, Gilles

    2011-01-01

    Background We analyzed detailed characteristics and salvage treatment in 175 follicular lymphoma patients from the FL2000 study who were in progression after first-line therapy with or without addition of rituximab to chemotherapy and interferon. Design and Methods The impact of using autologous stem cell transplantation and/or rituximab administration at first progression was investigated, taking into account initial therapy. With a median follow up of 31 months, 3-year event free and overall survival rates after progression were 50% (95%CI 42–58%) and 72% (95%CI 64–78%), respectively. Results The 3-year event free rate of rituximab re-treated patients (n=112) was 52% (95%CI 41–62%) versus 40% (95%CI 24–55%) for those not receiving rituximab second line (n=53) (P=0.075). There was a significant difference in 3-year overall survival between patients receiving autologous stem cell transplantation and those not: 92% (95%CI 78–97%) versus 63% (95%CI 51–72%) (P=0.0003), respectively. In multivariate analysis, both autologous stem cell transplantation and period of progression/relapse affected event free and overall survival. Conclusions Regardless of front-line rituximab exposure, this study supports incorporating autologous stem cell transplantation in the therapeutic approach at first relapse for follicular lymphoma patients. PMID:21486862

  4. Synovial Mesenchymal Stem Cells Promote Meniscus Regeneration Augmented by an Autologous Achilles Tendon Graft in a Rat Partial Meniscus Defect Model

    PubMed Central

    Ozeki, Nobutake; Muneta, Takeshi; Matsuta, Seiya; Koga, Hideyuki; Nakagawa, Yusuke; Mizuno, Mitsuru; Tsuji, Kunikazu; Mabuchi, Yo; Akazawa, Chihiro; Kobayashi, Eiji; Saito, Tomoyuki; Sekiya, Ichiro

    2015-01-01

    Although meniscus defects and degeneration are strongly correlated with the later development of osteoarthritis, the promise of regenerative medicine strategies is to prevent and/or delay the disease's progression. Meniscal reconstruction has been shown in animal models with tendon grafting and transplantation of mesenchymal stem cells (MSCs); however, these procedures have not shown the same efficacy in clinical studies. Here, our aim was to investigate the ability of tendon grafts pretreated with exogenous synovial-derived MSCs to prevent cartilage degeneration in a rat partial meniscus defect model. We removed the anterior half of the medial meniscus and grafted autologous Achilles tendons with or without a 10-minute pretreatment of the tendon with synovial MSCs. The meniscus and surrounding cartilage were evaluated at 2, 4, and 8 weeks (n = 5). Tendon grafts increased meniscus size irrespective of synovial MSCs. Histological scores for regenerated menisci were better in the tendon + MSC group than in the other two groups at 4 and 8 weeks. Both macroscopic and histological scores for articular cartilage were significantly better in the tendon + MSC group at 8 weeks. Implanted synovial MSCs survived around the grafted tendon and native meniscus integration site by cell tracking assays with luciferase+, LacZ+, DiI+, and/or GFP+ synovial MSCs and/or GFP+ tendons. Flow cytometric analysis showed that transplanted synovial MSCs retained their MSC properties at 7 days and host synovial tissue also contained cells with MSC characteristics. Synovial MSCs promoted meniscus regeneration augmented by autologous Achilles tendon grafts and prevented cartilage degeneration in rats. Stem Cells 2015;33:1927–1938 PMID:25993981

  5. Stem Cells

    MedlinePlus

    Stem cells are cells with the potential to develop into many different types of cells in the body. They serve as a repair ... body. There are two main types of stem cells: embryonic stem cells and adult stem cells. Stem ...

  6. Prognostic value of FDG-PET prior to autologous stem cell transplantation for relapsed and refractory diffuse large B-cell lymphoma.

    PubMed

    Sauter, Craig S; Matasar, Matthew J; Meikle, Jessica; Schoder, Heiko; Ulaner, Gary A; Migliacci, Jocelyn C; Hilden, Patrick; Devlin, Sean M; Zelenetz, Andrew D; Moskowitz, Craig H

    2015-04-16

    High-dose chemotherapy (HDT) plus autologous stem cell transplantation (ASCT) is the standard of care for chemosensitive relapsed and refractory diffuse large B-cell lymphoma (rel/ref DLBCL). Interim restaging with functional imaging by positron emission tomography using (18)F-deoxyglucose (FDG-PET) has not been established after salvage chemotherapy (ST) and before HDT-ASCT by modern criteria. Herein, we evaluated 129 patients with rel/ref DLBCL proceeding to HDT-ASCT, with ST response assessment by FDG-PET according to the contemporary Deauville 5-point scale. At 3 years, patients achieving a Deauville response of 1 to 3 to ST experienced superior progression-free survival (PFS) and overall survival (OS) rates of 77% and 86%, respectively, compared with patients achieving Deauville 4 (49% and 54%, respectively) (P < .001). No other pre-HDT-ASCT risk factors significantly impacted PFS or OS. Despite achieving remission to ST, patients with Deauville 4 should be the focus of risk-adapted investigational therapies.

  7. Clinical experience with plerixafor as a mobilization regimen for autologous peripheral blood stem cell transplantation in patients with refractory germ cell tumors

    PubMed Central

    GARCÍA-ESCOBAR, IGNACIO; PARRILLA, LUCÍA; ORTEGA, LAURA MONTEJANO; CASTELLANOS, DANIEL; PALLARÉS, MARÍA ÁNGELES MONTALBÁN; CORTÉS-FUNÉS, HERNÁN

    2014-01-01

    The purpose of this study was to report our experience with administration of plerixafor for the mobilization of hematopoietic stem cells (HSCs) in patients with refractory or recurrent germ cell tumors who were candidates for salvage therapy with high-dose chemotherapy and HSC transplantation and for whom mobilization of HSCs had not been achieved by standard therapies. This retrospective and observational study selected patients who were eligible for autologous HSC transplantation (AHSCT) and received plerixafor after failure of HSC mobilization by granulocyte colony-stimulating factor (G-CSF). A total of 5 patients (4 male and 1 female), aged 19–41 years (mean age, 29.6 years) were initially selected. Four patients (80%) achieved an adequate HSC mobilization with plerixafor and subsequently received high-dose chemotherapy followed by HSC transplantation. In these patients, the number of CD34+ cells collected following plerixafor mobilization was 1.8×106–10.3×106 cells/kg, with a peak CD34+ cell count of 7.0–32.0 cells/μl. Following HSC infusion, these 4 patients achieved a neutrophil count of >0.5×103/mm3 and a platelet count of >20,000/μl between days 10 and 14. Therefore, patients with high-risk germ cell tumors eligible for AHSCT who are refractory to mobilization by G-CSF, may benefit from the use of plerixafor, possibly to the same extent as patients with lymphoma and multiple myeloma. PMID:25279175

  8. Natural history and prognostic impact of oligoclonal humoral response in patients with multiple myeloma after autologous stem cell transplantation: long-term results from a single institution.

    PubMed

    Tovar, Natalia; de Larrea, Carlos Fernández; Aróstegui, Juan I; Cibeira, Maria Teresa; Rosiñol, Laura; Rovira, Montserrat; Elena, Montserrat; Filella, Xavier; Yagüe, Jordi; Bladé, Joan

    2013-07-01

    The emergence of an oligoclonal humoral response, resulting in the appearance of a different serum M-protein to that observed at diagnosis is a well-recognized event after autologous stem cell transplantation in multiple myeloma in complete response, and it has been considered to be a benign phenomenon. The aim of the present study was to investigate the incidence, biological characteristics and prognostic value of the oligoclonal bands in patients with myeloma who underwent autologous transplantation at our institution in the last 18 years. We proceed with a retrospective systematic review of all serum and urine immunofixation studies performed in the 211 patients with multiple myeloma who underwent melphalan-based autologous transplantation. Oligoclonal bands were observed in 34% of the patients, with a significantly higher prevalence with the use of novel agents versus conventional chemotherapy in induction (63% vs. 22%; P=0.0001). The incidence of oligoclonal bands was most frequent in non-IgG isotype, particularly in light chain only myeloma. The oligoclonal phenomenon was almost exclusive to patients in complete remission compared to other degrees of response (87% vs. 13%; P=0.0001), and lasted for a median of 1.35 years, persisting during follow up in all patients except in those who relapsed. In prognostic terms, the presence of oligoclonality resulted in a significantly longer progression-free and overall survival. Patients with oligoclonal humoral response lasting for more than one year after transplantation had a significantly longer clinical progression-free and overall survival than those with shorter duration (P=0.008 and P=0.0001, respectively), likely reflecting the importance of a robust humoral immune response. PMID:23645688

  9. Pertussis immunity and response to tetanus-reduced diphtheria-reduced pertussis vaccine (Tdap) after autologous peripheral blood stem cell transplantation.

    PubMed

    Small, Trudy N; Zelenetz, Andrew D; Noy, Ariela; Rice, R David; Trippett, Tanya M; Abrey, Lauren; Portlock, Carol S; McCullagh, Emily J; Vanak, Jill M; Mulligan, Ann Marie; Moskowitz, Craig H

    2009-12-01

    Pertussis is a highly contagious respiratory infection characterized by prolonged cough and inspiratory whoop. Despite widespread vaccination of children aged<7 years, its incidence is steadily increasing in adolescents and adults, because of the known decrease in immunity following childhood immunization. In an effort to reduce pertussis in adolescents and adults, 2 vaccines containing tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) (BOOSTRIX and Adacel) were licensed in 2005 for use in adolescents, 1 of which (Adacel) contains less pertussis toxoid (PT) for use in adults. This study assessed pertussis titers in 57 adult survivors of an autologous peripheral blood stem cell transplantation (PBSCT; median age, 37.5 years), 28 of whom were subsequently vaccinated with Tdap containing 2.5microg of PT (Adacel). The median time to Tdap administration was 3 years posttransplantation. Before vaccination, 87% of the patients lacked pertussis immunity. Only 2 of the 28 patients developed a >2-fold response to PT following vaccination with Tdap. These data suggest that autologous transplantation recipients are highly susceptible to pertussis and that immunization with 2.5microg of PT induces an inadequate response. Prospective trials evaluating BOOSTRIX, containing 8microg/dose of PT (approved for adults in December 2008) are warranted in this vulnerable population undergoing transplantation.

  10. International Myeloma Working Group Consensus Statement for the Management, Treatment, and Supportive Care of Patients With Myeloma Not Eligible for Standard Autologous Stem-Cell Transplantation

    PubMed Central

    Palumbo, Antonio; Rajkumar, S. Vincent; San Miguel, Jesus F.; Larocca, Alessandra; Niesvizky, Ruben; Morgan, Gareth; Landgren, Ola; Hajek, Roman; Einsele, Hermann; Anderson, Kenneth C.; Dimopoulos, Meletios A.; Richardson, Paul G.; Cavo, Michele; Spencer, Andrew; Stewart, A. Keith; Shimizu, Kazuyuki; Lonial, Sagar; Sonneveld, Pieter; Durie, Brian G.M.; Moreau, Philippe; Orlowski, Robert Z.

    2014-01-01

    Purpose To provide an update on recent advances in the management of patients with multiple myeloma who are not eligible for autologous stem-cell transplantation. Methods A comprehensive review of the literature on diagnostic criteria is provided, and treatment options and management of adverse events are summarized. Results Patients with symptomatic disease and organ damage (ie, hypercalcemia, renal failure, anemia, or bone lesions) require immediate treatment. The International Staging System and chromosomal abnormalities identify high- and standard-risk patients. Proteasome inhibitors, immunomodulatory drugs, corticosteroids, and alkylating agents are the most active agents. The presence of concomitant diseases, frailty, or disability should be assessed and, if present, treated with reduced-dose approaches. Bone disease, renal damage, hematologic toxicities, infections, thromboembolism, and peripheral neuropathy are the most frequent disabling events requiring prompt and active supportive care. Conclusion These recommendations will help clinicians ensure the most appropriate care for patients with myeloma in everyday clinical practice. PMID:24419113

  11. Outcomes of MYC-associated lymphomas after R-CHOP with and without consolidative autologous stem cell transplant: subset analysis of randomized trial intergroup SWOG S9704.

    PubMed

    Puvvada, Soham D; Stiff, Patrick J; Leblanc, Michael; Cook, James R; Couban, Stephen; Leonard, John P; Kahl, Brad; Marcellus, Deborah; Shea, Thomas C; Winter, Jane N; Li, Hongli; Rimsza, Lisa M; Friedberg, Jonathan W; Smith, Sonali M

    2016-09-01

    Double hit lymphoma (DHL) and double protein-expressing (MYC, BCL2) lymphomas (DPL) fare poorly with R-CHOP (rituximab + cyclophosphamide, doxorubicin, vincristine, prednisolone); consolidative autologous stem cell transplant (ASCT) may improve outcomes. S9704, a phase III randomized study of CHOP +/-R with or without ASCT enabled evaluation of intensive consolidation. Immunohistochemistry (IHC) identified 27 of 198 patients (13·6%) with MYC overexpression; 20 (74%) harboured concurrent BCL2 overexpression. Four had DHL and 16 had DPL only. With median 127 months follow-up, there is a trend favouring outcomes after ASCT in DPL and MYC protein overexpressing patients, whereas all DHL patients have died irrespective of ASCT. PMID:27072903

  12. Addition of Autologous Mesenchymal Stem Cells to Whole Blood for Bio-Enhanced ACL Repair has No Benefit in the Porcine Model

    PubMed Central

    Proffen, Benedikt L.; Vavken, Patrick; Haslauer, Carla M.; Fleming, Braden C.; Harris, Chad E.; Machan, Jason T.; Murray, Martha M.

    2015-01-01

    Background Co-culture of mesenchymal stem cells (MSCs) from the retropatellar fat pad and peripheral blood has been shown to stimulate anterior cruciate ligament (ACL) fibroblast proliferation and collagen production in vitro. Current techniques of bio-enhanced ACL repair in animal studies involve adding a biologic scaffold, in this case an extracellular matrix based scaffold saturated with autologous whole blood, to a simple suture repair of the ligament. Whether the enrichment of whole blood with MSCs would further improve the in vivo results of bio-enhanced ACL repair was investigated. Hypothesis/Purpose The hypothesis was that the addition of MSCs derived from adipose tissue or peripheral blood to the blood-extracellular matrix composite, which is used in bio-enhanced ACL repair to stimulate healing, would improve the biomechanical properties of a bio-enhanced ACL repair after 15 weeks of healing. Study Design Controlled laboratory study. Methods Twenty-four adolescent Yucatan mini-pigs underwent ACL transection followed by: 1) bio-enhanced ACL repair, 2) bio-enhanced ACL repair with the addition of autologous adipose-derived MSCs and 3) bio-enhanced ACL repair with the addition of autologous peripheral blood derived MSCs. After fifteen weeks of healing, structural properties of the ACL (yield & failure load, linear stiffness) were measured. Cell and vascular density were measured in the repaired ACL via histology, and its tissue structure was qualitatively evaluated using the Advanced Ligament Maturity Index. Results After fifteen weeks of healing, there were no significant improvements in the biomechanical or histological properties with the addition of adipose-derived MSCs. The only significant change with the addition of peripheral blood MSCs was an increase in knee anteroposterior (AP) laxity when measured at 30 degrees of flexion. Conclusions These findings suggest that the addition of adipose or peripheral blood MSCs to whole blood prior to saturation of

  13. Proceedings from the National Cancer Institute's Second International Workshop on the Biology, Prevention, and Treatment of Relapse after Hematopoietic Stem Cell Transplantation: part II. Autologous Transplantation-novel agents and immunomodulatory strategies.

    PubMed

    Avigan, David; Hari, Parameswaran; Battiwalla, Minoo; Bishop, Michael R; Giralt, Sergio A; Hardy, Nancy M; Kröger, Nicolaus; Wayne, Alan S; Hsu, Katharine C

    2013-12-01

    In the National Cancer Institute's Second International Workshop on the Biology, Prevention, and Treatment of Relapse after Hematopoietic Stem Cell Transplantation, the Scientific/Educational Session on Autologous Transplantation addressed the role of novel agents and immunomodulatory strategies in management of relapse after autologous hematopoietic stem cell transplantation (AHSCT). Concepts were illustrated through in-depth discussion of multiple myeloma, with broader discussion of areas relevant for relapse of other malignancies as well as in the setting of allogeneic transplantation. Dr. Hari provided an overview of the epidemiology of relapse after AHSCT in multiple myeloma, addressing clinical patterns, management implications, and treatment options at relapse, highlighting the implications of novel therapeutic agents in initial, maintenance, and relapse treatment. Dr. Avigan discussed current concepts in tumor vaccine design, including whole cell and antigen-specific strategies, use of an AHSCT platform to reverse tumor-associated immunosuppression and tolerance, and combining vaccines with immunomodulatory agents to promote establishment of durable antitumor immunity. Dr. Hsu reviewed the immunogenetics of natural killer (NK) cells and general NK biology, the clinical importance of autologous NK activity (eg, lymphoma and neuroblastoma), the impact of existing therapies on promotion of NK cell activity (eg, immunomodulatory drugs, monoclonal antibodies), and strategies for enhancing autologous and allogeneic NK cell effects through NK cell gene profiling.

  14. A case report and literature review of primary resistant Hodgkin lymphoma: a response to anti-PD-1 after failure of autologous stem cell transplantation and brentuximab vedotin

    PubMed Central

    Xu, Peipei; Wang, Fan; Guan, Chaoyang; Ouyang, Jian; Shao, Xiaoyan; Chen, Bing

    2016-01-01

    Hodgkin lymphoma (HL) is a highly curable hematologic malignancy, and ~70% of cases can be cured with combination chemotherapy with or without radiation. However, patients with primary resistant disease have a cure rate of <30%. For such patients, high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is considered to be the standard treatment. If patients fail to respond to ASCT or relapse soon thereafter, they usually receive another ASCT, allogeneic stem cell transplantation or treatment with novel agents. This case report presents the case of a 54-year-old patient with primary resistant HL who received single-agent treatment, brentuximab vedotin, after ASCT relapse. Despite treatment with brentuximab vedotin, the disease continued to progress. In patients with such highly resistant disease, the treatment options are limited. Depending on the physical condition and the willingness of the patient, pembrolizumab, a programmed cell death protein-1 inhibitor, can be given as salvage therapy. But, out of our expectation, the patient achieved a very good partial response after four cycles of pembrolizumab. No serious adverse events were observed with pembrolizumab treatment. This case provides support for a new and effective strategy for treating primary resistant Hodgkin lymphoma. PMID:27703376

  15. Autologous Hematopoietic Stem Cells transplantation and genetic modification of CCR5 m303/m303 mutant patient for HIV/AIDS.

    PubMed

    Esmaeilzadeh, Abdolreza; Farshbaf, Alieh; Erfanmanesh, Maryam

    2015-03-01

    HIV and AIDS is one of the biggest challenges all over the world. There are an approximately 34 million people living with the virus, and a large number of them become infected each year. Although there are some antiviral drugs for HIV viral load reduction, they are not sufficient. There is no cure for AIDS. Nowadays natural resistance or immunity has absorbed attentions. Because in some HIV positive patients progression trend is slow or even they indicate resistance to AIDS. One of the most interesting approaches in this category is CCR5 gene. CCR5 is a main cc-chemokine co-receptor that facilitates HIV-1 entry to macrophage and CD4(+) T cells. To now, many polymorphisms have been known by CCR5 gene that produces a truncated protein with no function. So, HIV-1 could not entry to immune-cells and the body resistant to HIV/AIDS. Δ32/Δ32 and m303/m303 homozygotes are example of mutations that could create this resistance mechanism. There is a new treatment, such as Hematopoietic Stem Cell transplantation (HSCT) in Berlin and Boston patients for Δ32/Δ32 mutation. It could eliminate co-receptor antagonist and highly-active-anti retroviral therapy (HAART) drugs problems such as toxicity, low safety and side-effects. Now there, the aim of this hypothesis will be evaluation of a new mutation CCR5 m303/m303 as autologous HSCT. This novel hypothesis indicates that autologous HSCT for m303/m303 could be effective treatment for anyone HIV/AIDS affected patient worldwide.

  16. An algorithm for utilizing peripheral blood CD34 count as a predictor of the need for plerixafor in autologous stem cell mobilization--cost-effectiveness analysis.

    PubMed

    Abusin, Ghada A; Abu-Arja, Rolla F; Gingrich, Roger D; Silverman, Margarida D; Zamba, Gideon K D; Schlueter, Annette J

    2013-08-01

    Certain patients who receive granulocyte colony-stimulating factor (GCSF) for autologous hematopoietic stem cell (AHSC) collection fail to mobilize well enough to proceed with transplant. When plerixafor is used with GCSF, the likelihood of achieving the CD34⁺ stem cell target in fewer collections is higher; plerixafor use in all patients is unlikely to be cost-effective. This study retrospectively evaluated the effectiveness of utilizing a peripheral blood CD34⁺ stem cell count (PBCD34) ≤8/µL on day 4 of GCSF-based AHSC mobilization as a threshold for plerixafor administration, and compared the efficacy of collection and cost analysis using historical controls. All patients in the study cohort reached their CD34⁺ targets in ≤3 collections. Significantly more patients who received plerixafor + GCSF versus GCSF alone reached their CD34⁺ target in one collection (P = 0.045); however, there were no significant differences in the number of collections or in cumulative product yields. The historical cohort had 10.3% mobilization failures; the number of collections per patient needed to reach the target was significantly higher in the historical cohort versus study cohort (P = 0.001) as was the number of patients requiring more than one collection to reach their target (P = 0.023). However, the average cost per patient was also significantly higher in the study cohort (P = 0.025). Further refinement of the algorithm may reduce the difference in cost between the two mobilization strategies.

  17. Regeneration of mandibular ameloblastoma defect with the help of autologous dental pulp stem cells and buccal pad of fat stromal vascular fraction

    PubMed Central

    Manimaran, K.; Sharma, Rohini; Sankaranarayanan, S.; Perumal, S. Mahendra

    2016-01-01

    Ameloblastoma is benign odontogenic tumor, which is locally aggressive in behavior. Till date, the treatment of choice is resection and reconstruction using a variety of modalities. Inadequate resection may lead to many complications such as bone deformity and dysfunction. This report is about a 14-year-old male with ameloblastoma treated with autologous dental pulp stem cells (DPSCs) and stromal vascular fraction (SVF) and evidence of bone regeneration. Marsupialization was performed; tooth was extracted and sent for DPSC cultivation. On the day of surgery, SVF was processed from buccal pad of fat, and platelet-rich fibrin (PRF) was prepared from patient's peripheral blood. During the procedure, labial plate resection and curating of tumor lining were done. After which, a mesh packed with SyboGraft T-plug, prepared SVF, DPSCs, and PRF were placed over lingual cortex and pressure dressing was done. After the 1st month of surgery the postoperative course was uneventful, the wound shrinkage led to exposure of mesh in the intraoral region. Removal of exposed mesh was done. The correction surgery with removal of part of mesh and primary closure was achieved with SyboGraft plug, SVF and PRF. Enhanced bone formation was seen in post-operative OPG and CT Scan after 10th month. In this article, we propose an innovative approach to manage these cases by using a combination of autologous DPSC and buccal pad of fat SVF to regenerate a mandibular defect left by the resection of an ameloblastoma with 1.5 year follow-up. We were able to demonstrate bone regeneration using this technique with no recurrence of tumor. PMID:27563616

  18. Regeneration of mandibular ameloblastoma defect with the help of autologous dental pulp stem cells and buccal pad of fat stromal vascular fraction.

    PubMed

    Manimaran, K; Sharma, Rohini; Sankaranarayanan, S; Perumal, S Mahendra

    2016-01-01

    Ameloblastoma is benign odontogenic tumor, which is locally aggressive in behavior. Till date, the treatment of choice is resection and reconstruction using a variety of modalities. Inadequate resection may lead to many complications such as bone deformity and dysfunction. This report is about a 14-year-old male with ameloblastoma treated with autologous dental pulp stem cells (DPSCs) and stromal vascular fraction (SVF) and evidence of bone regeneration. Marsupialization was performed; tooth was extracted and sent for DPSC cultivation. On the day of surgery, SVF was processed from buccal pad of fat, and platelet-rich fibrin (PRF) was prepared from patient's peripheral blood. During the procedure, labial plate resection and curating of tumor lining were done. After which, a mesh packed with SyboGraft T-plug, prepared SVF, DPSCs, and PRF were placed over lingual cortex and pressure dressing was done. After the 1(st) month of surgery the postoperative course was uneventful, the wound shrinkage led to exposure of mesh in the intraoral region. Removal of exposed mesh was done. The correction surgery with removal of part of mesh and primary closure was achieved with SyboGraft plug, SVF and PRF. Enhanced bone formation was seen in post-operative OPG and CT Scan after 10(th) month. In this article, we propose an innovative approach to manage these cases by using a combination of autologous DPSC and buccal pad of fat SVF to regenerate a mandibular defect left by the resection of an ameloblastoma with 1.5 year follow-up. We were able to demonstrate bone regeneration using this technique with no recurrence of tumor. PMID:27563616

  19. The prognostic impact of peripheral blood progenitor cell dose following high-dose therapy and autologous stem cell transplant for hematologic malignancies.

    PubMed

    Sauter, Craig S; Giralt, Sergio

    2015-06-01

    High-dose chemotherapy (HDT) followed by autologous peripheral blood progenitor cell transplant (PBPCT) has become a standard intervention in certain clinical settings of hematologic malignancies, particularly multiple myeloma and relapsed/refractory lymphoma. While the minimal required PBPCs infused, as defined by number of CD34 + cells, has been relatively well delineated for adequate hematopoietic recovery post-HDT, optimal PBPC dose has not been clearly defined. This is particularly relevant in the context of retrospective data suggesting improved survival outcomes with increased PBPC doses. The potential confounding of these data as they relate to disease risk is discussed within this review. Additionally, other retrospective data have suggested that enhanced quantitative lymphocyte subset reconstitution post-HDT-PBPCT may confer progression-free and overall survival advantage. These reported series herein reviewed may inform discussion of future, prospective clinical trials with the intent of defining optimal autologous PBPC dose following HDT, especially as it may relate to metrics beyond hematopoietic recovery.

  20. Co-infusion of autologous adipose tissue derived insulin-secreting mesenchymal stem cells and bone marrow derived hematopoietic stem cells: viable therapy for type III.C. a diabetes mellitus.

    PubMed

    Thakkar, Umang G; Vanikar, Aruna V; Trivedi, Hargovind L

    2013-01-01

    Transition from acute pancreatitis to insulin-dependent diabetes mellitus (IDDM) is a rare manifestation of primary hyperparathyroidism caused by parathyroid adenoma because of impaired glucose tolerance and suppresses insulin secretion. We report the case of a 26-year-old male with pancreatic diabetes caused by parathyroid adenoma induced chronic pancreatitis. He had serum C-peptide 0.12 ng/ml, glutamic acid decarboxylase antibody 5.0 IU/ml, and glycosylated hemoglobin (HbA1C) 8.9%, and required 72 IU/day of biphasic-isophane insulin injection for uncontrolled hyperglycemia. We treated him with his own adipose tissue derived insulin-secreting mesenchymal stem-cells (IS-ADMSC) along with his bone marrow derived hematopoietic stem cells (BM-HSC). Autologous IS-ADMSC + BM-HSC were infused into subcutaneous tissue, portal and thymic circulation without any conditioning. Over a follow-up of 27 months, the patient is maintaining fasting and postprandial blood sugar levels of 132 and 165 mg/dl, respectively, with HbA1C 6.8% and requiring 36 IU/day of biphasic-isophane insulin. Co-infusion of IS-ADMSC + BM-HSC offers a safe and viable therapy for type III.C.a Diabetes Mellitus.

  1. Co-infusion of autologous adipose tissue derived insulin-secreting mesenchymal stem cells and bone marrow derived hematopoietic stem cells: viable therapy for type III.C. a diabetes mellitus.

    PubMed

    Thakkar, Umang G; Vanikar, Aruna V; Trivedi, Hargovind L

    2013-01-01

    Transition from acute pancreatitis to insulin-dependent diabetes mellitus (IDDM) is a rare manifestation of primary hyperparathyroidism caused by parathyroid adenoma because of impaired glucose tolerance and suppresses insulin secretion. We report the case of a 26-year-old male with pancreatic diabetes caused by parathyroid adenoma induced chronic pancreatitis. He had serum C-peptide 0.12 ng/ml, glutamic acid decarboxylase antibody 5.0 IU/ml, and glycosylated hemoglobin (HbA1C) 8.9%, and required 72 IU/day of biphasic-isophane insulin injection for uncontrolled hyperglycemia. We treated him with his own adipose tissue derived insulin-secreting mesenchymal stem-cells (IS-ADMSC) along with his bone marrow derived hematopoietic stem cells (BM-HSC). Autologous IS-ADMSC + BM-HSC were infused into subcutaneous tissue, portal and thymic circulation without any conditioning. Over a follow-up of 27 months, the patient is maintaining fasting and postprandial blood sugar levels of 132 and 165 mg/dl, respectively, with HbA1C 6.8% and requiring 36 IU/day of biphasic-isophane insulin. Co-infusion of IS-ADMSC + BM-HSC offers a safe and viable therapy for type III.C.a Diabetes Mellitus. PMID:24385073

  2. [Relevant low toxicities with rhG-CSF mobilized and cryopreserved autologous peripheral blood stem cell return infusions in children].

    PubMed

    Wang, Jian-Wen; Tang, Suo-Qin; Lü, Shan-Gen; Ran, Chong-Rong; Yang, Guang; Liu, Ying; Gao, Xiao-Ning

    2007-04-01

    The purpose of this study was to evaluate the safety of cryopreserved and thawed peripheral blood stem cell (PBSC) fractionated return infusions in children. 35 children patients with malignant tumors (13 acute leukaemias, 15 neuroblastomas and 7 malignant lymphomas) received fractionated return infusions of cryopreserved stem cells after undergoing high-dose chemotherapy without or with total body irradiation. The toxicities of 70 return infusions were evaluated. All patients were mobilized by chemotherapy plus recombination human granulocyte colony-stimulating factor (rhG-CSF), and then PBSCs were collected by a separator CS-3000 plus or COBE spectra-4. The grafts were cryopreserved in 10% dimethyl sulfoxide (DMSD) and stored in liquid nitrogen. There were totally 70 PBSC transfusions. The total volume of PBSCs transfused: 190 - 420 ml (265 +/- 73 ml or 13.7 +/- 4.2 ml/kg) with a mean of (4.43 +/- 1.91) x 10(8)/kg of PBSCs, and 0.94 +/- 0.18 g/kg of DMSO. The single dose: 90 - 300 ml (132 +/- 37 ml or 6.6 +/- 5.2 ml/kg) with a mean of 0.68 +/- 0.12 g/kg of DMSO. Symptoms occurring during the infusions were recorded. All patients were monitored for 24 hours after infusion. Pulse, blood pressure, body temperature, and respiratory rate were recorded every 15 minutes. At four hours before and 8 hours after infusion, urinalysis was performed. Serum potassium, sodium, creatinine, total bilirubin, aspartate amino transferase (AST), and alanine amino transferase (ALT) levels were examined within 24 hours before and after the first infusion. The results showed that the toxicities observed included hemoglobinuria in 54 return infusions (77.1%), headache in 28 (40.0%), nausea in 24 (34.3%), vomiting in 17 (24.3%), and abdominal pain in 8 (11.4%). Patients who received a graft > 200 ml tended to have a higher frequency of hemoglobinuria, headache, nausea, vomiting, or abdominal pain (P<0.01), and they disappeared quickly, too. Total bilirubin increased after the first return

  3. High-dose chemotherapy with autologous hematopoietic stem-cell rescue for pediatric brain tumor patients: a single institution experience from UCLA.

    PubMed

    Panosyan, Eduard H; Ikeda, Alan K; Chang, Vivian Y; Laks, Dan R; Reeb, Charles L; Bowles, La Vette; Lasky, Joseph L; Moore, Theodore B

    2011-01-01

    Background. Dose-dependent response makes certain pediatric brain tumors appropriate targets for high-dose chemotherapy with autologous hematopoietic stem-cell rescue (HDCT-AHSCR). Methods. The clinical outcomes and toxicities were analyzed retrospectively for 18 consecutive patients ≤19 y/o treated with HDCT-AHSCR at UCLA (1999-2009). Results. Patients' median age was 2.3 years. Fourteen had primary and 4 recurrent tumors: 12 neural/embryonal (7 medulloblastomas, 4 primitive neuroectodermal tumors, and a pineoblastoma), 3 glial/mixed, and 3 germ cell tumors. Eight patients had initial gross-total and seven subtotal resections. HDCT mostly consisted of carboplatin and/or thiotepa ± etoposide (n = 16). Nine patients underwent a single AHSCR and nine ≥3 tandems. Three-year progression-free and overall survival probabilities were 60.5% ± 16 and 69.3% ± 11.5. Ten patients with pre-AHSCR complete remissions were alive/disease-free, whereas 5 of 8 with measurable disease were deceased (median followup: 2.3 yrs). Nine of 13 survivors avoided radiation. Single AHSCR regimens had greater toxicity than ≥3 AHSCR (P < .01). Conclusion. HDCT-AHSCR has a definitive, though limited role for selected pediatric brain tumors with poor prognosis and pretransplant complete/partial remissions. PMID:21559259

  4. High-Dose Chemotherapy with Autologous Hematopoietic Stem-Cell Rescue for Pediatric Brain Tumor Patients: A Single Institution Experience from UCLA

    PubMed Central

    Panosyan, Eduard H.; Ikeda, Alan K.; Chang, Vivian Y.; Laks, Dan R.; Reeb, Charles L.; Bowles, La Vette; Lasky, Joseph L.; Moore, Theodore B.

    2011-01-01

    Background. Dose-dependent response makes certain pediatric brain tumors appropriate targets for high-dose chemotherapy with autologous hematopoietic stem-cell rescue (HDCT-AHSCR). Methods. The clinical outcomes and toxicities were analyzed retrospectively for 18 consecutive patients ≤19 y/o treated with HDCT-AHSCR at UCLA (1999–2009). Results. Patients' median age was 2.3 years. Fourteen had primary and 4 recurrent tumors: 12 neural/embryonal (7 medulloblastomas, 4 primitive neuroectodermal tumors, and a pineoblastoma), 3 glial/mixed, and 3 germ cell tumors. Eight patients had initial gross-total and seven subtotal resections. HDCT mostly consisted of carboplatin and/or thiotepa ± etoposide (n = 16). Nine patients underwent a single AHSCR and nine ≥3 tandems. Three-year progression-free and overall survival probabilities were 60.5% ± 16 and 69.3% ± 11.5. Ten patients with pre-AHSCR complete remissions were alive/disease-free, whereas 5 of 8 with measurable disease were deceased (median followup: 2.3 yrs). Nine of 13 survivors avoided radiation. Single AHSCR regimens had greater toxicity than ≥3 AHSCR (P < .01). Conclusion. HDCT-AHSCR has a definitive, though limited role for selected pediatric brain tumors with poor prognosis and pretransplant complete/partial remissions. PMID:21559259

  5. Risk-adapted autologous stem cell transplantation with adjuvant dexamethasone +/- thalidomide for systemic light-chain amyloidosis: results of a phase II trial.

    PubMed

    Cohen, Adam D; Zhou, Ping; Chou, Joanne; Teruya-Feldstein, Julie; Reich, Lilian; Hassoun, Hani; Levine, Beth; Filippa, Daniel A; Riedel, Elyn; Kewalramani, Tarun; Stubblefield, Michael D; Fleisher, Martin; Nimer, Stephen; Comenzo, Raymond L

    2007-10-01

    High-dose melphalan (MEL) with autologous stem cell transplant (SCT) is an effective therapy for systemic AL amyloidosis (AL), but treatment-related mortality (TRM) has historically been high. We performed a phase II trial of risk-adapted SCT followed by adjuvant dexamethasone (dex) and thalidomide (thal) in an attempt to reduce TRM and improve response rates. Patients (n = 45) with newly diagnosed AL involving < or =2 organ systems were assigned to MEL 100, 140, or 200 mg/m(2) with SCT, based on age, renal function and cardiac involvement. Patients with persistent clonal plasma cell disease 3 months post-SCT received 9 months of adjuvant thal/dex (or dex if there was a history of deep vein thrombosis or neuropathy). Organ involvement was kidney (67%), heart (24%), liver/GI (22%) and peripheral nervous system (18%), with 31% having two organs involved. TRM was 4.4%. Thirty-one patients began adjuvant therapy, with 16 (52%) completing 9 months of treatment and 13 (42%) achieving an improvement in haematological response. By intention-to-treat, overall haematological response rate was 71% (36% complete response), with 44% having organ responses. With a median follow-up of 31 months, 2-year survival was 84% (95% confidence interval: 73%, 94%). Risk-adapted SCT with adjuvant thal/dex is feasible and results in low TRM and high haematological and organ response rates in AL patients. PMID:17897298

  6. High-dose cyclophosphamide, carboplatin, and etoposide with autologous stem cell rescue in patients with breast cancer.

    PubMed

    deMagalhaes-Silverman, M; Rybka, W B; Lembersky, B; Bloom, E J; Lister, J; Pincus, S M; Voloshin, M; Wilson, J; Ball, E D

    1996-04-01

    This study was designed to establish the toxicity and response rates o observed with a combination of high-dose cyclophosphamide, carboplatin, and etoposide with stem cell rescue in patients with breast carcinoma. Eligibility criteria included metastatic or locally advanced breast carcinoma ; aged < or equal to 60 years; performance status Eastern Cooperative Oncology Group (ECOG) 0-1; and creatinine clearance > or equal to 65 ml/min. Chemotherapy consisted of cyclophosphamide 25 mg/kg i.v. X 4 days, etoposide 400 mg/m(2) i.v. X 4 days, and carboplatin 375 mg/m(2) X 4 days. Bone marrow or peripheral blood stem cells were reinfused 48 h after completion of chemotherapy. Seventeen patients were treated in this study. The major toxicity was gastrointestinal (grades I and II). Fevers associated with neutropenia were observed in all the patients, but no episodes of bacteremia were documented. Hematopoietic toxicities were acceptable. No toxic deaths were observed. Six patients had chemotherapy-sensitive disease at time of transplant, nine had refractory disease, and two were untested. A response rate of 62% with 18% complete response (CR) was achieved. Two patients are free of disease at +7 and +9 months after transplantation. The combination of high-dose cyclophosphamide, carboplatin, and etoposide is well tolerated with a response rate comparable to previously reported high-dose chemotherapy regimens. However, in a poor prognostic risk group, namely patients with chemoinsensitive disease, this therapeutic approach seems to be of no advantage over standard chemotherapy. PMID:8610643

  7. High-dose chemotherapy and autologous stem cell support followed by posttransplantation doxorubicin as initial therapy for metastatic breast cancer.

    PubMed

    deMagalhaes-Silverman, M; Bloom, E; Lembersky, B; Lister, J; Pincus, S; Rybka, W; Voloshin, M; Wilson, J; Ball, E

    1997-02-01

    High-dose chemotherapy is associated with a high complete response rate and possibly some survival advantage in patients with metastatic breast cancer. We designed a clinical trial consisting of a two-step high-dose chemotherapy regimen followed by posttransplantation doxorubicin as the first chemotherapy treatment for metastatic disease. Twenty-one patients with metastatic breast cancer and no previous chemotherapy for metastatic disease were treated with high-dose cyclophosphamide (Cy; 5000 mg/m2), followed by granulocyte colony-stimulating factor. Peripheral blood stem cells were collected. Subsequently, patients received Cy (6000 mg/m2), thiotepa (500 mg/m2), and carboplatin (800 mg/m2) (CTCb) with hematopoietic rescue. Upon recovery of hematopoietic and gastrointestinal toxicity, three cycles of doxorubicin (Dox; 60 mg/m2) were delivered. After Cy, nine patients (45%) developed neutropenic fevers. There were no episodes of bacteremia. Patients received CTCb 37 days after starting Cy and had a hospital stay of 19 days. After CTCb, the median number of days to an absolute neutrophil count >5 x 10(9)/liter was 8, and the median number of days to a platelet count >20 x 10(9)/liter was 9. Neutropenic fevers occurred in 12 patients. There were no hemorrhagic complications. Fifty-five of the 63 planned courses of Dox were delivered. The median time from peripheral blood stem cell infusion to the first Dox cycle was 38 days. The median time to the second Dox cycle was 28 days, and to the last cycle was 30 days. Three episodes of neutropenic fevers were observed. Two patients developed herpes zoster. This regimen is feasible, with acceptable toxicity. PMID:9815672

  8. International Myeloma Working Group consensus approach to the treatment of multiple myeloma patients who are candidates for autologous stem cell transplantation

    PubMed Central

    Palumbo, Antonio; Moreau, Philippe; Orlowski, Robert; Bladé, Joan; Sezer, Orhan; Ludwig, Heinz; Dimopoulos, Meletios A.; Attal, Michel; Sonneveld, Pieter; Boccadoro, Mario; Anderson, Kenneth C.; Richardson, Paul G.; Bensinger, William; Johnsen, Hans E.; Kroeger, Nicolaus; Gahrton, Gösta; Bergsagel, P. Leif; Vesole, David H.; Einsele, Hermann; Jagannath, Sundar; Niesvizky, Ruben; Durie, Brian G. M.; San Miguel, Jesus; Lonial, Sagar

    2011-01-01

    The role of high-dose therapy followed by autologous stem cell transplantation (ASCT) in the treatment of multiple myeloma (MM) continues to evolve in the novel agent era. The choice of induction therapy has moved from conventional chemotherapy to newer regimens incorporating the immunomodulatory derivatives thalidomide or lenalidomide and the proteasome inhibitor bortezomib. These drugs combine well with traditional therapies and with one another to form various doublet, triplet, and quadruplet regimens. Up-front use of these induction treatments, in particular 3-drug combinations, has affected unprecedented rates of complete response that rival those previously seen with conventional chemotherapy and subsequent ASCT. Autotransplantation applied after novel-agent-based induction regimens provides further improvement in the depth of response, a gain that translates into extended progression-free survival and, potentially, overall survival. High activity shown by immunomodulatory derivatives and bortezomib before ASCT has recently led to their use as consolidation and maintenance therapies after autotransplantation. Novel agents and ASCT are complementary treatment strategies for MM. This article reviews the current literature and provides important perspectives and guidance on the major issues surrounding the optimal current management of younger, transplantation-eligible MM patients. PMID:21447828

  9. Late Relapses Following High-Dose Autologous Stem Cell Transplantation (HD-ASCT) for Hodgkin Lymphoma (HL) in the ABVD Therapeutic era

    PubMed Central

    Keller, Sarah F.; Kelly, Jennifer L.; Sensenig, Elizabeth; Andreozzi, Jennifer; Oliva, Jamie; Rich, Lynn; Constine, Louis; Becker, Michael; Phillips, Gordon; Liesveld, Jane; Fisher, Richard I.; Bernstein, Steven H.; Friedberg, Jonathan W.

    2011-01-01

    Salvage chemotherapy followed by high dose autologous stem cell transplantation (HD-ASCT) is the standard of care for patients who have relapsed or refractory Hodgkin Lymphoma (HL). Few trials have had long-term follow-up post HD-ASCT in the ABVD era of treatment. We reviewed 95 consecutive patients who received HD-ASCT for relapsed or refractory HL following ABVD failure between 1990 and 2006 at the University of Rochester. Median follow-up for survivors was 8.2 years. All patients received HD-ASCT following up-front ABVD (or equivalent) failure. At 5 years, overall survival (OS) and event-free survival (EFS) were 54% and 37%, respectively. In total, 54 patients have died; 37 of these patients died directly of HL. Notably, there were 19 deaths > 3 years post HD-ASCT and 13 of these late deaths are directly attributable to HL. Furthermore, there were 51 documented relapses, 9 of which occurred >3 years post HD-ASCT. In contrast to other studies, we did not observe a plateau in EFS following transplantation. Patients appear to be at continuous risk of recurrence beyond 3 years after HD-ASCT. Our results emphasize the importance of long-term follow-up for both toxicity and recurrence, and have important implications in defining success of post-transplant maintenance strategies. PMID:21871246

  10. The role of high-dose melphalan and autologous stem cell transplant in the rapidly evolving era of modern multiple myeloma therapy.

    PubMed

    Voorhees, Peter M; Usmani, Saad Z

    2016-09-01

    The advent of the immunomodulatory drugs thalido-mide, lenalidomide, and pomalidomide; the proteasome inhib-itors bortezomib, carfilzomib, and ixazomib; the histone deacet-ylase inhibitor panobinostat; and the monoclonal antibodies elotuzumab and daratumumab has led to dramatic improvements in outcomes for patients with multiple myeloma. Along with progress in nontransplant therapy have come questions regarding the continued role of high-dose melphalan (HDM) supported by autologous stem cell transplant (ASCT) in the treatment of multiple myeloma. Emerging evidence from phase 3 studies demonstrates that consolidation therapy with HDM/ASCT further improves depth of response and progression-free survival in the context of modern therapy for multiple myeloma. Moreover, unprecedented survival data from ongoing phase 3 studies of patients treated with modern myeloma therapy followed by HDM/ASCT in first-line or second-line therapy reaffirm single and tandem HDM/ASCT as important standards of care for eligible patients. Herein, we review the evolving role of HDM/ASCT for the treatment of patients with newly diagnosed or relapsed multiple myeloma. PMID:27673290

  11. High-risk cytogenetics and persistent minimal residual disease by multiparameter flow cytometry predict unsustained complete response after autologous stem cell transplantation in multiple myeloma.

    PubMed

    Paiva, Bruno; Gutiérrez, Norma C; Rosiñol, Laura; Vídriales, María-Belén; Montalbán, María-Ángeles; Martínez-López, Joaquín; Mateos, María-Victoria; Cibeira, María-Teresa; Cordón, Lourdes; Oriol, Albert; Terol, María-José; Echeveste, María-Asunción; de Paz, Raquel; de Arriba, Felipe; Palomera, Luis; de la Rubia, Javier; Díaz-Mediavilla, Joaquín; Sureda, Anna; Gorosquieta, Ana; Alegre, Adrian; Martin, Alejandro; Hernández, Miguel T; Lahuerta, Juan-José; Bladé, Joan; San Miguel, Jesús F

    2012-01-19

    The achievement of complete response (CR) after high-dose therapy/autologous stem cell transplantation (HDT/ASCT) is a surrogate for prolonged survival in multiple myeloma; however, patients who lose their CR status within 1 year of HDT/ASCT (unsustained CR) have poor prognosis. Thus, the identification of these patients is highly relevant. Here, we investigate which prognostic markers can predict unsustained CR in a series of 241 patients in CR at day +100 after HDT/ASCT who were enrolled in the Spanish GEM2000 (n = 140) and GEM2005 < 65y (n = 101) trials. Twenty-nine (12%) of the 241 patients showed unsustained CR and a dismal outcome (median overall survival 39 months). The presence of baseline high-risk cytogenetics by FISH (hazard ratio 17.3; P = .002) and persistent minimal residual disease by multiparameter flow cytometry at day +100 after HDT/ASCT (hazard ratio 8.0; P = .005) were the only independent factors that predicted unsustained CR. Thus, these 2 parameters may help to identify patients in CR at risk of early progression after HDT/ASCT in whom novel treatments should be investigated. PMID:22128143

  12. Tandem high-dose chemotherapy and autologous stem cell rescue in patients over 1 year of age with stage 4 neuroblastoma.

    PubMed

    Sung, K W; Lee, S H; Yoo, K H; Jung, H L; Cho, E J; Koo, H H; Lee, S K; Kim, J; Lim, D H; Suh, Y L; Kim, D W

    2007-07-01

    From June 1997 to August 2005, 52 consecutive newly diagnosed stage 4 neuroblastoma patients over 1 year of age were assigned to receive tandem high-dose chemotherapy and autologous stem cell rescue (HDCT/ASCR) as consolidation therapy. Fifty of the 52 patients underwent a first HDCT/ASCR and 44 patients underwent a second HDCT/ASCR. Eight patients (15.4%) died from treatment-related toxicity (seven during the second HDCT/ASCR). Total body irradiation (TBI) in the first HDCT/ASCR and a shorter interval (< 12 weeks) between the first and second HDCT/ASCR were associated with a higher rate of treatment-related death in the second HDCT/ASCR (P = 0.032 and 0.095, respectively). The tumor relapsed or progressed in 11 patients, and 33 patients remained event free with a median follow-up of 53 months (range 19-117) from diagnosis. The 5-year event-free survival (EFS) (+/- 95% confidence interval) for all 52 patients was 62.1+/-13.7%. The application of TBI and local radiotherapy, and a longer interval between the first and second HDCT/ASCR were independently associated with a better EFS (P = 0.026, 0.007 and 0.020, respectively). However, further studies will be needed to decrease the toxic death rate in the second HDCT/ASCR while reducing the relapse rate.

  13. Thalidomide-prednisone maintenance following autologous stem cell transplant for multiple myeloma: effect on thrombin generation and procoagulant markers in NCIC CTG MY.10.

    PubMed

    Kovacs, Michael J; Davies, Gwynivere A; Chapman, Judy-Anne W; Bahlis, Nizar; Voralia, Michael; Roy, Jean; Kouroukis, C Tom; Chen, Christine; Belch, Andrew; Reece, Donna; Zhu, Liting; Meyer, Ralph M; Shepherd, Lois; Stewart, Keith A

    2015-02-01

    Venous thromboembolism (VTE) has an increased incidence in patients with multiple myeloma (MM), especially during chemotherapy. Mechanisms including upregulation of procoagulant factors, such as factor VIII, have been postulated. The National Cancer Institute of Canada Clinical Trials Group MY.10 phase III clinical trial compared thalidomide-prednisone to observation for 332 patients with MM post-autologous stem cell transplantation (ASCT), with a primary endpoint of overall survival and various secondary endpoints including the incidence of VTE. One hundred and fifty-three patients had biomarker data, including D-dimer, factor VIII and thrombin anti-thrombin (TAT) levels collected post-ASCT at baseline and 2 months after intervention investigating in-vivo thrombin generation. Differences between the time-points included a significant reduction over time in D-dimer, factor VIII and TAT levels in the observation group and sustained elevation of D-dimer, significant increase in factor VIII and reduction in TAT levels in the thalidomide-prednisone group. Eight VTE events were reported in this subset of study patients, all in the thalidomide-prednisone arm, with a trend to increase in D-dimer levels over time in those patients with VTE. This study provides physiological and clinical evidence for an increased risk of VTE associated with thalidomide-prednisone maintenance therapy post-ASCT for MM.

  14. Early Results of Clinical Application of Autologous Whole Bone Marrow Stem Cell Transplantation for Critical Limb Ischemia with Buerger’s Disease

    PubMed Central

    Heo, Seon-Hee; Park, Yoong-Seok; Kang, Eun-Suk; Park, Kwang-Bo; Do, Young-Soo; Kang, Kyung-Sun; Kim, Dong-Ik

    2016-01-01

    Our goal was to evaluate early results of the clinical application of autologous whole bone marrow stem cell transplantation (AWBMSCT) for critical limb ischemia (CLI) in patients with Buerger’s disease. We retrospectively analyzed the data of 58 limbs of 37 patients (mean age, 43.0 years; range, 28–63 years; male, 91.9%) with Buerger’s disease with CLI who were treated with AWBMSCT from March 2013 to December 2014. We analyzed Rutherford category, pain score, pain-free walking time (PFWT), total walking time (TWT), ankle brachial pressure index (ABPI), and toe brachial pressure index (TBPI), and investigated wound healing and occurrence of unplanned amputations. The mean follow-up duration was 11.9 ± 7.2 months (range, 0.9–23.9 months) and 100%, 72.4%, and 74.1% of patients were available to follow-up 1, 3 and 6 months after AWBMST, respectively. At 6 months, patients demonstrated significant improvements in Rutherford category (P < 0.0001), pain score (P < 0.0001), PFWT (P < 0.0001) and TBPI (P < 0.0001). ABPI was increased compared to baseline, but the difference was not significant. A total of 76.5% ischemic wounds achieved complete or improved healing. AWBMSCT is a safe and effective alternative or adjunctive treatment modality to achieve clinical improvement in patients with CLI. PMID:26791280

  15. Infectious Complications during Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Children with High-Risk or Recurrent Solid Tumors

    PubMed Central

    Kang, Ji-Man; Lee, Ji Won; Yoo, Keon Hee; Kim, Yae-Jean; Sung, Ki Woong; Koo, Hong Hoe

    2016-01-01

    We retrospectively analyzed infectious complications during tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) in children and adolescents with high-risk or recurrent solid tumors. A total of 324 patients underwent their first HDCT/auto-SCT between October 2004 and September 2014, and 283 of them proceeded to their second HDCT/auto-SCT (a total of 607 HDCT/auto-SCTs). During the early transplant period of 607 HDCT/auto-SCTs (from the beginning of HDCT to day 30 post-transplant), bacteremia, urinary tract infection (UTI), respiratory virus infection, and varicella zoster virus (VZV) reactivation occurred in 7.1%, 2.3%, 13.0%, and 2.5% of HDCT/auto-SCTs, respectively. The early transplant period of the second HDCT/auto-SCT had infectious complications similar to the first HDCT/auto-SCT. During the late transplant period of HDCT/auto-SCT (from day 31 to 1 year post-transplant), bacteremia, UTI, and VZV reactivation occurred in 7.5%, 2.5%, and 3.9% of patients, respectively. Most infectious complications in the late transplant period occurred during the first 6 months post-transplant. There were no invasive fungal infections during the study period. Six patients died from infectious complications (4 from bacterial sepsis and 2 from respiratory virus infection). Our study suggests that infectious complications are similar following second and first HDCT/auto-SCT in children. PMID:27627440

  16. A Phase II trial of weekly bortezomib and dexamethasone in veterans with newly diagnosed multiple myeloma not eligible for or who deferred autologous stem cell transplantation.

    PubMed

    Girnius, Saulius K; Lee, Saem; Kambhampati, Suman; Rose, Michal G; Mohiuddin, Abid; Houranieh, Antoun; Zimelman, Abraham; Grady, Terrence; Mehta, Paulette; Behler, Caroline; Hayes, Teresa G; Efebera, Yvonne A; Prabhala, Rao H; Han, Andrew; Yellapragada, Sarvari V; Klein, Catherine E; Roodman, Garson D; Lichtenstein, Alan; Munshi, Nikhil C

    2015-04-01

    Once-weekly administration of bortezomib has reduced bortezomib-induced peripheral neuropathy without affecting response rates, but this has only been demonstrated prospectively in three- and four- drug combinations. We report a phase II trial of alternate dosing and schedule of bortezomib and dexamethasone in newly diagnosed multiple myeloma patients who are not eligible for or refused autologous stem cell transplantation. Bortezomib 1·6 mg/m(2) intravenously was given once-weekly for six cycles, together with dexamethasone 40 mg on the day of and day after bortezomib. Fifty patients were enrolled; 58% did not require any dose modification. The majority of patients had multiple co-morbidities, including cardiovascular (76%) and renal insufficiency (54%), and the median number of medications prior to enrollment was 13. Of all evaluable patients, the overall response rate was 79% and at least 45% had at least a very good partial response. The median time to first response was 1·3 months (range, 0·25-2·4 months). The progression-free and overall survivals were 8 months and 46·5 months, respectively. Twenty-four percent developed worsening neuropathy. We conclude that alternate dosing and scheduling of bortezomib and dexamethasone is both safe and effective for management of newly diagnosed multiple myeloma in frail patients. (ClinicalTrials.gov number, NCT01090921).

  17. Infectious Complications during Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Children with High-Risk or Recurrent Solid Tumors.

    PubMed

    Choi, Young Bae; Yi, Eun Sang; Kang, Ji-Man; Lee, Ji Won; Yoo, Keon Hee; Kim, Yae-Jean; Sung, Ki Woong; Koo, Hong Hoe

    2016-01-01

    We retrospectively analyzed infectious complications during tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) in children and adolescents with high-risk or recurrent solid tumors. A total of 324 patients underwent their first HDCT/auto-SCT between October 2004 and September 2014, and 283 of them proceeded to their second HDCT/auto-SCT (a total of 607 HDCT/auto-SCTs). During the early transplant period of 607 HDCT/auto-SCTs (from the beginning of HDCT to day 30 post-transplant), bacteremia, urinary tract infection (UTI), respiratory virus infection, and varicella zoster virus (VZV) reactivation occurred in 7.1%, 2.3%, 13.0%, and 2.5% of HDCT/auto-SCTs, respectively. The early transplant period of the second HDCT/auto-SCT had infectious complications similar to the first HDCT/auto-SCT. During the late transplant period of HDCT/auto-SCT (from day 31 to 1 year post-transplant), bacteremia, UTI, and VZV reactivation occurred in 7.5%, 2.5%, and 3.9% of patients, respectively. Most infectious complications in the late transplant period occurred during the first 6 months post-transplant. There were no invasive fungal infections during the study period. Six patients died from infectious complications (4 from bacterial sepsis and 2 from respiratory virus infection). Our study suggests that infectious complications are similar following second and first HDCT/auto-SCT in children. PMID:27627440

  18. Intensified therapy followed by autologous stem-cell transplantation (ASCT) versus conventional therapy as first-line treatment of follicular lymphoma: a meta-analysis.

    PubMed

    Wang, Baohong; Ren, Cuiai; Zhang, Weide; Ma, Xiaoyan; Xia, Bingsen; Sheng, Zhixin

    2013-03-01

    There are two different international standards for the treatment of follicular lymphoma (FL): intensified therapy followed by autologous stem-cell transplantation (ASCT) and conventional therapy in the first-line setting. However, their role remains unclear. Our aim was to define the treatment effect of intensified therapy followed by ASCT compared with conventional therapy as first-line treatment of patients with FL in terms of overall survival (OS) and event-free survival (EFS). We searched for randomised controlled trials in Medline, Embase, the Cochrane controlled trials register and the Science Citation Index (1985 to June 2011). Effect measures used were hazard ratios (HR) for OS, EFS and secondary tumour rate. Two independent review authors extracted data and assessed quality of trials. Four trials were identified, covering a total of 941 subjects. The random-effects summary HR by comparing the treatment effect on OS between intensified and conventional therapy was 0.95 [0.70, 1.30] (p = 0.75), indicating that no additional survival benefit was derived from the intensified therapy followed by ASCT. A significant benefit of intensified therapy followed by ASCT as first-line treatment was detected in terms of EFS: the random-effects summary HR (intensified versus conventional therapy) was 0.59 [0.44, 0.79] (p < 0.001). This meta-analysis showed that despite its superior EFS, intensified therapy followed by ASCT does not improve the OS compared with conventional therapy. PMID:22488650

  19. Secondary MGUS following by adenovirus-induced hemorrhagic cystitis after autologous peripheral blood stem cell transplantation in a patient with multiple myeloma.

    PubMed

    Hatsuse, Mayumi; Fuchida, Shin-ichi; Okano, Akira; Murakami, Satoshi; Shimazaki, Chihiro

    2014-11-01

    A 61-year-old man with multiple myeloma (IgG-κ) received autologous peripheral blood stem cell transplantation (PBSCT) after induction of VAD in July 2009, and obtained a very good partial response. In November 2009, he was admitted to our hospital because of adenovirus-induced hemorrhagic cystitis and pneumocystis jiroveci pneumonia. The pneumonia resolved with sulfamethoxazole and steroid pulse therapy, and cystitis subsided spontaneously. In December 2009, serum protein electrophoresis showed two abnormal protein bands (APB)(IgG-λ, IgA-λ), different from the original M-protein, and IgG thereafter increased to 2,771 mg/dl with a concomitant increase in anti-adenovirus antibody to 4,096. In October 2010, APB disappeared. To date, he has been in stable complete remission for five years since PBSCT. The emergence of APB is considered to be a surrogate marker for long-term remission. Immune reconstitution syndrome and APB after high dose chemotherapy following PBSCT are discussed herein.

  20. A multicenter clinical study to determine the feasible initial dose of lenalidomide for maintenance therapy in patients with multiple myeloma following autologous peripheral blood stem-cell transplantation

    PubMed Central

    YAMAMOTO, MASAHIDE; OHASHI, KAZUTERU; KAKIHANA, KAZUHIKO; NAKAMURA, YUICHI; KOMENO, TAKUYA; KOJIMA, HIROSHI; MORITA, SATOSHI; SAKAMAKI, HISASHI

    2016-01-01

    Maintenance therapy with lenalidomide (LEN) for patients with multiple myeloma (MM) following autologous peripheral blood stem cell transplantation (auto-PBSCT) may be a promising option for preventing relapse or disease progression. However, the recommended dose of LEN has yet to be firmly established. We herein report the results of a multicenter clinical study for determining the feasible initial dose (FID) of LEN. In this trial, a total of 11 patients who achieved a very good partial response or complete response following auto-PBSCT were enrolled from five transplant centers in Japan. Three dose levels of LEN (level 0, 5 mg; level 1, 10 mg; and level 2,:15 mg) were tested in this study. FID was defined as the maximum estimated dose at which 70% of the patients could receive maintenance therapy for 12 weeks without any serious adverse events or disease progression. Using a continual reassessment method, 6 patients were assigned to level 0 and the remaining 5 patients were assigned to level 1. All 6 patients (100%) at level 0, but only 2 patients (40%) at level 1, completed 12 weeks of administration with their assigned dose of LEN. The results of our study demonstrated that, although 5 mg of LEN was acceptable in terms of safety, 7.5 mg of LEN may also be an acceptable FID. PMID:27313858

  1. High-dose chemotherapy with carmustine, etoposide, cytarabine and melphalan followed by autologous stem cell transplant is an effective treatment for elderly patients with poor-prognosis lymphoma.

    PubMed

    Martin, Nicolas; Borchiellini, Delphine; Coso, Diane; Gastaud, Lauris; Boscagli, Annick; Saudes, Laurence; Re, Daniel; Gutnecht, Jean; Garnier, Georges; Petit, Emmanuel; Barriere, Jèrôme; Naman, Hervé; Rossignol, Benoit; Thyss, Antoine; Peyrade, Frederic

    2015-01-01

    Autologous stem cell transplant (ASCT) after high-dose chemotherapy (HDT) increases overall survival when used in relapsed non-Hodgkin lymphoma (NHL) in patients under 65 years old. Limited experience is available for older patients. We present a retrospective analysis of 73 consecutive patients aged over 65 years treated for aggressive or relapsed lymphoma by HDT with carmustine, etoposide, cytarabine and melphalan (BEAM) at full dosage followed by ASCT. Patient data were obtained from medical charts from two institutions. Median age was 67 years (65-74). Significant comorbidities were present in 24.7% of patients. The median number of days for grade 4 neutropenia was 9 (5-18). The early treatment-related mortality rate (<100 days) was 2.7%. The estimated 2-year progression-free survival and overall survival rates were 67.2% and 78.5%, respectively. In conclusion, the full-dose HDT-ASCT regimen is feasible, safe and efficient in selected patients over 65 years old.

  2. CHOP and DHAP plus rituximab followed by autologous stem cell transplantation in mantle cell lymphoma: a phase 2 study from the Groupe d'Etude des Lymphomes de l'Adulte.

    PubMed

    Delarue, Richard; Haioun, Corinne; Ribrag, Vincent; Brice, Pauline; Delmer, Alain; Tilly, Herve; Salles, Gilles; Van Hoof, Achiel; Casasnovas, Olivier; Brousse, Nicole; Lefrere, Francois; Hermine, Olivier

    2013-01-01

    Treatment of mantle cell lymphoma (MCL) in younger patients remains a challenge. We report results of a phase 2 trial using cytarabine and rituximab as induction regimen before autologous stem cell transplantation. Patients younger than 66 years with stage 3 or 4 MCL were included. Treatment consisted of 3 courses of CHOP(21) with rituximab at the third one and 3 of R-DHAP. Responding patients were eligible for autologous stem cell transplantation with TAM6 or BEAM. Sixty patients were included. Median age was 57 years. Characteristics of patients were: BM involvement 85%, leukemic disease 48%, gastrointestinal involvement 52%, Performance Status > 16%, lactate dehydrogenase > 1N 38%, Mantle Cell Lymphoma International Prognostic Index (low 55%, intermediate 38%, high 13%). The overall response rate was 93% after (R)-CHOP and 95% after R-DHAP. Although uncommon after (R)-CHOP (12%), 57% of patients were in complete response after R-DHAP. With median follow-up of 67 months, median event-free survival is 83 months, and median overall survival is not reached. Five-year overall survival is 75%. Comparison with a previous study without rituximab shows improvement of outcome (median event-free survival, 51 vs 83 months). No toxic death or unexpected toxicities were observed. This study confirms that induction with rituximab and cytarabine-based regimens is safe and effective in MCL patients. This regimen is currently compared with R-CHOP(21) induction in a multicentric European protocol. PMID:22718839

  3. Up-regulation of fas and fasL pro-apoptotic genes expression in type 1 diabetes patients after autologous haematopoietic stem cell transplantation

    PubMed Central

    de Oliveira, G L V; Malmegrim, K C R; Ferreira, A F; Tognon, R; Kashima, S; Couri, C E B; Covas, D T; Voltarelli, J C; de Castro, F A

    2012-01-01

    Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by T cell-mediated destruction of pancreatic β cells, resulting in insulin deficiency and hyperglycaemia. Recent studies have described that apoptosis impairment during central and peripheral tolerance is involved in T1D pathogenesis. In this study, the apoptosis-related gene expression in T1D patients was evaluated before and after treatment with high-dose immunosuppression followed by autologous haematopoietic stem cell transplantation (HDI-AHSCT). We also correlated gene expression results with clinical response to HDI-AHSCT. We observed a decreased expression of bad, bax and fasL pro-apoptotic genes and an increased expression of a1, bcl-xL and cIAP-2 anti-apoptotic genes in patients' peripheral blood mononuclear cells (PBMCs) compared to controls. After HDI-AHSCT, we found an up-regulation of fas and fasL and a down-regulation of anti-apoptotic bcl-xL genes expression in post-HDI-AHSCT periods compared to pre-transplantation. Additionally, the levels of bad, bax, bok, fasL, bcl-xL and cIAP-1 genes expression were found similar to controls 2 years after HDI-AHSCT. Furthermore, over-expression of pro-apoptotic noxa at 540 days post-HDI-AHSCT correlated positively with insulin-free patients and conversely with glutamic acid decarboxylase autoantibodies (GAD65) autoantibody levels. Taken together, the results suggest that apoptosis-related genes deregulation in patients' PBMCs might be involved in breakdown of immune tolerance and consequently contribute to T1D pathogenesis. Furthermore, HDI-AHSCT modulated the expression of some apoptotic genes towards the levels similar to controls. Possibly, the expression of these apoptotic molecules could be applied as biomarkers of clinical remission of T1D patients treated with HDI-AHSCT therapy. PMID:22519592

  4. Autologous hematopoietic stem cell transplantation for autoimmune diseases: an observational study on 12 years’ experience from the European Group for Blood and Marrow Transplantation Working Party on Autoimmune Diseases

    PubMed Central

    Farge, Dominique; Labopin, Myriam; Tyndall, Alan; Fassas, Athanasios; Mancardi, Gian Luigi; Van Laar, Jaap; Ouyang, Jian; Kozak, Tomas; Moore, John; Kötter, Ina; Chesnel, Virginie; Marmont, Alberto; Gratwohl, Alois; Saccardi, Riccardo

    2010-01-01

    Background Autologous hematopoietic stem cell transplantation has been used since 1996 for the treatment of severe autoimmune diseases refractory to approved therapies. We evaluated the long-term outcomes of these transplants and aimed to identify potential prognostic factors. Design and Methods In this observational study we analyzed all first autologous hematopoietic stem cell transplants for autoimmune diseases reported to the European Group for Blood and Marrow Transplantation (EBMT) registry between 1996–2007. The primary end-points for analysis were overall survival, progression-free survival and transplant-related mortality at 100 days. Results Nine hundred patients with autoimmune diseases (64% female; median age, 35 years) who underwent a first autologous hematopoietic stem cell transplant were included. The main diseases were multiple sclerosis (n=345), systemic sclerosis (n=175), systemic lupus erythematosus (n=85), rheumatoid arthritis (n=89), juvenile arthritis (n=65), and hematologic immune cytopenia (n=37). Among all patients, the 5-year survival was 85% and the progression-free survival 43%, although the rates varied widely according to the type of autoimmune disease. By multivariate analysis, the 100-day transplant-related mortality was associated with the transplant centers’ experience (P=0.003) and type of autoimmune disease (P=0.03). No significant influence of transplant technique was identified. Age less than 35 years (P=0.004), transplantation after 2000 (P=0.0015) and diagnosis (P=0.0007) were associated with progression-free survival. Conclusions This largest cohort studied worldwide shows that autologous hematopoietic stem cell transplantation can induce sustained remissions for more than 5 years in patients with severe autoimmune diseases refractory to conventional therapy. The type of autoimmune disease, rather than transplant technique, was the most relevant determinant of outcome. Results improved with time and were associated with

  5. Autologous hematopoietic stem cell transplantation reverses skin fibrosis but does not change skin vessel density in patients with systemic sclerosis.

    PubMed

    Daikeler, T; Kump, E; Stern, M; Hügle, T; Hij, A; Haeuserman, P; Farge, D

    2015-09-01

    Hematopoetic stem cell transplantation (HSCT) improves survival in patients with severe systemic sclerosis (SSc) by resetting the immune system. We studied how HSCT acts on the key SSc skin pathology findings (fibrosis and vascularization). In mean, 3 skin punch biopsies per patient (range 2-6) were analyzed from 13 patients (5 females) with severe diffuse SSc before and up to 96 months after HSCT. Fibrosis of the four skin layers was graded semi-quantitatively and an overall fibrosis score was then calculated. Vessel numbers and calibers were assessed in the superficial and deeper dermis after immune-staining for endothelial antigens (CD31, VE-cadherin and vWF). The median age of patients at HSCT was 47 (24-64) years. The overall median modified Rodnan skin score decreased from 24 to 10 (P=0.003) at first follow-up within a median of 9 (6-36) months after HSCT as did the histological skin score (P=0.03). The modified Rodnan skin score and the fibrosis score correlated positively (r=0.589, P<0.001). The vessels density did not significantly change after HSCT nor did the expression of the tested endothelial markers. Although improving skin fibrosis in patients with SSc, HSCT does not alter vessel density within skin biopsies.

  6. Prolonged remission state of refractory adult onset Still's disease following CD34-selected autologous peripheral blood stem cell transplantation.

    PubMed

    Lanza, F; Dominici, M; Govoni, M; Moretti, S; Campioni, D; Corte, R L; Latorraca, A; Tieghi, A; Castagnari, B; Trotta, F; Castoldi, G

    2000-06-01

    We report a 38-year-old patient affected by refractory adult onset Still's disease who achieved a prolonged remission following CD34-selected ABMT. The conditioning regimen was based on the use of CY and anti-thymocyte globulin. A 3.0 and 2.0 log reduction of T (CD3+) and B (CD19+) lymphocytes, respectively, was obtained using a Ceprate device to select CD34+ cells from PBSC. In the pre-transplant period (1994-1998) the patient had a chronic persistent disease course with frequent and recurrent systemic articular flares and loss of some functional abilities, despite daily prednisone, pulses of CY and immunosuppressive therapy (CYA or MTX). At the time of ABMT the patient had become non-ambulatory. Within 3 weeks of ABMT the patient showed a marked decrease in joint swelling, and morning stiffness. Joint pain and systemic symptoms disappeared, the patient was able to walk and run and gained general well being. ESR, C-reactive protein and WBC count were significantly decreased, while Hb level increased. This partial remission persisted for at least 1 year after ABMT, although at 15 months of follow-up a reappearance of moderate synovitis in the knees and wrists was noted. Our data further showed that both patient BM microenvironment and stem-progenitor cell function (as assessed by LTC-IC assay) were damaged even 1 year after CD34-selected ABMT, suggesting that the persistence of these alterations could have facilitated the favorable outcome of the disease following ABMT. Bone Marrow Transplantation (2000) 25, 1307-1310. PMID:10871738

  7. Effects of Intracoronary Administration of Autologous Adipose Tissue-Derived Stem Cells on Acute Myocardial Infarction in a Porcine Model

    PubMed Central

    Lee, Hye Won; Park, Jong Ha; Kim, Bo Won; Ahn, Jinhee; Kim, Jin Hee; Park, Jin Sup; Oh, Jun-Hyok; Choi, Jung Hyun; Cha, Kwang Soo; Hong, Taek Jong; Park, Tae Sik; Kim, Sang-Pil; Song, Seunghwan; Kim, Ji Yeon; Park, Mi Hwa; Jung, Jin Sup

    2015-01-01

    Purpose Adipose-derived stem cells (ADSCs) are known to be potentially effective in regeneration of damaged tissue. We aimed to assess the effectiveness of intracoronary administration of ADSCs in reducing the infarction area and improving function after acute transmural myocardial infarction (MI) in a porcine model. Materials and Methods ADSCs were obtained from each pig's abdominal subcutaneous fat tissue by simple liposuction. After 3 passages of 14-days culture, 2 million ADSCs were injected into the coronary artery 30 min after acute transmural MI. At baseline and 4 weeks after the ADSC injection, 99mTc methoxyisobutylisonitrile-single photon emission computed tomography (MIBI-SPECT) was performed to evaluate the left ventricular volume, left ventricular ejection fraction (LVEF; %), and perfusion defects as well as the myocardial salvage (%) and salvage index. At 4 weeks, each pig was sacrificed, and the heart was extracted and dissected. Gross and microscopic analyses with specific immunohistochemistry staining were then performed. Results Analysis showed improvement in the perfusion defect, but not in the LVEF in the ADSC group (n=14), compared with the control group (n=14) (perfusion defect, -13.0±10.0 vs. -2.6±12.0, p=0.019; LVEF, -8.0±15.4 vs. -15.9±14.8, p=0.181). There was a tendency of reducing left ventricular volume in ADSC group. The ADSCs identified by stromal cell-derived factor-1 (SDF-1) staining were well co-localized by von Willebrand factor and Troponin T staining. Conclusion Intracoronary injection of cultured ADSCs improved myocardial perfusion in this porcine acute transmural MI model. PMID:26446632

  8. Autologous stem cell transplantation in the treatment of systemic sclerosis: report from the EBMT/EULAR Registry

    PubMed Central

    Farge, D; Passweg, J; van Laar, J M; Marjanovic, Z; Besenthal, C; Finke, J; Peter, H; Breedveld, F; Fibbe, W; Black, C; Denton, C; Koetter, I; Locatelli, F; Martini, A; Schattenberg, A; van den Hoogen, F; van de Putte, L; Lanza, F; Arnold, R; Bacon, P; Bingham, S; Ciceri, F; Didier, B; Diez-Martin, J; Emery, P; Feremans, W; Hertenstein, B; Hiepe, F; Luosujarvi, R; Leon, L; Marmont, A; Martinez, A; Pascual, C; Bocelli-Tyndall, C; Gluckman, E; Gratwohl, A; Tyndall, A

    2004-01-01

    Objective: To analyse the durability of the responses after haematopoietic stem cell transplantation (HSCT) for severe systemic sclerosis (SSc) and determine whether the high transplant related mortality (TRM) improved with experience. This EBMT/EULAR report describes the longer outcome of patients originally described in addition to newly recruited cases. Methods: Only patients with SSc, treated by HSCT in European phase I–II studies from 1996 up to 2002, with more than 6 months of follow up were included. Transplant regimens were according to the international consensus statements. Repeated evaluations analysed complete, partial, or non-response and the probability of disease progression and survival after HSCT (Kaplan-Meier). Results: Given as median (range). Among 57 patients aged 40 (9.1–68.7) years the skin scores improved at 6 (n = 37 patients), 12 (n = 30), 24 (n = 19), and 36 (n = 10) months after HSCT (p<0.005). After 22.9 (4.5–81.1) months, partial (n = 32) or complete response (n = 14) was seen in 92% and non-response in 8% (n = 4) of 50 observed cases. 35% of the patients with initial partial (n = 13/32) or complete response (n = 3/14) relapsed within 10 (2.2–48.7) months after HSCT. The TRM was 8.7% (n = 5/57). Deaths related to progression accounted for 14% (n = 8/57) of the 23% (n = 13/57) total mortality rate. At 5 years, progression probability was 48% (95% CI 28 to 68) and the projected survival was 72% (95% CI 59 to 75). Conclusion: This EBMT/EULAR report showed that response in two thirds of the patients after HSCT was durable with an acceptable TRM. Based on these results prospective, randomised trials are proceeding. PMID:15249325

  9. Lack of survival advantage with autologous stem-cell transplantation in high-risk neuroblastoma consolidated by anti-GD2 immunotherapy and isotretinoin.

    PubMed

    Kushner, Brian H; Ostrovnaya, Irina; Cheung, Irene Y; Kuk, Deborah; Modak, Shakeel; Kramer, Kim; Roberts, Stephen S; Basu, Ellen M; Yataghene, Karima; Cheung, Nai-Kong V

    2016-01-26

    Since 2003, high-risk neuroblastoma (HR-NB) patients at our center received anti-GD2 antibody 3F8/GM-CSF + isotretinoin - but not myeloablative therapy with autologous stem-cell transplantation (ASCT). Post-ASCT patients referred from elsewhere also received 3F8/GM-CSF + isotretinoin. We therefore accrued a study population of two groups treated during the same period and whose consolidative therapy, aside from ASCT, was identical. We analyzed patients enrolled in 1st complete/very good partial remission (CR/VGPR). Their event-free survival (EFS) and overall survival (OS) were calculated from study entry. Large study size allowed robust statistical analyses of key prognosticators including MYCN amplification, minimal residual disease (MRD), FCGR2A polymorphisms, and killer immunoglobulin-like receptor genotypes of natural killer cells. The 170 study patients included 60 enrolled following ASCT and 110 following conventional chemotherapy. The two cohorts had similar clinical and biological features. Five-year rates for ASCT and non-ASCT patients were, respectively: EFS 65% vs. 51% (p = .128), and OS 76% vs. 75% (p = .975). In multivariate analysis, ASCT was not prognostic and only MRD-negativity after two cycles of 3F8/GM-CSF correlated with significantly improved EFS and OS. Although a trend towards better EFS is seen with ASCT, OS is near identical. Cure rates may be similar, as close surveillance detects localized relapse and effective salvage treatments are applied. ASCT may not be needed to improve outcome when anti-GD2 immunotherapy is used for consolidation after dose-intensive conventional chemotherapy.

  10. Lack of survival advantage with autologous stem-cell transplantation in high-risk neuroblastoma consolidated by anti-GD2 immunotherapy and isotretinoin.

    PubMed

    Kushner, Brian H; Ostrovnaya, Irina; Cheung, Irene Y; Kuk, Deborah; Modak, Shakeel; Kramer, Kim; Roberts, Stephen S; Basu, Ellen M; Yataghene, Karima; Cheung, Nai-Kong V

    2016-01-26

    Since 2003, high-risk neuroblastoma (HR-NB) patients at our center received anti-GD2 antibody 3F8/GM-CSF + isotretinoin - but not myeloablative therapy with autologous stem-cell transplantation (ASCT). Post-ASCT patients referred from elsewhere also received 3F8/GM-CSF + isotretinoin. We therefore accrued a study population of two groups treated during the same period and whose consolidative therapy, aside from ASCT, was identical. We analyzed patients enrolled in 1st complete/very good partial remission (CR/VGPR). Their event-free survival (EFS) and overall survival (OS) were calculated from study entry. Large study size allowed robust statistical analyses of key prognosticators including MYCN amplification, minimal residual disease (MRD), FCGR2A polymorphisms, and killer immunoglobulin-like receptor genotypes of natural killer cells. The 170 study patients included 60 enrolled following ASCT and 110 following conventional chemotherapy. The two cohorts had similar clinical and biological features. Five-year rates for ASCT and non-ASCT patients were, respectively: EFS 65% vs. 51% (p = .128), and OS 76% vs. 75% (p = .975). In multivariate analysis, ASCT was not prognostic and only MRD-negativity after two cycles of 3F8/GM-CSF correlated with significantly improved EFS and OS. Although a trend towards better EFS is seen with ASCT, OS is near identical. Cure rates may be similar, as close surveillance detects localized relapse and effective salvage treatments are applied. ASCT may not be needed to improve outcome when anti-GD2 immunotherapy is used for consolidation after dose-intensive conventional chemotherapy. PMID:26623730

  11. Adjuvant high-dose chemotherapy with autologous hematopoietic stem cell support for high-risk primary breast cancer: results from the Italian national registry.

    PubMed

    Pedrazzoli, Paolo; Martinelli, Giovanni; Gianni, Alessandro Massimo; Da Prada, Gian Antonio; Ballestrero, Alberto; Rosti, Giovanni; Frassineti, Giovanni Luca; Aieta, Michele; Secondino, Simona; Cinieri, Saverio; Fedele, Roberta; Bengala, Carmelo; Bregni, Marco; Grasso, Donatella; De Giorgi, Ugo; Lanza, Francesco; Castagna, Luca; Bruno, Barbara; Martino, Massimo

    2014-04-01

    The efficacy of high-dose chemotherapy (HDC) and autologous hemopoietic progenitor cell transplantation (AHPCT) for breast cancer (BC) patients has been an area of intense controversy among the medical oncology community. The aim of this study was to assess toxicity and efficacy of this procedure in a large cohort of high-risk primary BC patients who underwent AHPCT in Italy. A total of 1183 patients receiving HDC for high-risk BC (HRBC) (>3 positive nodes) were identified in the Italian registry. The median age was 46 years, 62% of patients were premenopausal at treatment, 60.1% had endocrine-responsive tumors, and 20.7% had a human epidermal growth factor receptor 2 (HER2)-positive tumor. The median number of positive lymph nodes (LN) at surgery was 15, with 71.5% of patients having ≥ 10 positive nodes. Seventy-three percent received an alkylating agent-based HDC as a single procedure, whereas 27% received epirubicin or mitoxantrone-containing HDC, usually within a multitransplantation program. The source of stem cells was peripheral blood in the vast majority of patients. Transplantation-related mortality was .8%, whereas late cardiac and secondary tumor-related mortality were around 1%, overall. With a median follow-up of 79 months, median disease-free and overall survival (OS) in the entire population were 101 and 134 months, respectively. Subgroup analysis demonstrated that OS was significantly better in patients with endocrine-responsive tumors and in patients receiving multiple transplantation procedures. HER2 status did not affect survival probability. The size of the primary tumor and number of involved LN negatively affected OS. Adjuvant HDC with AHPCT has a low mortality rate and provides impressive long-term survival rates in patients with high-risk primary BC. Our results suggest that this treatment modality should be proposed in selected HRBC patients and further investigated in clinical trials.

  12. An overview of the use of high-dose melphalan with autologous stem cell transplantation for the treatment of AL amyloidosis.

    PubMed

    Sanchorawala, V; Wright, D G; Seldin, D C; Dember, L M; Finn, K; Falk, R H; Berk, J; Quillen, K; Skinner, M

    2001-10-01

    Primary or AL amyloidosis results from a plasma cell dyscrasia in which fibrillar light chain protein deposition leads to organ failure and death. Standard treatment for AL amyloidosis has been oral melphalan and prednisone. However, this form of treatment modifies the natural history of this lethal disease only marginally, extending median survival from 13 months following diagnosis to 17 months. At Boston University Medical Center, we have developed treatment protocols using high-dose intravenous melphalan with autologous peripheral blood stem cell transplantation (HDM/SCT) to treat AL amyloidosis, and we have treated over 200 patients with HDM/SCT during the past six years. This extensive experience has shown that patients with AL amyloidosis, despite multisystem involvement and compromised organ function can tolerate this aggressive form of treatment. Furthermore, HDM/SCT results in durable hematologic responses in a substantial proportion of patients, and such responses are associated with clinical improvement, decreased amyloid-related organ dysfunction, and prolonged survival. However, toxicity from treatment is high (overall peri-transplant mortality, 14%), particularly for those patients with clinically significant cardiac involvement. For this reason, we believe a multidisciplinary management approach is essential when using HDM/SCT for treatment of AL amyloidosis. Based on our experience, we believe that HDM/SCT is the treatment of choice for patients with AL amyloidosis who have a good performance status and limited cardiac involvement at the time of diagnosis. HDM/SCT offers the best chance for hematologic remission, prolongation of survival, and reversal of amyloid-related disease. At the same time, we believe that HDM/SCT should continue to be examined in the context of clinical trials, directed at developing approaches to broaden the applicability of this therapy by minimizing toxicity and to increase the likelihood of complete hematologic responses

  13. γ-Herpesvirus load as surrogate marker of early death in HIV-1 lymphoma patients submitted to high dose chemotherapy and autologous peripheral blood stem cell transplantation.

    PubMed

    Pratesi, Chiara; Zanussi, Stefania; Tedeschi, Rosamaria; Bortolin, Maria Teresa; Talamini, Renato; Rupolo, Maurizio; Scaini, Chiara; Basaglia, Giancarlo; Di Maso, Matteo; Mazzucato, Mario; Zanet, Ernesto; Tirelli, Umberto; Michieli, Mariagrazia; Carbone, Antonino; De Paoli, Paolo

    2015-01-01

    Autologous stem cell transplantation (ASCT) is a feasible procedure for human immunodeficiency virus-1 (HIV-1) lymphoma patients, whose underlying disease and intrinsic HIV-1- and ASCT-associated immunodeficiency might increase the risk for γ-herpesvirus load persistence and/or reactivation. We evaluated this hypothesis by investigating the levels of Epstein-Barr virus (EBV)- and Kaposi sarcoma-associated herpesvirus (KSHV)-DNA levels in the peripheral blood of 22 HIV-1-associated lymphoma patients during ASCT, highlighting their relationship with γ-herpesvirus lymphoma status, immunological parameters, and clinical events. EBV-DNA was detected in the pre-treatment plasma and peripheral blood mononuclear cells (PBMCs) of 12 (median 12,135 copies/mL) and 18 patients (median 417 copies/10(6) PBMCs), respectively; the values in the two compartments were correlated (r = 0.77, p = 0.0001). Only EBV-positive lymphomas showed detectable levels of plasma EBV-DNA. After debulking chemotherapy, plasma EBV-DNA was associated with lymphoma chemosensitivity (p = 0.03) and a significant higher mortality risk by multivariate Cox analysis adjusted for EBV-lymphoma status (HR, 10.46, 95% CI, 1.11-98.32, p = 0.04). After infusion, EBV-DNA was detectable in five EBV-positive lymphoma patients who died within six months. KSHV-DNA load was positive in only one patient, who died from primary effusion lymphoma. Fluctuations in levels of KSHV-DNA reflected the patient's therapy and evolution of his underlying lymphoma. Other γ-herpesvirus-associated malignancies, such as multicentric Castleman disease and Kaposi sarcoma, or end-organ complications after salvage treatment were not found. Overall, these findings suggest a prognostic and predictive value of EBV-DNA and KSHV-DNA, the monitoring of which could be a simple, complementary tool for the management of γ-herpesvirus-positive lymphomas in HIV-1 patients submitted to ASCT. PMID:25668032

  14. Infectious complications in 126 patients treated with high-dose chemotherapy and autologous peripheral blood stem cell transplantation.

    PubMed

    Salazar, R; Solá, C; Maroto, P; Tabernero, J M; Brunet, J; Verger, G; Valentí, V; Cancelas, J A; Ojeda, B; Mendoza, L; Rodríguez, M; Montesinos, J; López-López, J J

    1999-01-01

    The effect of an extensive prophylactic antimicrobial regimen was prospectively assessed in 126 patients after high-dose chemotherapy and autologous PBSC. They received ciprofloxacin (500 mg/12 h), acyclovir (200 mg/6 h), and itraconazole (200 mg/12 h) orally until neutrophil recovery. Febrile patients received i.v. imipenem (500 mg/6 h) to which vancomycin and amikacin were added if fever persisted for 2-3 and 5 days, respectively. Amphotericin B lipid complex was further given on day 7 or 8 of fever. Median times for a neutrophil count of >0.5 x 10(9)/l and a platelet count of >20 x 10(9)/l were 9 and 11 days. Severe neutropenia (<0.1 x 10(9)/l) lasted for a median of 5 days in which 72% of febrile episodes and 50% of cases of bacteremia occurred. Gram-positive bacteria were isolated in 30 of 40 episodes of bacteremia, 25 of which were caused by Staphylococcus epidermidis. Clinical foci were the intravascular catheter in 35 cases, respiratory infection in 11, cellulitis in two, anal abscess in one, and neutropenic enterocolitis in one. The high incidence of febrile episodes (94%) and bacteremias (31%) may be due to the lack of efficacy of antimicrobial prophylaxis and the persistence of a 5-day period of severe neutropenia.

  15. Cost and clinical analysis of autologous hematopoietic stem cell mobilization with G-CSF and plerixafor compared to G-CSF and cyclophosphamide.

    PubMed

    Shaughnessy, Paul; Islas-Ohlmayer, Miguel; Murphy, Julie; Hougham, Maureen; MacPherson, Jill; Winkler, Kurt; Silva, Matthew; Steinberg, Michael; Matous, Jeffrey; Selvey, Sheryl; Maris, Michael; McSweeney, Peter A

    2011-05-01

    Plerixafor plus granulocyte-colony stimulating factor (G-CSF) has been shown to mobilize more CD34(+) cells than G-CSF alone for autologous hematopoietic stem cell transplantation (HSCT). However, many centers use chemotherapy followed by G-CSF to mobilize CD34(+) cells prior to HSCT. We performed a retrospective study of patients who participated in the expanded access program (EAP) of plerixafor and G-CSF for initial mobilization of CD34(+) cells, and compared outcomes to matched historic controls mobilized with cyclophosphamide 3-5 g/m(2) and G-CSF at 2 centers that participated in the EAP Control patients were matched for age, sex, disease, disease stage, and number of prior therapies. Mobilization costs were defined to be the costs of medical procedures, resource utilization, and medications. Median national CMS reimbursement rates were used to establish the costs of procedures, hospitalization, provider visits, apheresis, CD34(+) cell processing and cryopreservation. Average sale price was used for G-CSF, plerixafor, cyclophosphamide, MESNA, antiemetics, and antimicrobials. A total of 33 patients from the EAP and 33 matched controls were studied. Two patients in the control group were hospitalized for neutropenic fever during the mobilization period. Apheresis started on the scheduled day in 33 (100%) study patients and in 29 (88%) control patients (P = 0.04). Sixteen (48%) control patients required weekend apheresis. There was no difference in number of CD34(+) cells collected between the groups, and all patients proceeded to HSCT with no difference in engraftment outcomes. Median total cost of mobilization was not different between the plerixafor/G-CSF and control groups ($14,224 versus $18,824; P = .45). In conclusion, plerixafor/G-CSF and cyclophosphamide/G-CSF for upfront mobilization of CD34(-) cells resulted in similar numbers of cells collected, costs of mobilization, and clinical outcomes. Additionally, plerixafor/G-CSF mobilization resulted in more

  16. Phase I/II study of bortezomib-BEAM and autologous hematopoietic stem cell transplantation for relapsed indolent non-Hodgkin lymphoma, transformed, or mantle cell lymphoma.

    PubMed

    William, Basem M; Allen, Mary S; Loberiza, Fausto R; Bociek, Robert Gregory; Bierman, Philip J; Armitage, James O; Vose, Julie M

    2014-04-01

    A phase I/II trial was designed to evaluate the safety and efficacy of adding bortezomib to standard BEAM (BCNU, etoposide, cytarabine, melphalan) and autologous hematopoietic stem cell transplantation (ASCT). Eligible patients had relapsed/refractory indolent or transformed non-Hodgkin lymphoma or mantle cell lymphoma (MCL) that was relapsed/refractory or in first partial (PR) or complete remission (CR). Patients received bortezomib on days -11, -8, -5, and -2 before ASCT. Phase I had 4 dose cohorts (.8, 1, 1.3, and 1.5 mg/m(2)) and 3 patients were accrued to each. Any nonhematological ASCT-related toxicity >2 on the Bearman scale occurring between day -11 and engraftment defined the maximum tolerated dose (MTD). After the MTD has been reached, another 20 patients were enrolled at this dose to determine a preliminary overall response rate (ORR). Patients who were in CR or PR at day +100 were considered responders. The study enrolled 42 patients through August 14, 2009. The median age was 58 (range, 34 to 73) years, with 33 males and 9 females. The most common diagnoses were MCL (23 patients) and follicular lymphoma (7 patients). The median number of prior therapies was 1 (range, 0 to 6). The median follow-up was 4.88 (range, 1.07 to 6.98) years. Thirteen patients were treated in phase I and 29 patients were treated in phase II. The MTD was initially determined to be 1.5 mg/m(2) but it was later decreased to 1 mg/m(2) because of excessive gastrointestinal toxicity and peripheral neuropathy. The ORR was 95% at 100 days and 87% at 1 year. For all 38 evaluable patients at 1 year, responses were CR 84%, PR 1%, and progressive disease 13%. Progression-free survival (PFS) was 83% (95% CI, 68% to 92%) at 1 year, and 32% (15% to 51%) at 5 years. Overall survival (OS) was 91% (95% CI, 79% to 96%) at 1 year and 67% (50% to 79%) at 5 years. The most common National Cancer Institute grade 3 toxicities were neutropenic fever (59%), anorexia (21%), peripheral neuropathy (19

  17. Intraoperative Stem Cell Therapy

    PubMed Central

    Coelho, Mónica Beato; Cabral, Joaquim M.S.; Karp, Jeffrey M.

    2013-01-01

    Stem cells hold significant promise for regeneration of tissue defects and disease-modifying therapies. Although numerous promising stem cell approaches are advancing in clinical trials, intraoperative stem cell therapies offer more immediate hope by integrating an autologous cell source with a well-established surgical intervention in a single procedure. Herein, the major developments in intraoperative stem cell approaches, from in vivo models to clinical studies, are reviewed, and the potential regenerative mechanisms and the roles of different cell populations in the regeneration process are discussed. Although intraoperative stem cell therapies have been shown to be safe and effective for several indications, there are still critical challenges to be tackled prior to adoption into the standard surgical armamentarium. PMID:22809140

  18. Phase II trial of high-dose topotecan, melphalan and CY with autologous stem cell support for multiple myeloma

    PubMed Central

    Kazmi, SMA; Saliba, RM; Donato, M; Wang, M; Hosing, C; Qureshi, S; Anderlini, P; Popat, U; Champlin, RE; Giralt, SA; Qazilbash, MH

    2014-01-01

    In spite of high-dose chemotherapy followed by autologous hematopoietic SCT multiple myeloma (MM) eventually recurs, highlighting the need for more effective treatment approaches. Patients received topotecan 3.5 mg/m2 intravenously on days −6 to −2, melphalan 70 mg/m2 intravenously on days −3 and −2 and CY 1 g/m2 intravenously on days −6, −5 and −4. Overall response rate (ORR) consisting of complete response and partial response (CR + PR, PFS, OS and toxicity are reported. Between August 2002 to March 2004, 60 patients (34 men and 26 women) with a median age of 61 years (range 45–72) were enrolled. Forty-one patients were treated for consolidation of first remission, while 19 patients had relapsed/refractory disease. ORR was 85% (CR 12%, very good PR 43% and PR 30%). Median time to neutrophil (ANC>0.5 × 109/L) and plt engraftment (>20 × 109/L) was 10 (range 7–12 days) and 9 days (range 6–79 days), respectively. A majority of the common adverse events were grade 1–3 mucositis/stomatitis (65%), grade 1 or 2 nausea (59%) and grade 1 or 2 diarrhea (41%). Median PFS was 18.5 months and median OS has yet not been reached. In conclusion, topotecan, melphalan and CY is a safe and active conditioning regimen for auto hematopoietic SCT in MM. The ORR and PFS were comparable to high-dose melphalan. PMID:20581887

  19. GWAS of 972 autologous stem cell recipients with multiple myeloma identifies 11 genetic variants associated with chemotherapy-induced oral mucositis

    PubMed Central

    Coleman, Elizabeth Ann; Lee, Jeannette Y.; Erickson, Stephen W.; Sanathkumar, Naveen; Raj, Vinay R.; Zhou, Daohong; McKelvey, Kent D.; Apewokin, Senu; Stephens, Owen; Enderlin, Carol A.; Vangsted, Annette Juul; Reed, Patty J.; Anaissie, Elias J.

    2015-01-01

    Purpose High-dose chemotherapy and autologous stem cell transplant (ASCT) to treat multiple myeloma (MM) and other cancers carries the risk of oral mucositis (OM) with sequelae including impaired nutritional and fluid intake, pain, and infectious complications. As a result of these problems, cancer treatment may have to be interrupted or delayed. In this study we looked beyond OM's known risk factors of renal function and melphalan dose with a genome-wide association study (GWAS) to evaluate whether genetic variants in conjunction with clinical risk factors influence predisposition for OM. Methods Genotyping was performed using Illumina HumanOmnil-Quad vl.O BeadChip and further assessed for data quality. We tested 892,589 germline single-nucleotide polymorphisms (SNPs) for association with OM among 972 Caucasian patients treated with high-dose melphalan and ASCT in Total Therapy clinical trials (TT2, TT3, TT4) for newly diagnosed MM. Statistical analyses included t tests, stepwise regression modeling, and logistic regression modeling to find baseline clinical factors and genotypes associated with OM. Results We found that 353 (36.3 %) patients had grades 2–4 OM. Type of treatment protocol, baseline estimated glomerular filtration rate, and melphalan dose along with baseline serum albumin and female gender predicted 43.6 % of grades 2–4 OM cases. Eleven SNPs located in or near matrix metalloproteinase 13, JPH3, DHRS7C, CEP192, CPEB1/LINC00692, FBN2, ALDH1A1, and DMRTA1/FLJ35282 were associated with grades 2–4 OM. The addition of these SNPs increased sensitivity in detecting grades 2–1 OM cases to 52 %. Conclusions These SNPs may be important for their roles in inflammatory pathways, epithelial healing, and chemotherapy detoxification. PMID:25218607

  20. Comparative Study of Autologous Stromal Vascular Fraction and Adipose-Derived Stem Cells for Erectile Function Recovery in a Rat Model of Cavernous Nerve Injury

    PubMed Central

    You, Dalsan; Jang, Myoung Jin; Kim, Bo Hyun; Song, Geehyun; Lee, Chunwoo; Suh, Nayoung; Jeong, In Gab; Ahn, Tai Young

    2015-01-01

    The abilities of intracavernous injection of autologous stromal vascular fraction (SVF) and adipose-derived stem cells (ADSCs) to facilitate recovery of erectile function in a rat model of cavernous nerve (CN) injury were compared. Forty male Sprague-Dawley rats were randomly divided into four groups: sham and control groups (intracavernous injection of phosphate-buffered saline), SVF group (intracavernous injection of SVF), and ADSC group (intracavernous injection of ADSCs). Rats in the latter three groups underwent bilateral CN injury prior to injection. The evaluation of erectile function and histomorphometric studies were performed 4 weeks after injection. The ratio of maximal intracavernous pressure to mean arterial pressure was significantly lower in the control group than in the sham group (0.18 vs. 0.56, p < .001). Intracavernous injection of SVF (0.36, p = .035) significantly improved erectile function compared with that in the control group, whereas the ADSC group (0.35, p = .052) showed marginally significant improvement. The smooth muscle/collagen ratio, smooth muscle content, number of neuronal nitric-oxide synthase-positive nerve fibers, and expression of von Willebrand factor were significantly higher in the SVF and ADSC groups than in the control group. Expression of endothelial nitric-oxide synthase was significantly increased in the SVF group. The increases in the smooth muscle/collagen ratio and von Willebrand factor expression were larger in the SVF group than in the ADSC group. Intracavernous injection of SVF or ADSCs was equally effective in recovering penile erection in a rat model of CN injury. PMID:25792486

  1. Second malignancies after autologous haematopoietic stem cell transplantation following modified BEAM conditioning regimen in patients with Hodgkin lymphoma – characteristics and risk factor analysis

    PubMed Central

    Łojko-Dankowska, Anna; Matuszak, Magdalena; Dytfeld, Dominik; Kaźmierczak, Maciej; Komarnicki, Mieczysław

    2013-01-01

    Aim of the study The aim of the study was to determine the incidence of second malignancies among patients with Hodgkin lymphoma (HL) treated with autologous haematopoietic stem cell transplantation (ASCT) following a modified BEAM (BCNU, etoposide, cytarabine, melphalan, dexamethasone) regimen between 1992 and 2012 at our department. We also intended to define the risk factors for the occurrence of second neoplasm after ASCT. Material and methods The long-term outcomes after transplant were evaluated in 170 patients, median age 31 years (range 17–61), who received a median of two pre-transplant chemotherapy lines (range 1–5). Results MOPP (mechlorethamine, vincristine, procarbazine, prednisone) or MOPP-type regimens were given to 12% of patients prior to ASCT. The median follow-up of the survivors was 73 (12–242) months. The 7-year overall survival and progression-free survival were 75% and 64%, respectively. Second malignancies occurred in 7 of the 170 patients, including 5 haematological malignancies, and 2 solid tumors. They developed at a median of 8 years (range 0.4–13.5) from ASCT. The 10-year and 15-year cumulative incidence of developing a second malignancy were 7% and 13%, respectively. In multivariate analysis, age ≥ 40 years at transplant (HR = 8.8; p = 0.008) and pre-transplant MOPP-type chemotherapy (HR = 5.6; p = 0.030) were the only factors significant for developing a second malignancy. Conclusions Our results indicate that age of patient and the type of pre-transplant chemotherapy contribute to the risk of the development of a second neoplasm after ASCT in patients with HL. We believe that better characterization of second malignancies and associated risk factors may be useful for clinicians who care for these patients. PMID:23788991

  2. R-MPV followed by high-dose chemotherapy with TBC and autologous stem-cell transplant for newly diagnosed primary CNS lymphoma.

    PubMed

    Omuro, Antonio; Correa, Denise D; DeAngelis, Lisa M; Moskowitz, Craig H; Matasar, Matthew J; Kaley, Thomas J; Gavrilovic, Igor T; Nolan, Craig; Pentsova, Elena; Grommes, Christian C; Panageas, Katherine S; Baser, Raymond E; Faivre, Geraldine; Abrey, Lauren E; Sauter, Craig S

    2015-02-26

    High-dose methotrexate-based chemotherapy is the mainstay of treatment of primary central nervous system lymphoma (PCNSL), but relapses remain frequent. High-dose chemotherapy (HDC) with autologous stem-cell transplant (ASCT) may provide an alternative to address chemoresistance and overcome the blood-brain barrier. In this single-center phase-2 study, newly diagnosed PCNSL patients received 5 to 7 cycles of chemotherapy with rituximab, methotrexate (3.5 g/m(2)), procarbazine, and vincristine (R-MPV). Those with a complete or partial response proceeded with consolidation HDC with thiotepa, cyclophosphamide, and busulfan, followed by ASCT and no radiotherapy. Primary end point was 1-year progression-free survival (PFS), N = 32. Median age was 57, and median Karnofsky performance status 80. Following R-MPV, objective response rate was 97%, and 26 (81%) patients proceeded with HDC-ASCT. Among all patients, median PFS and overall survival (OS) were not reached (median follow-up: 45 months). Two-year PFS was 79% (95% confidence interval [CI], 58-90), with no events observed beyond 2 years. Two-year OS was 81% (95% CI, 63-91). In transplanted patients, 2-year PFS and OS were 81%. There were 3 treatment-related deaths. Prospective neuropsychological evaluations suggested relatively stable cognitive functions posttransplant. In conclusion, this treatment was associated with excellent disease control and survival, an acceptable toxicity profile, and no evidence of neurotoxicity thus far. This trial was registered at www.clinicaltrials.gov as NCT00596154.

  3. High-Dose Chemotherapy and Autologous Stem Cell Transplantation in Children with High-Risk or Recurrent Bone and Soft Tissue Sarcomas

    PubMed Central

    2016-01-01

    Despite increasing evidence that high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) might improve the survival of patients with high-risk or recurrent solid tumors, therapy effectiveness for bone and soft tissue sarcoma treatment remains unclear. This study retrospectively investigated the feasibility and effectiveness of HDCT/auto-SCT for high-risk or recurrent bone and soft tissue sarcoma. A total of 28 patients (18 high-risk and 10 recurrent) underwent single or tandem HDCT/auto-SCT between October 2004 and September 2014. During follow-up of a median 15.3 months, 18 patients exhibited disease progression and 2 died of treatment-related toxicities (1 veno-occlusive disease and 1 sepsis). Overall, 8 patients remained alive and progression-free. The 3-year overall survival (OS) and event-free survival (EFS) rates for all 28 patients were 28.7% and 26.3%, respectively. In the subgroup analysis, OS and EFS rates were higher in patients with complete or partial remission prior to HDCT/auto-SCT than in those with worse responses (OS, 39.1% vs. 0.0%, P = 0.002; EFS, 36.8% vs. 0.0%, P < 0.001). Therefore, careful selection of patients who can benefit from HDCT/auto-SCT and maximal effort to reduce tumor burden prior to treatment will be important to achieve favorable outcomes in patients with high-risk or recurrent bone and soft tissue sarcomas. PMID:27366002

  4. Total Body Irradiation Compared With BEAM: Long-Term Outcomes of Peripheral Blood Autologous Stem Cell Transplantation for Non-Hodgkin's Lymphoma

    SciTech Connect

    Liu, Hong-Wei; Seftel, Matthew D.; Rubinger, Morel; Szwajcer, David; Demers, Alain

    2010-10-01

    Purpose: The optimal preparative regimen for non-Hodgkin's lymphoma patients undergoing autologous peripheral blood stem cell transplantation (PBSCT) is unknown. We compared a total body irradiation (TBI)-based regimen with a chemotherapy-alone regimen. Methods and Materials: A retrospective cohort study was performed at a Canadian cancer center. The TBI regimen consisted of cyclophosphamide, etoposide, and TBI 12 Gy in six fractions (CY/E/TBI). The chemotherapy-alone regimen consisted of carmustine, etoposide, cytarabine, and melphalan (BEAM). We compared the acute and long-term toxicities, disease relapse-free survival, and overall survival (OS). Results: Of 73 patients, 26 received CY/E/TBI and 47 received BEAM. The median follow-up for the CY/E/TBI group was 12.0 years and for the BEAM group was 7.3 years. After PBSCT, no differences in acute toxicity were seen between the two groups. The 5-year disease relapse-free survival rate was 50.0% and 50.7% in the CY/E/TBI and BEAM groups, respectively (p = .808). The 5-year OS rate was 53.9% and 63.8% for the CY/E/TBI and BEAM groups, respectivey (p = .492). The univariate analysis results indicated that patients with Stage IV, with chemotherapy-resistant disease, and who had received PBSCT before 2000 had inferior OS. A three-way categorical analysis revealed that transplantation before 2000, rather than the conditioning regimen, was a more important predictive factor of long-term outcome (p = .034). Conclusion: A 12-Gy TBI-based conditioning regimen for PBSCT for non-Hodgkin's lymphoma resulted in disease relapse-free survival and OS similar to that after BEAM. PBSCT before 2000, and not the conditioning regimen, was an important predictor of long-term outcomes. TBI was not associated with more acute toxicity or pneumonitis. We found no indication that the TBI regimen was inferior or superior to BEAM.

  5. Prospective evaluation of pulmonary function in cancer patients treated with total body irradiation, high-dose melphalan, and autologous hematopoietic stem cell transplantation

    SciTech Connect

    Gandola, L.; Siena, S.; Bregni, M.; Sverzellati, E.; Piotti, P.; Stucchi, C.; Gianni, A.M.; Lombardi, F. )

    1990-09-01

    Pulmonary function tests (standard vital capacity, SVC; total lung capacity, TLC; forced expiratory volume in 1 second-forced vital capacity ratio, FEV1/FVC; carbon monoxide transfer factor, DLCO) were prospectively evaluated in patients (median age 25 years, 13-52 years; median follow-up 20 months, 6-51 months) with Hodgkin's disease (15 patients), non-Hodgkin's lymphoma (9 patients), and inflammatory breast cancer (3 patients) treated with sequential high-dose therapy comprising the following phases over approximately 2 months: (a) cyclophosphamide (7 g/m2); (b) vincristine (1.4 mg/m2), methotrexate (8 g/m2), and cisplatinum (120 mg/m2) or etoposide (2 g/m2); (c) total body irradiation (TBI; 12.5 gy, 5 fractions over 48 hours), intravenous melphalan (120-180 mg/m2), and transplantation of autologous peripheral blood and/or bone marrow hematopoietic stem cells. Within 2 months after transplantation, 12 patients also received 25 Gy radiotherapy boost to mediastinum and clavicular regions. In vivo dosimetry evaluations of fractionated TBI treatments showed that mean radiation dose absorbed by lungs was 12.18 Gy (97.4% of TBI dose). Despite such a high radiation dose, we observed only transient and subclinical decrease of SVC, TLC, and DLCO. The decrease of SVC, TLC, and DLCO was more evident and prolonged in patients receiving radiotherapy boost. All parameters progressively recovered to normal values within 2 years after transplantation. In contrast, FEV1/FVC remained within normal limits in all patients, thus demonstrating the absence of obstructive ventilatory changes. In addition, no interstitial pneumonia was observed.

  6. The Effects of Oral Cryotherapy on Chemotherapy-Induced Oral Mucositis in Patients Undergoing Autologous Transplantation of Blood Stem Cells: A Clinical Trial

    PubMed Central

    Askarifar, Marzieh; Lakdizaji, Sima; Ramzi, Mani; Rahmani, Azad; Jabbarzadeh, Faranak

    2016-01-01

    Background Oral mucositis is one of the irritating side effects of chemotherapy in patients undergoing bone marrow transplantation. However, up until now, the common methods of oral mucositis therapy have failed to show significant effects. Objectives The aim of this study was to investigate the effects of local cryotherapy on the intensity of chemotherapy-induced oral mucositis in autologous bone marrow transplantation patients. Patients and Methods In this single, blinded, randomized clinical trial, 29 patients undergoing stem cell transplantation in Iran were selected by convenience sampling, and randomly allocated to control (n = 13) and intervention groups (n = 16). In the intervention group, cryotherapy was applied, while the control group received a normal saline mouthwash. The severity of the mucositis and neutrophil rate were investigated in five periods, based on the world health organization (WHO) scales. The data were analyzed using descriptive statistics, the Mann-Whitney test, repeated measures analysis of variance (ANOVA), and linear regression. Results In both groups, the mucositis reached its peak intensity on the 7th day, and the least intensity was obtained on the 21st day. The neutrophil rate reached the minimum value on the 7th day, then increased up to the 21st day. The two groups showed no significant differences between the mucositis severity on the 14th and 21st days (P = 0.164), while the severity of the mucositis in the cryotherapy group was significantly less than that in the saline mouthwash group (1.81 < 2.54 and 0.13 < 0.92, respectively) on the 7th and 14th days (P < 0.05). There was no significant difference in the neutrophil rate between the groups. Conclusions The results showed that cryotherapy is more effective than the saline mouthwash in reducing the severity of mucositis. This method is recommended for the prevention of mucositis in bone marrow transplantation. PMID:27257512

  7. Clinical results of high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation in children with advanced stage rhabdomyosarcoma.

    PubMed

    Kim, Nam Kyun; Kim, Hyo Sun; Suh, Chang-Ok; Kim, Hyun Ok; Lyu, Chuhl Joo

    2012-09-01

    Regardless of improvement in cure of Rhabdomyosarcoma (RMS), the results in treatment of advanced stage of RMS in children are still dismal. Recently, high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (HDC/APBSCT) has been tried to manage the advanced high-risk RMS patients. We investigated the effectiveness of HDC/APBSCT by reviewing the clinical records of high-risk pediatric RMS patients in single institute database. Over twenty years, 37 patients were diagnosed as RMS with high-risk at the time of first diagnosis. These patients were classified as two groups according to treatment method. The first group was HDC/APBSCT and the other was conventional multi-agent chemotherapy group. Differences of clinical results between the two groups were analyzed. The median age of patients was 5 yr, ranging from 6 months to 15 yr. The 5-yr event free survival rate (EFS) of all patients was 24.8% ± 4.8%. HDC/APBSCT group and conventional multi-agent chemotherapy group were 41.3% ± 17.8% and 16.7% ± 7.6% for 5-yr EFS, respectively (P = 0.023). There was a significant difference in the result of HDC/APBSCT between complete remission or very good partial response group and poor response group (50% ± 20.4% vs 37.5% ± 28.6%, P = 0.018). HDC/APBSCT can be a promising treatment modality in high-risk RMS patients. PMID:22969254

  8. Cost-Effectiveness of Autologous Hematopoietic Stem Cell Transplantation for Elderly Patients with Multiple Myeloma using the Surveillance, Epidemiology, and End Results-Medicare Database.

    PubMed

    Shah, Gunjan L; Winn, Aaron N; Lin, Pei-Jung; Klein, Andreas; Sprague, Kellie A; Smith, Hedy P; Buchsbaum, Rachel; Cohen, Joshua T; Miller, Kenneth B; Comenzo, Raymond; Parsons, Susan K

    2015-10-01

    In the past decade, the number of autologous hematopoietic stem cell transplants (Auto HSCT) for older patients with multiple myeloma (MM) has increased dramatically, as has the cost of transplantation. The cost-effectiveness of this modality in patients over age 65 is unclear. Using the Surveillance, Epidemiology, and End Results-Medicare database to create a propensity-score matched sample of patients over age 65 between 2000 and 2007, we compared the survival and cost for those who received Auto HSCT to those who did not undergo transplantation but survived at least 6 months after diagnosis, and we calculated an incremental cost-effectiveness ratio (ICER). Two hundred seventy patients underwent transplantation. Median overall survival from diagnosis in those who underwent transplantation was significantly longer than in patients who did not (58 months versus 37 months, P < .001). For patients living longer than 2 years, the median monthly cost during the first year was significantly different, but the middle and last year of life costs were similar. The median cost of the first 100 days after transplantation was $60,000 (range, $37,000 to $85,000). The resultant ICER was $72,852 per life-year gained. Survival after transplantation was comparable to that in those who underwent transplantation patients under 65 years and significantly longer than older patients who did not undergo transplantation. With an ICER less than $100,000/life-year gained, Auto HSCT is cost-effective when compared with nontransplantation care in the era of novel agents and should be considered, where clinically indicated, for patients over the age of 65.

  9. Phase II study of central nervous system (CNS)-directed chemotherapy including high-dose chemotherapy with autologous stem cell transplantation for CNS relapse of aggressive lymphomas

    PubMed Central

    Korfel, Agnieszka; Elter, Thomas; Thiel, Eckhard; Hänel, Matthias; Möhle, Robert; Schroers, Roland; Reiser, Marcel; Dreyling, Martin; Eucker, Jan; Scholz, Christian; Metzner, Bernd; Röth, Alexander; Birkmann, Josef; Schlegel, Uwe; Martus, Peter; Illerhaus, Gerard; Fischer, Lars

    2013-01-01

    The prognosis of patients with central nervous system relapse of aggressive lymphoma is very poor with no therapy established so far. In a prospective multicenter phase II study, we evaluated a potentially curative chemotherapy-only regimen in these patients. Adult immunocompetent patients 65 years of age or under received induction chemotherapy with MTX/IFO/DEP (methotrexate 4 g/m2 intravenously (i.v.) Day 1, ifosfamide 2 g/m2 i.v. Days 3– 5 and liposomal cytarabine 50 mg intrathecally (i.th) Day 6) and AraC/TT/DEP (cytarabine 3g/m2 i.v. Days 1–2, thiotepa 40 mg/m2 i.v. Day 2 and i.th. liposomal cytarabine 50 mg i.th. Day 3) followed by high-dose chemotherapy with carmustine 400 mg/m2 i.v. Day −5, thiotepa 2×5 mg/kg i.v. Days −4 to −3 and etoposide 150 mg/m2 i.v. Days −5 to −3, and autologous stem cell transplantation Day 0 (HD-ASCT). Thirty eligible patients (median age 58 years) were enrolled. After HD-ASCT (n=24), there was a complete remission in 15 (63%), partial remission in 2 (8%) and progressive disease in 7 (29%) patients. Myelotoxicity was the most adverse event with CTC grade 3/4 infections in 12% of MTX/IFO/DEP courses, 21% of AraC/TT/DEP courses and 46% of HD-ASCT courses. The 2-year time to treatment failure was 49%±19 for all patients and 58%±22 for patients completing HD-ASCT. The protocol assessed proved feasible and highly active with long-lasting remissions in a large proportion of patients. (ClinicalTrials.govIdentifier NCT01148173) PMID:23242601

  10. Busulfan, Melphalan, and Bortezomib versus High-Dose Melphalan as a Conditioning Regimen for Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma

    PubMed Central

    Rodriguez, Tulio E.; Hari, Parameswaran; Stiff, Patrick J.; Smith, Scott E.; Sterrenberg, Danielle; Vesole, David H.

    2016-01-01

    High-dose melphalan 200 mg/m2 (MEL 200) is the standard of care as a conditioning regimen for autologous hematopoietic stem cell transplantation (AHSCT) for multiple myeloma (MM). We compared a novel conditioning combination incorporating busulfan, melphalan, and bortezomib (BUMELVEL) versus standard MEL 200 in newly diagnosed patients undergoing AHSCT for MM. Between July 2009 and May 2012, 43 eligible patients received BUMELVEL conditioning followed by AHSCT. BU was administered i.v. daily for 4 days to achieve a target area under the concentration-time curve total of 20,000 mM·min based on pharmacokinetic analysis after the first dose. MEL 140 mg/m2 (MEL 140) and VEL 1.6 mg/m2 were administered i.v. on days −2 and −1, respectively. Outcomes were compared with a contemporaneous North American cohort (n = 162) receiving MEL 200 matched for age, sex, performance status, stage, interval from diagnosis to AHSCT, and disease status before AHSCT. Multivariate analysis of relapse, progression-free survival (PFS), and overall survival (OS) was performed. The median follow-up was 25 months. No transplant-related mortality was observed in the study cohort at 1 year. PFS at 1 year was superior in the BUMELVEL cohort (90%) in comparison with 77% in MEL 200 historical control subjects (P = .02). Cumulative incidence of relapse was lower in the BUMELVEL group versus the MEL 200 group (10% at 1 year versus 21%; P = .047). OS at 1 year was similar between cohorts (93% versus 93%; P =.89). BU can be safely combined with MEL 140 and VEL without an increase in toxicities or transplant-related mortality. We observed a superior PFS in the BUMELVEL cohort without maintenance therapy, warranting further trials. PMID:27164062

  11. Toward Personalized Cell Therapies: Autologous Menstrual Blood Cells for Stroke

    PubMed Central

    Rodrigues, Maria Carolina O.; Glover, Loren E.; Weinbren, Nathan; Rizzi, Jessica A.; Ishikawa, Hiroto; Shinozuka, Kazutaka; Tajiri, Naoki; Kaneko, Yuji; Sanberg, Paul R.; Allickson, Julie G.; Kuzmin-Nichols, Nicole; Garbuzova-Davis, Svitlana; Voltarelli, Julio Cesar; Cruz, Eduardo; Borlongan, Cesar V.

    2011-01-01

    Cell therapy has been established as an important field of research with considerable progress in the last years. At the same time, the progressive aging of the population has highlighted the importance of discovering therapeutic alternatives for diseases of high incidence and disability, such as stroke. Menstrual blood is a recently discovered source of stem cells with potential relevance for the treatment of stroke. Migration to the infarct site, modulation of the inflammatory reaction, secretion of neurotrophic factors, and possible differentiation warrant these cells as therapeutic tools. We here propose the use of autologous menstrual blood cells in the restorative treatment of the subacute phase of stroke. We highlight the availability, proliferative capacity, pluripotency, and angiogenic features of these cells and explore their mechanistic pathways of repair. Practical aspects of clinical application of menstrual blood cells for stroke will be discussed, from cell harvesting and cryopreservation to administration to the patient. PMID:22162629

  12. Improved targeting and enhanced retention of the human, autologous, fibroblast-derived, induced, pluripotent stem cells to the sarcomeres of the infarcted myocardium with the aid of the bioengineered, heterospecific, tetravalent antibodies**

    PubMed Central

    Malecki, Marek

    2013-01-01

    Clinical trials, to regenerate the human heart injured by myocardial infarction, involve the delivery of stem cells to the site of the injury. However, only a small fraction of the introduced stem cells are detected at the site of the injury, merely two weeks after this therapeutic intervention. This significantly hampers the effectiveness of the stem cell therapy. To resolve the aforementioned problem, we genetically and molecularly bioengineered heterospecific, tetravalent antibodies (htAbs), which have both exquisite specificity and high affinity towards human, pluripotent, stem cells through the htAbs’ domains binding SSEA-4, SSEA-3, TRA-1-60, and TRA-1-81, as well as towards the injured cardiac muscle through the htAbs’ domains binding human cardiac myosin, α-actinin, actin, and titin. The cardiac tissue was acquired from the patients, who were receiving heart transplants. The autologous, human, induced, pluripotent stem cells (hiPSCs) were generated from the patients’ fibroblasts by non-viral delivery and transient expression of the DNA constructs for: Oct4, Nanog, Sox2, Lin28, Klf4, c-Myc. In the trials involving the htAbs, the human, induced, pluripotent stem cells anchored to the myocardial sarcomeres with the efficiency, statistically, significantly higher, than in the trials with non-specific or without antibodies (p < 0.0003). Moreover, application of the htAbs resulted in cross-linking of the sarcomeric proteins to create the stable scaffolds for anchoring of the stem cells. Thereafter, these human, induced pluripotent stem cells differentiated into cardiomyocytes at their anchorage sites. By bioengineering of these novel heterospecific, tetravalent antibodies and using them to guide and to anchor the stem cells specifically to the stabilized sarcomeric scaffolds, we demonstrated the proof of concept in vitro for improving effectiveness of regenerative therapy of myocardial infarction and created the foundations for the trials in vivo. PMID

  13. Efficacy of Pharmacokinetics-Directed Busulfan, Cyclophosphamide, and Etoposide Conditioning and Autologous Stem Cell Transplantation for Lymphoma: Comparison of a Multicenter Phase II Study and CIBMTR Outcomes.

    PubMed

    Flowers, Christopher R; Costa, Luciano J; Pasquini, Marcelo C; Le-Rademacher, Jennifer; Lill, Michael; Shore, Tsiporah B; Vaughan, William; Craig, Michael; Freytes, Cesar O; Shea, Thomas C; Horwitz, Mitchell E; Fay, Joseph W; Mineishi, Shin; Rondelli, Damiano; Mason, James; Braunschweig, Ira; Ai, Weiyun; Yeh, Rosa F; Rodriguez, Tulio E; Flinn, Ian; Comeau, Terrance; Yeager, Andrew M; Pulsipher, Michael A; Bence-Bruckler, Isabelle; Laneuville, Pierre; Bierman, Philip; Chen, Andy I; Kato, Kazunobu; Wang, Yanlin; Xu, Cong; Smith, Angela J; Waller, Edmund K

    2016-07-01

    Busulfan, cyclophosphamide, and etoposide (BuCyE) is a commonly used conditioning regimen for autologous stem cell transplantation (ASCT). This multicenter, phase II study examined the safety and efficacy of BuCyE with individually adjusted busulfan based on preconditioning pharmacokinetics. The study initially enrolled Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients ages 18 to 80 years but was amended due to high early treatment-related mortality (TRM) in patients > 65 years. BuCyE outcomes were compared with contemporaneous recipients of carmustine, etoposide, cytarabine, and melphalan (BEAM) from the Center for International Blood and Marrow Transplant Research. Two hundred seven subjects with HL (n = 66) or NHL (n = 141) were enrolled from 32 centers in North America, and 203 underwent ASCT. Day 100 TRM for all subjects (n = 203), patients > 65 years (n = 17), and patients ≤ 65 years (n = 186) were 4.5%, 23.5%, and 2.7%, respectively. The estimated rates of 2-year progression-free survival (PFS) were 33% for HL and 58%, 77%, and 43% for diffuse large B cell lymphoma (DLBCL; n = 63), mantle cell lymphoma (MCL; n = 29), and follicular lymphoma (FL; n = 23), respectively. The estimated rates of 2-year overall survival (OS) were 76% for HL and 65%, 89%, and 89% for DLBCL, MCL, and FL, respectively. In the matched analysis rates of 2-year TRM were 3.3% for BuCyE and 3.9% for BEAM, and there were no differences in outcomes for NHL. Patients with HL had lower rates of 2-year PFS with BuCyE, 33% (95% CI, 21% to 46%), than with BEAM, 59% (95% CI, 52% to 66%), with no differences in TRM or OS. BuCyE provided adequate disease control and safety in B cell NHL patients ≤ 65 years but produced worse PFS in HL patients when compared with BEAM. PMID:27040394

  14. A randomized trial of amifostine in patients with high-dose VIC chemotherapy plus autologous blood stem cell transplanation

    PubMed Central

    Hartmann, J T; Vangerow, A von; Fels, L M; Knop, S; Stolte, H; Kanz, L; Bokemeyer, C

    2001-01-01

    This pilot study evaluates the degree of side effects during high-dose chemotherapy (HD-VIC) plus autologous bone marrow transplant (HDCT) and its possible prevention by the cytoprotective thiol-derivate amifostine. Additionally, the in-patient medical costs of both treatment arms were compared. 40 patients with solid tumours were randomized to receive HD-VIC chemotherapy with or without amifostine (910 mg/m2 at day 1–3) given as a short infusion prior to carboplatin and ifosfamide. Patients were stratified according to pretreatment. HDCT consisted of an 18 h infusion of carboplatin (500 mg/m2/d over 18 h), ifosfamide (4 g/m2/d over 4 h) and etoposide (500 mg/m2/d) all given for 3 consecutive days. All patients received prophylactic application of G-CSF (5 μg kg−1 subcutaneously) to ameliorate neutropenia after treatment. Patients were monitored for nephrotoxicity, gastrointestinal side effects, haematopoietic recovery, as well as frequency of fever and infections. The median fall of the glomerular filtration rate (GFR) was 10% from baseline in the amifostine group (105 to 95 ml min−1) and 37% in the control patient group (107 to 67 ml min−1) (P< 0.01). Amifostine-treated patients revealed a less pronounced increase in albumine and low molecular weight protein urinary excretion. Stomatitis grade III/IV occurred in 25% without versus 0% of patients with amifostine (P = 0.01). Acute nausea/vomiting was frequently observed immediately during or after the application of amifostine despite intensive antiemetic prophylaxis consisting of 5-HT3-receptor antagonists/dexamethasone/trifluorpromazine. However, delayed emesis occurred more often in the control patients. Engraftment of neutrophil (> 500 μl−1) and thrombocytes (> 25 000 μl−1)were observed at days 9 versus 10 and 10 versus 12, respectively, both slightly in favour of the amifostine arm. In addition, a lower number of days with fever and a shortened duration of hospital stay were observed in the

  15. Concomitant systemic and central nervous system non-Hodgkin lymphoma: the role of consolidation in terms of high dose therapy and autologous stem cell transplantation. A 60-case retrospective study from LYSA and the LOC network.

    PubMed

    Damaj, Gandhi; Ivanoff, Sarah; Coso, Diane; Ysaebert, Loïc; Choquet, Sylvain; Houillier, Caroline; Parcelier, Anne; Abarah, Wajed; Marjanovic, Zora; Gressin, Rémy; Garidi, Reda; Diouf, Momar; Gac, Anne-Claire; Dupuis, Jehan; Troussard, Xavier; Morschhauseur, Franck; Ghesquières, Hervé; Soussain, Carole

    2015-09-01

    The purpose of our study is to determine the outcome of patients with systemic non-Hodgkin lymphoma presenting with neurologic localization at diagnosis, as well as the impact of consolidation in terms of high-dose therapy followed by autologous stem cell transplantation. Newly diagnosed non-Hodgkin lymphoma patients with concomitant systemic and neurological involvement at diagnosis were included in this study. Sixty patients (37 males; 25 females) were included. Median age was 61 years (23-85 years). Histological subtype was mainly diffuse large B-cell lymphoma (n = 54; 90%). The International prognostic index was over 2 in 41 (72%) patients. Median number of extranodal sites was 2 (range: 1-5). Central nervous system involvement alone was documented in 48 patients. Paravertebral involvement with epidural mass and cord compression and positive cerebrospinal fluid were present in 7 patients. Five patients had both central nervous system and epidural involvement. First-line chemotherapy was mainly anthracycline-based (88%) plus high-dose methotrexate (74%) with or without cytarabine. Consolidation with high-dose therapy followed by autologous stem cell transplantation was performed in 19 patients. For the whole population, overall response rate after induction chemotherapy was 76%. Three-year progression-free survival and overall survival were 42 ± 7% and 44 ± 7%, respectively. For patients under 66 years of age, consolidation strategy using high-dose therapy followed by autologous stem cell transplantation positively impacted 3-year overall survival and progression free survival (P = 0.008) and (P = 0.003), respectively. In multivariate analysis, high-dose therapy had a positive impact on 3-year overall survival and progression-free survival for the whole population as well as for patients under 66 years old in CR after induction therapy (OS [HR=0.22 (0.07-0.67)] and progression-free survival [HR = 0.17 (0.05-0.54)]). In conclusion, non-Hodgkin lymphoma

  16. Concomitant systemic and central nervous system non-Hodgkin lymphoma: the role of consolidation in terms of high dose therapy and autologous stem cell transplantation. A 60-case retrospective study from LYSA and the LOC network

    PubMed Central

    Damaj, Gandhi; Ivanoff, Sarah; Coso, Diane; Ysaebert, Loïc; Choquet, Sylvain; Houillier, Caroline; Parcelier, Anne; Abarah, Wajed; Marjanovic, Zora; Gressin, Rémy; Garidi, Reda; Diouf, Momar; Gac, Anne-Claire; Dupuis, Jehan; Troussard, Xavier; Morschhauseur, Franck; Ghesquières, Hervé; Soussain, Carole

    2015-01-01

    The purpose of our study is to determine the outcome of patients with systemic non-Hodgkin lymphoma presenting with neurologic localization at diagnosis, as well as the impact of consolidation in terms of high-dose therapy followed by autologous stem cell transplantation. Newly diagnosed non-Hodgkin lymphoma patients with concomitant systemic and neurological involvement at diagnosis were included in this study. Sixty patients (37 males; 25 females) were included. Median age was 61 years (23–85 years). Histological subtype was mainly diffuse large B-cell lymphoma (n=54; 90%). The International prognostic index was over 2 in 41 (72%) patients. Median number of extranodal sites was 2 (range: 1–5). Central nervous system involvement alone was documented in 48 patients. Paravertebral involvement with epidural mass and cord compression and positive cerebrospinal fluid were present in 7 patients. Five patients had both central nervous system and epidural involvement. First-line chemotherapy was mainly anthracycline-based (88%) plus high-dose methotrexate (74%) with or without cytarabine. Consolidation with high-dose therapy followed by autologous stem cell transplantation was performed in 19 patients. For the whole population, overall response rate after induction chemotherapy was 76%. Three-year progression-free survival and overall survival were 42±7% and 44±7%, respectively. For patients under 66 years of age, consolidation strategy using high-dose therapy followed by autologous stem cell transplantation positively impacted 3-year overall survival and progression free survival (P=0.008) and (P=0.003), respectively. In multivariate analysis, high-dose therapy had a positive impact on 3-year overall survival and progression-free survival for the whole population as well as for patients under 66 years old in CR after induction therapy (OS [HR=0.22 (0.07–0.67)] and progression-free survival [HR=0.17 (0.05–0.54)]). In conclusion, non-Hodgkin lymphoma prognosis

  17. Positron emission tomography response at the time of autologous stem cell transplantation predicts outcome of patients with relapsed and/or refractory Hodgkin’s lymphoma responding to prior salvage therapy

    PubMed Central

    Devillier, Raynier; Coso, Diane; Castagna, Luca; Brenot Rossi, Isabelle; Anastasia, Antonella; Chiti, Arturo; Ivanov, Vadim; Schiano, Jean Marc; Santoro, Armando; Chabannon, Christian; Balzarotti, Monica; Blaise, Didier; Bouabdallah, Reda

    2012-01-01

    Background High-dose chemotherapy followed by autologous stem cell transplantation is the standard treatment for relapsed and/or refractory Hodgkin’s lymphoma although half of patients relapse after transplantation. Predictive factors, such as relapse within 12 months, Ann-Arbor stage at relapse, and relapse in previously irradiated fields are classically used to identify patients with poor outcome. Recently, 18-fluorodeoxyglucose positron emission tomography has emerged as a new method for providing information to predict outcome. The aim of this study was to confirm the predictive value of positron emission tomography status after salvage therapy and to compare single versus tandem autologous stem cell transplantation in patients with relapsed and/or refractory Hodgkin’s lymphoma. Design and Methods We report a series of 111 consecutive patients with treatment-sensitive relapsed and/or treatment-refractory Hodgkin’s lymphoma who achieved complete (positron emission tomography-negative group) or partial remission (positron emission tomography-positive group) at positron emission tomography evaluation after salvage chemotherapy and who underwent single or tandem autologous stem cell transplantation. Results Five-year overall and progression-free survival rates were 81% and 64%, respectively. There were significant differences in 5-year progression-free survival (79% versus 23%; P<0.001) and 5-year overall survival (90% versus 55%, P=0.001) between the positron emission tomography-negative and -positive groups, respectively. A complete response, as determined by positron emission tomography evaluation, after salvage therapy predicted significantly better 5-year overall survival rates in both intermediate (91% versus 50%; P=0.029) and unfavorable (89% versus 58%; P=0.026) risk subgroup analyses. In the positron emission tomography-positive subgroup, tandem transplantation improved 5-year progression-free survival from 0% (in the single transplantation group) to

  18. Supersaturated Calcium Phosphate Rinse in Preventing Oral Mucositis in Young Patients Undergoing Autologous or Donor Stem Cell Transplant

    ClinicalTrials.gov

    2016-10-21

    Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; de Novo Myelodysplastic Syndromes; Disseminated Neuroblastoma; Juvenile Myelomonocytic Leukemia; Mucositis; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Childhood Rhabdomyosarcoma; Previously Treated Myelodysplastic Syndromes; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Wilms Tumor and Other Childhood Kidney Tumors; Recurrent/Refractory Childhood Hodgkin Lymphoma; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Unspecified Childhood Solid Tumor, Protocol Specific

  19. Development of T cell-mediated immunity after autologous stem cell transplantation: prolonged impairment of antigen-stimulated production of gamma-interferon.

    PubMed

    van der Velden, A M T; Claessen, A M E; van Velzen-Blad, H; Biesma, D H; Rijkers, G T

    2007-08-01

    The conditioning regimens for autologous SCT (auto-SCT) lead to impairment of the immune system and concomitant increase in susceptibility to infections. We studied the recovery of cellular immunity by in vitro analysis of T-cell proliferation and cytokine production profiles during the first 15 months after auto-SCT in patients with multiple myeloma and non-Hodgkin's lymphoma. PBMC were collected at 6, 9 and 15 months after transplantation and stimulated with a combination of CD2 and CD28 monoclonal antibodies, with PHA or with tetanus toxoid as recall antigen. A multiplex enzyme linked immunoassay was used to determine levels of Th1 cytokines IL-2, IFN-gamma and tumour-necrosis factor-alpha (TNF-alpha), Th2 cytokines IL-4, IL-5 and IL-13, the regulatory cytokine IL-10 and the proinflammatory cytokines IL-1alpha, IL-1beta, IL-6 and the chemokine IL-8. T-cell proliferation progressively increased from 6 to 15 months after auto-SCT. Overall, cytokine production increased after auto-SCT. Production of Th2 cytokines IL-5 and IL-13 was superior to production of Th1 cytokines IFN-gamma and TNF-alpha. We hypothesize that prolonged impairment of IFN-gamma production might contribute to the relatively high incidence of viral infections after auto-SCT.

  20. Outcome analysis of high-dose chemotherapy and autologous stem cell transplantation in adolescent and young adults with relapsed or refractory Hodgkin lymphoma.

    PubMed

    Akhtar, Saad; Rauf, Shahzad M; Elhassan, Tusneem A M; Maghfoor, Irfan

    2016-09-01

    High-dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT) can salvage many patients with relapsed or refractory Hodgkin's lymphoma (HL). We are reporting the outcome of HDC auto-SCT and the impact of 21 prognostic factors in relapsed and refractory adolescent (14-21 years) and young adult (>21-30 years) (AYA) HL patients. We used Fine and Gray's competing risk analysis method and regression model for outcome analysis. From 1996 to 2013, 290 consecutive patients with biopsy-proven HL underwent HDC auto-SCT for relapsed/refractory HL; 216 patients (74.5 %) were AYA at the time of auto-SCT. Male/female were equal, median age at auto-SCT was 22.4 years, and there were 94 adolescent (43.5 %) and 122 young adults (56.5 %). There was refractory disease in 121 (56 %) patients, relapsed in 95 (44 %). Median follow-up was 72.6 months. The Kaplan-Meier method estimated that 5-year overall survival is 62.7 % (adolescents (63.5 %), young adults (62 %)) and event-free survival was 51.3 %. Five-year cumulative incidence of disease-specific death (DS-death) is 33 % and that of DS-event is 45 %. For DS-death, the multivariate analysis identified complete remission (CR) duration of <12 months (hazard ratio (HR) 3.61, P = 0.0009), no CR after salvage (HR: 3.93, P = 0.0002), and nodular sclerosis pathology (HR 3.3, P = 0.016) and positive B symptoms (HR 2, P = 0.028) as negative factors. For DS-event, CR duration of <12 months (HR 1.88, P = 0.02), no CR after salvage (HR 3.47, P = 0.000005) and nodular sclerosis pathology (HR 1.88, P = 0.02) were found significant. The Kaplan-Meier method estimated overall survival (OS) at 36 months with 0-2:3:4 factors being 93.6:54:21 %, respectively (P value <0.001). Kaplan-Meier estimated event-free survival (EFS) at 36 months with 0-1:2:3 factors being 84.6:65:31 %, respectively (P value <0.001). Clinically, adolescents have similar outcomes as young adults. PMID:27376363

  1. First-line therapy of peripheral T-cell lymphoma: extension and long-term follow-up of a study investigating the role of autologous stem cell transplantation

    PubMed Central

    Wilhelm, M; Smetak, M; Reimer, P; Geissinger, E; Ruediger, T; Metzner, B; Schmitz, N; Engert, A; Schaefer-Eckart, K; Birkmann, J

    2016-01-01

    Current guidelines recommend consolidation with autologous stem cell transplantation (autoSCT) after induction chemotherapy for most patients with peripheral T-cell lymphoma (PTCL). This assumption is based on five prospective phase II studies, three of which included <50 patients with limited follow-up. Here we present the final analysis of the prospective German study. The treatment regimen consisted of four to six cycles of CHOP chemotherapy followed by mobilizing therapy and stem cell collection. Patients in complete remission (CR) or partial remission (PR) underwent myeloablative chemo(radio)therapy and autoSCT. From January 2001 to July 2010, 111 patients were enrolled in the study. The main subgroups were PTCL not specified (n=42) and angioimmunoblastic T-cell lymphoma (n=37). Seventy-five (68%) of the 111 patients received transplantation. The main reason for not receiving autoSCT was progressive disease. In an intent-to-treat analysis, the complete response rate after myeloablative therapy was 59%. The estimated 5-year overall survival, disease-free survival and progression-free survival rates were 44%, 54% and 39%, respectively. The results of this study confirm that upfront autoSCT can result in long-term remissions in patients with all major subtypes of PTCL and therefore should be part of first-line therapy whenever possible. PMID:27471868

  2. First-line therapy of peripheral T-cell lymphoma: extension and long-term follow-up of a study investigating the role of autologous stem cell transplantation.

    PubMed

    Wilhelm, M; Smetak, M; Reimer, P; Geissinger, E; Ruediger, T; Metzner, B; Schmitz, N; Engert, A; Schaefer-Eckart, K; Birkmann, J

    2016-01-01

    Current guidelines recommend consolidation with autologous stem cell transplantation (autoSCT) after induction chemotherapy for most patients with peripheral T-cell lymphoma (PTCL). This assumption is based on five prospective phase II studies, three of which included <50 patients with limited follow-up. Here we present the final analysis of the prospective German study. The treatment regimen consisted of four to six cycles of CHOP chemotherapy followed by mobilizing therapy and stem cell collection. Patients in complete remission (CR) or partial remission (PR) underwent myeloablative chemo(radio)therapy and autoSCT. From January 2001 to July 2010, 111 patients were enrolled in the study. The main subgroups were PTCL not specified (n=42) and angioimmunoblastic T-cell lymphoma (n=37). Seventy-five (68%) of the 111 patients received transplantation. The main reason for not receiving autoSCT was progressive disease. In an intent-to-treat analysis, the complete response rate after myeloablative therapy was 59%. The estimated 5-year overall survival, disease-free survival and progression-free survival rates were 44%, 54% and 39%, respectively. The results of this study confirm that upfront autoSCT can result in long-term remissions in patients with all major subtypes of PTCL and therefore should be part of first-line therapy whenever possible. PMID:27471868

  3. Autologous cell therapy: will it replace dermal fillers?

    PubMed

    Weiss, Robert A

    2013-05-01

    This article discusses autologous cell therapy for wrinkles in the face. Autologous fibroblast therapy is compared with dermal fillers. Study outcomes of LaViv are detailed, including a summary of adverse events. The technique for injection of autologous cells is described in addition to the duration of effect of treatment.

  4. Types of Stem Cells

    MedlinePlus

    ... PDF) Download an introduction to stem cells and stem cell research. Stem Cell Glossary Stem cell terms to know. ... stem cells blog from the International Society for Stem Cell Research. Learn About Stem Cells From Lab to You ...

  5. Treatment of chondral defects of the knee with one step matrix-assisted technique enhanced by autologous concentrated bone marrow: in vitro characterisation of mesenchymal stem cells from iliac crest and subchondral bone.

    PubMed

    de Girolamo, Laura; Bertolini, Giulia; Cervellin, Matteo; Sozzi, Gabriella; Volpi, Piero

    2010-11-01

    Cartilage repair is still an unsolved problem. In the last years many cell-based treatments have been proposed, in order to obtain good regeneration of cartilage defects. The Autologous Matrix-Induced Chondrogenesis technique (AMIC(®)) combines the micro-fracture procedure with the use of a specific biological membrane. The phenotypic feature of bone marrow cell population, harvested from iliac crest and knee subchondral bone of patients treated with the AMIC(®) technique, enhanced by autologous concentrated bone marrow, was analysed to evaluate potential variations of the cell population. Samples of eleven patients, with isolated chondral lesions grade III or IV were treated with the AMIC(®) technique, enhanced by the use of autologous concentrated bone marrow. A small fraction of bone marrow samples, both from iliac crest and from the created micro-fractures, was analysed by FACS analysis and then cultured to verify their proliferative and differentiation potential. An average of 0.04% of concentrated bone marrow cells harvested from the iliac crest, presented mesenchymal stem cell phenotype (CD34(-)/CD45(low)/CD271(high)), whereas just 0.02% of these cells were identified from the samples harvested during the creation of micro-fractures at the knee. After two passages in culture, cells expressed a peculiar profile for MSC. Only MSC from bone marrow could be long-term propagated and were able to efficiently differentiate in the cultures. Although the AMIC(®) approach has many advantages, the surgical technique in the application of the microfracture technique remains essential and affects the final result.

  6. Stem cell transplantation for neuroblastoma.

    PubMed

    Fish, J D; Grupp, S A

    2008-01-01

    High-risk neuroblastoma is a childhood malignancy with a poor prognosis. Gradual improvements in survival have correlated with therapeutic intensity, and the ability to harvest, process and store autologous hematopoietic stem cells has allowed for dose intensification beyond marrow tolerance. The use of high-dose chemotherapy with autologous hematopoietic stem cell rescue in consolidation has resulted in improvements in survival, although further advances are still needed. Newer approaches to SCT and supportive care, most notably the transition to PBSC, have resulted in further improvement in survival and decreases in treatment-related mortality. Research into experimental approaches to hematopoietic SCT is ongoing.

  7. Immunomodulatory effects of the Agaricus blazei Murrill-based mushroom extract AndoSan in patients with multiple myeloma undergoing high dose chemotherapy and autologous stem cell transplantation: a randomized, double blinded clinical study.

    PubMed

    Tangen, Jon-Magnus; Tierens, Anne; Caers, Jo; Binsfeld, Marilene; Olstad, Ole Kristoffer; Trøseid, Anne-Marie Siebke; Wang, Junbai; Tjønnfjord, Geir Erland; Hetland, Geir

    2015-01-01

    Forty patients with multiple myeloma scheduled to undergo high dose chemotherapy with autologous stem cell support were randomized in a double blinded fashion to receive adjuvant treatment with the mushroom extract AndoSan, containing 82% of Agaricus blazei Murrill (19 patients) or placebo (21 patients). Intake of the study product started on the day of stem cell mobilizing chemotherapy and continued until the end of aplasia after high dose chemotherapy, a period of about seven weeks. Thirty-three patients were evaluable for all study endpoints, while all 40 included patients were evaluable for survival endpoints. In the leukapheresis product harvested after stem cell mobilisation, increased percentages of Treg cells and plasmacytoid dendritic cells were found in patients receiving AndoSan. Also, in this group, a significant increase of serum levels of IL-1ra, IL-5, and IL-7 at the end of treatment was found. Whole genome microarray showed increased expression of immunoglobulin genes, Killer Immunoglobulin Receptor (KIR) genes, and HLA genes in the Agaricus group. Furthermore, AndoSan displayed a concentration dependent antiproliferative effect on mouse myeloma cells in vitro. There were no statistically significant differences in treatment response, overall survival, and time to new treatment. The study was registered with Clinicaltrials.gov NCT00970021.

  8. [Perinatal sources of stem cells].

    PubMed

    Piskorska-Jasiulewicz, Magdalena Maria; Witkowska-Zimny, Małgorzata

    2015-03-08

    Recently, stem cell biology has become an interesting topic. Several varieties of human stem cells have been isolated and identified in vivo and in vitro. Successful application of hematopoietic stem cells in hematology has led to the search for other sources of stem cells and expanding the scale of their application. Perinatal stem cells are a versatile cell population, and they are interesting for both scientific and practical objectives. Stem cells from perinatal tissue may be particularly useful in the clinic for autologous transplantation for fetuses and newborns, and after banking in later stages of life, as well as for in utero transplantation in the case of genetic disorders. In this review paper we focus on the extraction and therapeutic potential of stem cells derived from perinatal tissues such as the placenta, the amnion, amniotic fluid, umbilical cord blood and Wharton's jelly.

  9. Autologous haematopoietic stem cell transplants for autoimmune disease--feasibility and transplant-related mortality. Autoimmune Disease and Lymphoma Working Parties of the European Group for Blood and Marrow Transplantation, the European League Against Rheumatism and the International Stem Cell Project for Autoimmune Disease.

    PubMed

    Tyndall, A; Fassas, A; Passweg, J; Ruiz de Elvira, C; Attal, M; Brooks, P; Black, C; Durez, P; Finke, J; Forman, S; Fouillard, L; Furst, D; Holmes, J; Joske, D; Jouet, J; Kötter, I; Locatelli, F; Prentice, H; Marmont, A M; McSweeney, P; Musso, M; Peter, H H; Snowden, J A; Sullivan, K; Gratwohl, A

    1999-10-01

    This ongoing multicentre prospective phase I/II trial enrolled 74 consecutive patients from 22 centres worldwide with severe autoimmune disease, 35 with rheumatological disorders, 31 with neurological, five with haematological and three with vasculitides. They were treated with autologous peripheral blood or bone marrow transplants according to predetermined criteria. Two patients died after mobilisation before transplant. Seventy-two patients were given 73 transplants, seven bone marrow, and 66 mobilised peripheral blood stem cell transplants. The graft was manipulated to remove T and/or B cells in 43 cases. All 73 transplants engrafted. Five patients died of transplant-related complications: two from bleeding, three from infections. Two patients died of progressive disease. The transplant-related mortality at 1 year of 9% (1-17%; 95% CI) is comparable to the transplant-related mortality of 6% (3-9%; 95% CI) in patients transplanted during the same period in Europe for non-Hodgkin's lymphoma in sensitive relapse (P = 0.39). Sixty patients are evaluable for response, 40 patients (65%) showed some improvement in their disease. Haematopoietic stem cell transplants are feasible for patients with severe refractory autoimmune disease. Transplant-related mortality is comparable to results in patients with non-Hodgkin's lymphoma in responsive relapse. Two-thirds of the patients show at least some response. These preliminary data are promising. Although associated with considerable risk, randomised trials comparing autologous stem cell transplants to conventional therapy are warranted.

  10. Higher infused lymphocyte dose predicts higher lymphocyte recovery, which in turn, predicts superior overall survival following autologous hematopoietic stem cell transplantation for multiple myeloma.

    PubMed

    Hiwase, Devendra K; Hiwase, Smita; Bailey, Michael; Bollard, Geraldine; Schwarer, Anthony P

    2008-01-01

    Autologous stem cell transplantation (ASCT) is the standard of care for patients with multiple myeloma (MM) younger than 70 years. However, despite this aggressive therapy most patients will still die of progressive disease. Recent reports have suggested that lymphocyte recovery is an important predictor of relapse or progressive disease in a number of hematologic malignancies including MM. We have conducted retrospective analysis of factors that could predict overall (OS) and progression free survival (PFS) in patients with MM who had ASCT. One hundred nineteen patients with multiple myeloma underwent ASCT. The median OS and PFS were 64 and 32 months, respectively. Univariate and multivariate analysis using Cox proportional hazards regression model showed that absolute lymphocyte count on day 30 following ASCT (ALC-30), international staging system (ISS) stage at diagnosis, and age at diagnosis significantly influenced OS and PFS following ASCT. OS (96 versus 48 months, P = .04) and PFS (43 versus 29 months, P = .03) following ASCT were higher in patients with ALC-30 >or=1.0 x 10(9)/L compared to patients ALC-30 <1.0 x 10(9)/L. Higher ALC-60, ALC-100, ALC-180, and ALC-365 did not predict superior OS and PFS. Patients with early-stage disease had significantly higher OS (ISS stages I, II, and III: 96, 53, and 29 months, respectively; P = .0023) and PFS (ISS stages I, II, and III: 55.5, 31, and 12 months, respectively; P = .027) compared to patients with advanced-stage disease at diagnosis. On univariate analysis, the type of initial chemotherapy (melphalan, VAD, PCAB), lymphocyte count on day of leukapheresis, and the lymphocyte dose infused (LY-DO) significantly influenced lymphocyte recovery following ASCT. Patients who received higher lymphocyte dose (LY-DO) >or=0.2 x 10(9)/kg had higher median ALC-15 (0.25 versus 0.19 x 10(9)/L; P = .3), ALC-30 (1.20 versus 0.99 x 10(9)/L; P = .08), ALC-60 (1.90 versus 1.01 x 10(9)/L; P = .013), ALC-100 (1.58 versus 1.03 x 10

  11. Safeguarding Stem Cell-Based Regenerative Therapy against Iatrogenic Cancerogenesis: Transgenic Expression of DNASE1, DNASE1L3, DNASE2, DFFB Controlled By POLA1 Promoter in Proliferating and Directed Differentiation Resisting Human Autologous Pluripotent Induced Stem Cells Leads to their Death

    PubMed Central

    Malecki, Marek; LaVanne, Christine; Alhambra, Dominique; Dodivenaka, Chaitanya; Nagel, Sarah; Malecki, Raf

    2014-01-01

    Introduction The worst possible complication of using stem cells for regenerative therapy is iatrogenic cancerogenesis. The ultimate goal of our work is to develop a self-triggering feedback mechanism aimed at causing death of all stem cells, which resist directed differentiation, keep proliferating, and can grow into tumors. Specific aim The specific aim was threefold: (1) to genetically engineer the DNA constructs for the human, recombinant DNASE1, DNASE1L3, DNASE2, DFFB controlled by POLA promoter; (2) to bioengineer anti-SSEA-4 antibody guided vectors delivering transgenes to human undifferentiated and proliferating pluripotent stem cells; (3) to cause death of proliferating and directed differentiation resisting stem cells by transgenic expression of the human recombinant the DNases (hrDNases). Methods The DNA constructs for the human, recombinant DNASE1, DNASE1L3, DNASE2, DFFB controlled by POLA promoter were genetically engineered. The vectors targeting specifically SSEA-4 expressing stem cells were bioengineered. The healthy volunteers’ bone marrow mononuclear cells (BMMCs) were induced into human, autologous, pluripotent stem cells with non-integrating plasmids. Directed differentiation of the induced stem cells into endothelial cells was accomplished with EGF and BMP. The anti-SSEA 4 antibodies’ guided DNA vectors delivered the transgenes for the human recombinant DNases’ into proliferating stem cells. Results Differentiation of the pluripotent induced stem cells into the endothelial cells was verified by highlighting formation of tight and adherens junctions through transgenic expression of recombinant fluorescent fusion proteins: VE cadherin, claudin, zona occludens 1, and catenin. Proliferation of the stem cells was determined through highlighting transgenic expression of recombinant fluorescent proteins controlled by POLA promoter, while also reporting expression of the transgenes for the hrDNases. Expression of the transgenes for the DNases

  12. Autologous mesenchymal stem cell–derived dopaminergic neurons function in parkinsonian macaques

    PubMed Central

    Hayashi, Takuya; Wakao, Shohei; Kitada, Masaaki; Ose, Takayuki; Watabe, Hiroshi; Kuroda, Yasumasa; Mitsunaga, Kanae; Matsuse, Dai; Shigemoto, Taeko; Ito, Akihito; Ikeda, Hironobu; Fukuyama, Hidenao; Onoe, Hirotaka; Tabata, Yasuhiko; Dezawa, Mari

    2012-01-01

    A cell-based therapy for the replacement of dopaminergic neurons has been a long-term goal in Parkinson’s disease research. Here, we show that autologous engraftment of A9 dopaminergic neuron-like cells induced from mesenchymal stem cells (MSCs) leads to long-term survival of the cells and restoration of motor function in hemiparkinsonian macaques. Differentiated MSCs expressed markers of A9 dopaminergic neurons and released dopamine after depolarization in vitro. The differentiated autologous cells were engrafted in the affected portion of the striatum. Animals that received transplants showed modest and gradual improvements in motor behaviors. Positron emission tomography (PET) using [11C]-CFT, a ligand for the dopamine transporter (DAT), revealed a dramatic increase in DAT expression, with a subsequent exponential decline over a period of 7 months. Kinetic analysis of the PET findings revealed that DAT expression remained above baseline levels for over 7 months. Immunohistochemical evaluations at 9 months consistently demonstrated the existence of cells positive for DAT and other A9 dopaminergic neuron markers in the engrafted striatum. These data suggest that transplantation of differentiated autologous MSCs may represent a safe and effective cell therapy for Parkinson’s disease. PMID:23202734

  13. Treatment of Oral Mucositis in Hematologic Patients Undergoing Autologous or Allogeneic Transplantation of Peripheral Blood Stem Cells: a Prospective, Randomized Study with a Mouthwash Containing Camelia Sinensis Leaf Extract

    PubMed Central

    Carulli, Giovanni; Rocco, Melania; Panichi, Alessia; Chios, Chiara Feira; Ciurli, Ester; Mannucci, Chiara; Sordi, Elisabetta; Caracciolo, Francesco; Papineschi, Federico; Benedetti, Edoardo; Petrini, Mario

    2013-01-01

    Oral mucositis is an important side effect of hematopoietic stem cell transplantation (HCST), mainly due to toxicity of conditioning regimens. It produces significant pain and morbidity. The present study reports a prospective, randomized, non-blinded study testing the efficacy of a new mouthwash, called Baxidil Onco® (Sanitas Farmaceutici Srl, Tortona, Italy) in 60 hematologic patients undergoing HCST (28 autologous, 32 allogeneic). Baxidil Onco®, used three times a day from Day -1 to Day +30, in addition to standard prophylactic schedules, was administered to 14 patients undergoing autologous and 14 patients undergoing allogeneic HCST. The remaining 32 patients (14 autologous and 18 HCST) were treated only with standard prophylactic schedules and served as control. In our study, the overall incidence of oral mucositis, measured according to the World Health Organization 0-4 scale, was 50% in the Baxidl Onco® group versus 82% in the control group (P=0.022). In addition, a significant reduction in scale 2-4 oral mucositis was observed in the Baxidil Onco® group (25% vs 56.2%; P=0.0029). The results obtained indicate that incidence, severity and duration of oral mucositis induced by conditioning regimens for HCST can be significantly reduced by oral rinsing with Baxidil Onco®, in addition to the standard prophylaxis scheme. Since Camelia Sinensin extract, which is used to produce green tea, is the main agent in this mouthwash, we hypothesize that the anti-oxidative properties of polyphenolic compounds of tea might exert protective effects on oral mucosa. PMID:23888242

  14. Autologous stem cell transplantation for patients aged 60 years or older with refractory or relapsed classical Hodgkin's lymphoma: a retrospective analysis from the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC).

    PubMed

    Stamatoullas, A; Brice, P; Gueye, M S; Mareschal, S; Chevallier, P; Bouabdallah, R; Nguyenquoc, S; Francois, S; Turlure, P; Ceballos, P; Monjanel, H; Bourhis, J-H; Guillerm, G; Mohty, M; Biron, P; Cornillon, J; Belhadj, K; Bonmati, C; Dilhuydy, M-S; Huynh, A; Bernard, M; Chrétien, M-L; Peffault de Latour, R; Tilly, H

    2016-07-01

    This report retrospectively analyzed the outcome of 91 patients aged 60 years or older with refractory/relapsed (R/R) classical Hodgkin's lymphoma (cHL) who underwent autologous stem cell transplantation (ASCT) between 1992 and 2013 and were reported to the French Society of Bone Marrow Transplantation and Cell Therapies registry. The median age at transplant was 63 years. The majority of patients exhibited disease chemosensitivity to salvage treatment (57 complete responses, 30 partial responses, 1 progressive disease and 3 unknown). The most frequent conditioning regimen consisted of BCNU, cytarabine, etoposide, melphalan (BEAM) chemotherapy (93%). With a median follow-up of 54 months, 5-year estimates of overall survival (OS) and progression free survival (PFS) for the entire group were 67 and 54%, respectively. Despite the missing data, in univariate analysis, the number of salvage chemotherapy lines (1-2 versus ⩾3) significantly influenced the OS, unlike the other prognostic factors (stage III-IV at relapse, disease status before ASCT and negative positron emission tomography (PET) scan) encountered in younger patients. In spite of its limitations, this retrospective study with a long-term follow-up suggests that ASCT is a valid treatment option for chemosensitive R/R cHL in selected elderly patients, with an acceptable rate of toxicity.

  15. Autologous stem cell transplantation for patients aged 60 years or older with refractory or relapsed classical Hodgkin's lymphoma: a retrospective analysis from the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC).

    PubMed

    Stamatoullas, A; Brice, P; Gueye, M S; Mareschal, S; Chevallier, P; Bouabdallah, R; Nguyenquoc, S; Francois, S; Turlure, P; Ceballos, P; Monjanel, H; Bourhis, J-H; Guillerm, G; Mohty, M; Biron, P; Cornillon, J; Belhadj, K; Bonmati, C; Dilhuydy, M-S; Huynh, A; Bernard, M; Chrétien, M-L; Peffault de Latour, R; Tilly, H

    2016-07-01

    This report retrospectively analyzed the outcome of 91 patients aged 60 years or older with refractory/relapsed (R/R) classical Hodgkin's lymphoma (cHL) who underwent autologous stem cell transplantation (ASCT) between 1992 and 2013 and were reported to the French Society of Bone Marrow Transplantation and Cell Therapies registry. The median age at transplant was 63 years. The majority of patients exhibited disease chemosensitivity to salvage treatment (57 complete responses, 30 partial responses, 1 progressive disease and 3 unknown). The most frequent conditioning regimen consisted of BCNU, cytarabine, etoposide, melphalan (BEAM) chemotherapy (93%). With a median follow-up of 54 months, 5-year estimates of overall survival (OS) and progression free survival (PFS) for the entire group were 67 and 54%, respectively. Despite the missing data, in univariate analysis, the number of salvage chemotherapy lines (1-2 versus ⩾3) significantly influenced the OS, unlike the other prognostic factors (stage III-IV at relapse, disease status before ASCT and negative positron emission tomography (PET) scan) encountered in younger patients. In spite of its limitations, this retrospective study with a long-term follow-up suggests that ASCT is a valid treatment option for chemosensitive R/R cHL in selected elderly patients, with an acceptable rate of toxicity. PMID:27042842

  16. Co-infusion of autologous adipose tissue derived neuronal differentiated mesenchymal stem cells and bone marrow derived hematopoietic stem cells, a viable therapy for post-traumatic brachial plexus injury: a case report.

    PubMed

    Thakkar, Umang G; Vanikar, Aruna V; Trivedi, Hargovind L

    2014-01-01

    Stem cell therapy is emerging as a viable approach in regenerative medicine. A 31-year-old male with brachial plexus injury had complete sensory-motor loss since 16 years with right pseudo-meningocele at C5-D1 levels and extra-spinal extension up to C7-D1, with avulsion on magnetic resonance imaging and irreversible damage. We generated adipose tissue derived neuronal differentiated mesenchymal stem cells (N-AD-MSC) and bone marrow derived hematopoietic stem cells (HSC-BM). Neuronal stem cells expressed β-3 tubulin and glial fibrillary acid protein which was confirmed on immunofluorescence. On day 14, 2.8 ml stem cell inoculum was infused under local anesthesia in right brachial plexus sheath by brachial block technique under ultrasonography guidance with a 1.5-inch-long 23 gauge needle. Nucleated cell count was 2 × 10 4 /μl, CD34+ was 0.06%, and CD45-/90+ and CD45-/73+ were 41.63% and 20.36%, respectively. No untoward effects were noted. He has sustained recovery with re-innervation over a follow-up of 4 years documented on electromyography-nerve conduction velocity study. PMID:25116721

  17. The Role of E-Cadherin in Maintaining the Barrier Function of Corneal Epithelium after Treatment with Cultured Autologous Oral Mucosa Epithelial Cell Sheet Grafts for Limbal Stem Deficiency

    PubMed Central

    Hoft, Richard H.; Wood, Andrew; Oliva, Joan; Niihara, Hope; Makalinao, Andrew; Thropay, Jacquelyn; Pan, Derek; Tiger, Kumar; Garcia, Julio; Laporte, Amanda; French, Samuel W.; Niihara, Yutaka

    2016-01-01

    The role of E-cadherin in epithelial barrier function of cultured autologous oral mucosa epithelial cell sheet (CAOMECS) grafts was examined. CAOMECS were cultured on a temperature-responsive surface and grafted onto rabbit corneas with Limbal Stem Cell Deficiency (LSCD). E-cadherin levels were significantly higher in CAOMECS compared to normal and LSCD epithelium. Beta-catenin colocalized with E-cadherin in CAOMECS cell membranes while phosphorylated beta-catenin was significantly increased. ZO-1, occludin, and Cnx43 were also strongly expressed in CAOMECS. E-cadherin and beta-catenin localization at the cell membrane was reduced in LSCD corneas, while CAOMECS-grafted corneas showed a restoration of E-cadherin and beta-catenin expression. LSCD corneas did not show continuous staining for ZO-1 or for Cnx43, while CAOMECS-grafted corneas showed a positive expression of ZO-1 and Cnx43. Cascade Blue® hydrazide did not pass through CAOMECS. Because E-cadherin interactions are calcium-dependent, EGTA was used to chelate calcium and disrupt cell adhesion. EGTA-treated CAOMECS completely detached from cell culture surface, and E-cadherin levels were significantly decreased. In conclusion, E cadherin high expression contributed to CAOMECS tight and gap junction protein recruitment at the cell membrane, thus promoting cellular adhesion and a functional barrier to protect the ocular surface. PMID:27777792

  18. Stem cells for spine surgery.

    PubMed

    Schroeder, Joshua; Kueper, Janina; Leon, Kaplan; Liebergall, Meir

    2015-01-26

    In the past few years, stem cells have become the focus of research by regenerative medicine professionals and tissue engineers. Embryonic stem cells, although capable of differentiating into cell lineages of all three germ layers, are limited in their utilization due to ethical issues. In contrast, the autologous harvest and subsequent transplantation of adult stem cells from bone marrow, adipose tissue or blood have been experimentally utilized in the treatment of a wide variety of diseases ranging from myocardial infarction to Alzheimer's disease. The physiologic consequences of stem cell transplantation and its impact on functional recovery have been studied in countless animal models and select clinical trials. Unfortunately, the bench to bedside translation of this research has been slow. Nonetheless, stem cell therapy has received the attention of spinal surgeons due to its potential benefits in the treatment of neural damage, muscle trauma, disk degeneration and its potential contribution to bone fusion.

  19. Steady-state pharmacokinetics of oral voriconazole and its primary metabolite, N-oxide voriconazole, pre- and post-autologous peripheral stem cell transplantation.

    PubMed

    Amsden, Jarrett R; Gubbins, Paul O; McConnell, Scott; Anaissie, Elias

    2013-07-01

    Voriconazole (VCZ) is frequently utilized for prevention and treatment of invasive fungal infections in peripheral stem cell transplant (PSCT) patients. We performed an open-label pharmacokinetic study to compare VCZ and N-oxide voriconazole (N-oxide VCZ) pharmacokinetics in patients pre- and post-PSCT. Ten patients completed both sampling periods. The pharmacokinetics of VCZ were unchanged; however, those of N-oxide VCZ were significantly different pre- and post-PSCT. PMID:23629717

  20. Steady-State Pharmacokinetics of Oral Voriconazole and Its Primary Metabolite, N-Oxide Voriconazole, Pre- and Post-Autologous Peripheral Stem Cell Transplantation

    PubMed Central

    Gubbins, Paul O.; McConnell, Scott; Anaissie, Elias

    2013-01-01

    Voriconazole (VCZ) is frequently utilized for prevention and treatment of invasive fungal infections in peripheral stem cell transplant (PSCT) patients. We performed an open-label pharmacokinetic study to compare VCZ and N-oxide voriconazole (N-oxide VCZ) pharmacokinetics in patients pre- and post-PSCT. Ten patients completed both sampling periods. The pharmacokinetics of VCZ were unchanged; however, those of N-oxide VCZ were significantly different pre- and post-PSCT. PMID:23629717

  1. Depletion of autoreactive immunologic memory followed by autologous hematopoietic stem cell transplantation in patients with refractory SLE induces long-term remission through de novo generation of a juvenile and tolerant immune system.

    PubMed

    Alexander, Tobias; Thiel, Andreas; Rosen, Oliver; Massenkeil, Gero; Sattler, Arne; Kohler, Siegfried; Mei, Henrik; Radtke, Hartmut; Gromnica-Ihle, Erika; Burmester, Gerd-Rüdiger; Arnold, Renate; Radbruch, Andreas; Hiepe, Falk

    2009-01-01

    Clinical trials have indicated that immunoablation followed by autologous hematopoietic stem cell transplantation (ASCT) has the potential to induce clinical remission in patients with refractory systemic lupus erythematosus (SLE), but the mechanisms have remained unclear. We now report the results of a single-center prospective study of long-term immune reconstitution after ASCT in 7 patients with SLE. The clinical remissions observed in these patients are accompanied by the depletion of autoreactive immunologic memory, reflected by the disappearance of pathogenic anti-double-stranded DNA (dsDNA) antibodies and protective antibodies in serum and a fundamental resetting of the adaptive immune system. The latter comprises recurrence of CD31(+)CD45RA(+)CD4(+) T cells (recent thymic emigrants) with a doubling in absolute numbers compared with age-matched healthy controls at the 3-year follow-up (P = .016), the regeneration of thymic-derived FoxP3(+) regulatory T cells, and normalization of peripheral T-cell receptor (TCR) repertoire usage. Likewise, responders exhibited normalization of the previously disturbed B-cell homeostasis with numeric recovery of the naive B-cell compartment within 1 year after ASCT. These data are the first to demonstrate that both depletion of the autoreactive immunologic memory and a profound resetting of the adaptive immune system are required to reestablish self-tolerance in SLE.

  2. Stem Cell Basics

    MedlinePlus

    ... stem cells? What are the potential uses of human stem cells and the obstacles that must be overcome before ... two kinds of stem cells from animals and humans: embryonic stem cells and non-embryonic "somatic" or "adult" stem cells . ...

  3. Learn About Stem Cells

    MedlinePlus

    ... PDF) Download an introduction to stem cells and stem cell research. Stem Cell Glossary Stem cell terms to know. ... ISSCR Get Involved Media © 2015 International Society for Stem Cell Research Terms of Use Disclaimer Privacy Policy

  4. Rituximab Maintenance Therapy After Autologous Stem-Cell Transplantation in Patients With Relapsed CD20+ Diffuse Large B-Cell Lymphoma: Final Analysis of the Collaborative Trial in Relapsed Aggressive Lymphoma

    PubMed Central

    Gisselbrecht, Christian; Schmitz, Norbert; Mounier, Nicolas; Singh Gill, Devinder; Linch, David C.; Trneny, Marek; Bosly, Andre; Milpied, Noel J.; Radford, John; Ketterer, Nicolas; Shpilberg, Ofer; Dührsen, Ulrich; Hagberg, Hans; Ma, David D.; Viardot, Andreas; Lowenthal, Ray; Brière, Josette; Salles, Gilles; Moskowitz, Craig H.; Glass, Bertram

    2012-01-01

    Purpose The standard treatment for relapsed diffuse large B-cell lymphoma (DLBCL) is salvage chemotherapy followed by high-dose therapy and autologous stem-cell transplantation (ASCT). The impact of maintenance rituximab after ASCT is not known. Patients and Methods In total, 477 patients with CD20+ DLBCL who were in their first relapse or refractory to initial therapy were randomly assigned to one of two salvage regimens. After three cycles of salvage chemotherapy, the responding patients received high-dose chemotherapy followed by ASCT. Then, 242 patients were randomly assigned to either rituximab every 2 months for 1 year or observation. Results After ASCT, 122 patients received rituximab, and 120 patients were observed only. The median follow-up time was 44 months. The 4-year event-free survival (EFS) rates after ASCT were 52% and 53% for the rituximab and observation groups, respectively (P = .7). Treatment with rituximab was associated with a 15% attributable risk of serious adverse events after day 100, with more deaths (six deaths v three deaths in the observation arm). Several factors affected EFS after ASCT (P < .05), including relapsed disease within 12 months (EFS: 46% v 56% for relapsed disease after 12 months), secondary age-adjusted International Prognostic Index (saaIPI) more than 1 (EFS: 37% v 61% for saaIPI < 1), and prior treatment with rituximab (EFS: 47% v 59% for no prior rituximab). A significant difference in EFS between women (63%) and men (46%) was also observed in the rituximab group. In the Cox model for maintenance, the saaIPI was a significant prognostic factor (P < .001), as was male sex (P = .01). Conclusion In relapsed DLBCL, we observed no difference between the control group and the rituximab maintenance group and do not recommend rituximab after ASCT. PMID:23091101

  5. High-Dose [131I]Tositumomab (anti-CD20) Radioimmunotherapy and Autologous Hematopoietic Stem Cell Transplantation for Adults ≥ 60 Years Old with Relapsed or Refractory B-Cell Lymphoma

    SciTech Connect

    Gopal, Ajay K.; Rajendran, Joseph G.; Gooley, Ted; Pagel, John M.; Fisher, Darrell R.; Petersdorf, Stephen; Maloney, David G.; Eary, Janet F.; Appelbaum, Frederick R.; Press, Oliver W.

    2007-04-10

    Purpose: The majority of patients with relapsed or refractory B-cell, non-Hodgkin’s lymphoma (NHL) are over 60 years of age, yet they are often denied potentially curative high-dose therapy and autologous stem cell transplants (ASCT) due to the risk of excessive treatment-related morbidity and mortality. Myeloablative anti-CD20 radioimmunotherapy (RIT) can deliver curative radiation doses to tumor sites while limiting exposure to normal organs and may be particularly suited for older adults requiring high-dose therapy. Methods: Patients over age 60 with relapsed B-NHL received infusions of tositumomab anti-CD20 antibody labeled with 5-10mCi I-131 tracer for dosimetry purposes followed 10 days later by individualized therapeutic infusions of I-131-tositumomab (median 525 mCi, range 328-1154 mCi) to deliver 25-27Gy to the critical normal organ receiving the highest radiation dose. ASCT was performed approximately 2 weeks after therapy. Results: Twenty-four patients with a median age of 64 (range 60-76) who had received a median of four prior regimens (range 2-14) were treated. Thirteen (54%) had chemotherapy-resistant disease. The estimated 3-year overall and progression-free survivals were 59% and 51%, respectively with a median follow-up of 2.9 years (range 1-6 years). All patients experienced expected myeloablation with engraftment of platelets (≥20K/µL) and neutrophils (≥500/µL) occurring a median of 9 and 15 days, respectively following ASCT. There were no treatment-related deaths, and only two patients experienced grade 4 non-hematologic toxicity. Conclusions: Myeloablative RIT and ASCT is a safe and effective therapeutic option for older adults with relapsed B-NHL.

  6. Myeloablative Anti-CD20 Radioimmunotherapy +/- High-Dose Chemotherapy Followed by Autologous Stem Cell Support for Relapsed/Refractory B-Cell Lymphoma Results in Excellent Long-Term Survival

    PubMed Central

    Schreiber, Susanne; Schmidt, Burkhard; Wester, Hans-Jürgen; Schwaiger, Markus; Peschel, Christian; von Schilling, Christoph

    2013-01-01

    Background Radioimmunotherapy (RIT) has been used to treat relapsed/refractory CD20+ Non-Hodgkin lymphoma (NHL). Myeloablative anti-CD20 RIT followed by autologous stem cell infusion (ASCT) enables high radiation doses to lymphoma sites. We performed a phase I/II trial to assess feasibility and survival. Methods Twenty-three patients with relapsed/refractory NHL without complete remission (CR) to salvage chemotherapy were enrolled to evaluate RIT with Iodine-131 labelled rituximab (131I-rituximab) in a myeloablative setting. Biodistribution and dosimetric studies were performed to determine 131I activity required to induce a total body dose of 21-27Gy to critical organs. In 6/23 patients RIT was combined with high-dose chemotherapy. 8/23 patients received a sequential high-dose chemotherapy with a second ASCT. The median follow-up is 9.5 years. Results 6.956-19.425GBq of 131I was delivered to achieve the limiting organ dose to lungs or kidneys. No grade III/IV non-hematologic toxicity was seen with RIT alone. Significant grade III/IV toxicity (mucositis, fever, infection, one therapy related death) was observed in patients treated with RIT combined with high-dose chemotherapy. The overall response rate was 87% (64% CR). The median progression-free (PFS) and overall survival (OS) is 47.5 and 101.5 months. An international prognostic index score >1 was predictive for OS. Conclusion Myeloablative RIT with 131I-rituximab followed by ASCT is feasible, well-tolerated and effective in high risk CD20+ NHL. Combination of RIT and high-dose chemotherapy increased toxicity significantly. Long-term results for PFS and OS are encouraging. PMID:23765188

  7. Plerixafor and granulocyte colony-stimulating factor for first-line steady-state autologous peripheral blood stem cell mobilization in lymphoma and multiple myeloma: results of the prospective PREDICT trial

    PubMed Central

    Russell, Nigel; Douglas, Kenny; Ho, Anthony D.; Mohty, Mohamad; Carlson, Kristina; Ossenkoppele, G.J.; Milone, Giuseppe; Pareja, Macarena Ortiz; Shaheen, Daniel; Willemsen, Arnold; Whitaker, Nicky; Chabannon, Christian

    2013-01-01

    In Europe, the combination of plerixafor + granulocyte colony-stimulating factor is approved for the mobilization of hematopoietic stem cells for autologous transplantation in patients with lymphoma and myeloma whose cells mobilize poorly. The purpose of this study was to further assess the safety and efficacy of plerixafor + granulocyte colony-stimulating factor for front-line mobilization in European patients with lymphoma or myeloma. In this multicenter, open label, single-arm study, patients received granulocyte colony-stimulating factor (10 μg/kg/day) subcutaneously for 4 days; on the evening of day 4 they were given plerixafor (0.24 mg/kg) subcutaneously. Patients underwent apheresis on day 5 after a morning dose of granulocyte colony-stimulating factor. The primary study objective was to confirm the safety of mobilization with plerixafor. Secondary objectives included assessment of efficacy (apheresis yield, time to engraftment). The combination of plerixafor + granulocyte colony-stimulating factor was used to mobilize hematopoietic stem cells in 118 patients (90 with myeloma, 25 with non-Hodgkin's lymphoma, 3 with Hodgkin's disease). Treatment-emergent plerixafor-related adverse events were reported in 24 patients. Most adverse events occurred within 1 hour after injection, were grade 1 or 2 in severity and included gastrointestinal disorders or injection-site reactions. The minimum cell yield (≥2×106 CD34+ cells/kg) was harvested in 98% of patients with myeloma and in 80% of those with non-Hodgkin's lymphoma in a median of one apheresis. The optimum cell dose (≥5×106 CD34+ cells/kg for non-Hodgkin's lymphoma or ≥6×106 CD34+ cells/kg for myeloma) was harvested in 89% of myeloma patients and 48% of non-Hodgkin's lymphoma patients. In this prospective, multicenter European study, mobilization with plerixafor + granulocyte colony-stimulating factor allowed the majority of patients with myeloma or non-Hodgkin's lymphoma to undergo transplantation with

  8. Stem cells in cardiac repair.

    PubMed

    Henning, Robert J

    2011-01-01

    Myocardial infarction is the leading cause of death among people in industrialized nations. Although the heart has some ability to regenerate after infarction, myocardial restoration is inadequate. Consequently, investigators are currently exploring the use of human embryonic stem cells (hESCs), skeletal myoblasts and adult bone marrow stem cells to limit infarct size. hESCs are pluripotent cells that can regenerate myocardium in infarcted hearts, attenuate heart remodeling and contribute to left ventricle (LV) systolic force development. Since hESCs can form heart teratomas, investigators are differentiating hESCs toward cardiac progenitor cells prior to transplantation into hearts. Large quantities of hESCs cardiac progenitor cells, however, must be generated, immune rejection must be prevented and grafts must survive over the long term to significantly improve myocardial performance. Transplanted autologous skeletal myoblasts can survive in infarcted myocardium in small numbers, proliferate, differentiate into skeletal myofibers and increase the LV ejection fraction. These cells, however, do not form electromechanical connections with host cardiomyocytes. Consequently, electrical re-entry can occur and cause cardiac arrhythmias. Autologous bone marrow mononuclear cells contain hematopoietic and mesenchymal stem cells. In several meta-analyses, patients with coronary disease who received autologous bone marrow cells by intracoronary injection show significant 3.7% (range: 1.9-5.4%) increases in LV ejection fraction, decreases in LV end-systolic volume of -4.8 ml (range: -1.4 to -8.2 ml) and reductions in infarct size of 5.5% (-1.9 to -9.1%), without experiencing arrhythmias. Bone marrow cells appear to release biologically active factors that limit myocardial damage. Unfortunately, bone marrow cells from patients with chronic diseases propagate poorly and can die prematurely. Substantial challenges must be addressed and resolved to advance the use of stem cells

  9. Challenging the FDA's authority to regulate autologous adult stem cells for therapeutic use: Celltex therapeutics' partnership with RNL Bio, substantial medical risks, and the implications of United States v. Regenerative Sciences.

    PubMed

    Drabiak-Syed, Katherine

    2013-01-01

    This Article examines the convergence of three corporations that have attempted to capitalize on translating emerging research into clinical procedures by manufacturing and facilitating the process for patients to obtain mesenchymal stem cell (MSC) injections. Although the Food and Drug Administration (FDA) has asserted its authority to regulate somatic cell therapy products like MSCs under the Public Health Service Act and the Food, Drug, and Cosmetic Act, some manufacturers have attempted to circumvent FDA regulation through various mechanisms and argue that their products do not fall within the definition of a biological product or drug. However, scientific knowledge of using MSCs for clinical therapy remains in its infancy, and MSCs pose a number of serious risks to patients. This Article focuses on the development of Celltex, a company based in Sugar Land, Texas that manufactures and facilitates the injection of autologous MSCs; RNL Bio, a company that licenses its operations technology to Celltex; and Regenerative Sciences, a company based in Broomfield, Colorado that was recently involved in litigation with the FDA. Corporate circumvention of intended regulatory oversight exposes patients to potentially inefficacious products that could contribute to serious medical injuries such as viruses, myocardial infarction, cancer, or death.

  10. Interaction between IL-6 and TNF-α genotypes associated with bacteremia in multiple myeloma patients submitted to autologous stem cell transplantation (ASCT).

    PubMed

    Trigo, Fernanda M B; Luizon, Marcelo R; Dutra, Hélio S; Maiolino, Angelo; Nucci, Márcio; Simões, Belinda P

    2014-01-01

    Stem cell transplantation affects patient׳s vulnerability to infections due to immunological changes related to chemotherapy. Multiple myeloma is characterized by susceptibility to infections, and IL-6 and TNF-α increased levels affect immune response (IR). Polymorphisms in promoter region of cytokine genes may alter expression levels and affect IR. We performed interaction analysis of IL-6 (-174G/C) and TNF-α (-308G/A) polymorphisms with infection susceptibility in 148 patients classified accordingly to infection status and found an interaction when compared groups with and without bacteremia (p=0.0380). The interaction may be more important than single effects for the IR associated with the infection susceptibility in ASCT.

  11. Safety and efficacy of G-CSF mobilization and collection of autologous peripheral blood stem cells in children with cerebral palsy.

    PubMed

    Moon, Jin-Hwa; Kim, Mi Jung; Song, Soon-Young; Lee, Young-Jun; Choi, Yun Young; Kim, Seung Hyun; Lee, Young-Ho

    2013-12-01

    We hypothesized that mobilized peripheral blood stem cells (PBSCs) could be useful for treating neurological impairments and therefore assessed the safety of administering G-CSF followed by collecting PBSC in children with cerebral palsy (CP). G-CSF (10 μg/kg/day) was administered subcutaneously for 5 days, and apheresis was performed to collect PBSC via central venous catheter. G-CSF-related events occurred in 3 patients (fever in 2, irritability in 1). No catheter-related complications were reported. None of the patients needed platelet transfusion or calcium replacement during apheresis. Mobilization with G-CSF followed by PBSC collection appears to be safe and feasible in CP children.

  12. Histological and Immunohistochemical Evaluation of Autologous Cultured Bone Marrow Mesenchymal Stem Cells and Bone Marrow Mononucleated Cells in Collagenase-Induced Tendinitis of Equine Superficial Digital Flexor Tendon

    PubMed Central

    Crovace, Antonio; Lacitignola, Luca; Rossi, Giacomo; Francioso, Edda

    2010-01-01

    The aim of this study was to compare treatment with cultured bone marrow stromal cells (cBMSCs), bone marrow Mononucleated Cells (BMMNCs), and placebo to repair collagenase-induced tendinitis in horses. In six adult Standardbred horses, 4000 IU of collagenase were injected in the superficial digital flexor tendon (SDFT). Three weeks after collagenase treatment, an average of either 5.5 × 106 cBMSCs or 1.2 × 108 BMMNCs, fibrin glue, and saline solution was injected intralesionally in random order. In cBMSC- and BMMNCS-treated tendons, a high expression of cartilage oligomeric matrix protein (COMP) and type I collagen, but low levels of type III collagen were revealed by immunohistochemistry, with a normal longitudinally oriented fiber pattern. Placebo-treated tendons expressed very low quantities of COMP and type I collagen but large numbers of randomly oriented type III collagen fibers. Both cBMSC and BMMNCS grafts resulted in a qualitatively similar heling improvement of tendon extracellular matrix, in terms of the type I/III collagen ratio, fiber orientation, and COMP expression. PMID:20445779

  13. Outcome with lenalidomide plus dexamethasone followed by early autologous stem cell transplantation in patients with newly diagnosed multiple myeloma on the ECOG-ACRIN E4A03 randomized clinical trial: long-term follow-up.

    PubMed

    Biran, N; Jacobus, S; Vesole, D H; Callander, N S; Fonseca, R; Williams, M E; Abonour, R; Katz, M S; Rajkumar, S V; Greipp, P R; Siegel, D S

    2016-01-01

    In Eastern Cooperative Oncology Group-ACRIN E4A03, on completion of four cycles of therapy, newly diagnosed multiple myeloma patients had the option of proceeding to autologous peripheral blood stem cell transplant (ASCT) or continuing on their assigned therapy lenalidomide plus low-dose dexamethasone (Ld) or lenalidomide plus high-dose dexamethasone (LD). This landmark analysis compared the outcome of 431 patients surviving their first four cycles of therapy pursuing early ASCT to those continuing on their assigned therapy. Survival distributions were estimated using the Kaplan-Meier method and compared with log-rank test. Ninety patients (21%) opted for early ASCT. The 1-, 2-, 3-, 4- and 5-year survival probability estimates were higher for early ASCT versus no early ASCT at 99, 93, 91, 85 and 80% versus 94, 84, 75, 65 and 57%, respectively. The median overall survival (OS) in the early versus no early ASCT group was not reached (NR) versus 5.78 years. In patients <65 years of age, median OS in the early versus no early ASCT groups was NR in both, hazard ratio 0.79, 95% confidence interval: (0.50, 0.25). In patients ⩾65 years of age, median OS in the early versus no early ASCT was NR versus 5.11 years. ASCT dropped out of statistical significance (P=0.080). Patients opting for ASCT after induction Ld/LD had a higher survival probability and improvement in OS regardless of dexamethasone dose density. PMID:27588519

  14. Survival of multiple myeloma patients aged 65-70 years in the era of novel agents and autologous stem cell transplantation. A multicenter retrospective collaborative study of the Japanese Society of Myeloma and the European Myeloma Network.

    PubMed

    Ozaki, Shuji; Harada, Takeshi; Saitoh, Takayuki; Shimazaki, Chihiro; Itagaki, Mitsuhiro; Asaoku, Hideki; Kuroda, Yoshiaki; Chou, Takaaki; Yoshiki, Yumiko; Suzuki, Kenshi; Murakami, Hirokazu; Hayashi, Kunihiko; Mina, Roberto; Palumbo, Antonio; Shimizu, Kazuyuki

    2014-01-01

    Novel agents such as thalidomide, lenalidomide and bortezomib have dramatically changed the treatment paradigm of multiple myeloma (MM). However, it is not clear whether these agents improve the prognosis of elderly patients who have undergone autologous stem cell transplantation (auto-SCT). We retrospectively analyzed the outcome of 318 newly diagnosed patients aged 65–70 years who were treated between January 1, 2004, and December 31, 2009. As initial therapy, 192 patients were treated with conventional chemotherapy,88 with novel agent-containing regimens, 21 with conventional chemotherapy plus auto-SCT and the remaining 17 with novel agents plus auto-SCT. The median progression-free survival was 19.1, 24.5, 26.8 and 35.2 months, respectively, and the 5-year overall survival (OS) was 40, 62, 63 and 87%, respectively. Initial therapy with novel agents (p < 0.001) or auto-SCT (p < 0.02) significantly improved OS compared with the group without these treatment modalities. Salvage therapy with novel agents also significantly improved survival after relapse compared with conventional chemotherapy alone (p < 0.04). In a multivariate analysis, the use of novel agents was an independent prognostic factor significantly associated with extended OS(p < 0.003). These results indicate that novel agents and auto-SCT had a major impact on OS in eligible patients in this subgroup of MM.

  15. Outcome with lenalidomide plus dexamethasone followed by early autologous stem cell transplantation in patients with newly diagnosed multiple myeloma on the ECOG-ACRIN E4A03 randomized clinical trial: long-term follow-up

    PubMed Central

    Biran, N; Jacobus, S; Vesole, D H; Callander, N S; Fonseca, R; Williams, M E; Abonour, R; Katz, M S; Rajkumar, S V; Greipp, P R; Siegel, D S

    2016-01-01

    In Eastern Cooperative Oncology Group-ACRIN E4A03, on completion of four cycles of therapy, newly diagnosed multiple myeloma patients had the option of proceeding to autologous peripheral blood stem cell transplant (ASCT) or continuing on their assigned therapy lenalidomide plus low-dose dexamethasone (Ld) or lenalidomide plus high-dose dexamethasone (LD). This landmark analysis compared the outcome of 431 patients surviving their first four cycles of therapy pursuing early ASCT to those continuing on their assigned therapy. Survival distributions were estimated using the Kaplan–Meier method and compared with log-rank test. Ninety patients (21%) opted for early ASCT. The 1-, 2-, 3-, 4- and 5-year survival probability estimates were higher for early ASCT versus no early ASCT at 99, 93, 91, 85 and 80% versus 94, 84, 75, 65 and 57%, respectively. The median overall survival (OS) in the early versus no early ASCT group was not reached (NR) versus 5.78 years. In patients <65 years of age, median OS in the early versus no early ASCT groups was NR in both, hazard ratio 0.79, 95% confidence interval: (0.50, 0.25). In patients ⩾65 years of age, median OS in the early versus no early ASCT was NR versus 5.11 years. ASCT dropped out of statistical significance (P=0.080). Patients opting for ASCT after induction Ld/LD had a higher survival probability and improvement in OS regardless of dexamethasone dose density. PMID:27588519

  16. High pre-transplant serum ferritin and busulfan-thiotepa conditioning regimen as risk factors for hepatic sinusoidal obstructive syndrome after autologous stem cell transplantation in patients with malignant lymphoma.

    PubMed

    Hwang, Doh Yu; Kim, Soo-Jeong; Cheong, June-Won; Kim, Yundeok; Jang, Ji Eun; Lee, Jung Yeon; Min, Yoo Hong; Yang, Woo Ick; Kim, Jin Seok

    2016-01-01

    Few studies have evaluated the risk factors for hepatic sinusoidal obstructive syndrome (SOS) in patients with malignant lymphoma receiving autologous stem cell transplantation (ASCT). We retrospectively analyzed 132 malignant lymphoma patients who underwent ASCT. Intravenous busulfan-based conditioning regimens were used in 108 (81.8%) patients. The combination of heparin and ursodeoxycholic acid was used for prophylaxis of SOS. Hepatic SOS was developed in 10 (7.6%) patients at a median of 30 days post-ASCT. In nine (90.0%) patients, SOS was diagnosed after 20 days post-ASCT. Two patients developed severe SOS and eventually died from multiple organ failure. In multivariate analysis, the use of the busulfan-thiotepa conditioning regimen (p = 0.003) and a high pre-transplant serum ferritin level (≥ 950 ng/mL) (p = 0.003) were risk factors for hepatic SOS. The evaluation of pre-transplant serum ferritin may be helpful in determining the most appropriate conditioning regimen with a lower risk of SOS.

  17. Effect of melphalan 140 mg/m(2) vs 200 mg/m(2) on toxicities and outcomes in multiple myeloma patients undergoing single autologous stem cell transplantation-a single center experience.

    PubMed

    Katragadda, Lakshmikanth; McCullough, Lindsay M; Dai, Yunfeng; Hsu, Jack; Byrne, Michael; Hiemenz, John; May, Stratford; Cogle, Christopher R; Norkin, Maxim; Brown, Randy A; Wingard, John R; Chang, Myron; Moreb, Jan S

    2016-08-01

    Although melphalan at a dose of 140 mg/m(2) (MEL140) is an acceptable conditioning regimen for autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients, very few studies compared it to the most commonly used dose of 200 mg/m(2) (MEL200). A retrospective review of records of MM patients (2001-2010) identified 33 patients who received MEL140 and 96 patients who received MEL200. As expected, significantly higher percentage of patients in the MEL140 arm were >65 years or had cardiac ejection fraction <50%, had Karnofsky score <80, or had creatinine >2 at the time of ASCT (P≤.01). There were no significant differences in incidence of treatment related mortality and morbidity. At a median follow-up of 74 months from ASCT, there were no significant differences in relapse free survival (RFS) and overall survival (OS) between the two groups. Similar proportion had myeloma status improve to ≥VGPR at 3 months post-ASCT. Usage of post-ASCT maintenance was similar. In multivariate cox proportional hazards model, only disease status of ≥VGPR at the time of ASCT significantly improved RFS (P=.024), but not OS (P=.104). In conclusion, MM patients who received MEL140 had similar long-term outcomes to MEL200 patients despite their older age and co-morbidities.

  18. Salvage bortezomib-dexamethasone and high-dose melphalan (HDM) and autologous stem cell support (ASCT) in myeloma patients at first relapse after HDM with ASCT. A phase-2 trial.

    PubMed

    Gimsing, P; Hjertner, Ø; Abildgaard, N; Andersen, N F; Dahl, T G; Gregersen, H; Klausen, T W; Mellqvist, U-H; Linder, O; Lindås, R; Tøffner Clausen, N; Lenhoff, S

    2015-10-01

    Until recently, only retrospective studies had been published on salvage high-dose melphalan (HDM) with autologous stem cell 'transplantation' (ASCT). In a prospective, nonrandomized phase-2 study, we treated 53 bortezomib-naïve patients with bortezomib-dexamethasone as induction and bortezomib included in the conditioning regimen along with the HDM. Median progression-free survival (PFS), time to next treatment (TNT) and overall survival (OS) after start of reinduction therapy were 21.6, 22.8 and 46.6 months, respectively. For 49 patients who completed salvage bortezomib-HDM(II) with ASCT, there was no significant difference of PFS and TNT after HDM (II) compared with after the initial HDM(I), and thus patients were their own controls (PFS (I: 20.1 vs II: 19.3 months (P=0.8)) or TNT (I: 24.4 vs II: 20.7 months (P=0.8)). No significant differences in the response rates after salvage ASCT compared with the initial ASCT. Bortezomib-HDM conditioning combo was feasible, and toxicity was as expected for patients treated with bortezomib and ASCT. In conclusion, in bortezomib-naïve patients treated at first relapse with salvage ASCT including bortezomib, PSF and TNT did not differ significantly from initial ASCT and median OS was almost 5.5 years with acceptable toxicity. A recent prospective randomized study confirms salvage ASCT to be an effective treatment.

  19. A commentary on iPS cells: potential applications in autologous transplantation, study of illnesses and drug screening.

    PubMed

    Romano, Gaetano; Morales, Fátima; Marino, Ignazio R; Giordano, Antonio

    2014-02-01

    Undoubtedly, the focus of the field of stem cell research is predominantly aimed at the artificial reprogramming of human somatic cells for the production of induced pluripotent stem (iPS) cells. This relatively new technology may circumvent the ethical issues of using human embryonic stem (hES) cells for the potential applications in cell replacement therapy. Besides such ethical issues, iPS cell technology offers the advantage of obtaining patient-derived tissues and/or cells, which may be utilized for autologous transplantation and tissue regeneration, investigation of a variety of human illnesses and for the screening of new drugs. The field of stem cell research has placed a major emphasis in understanding the genetic and epigenetic codes for pluripotency, in order to control and optimize autologous transplantation techniques and avoid teratoma formation.

  20. Bevacizumab/high-dose chemotherapy with autologous stem-cell transplant for poor-risk relapsed or refractory germ-cell tumors

    PubMed Central

    Nieto, Y.; Tu, S. -M.; Bassett, R.; Jones, R. B.; Gulbis, A. M.; Tannir, N.; Kingham, A.; Ledesma, C.; Margolin, K.; Holmberg, L.; Champlin, R.; Pagliaro, L.

    2015-01-01

    Background High-dose chemotherapy (HDC) using sequential cycles of carboplatin/etoposide is curative for relapsed germ-cell tumors (GCT). However, outcomes of high-risk patients in advanced relapse remain poor. We previously developed a new HDC regimen combining infusional gemcitabine with docetaxel/melphalan/carboplatin (GemDMC), with preliminary high activity in refractory GCT. Given the high vascular endothelial growth factor expression in metastatic GCT and the synergy between bevacizumab and chemotherapy, we studied concurrent bevacizumab and sequential HDC using GemDMC and ifosfamide/carboplatin/etoposide (ICE) in patients with poor-risk relapsed or refractory disease. Patients and methods Eligibility criteria included intermediate/high-risk relapse (Beyer Model), serum creatinine ≤1.8 mg/dl and adequate pulmonary/cardiac/hepatic function. Patients received sequential HDC cycles with bevacizumab preceding GemDMC (cycle 1) and ICE (cycle 2). The trial was powered to distinguish a target 50% 2-year relapse-free survival (RFS) from an expected 25% 2-year RFS in this population. Results We enrolled 43 male patients, median age 30 (20–49) years, with absolute refractory (N = 20), refractory (N = 17) or cisplatin-sensitive (N = 6) disease, after a median 3 (1–5) prior relapses. Disease status right before HDC was unresponsive (N = 24, progressive disease 22, stable disease 2), partial response with positive markers (PRm+) (N = 8), PRm− (N = 7) or complete response (N = 4). Main toxicities were mucositis and renal. Four patients (three with baseline marginal renal function) died from HDC-related complications. Tumor markers normalized in 85% patients. Resection of residual lesions (N = 13) showed necrosis (N = 4), mature teratoma (N = 2), necrosis/teratoma (N = 3) and viable tumor (N = 4). At median follow-up of 46 (9–84) months, the RFS and overall survival rates are 55.8% and 58.1%, respectively. Conclusions Sequential bevacizumab

  1. Autologous bone marrow mesenchymal stem cells associated with tantalum rod implantation and vascularized iliac grafting for the treatment of end-stage osteonecrosis of the femoral head.

    PubMed

    Zhao, Dewei; Liu, Baoyi; Wang, Benjie; Yang, Lei; Xie, Hui; Huang, Shibo; Zhang, Yao; Wei, Xiaowei

    2015-01-01

    Tantalum rod implantation with vascularized iliac grafting has been reported to be an effective method for the treatment of young patients with osteonecrosis of the femoral head (ONFH) to avert the need for total hip arthroplasty (THA). However, there have been unsatisfactory success rates for end-stage ONFH. The authors describe a modified technique using bone marrow mesenchymal stem cells (BMMSCs) associated with porous tantalum rod implantation combined with vascularized iliac grafting for the treatment of end-stage ONFH. A total of 24 patients (31 hips) with end-stage ONFH were treated with surgery; ARCO IIIc stage was observed in 19 hips and ARCO IV stage was observed in 12 hips. All patients were followed for a mean time of 64.35 ± 13.03 months (range 26-78). Operations on only five hips were converted to THA. The joint-preserving success rate of the entire group was 89.47% for ARCO stage IIIc and 75% for ARCO stage IV. The mean Harris hip score of the 31 hips improved significantly from 38.74 ± 5.88 points (range 22-50) to 77.23 ± 14.75 points (range 33-95). This intervention was safe and effective in delaying or avoiding total hip replacement for end-stage ONFH.

  2. Repair of segmental load-bearing bone defect by autologous mesenchymal stem cells and plasma-derived fibrin impregnated ceramic block results in early recovery of limb function.

    PubMed

    Ng, Min Hwei; Duski, Suryasmi; Tan, Kok Keong; Yusof, Mohd Reusmaazran; Low, Kiat Cheong; Rose, Isa Mohamed; Mohamed, Zahiah; Bin Saim, Aminuddin; Idrus, Ruszymah Bt Hj

    2014-01-01

    Calcium phosphate-based bone substitutes have not been used to repair load-bearing bone defects due to their weak mechanical property. In this study, we reevaluated the functional outcomes of combining ceramic block with osteogenic-induced mesenchymal stem cells and platelet-rich plasma (TEB) to repair critical-sized segmental tibial defect. Comparisons were made with fresh marrow-impregnated ceramic block (MIC) and partially demineralized allogeneic bone block (ALLO). Six New Zealand White female rabbits were used in each study group and three rabbits with no implants were used as negative controls. By Day 90, 4/6 rabbits in TEB group and 2/6 in ALLO and MIC groups resumed normal gait pattern. Union was achieved significantly faster in TEB group with a radiological score of 4.50 ± 0.78 versus ALLO (1.06 ± 0.32), MIC (1.28 ± 0.24), and negative controls (0). Histologically, TEB group scored the highest percentage of new bone (82% ± 5.1%) compared to ALLO (5% ± 2.5%) and MIC (26% ± 5.2%). Biomechanically, TEB-treated tibiae achieved the highest compressive strength (43.50 ± 12.72 MPa) compared to those treated with ALLO (15.15 ± 3.57 MPa) and MIC (23.28 ± 6.14 MPa). In conclusion, TEB can repair critical-sized segmental load-bearing bone defects and restore limb function.

  3. Short-Term Effect of Autologous Bone Marrow Stem Cells to Treat Acute Myocardial Infarction: A Meta-Analysis of Randomized Controlled Clinical Trials.

    PubMed

    Cong, Xiao-Qiang; Li, Ying; Zhao, Xin; Dai, Yan-Jian; Liu, Ya

    2015-06-01

    Bone marrow stem cells (BMSCs) have been used to treat patient with ST-segment elevation myocardial infarction (STEMI) via intracoronary route. We performed a meta-analysis to evaluate the short-term efficacy and safety of this modality. Seventeen randomized controlled trials (RCTs) of BMSC-based therapy for STEMI, delivered with 9 days of reperfusion and followed up shorter than 12 months, were identified by systematic review. Intracoronary BMSC therapy resulted in an overall significant improvement in left ventricular ejection fraction (LVEF) by 2.74 % (95 % confidence interval (CI) 2.09-3.39, P < 0.00001, I(2) = 84 %) at 3-6-month follow-up and 5.1 % (95 % CI 4.16-6.03, P < 0.00001 and I(2) = 85 %) at 12 months. The left ventricular end-systolic volume (LVESV) and wall motion score index (WMSI) were also reduced at 3-6 months. At 12 months, left ventricular end-diastolic volume (LVEDV), LVESV, and WMSI were significantly reduced in BMSC group. In conclusion, intracoronary BMSC therapy at post-STEMI is safe and effective in patient with acute STEMI.

  4. Assessment of the effect of intraarticular injection of autologous adipose-derived mesenchymal stem cells in osteoarthritic dogs using a double blinded force platform analysis

    PubMed Central

    2014-01-01

    Background Regenerative medicine using Mesenchymal Stem Cells (MSC) alone or combined with Plasma Rich in Growth Factors (PRGF) is a rapidly growing area of clinical research and is currently also being used to treat osteoarthritis (OA). Force platform analysis has been consistently used to verify and quantify the efficacy of different therapeutic strategies for the treatment of OA in dogs including MSC associated to PRGF, but never with AD-MSC alone. The aim of this study was to use a force platform to measure the efficacy of intraarticular ADMSC administration for limb function improvement in dogs with severe OA. Results Ten lame dogs with severe hip OA and a control group of 5 sound dogs were used for this study. Results were statistically analyzed to detect a significant increase in peak vertical force (PVF) and vertical impulse (VI) in treated dogs. Mean values of PVF and VI were significantly improved within the first three months post-treatment in the OA group, increasing 9% and 2.5% body weight, respectively, at day 30. After this, the effect seems to decrease reaching initial values. Conclusion Intraarticular ADMSC therapy objectively improved limb function in dogs with hip OA. The duration of maximal effect was less than 3 months. PMID:24984756

  5. Controlled, blinded force platform analysis of the effect of intraarticular injection of autologous adipose-derived mesenchymal stem cells associated to PRGF-Endoret in osteoarthritic dogs

    PubMed Central

    2013-01-01

    Background Adipose-derived mesenchymal stem cell (ADMSC) therapy in regenerative medicine is a rapidly growing area of research and is currently also being used to treat osteoarthritis (OA). Force platform analysis has been consistently used to verify the efficacy of different therapeutic strategies for the treatment of OA in dogs, but never with AD-MSC. The aim of this study was to use a force platform to measure the efficacy of intraarticular ADMSC administration for limb function improvement in dogs with severe OA. Results Eight lame dogs with severe hip OA and a control group of 5 sound dogs were used for this study. Results were statistically analyzed to detect a significant increase in peak vertical force (PVF) and vertical impulse (VI) in treated dogs. Mean values of PVF and VI were significantly improved after treatment of the OA groups, reaching 53.02% and 14.84% of body weight, respectively, at day 180, compared with only 43.56% and 12.16% at day 0. Conclusion This study objectively demonstrated that intraarticular ADMSC therapy resulted in reduced lameness due to OA. PMID:23819757

  6. Multipotent stromal cells for autologous cell therapy approaches in the guinea pig model.

    PubMed

    Frölich, Katrin; Scherzed, Agmal; Mlynski, Robert; Technau, Antje; Hagen, Rudolf; Kleinsasser, Norbert; Radeloff, Andreas

    2011-01-01

    Multipotent stromal cells have become of increasing interest due to their potential to provide therapeutic approaches for autologous tissue repair. However, these cells are not well defined in the guinea pig, which represents an important model in hearing research. Adipose-tissue-derived stem cells (ADSC) and bone-marrow-derived stem cells (BMSC) were isolated from different donor sites, and growth curves were generated to judge the proliferation potential. Adipogenic, chondrogenic and osteogenic differentiation was induced and confirmed histologically. Finally, the capability of guinea pig ADSC to differentiate into neuron-like cells was investigated. With regard to the expansion potential, total cell number and doubling time, ADSC from the neck were the most suitable cells of the tested donor sites. Both ADSC and BMSC showed nearly identical behaviour and ability to undergo multilineage differentiation. Thus, we identified ADSC from the neck as a promising cell source for autologous cell-based approaches in hearing research using the guinea pig model. PMID:20975314

  7. Corneal recovery in a rabbit limbal stem cell deficiency model by autologous grafts of tertiary outgrowths from cultivated limbal biopsy explants

    PubMed Central

    Durak, Ismet; Gürdal, Mehmet; Baysal, Kemal; Ates, Halil; Ozbek, Zeynep; Wang, Zheng; Wu, Albert; Wolosin, J. Mario

    2016-01-01

    Purpose To determine the corneal regenerative capacity of sequentially generated primary, secondary, and tertiary limbal explant outgrowths in a limbal stem cell deficiency (LSCD) surgical model. Methods Two-millimeter-long limbal shallow biopsies were surgically excised from the upper quadrant of the right eye of rabbits and set on preserved amniotic membrane for explant culture. After the generation of primary outgrowth, the biopsies were sequentially transferred to new amniotic membrane to generate secondary and then tertiary outgrowths. Eighteen rabbits were subjected to a 360° limbal peritomy extending into the scleral zone and combined with superficial keratectomy of the corneal periphery and thorough mechanical debridement of the central cornea in their left eye. Right eye outgrowths, six of each generation, were engrafted on the ocular surface. Clinical outcomes (neovascularization, corneal clarity, and corneal fluorescein staining) were graded after 6 months. Post-mortem corneas were compared with histology, immunochemistry for p63 and Krt3, ABCG2-dependent dye exclusion, and capacity for outgrowths in explant culture. Results Immunohistology and western blot of the outgrowths for p63 and Krt3 indicated no differences in expression between the primary and tertiary outgrowths for these two markers of growth and differentiation. Clinically, all rabbits treated with amniotic membrane alone developed severe LSCD. Most rabbits grafted with cell outgrowths from all three outgrowth generations achieved stable (>6 months) recovery of the ocular surface. There were partial failures of grafts performed with two secondary and tertiary outgrowths. However, Kruskal–Wallis statistical analysis of the clinical scores yielded no significant difference between the three groups (p=0.524). Histology showed full anatomic recovery of grafts made with primary and tertiary outgrowths. Krt3 and p63 expression throughout the whole limbal corneal epithelium with primary or

  8. Quality of life of long-term survivors with Hodgkin lymphoma after high-dose chemotherapy, autologous stem cell transplantation, and conventional chemotherapy.

    PubMed

    Brandt, Juliane; Dietrich, Sascha; Meissner, Julia; Neben, Kai; Ho, Anthony D; Witzens-Harig, Mathias

    2010-11-01

    In this study, we investigated the quality of life (QoL) of long-term survivors with Hodgkin lymphoma who received high-dose chemotherapy (HDCT) followed by peripheral blood stem cell transplantation (PBSCT). QoL of this group was compared with QoL of patients who were treated with conventional chemotherapy and with QoL of the healthy German population. Two standardized questionnaires, the EORTC QLQ-C30 and the EQ-5D, including the visual analogue scale (VAS) were applied. A total of 98 patients were included in the study, all of them treated in our institution. Thirty-seven patients who received HDCT with PBSCT between 1986 and 2007 were compared with 61 patients treated with conventional chemotherapy and supplementary radiation between 1998 and 2009. The median follow-up for the HDCT group was 11 years. Statistical analysis with the one-sample t-test shows a reduced QoL of both groups of patients compared to the healthy population. Compared to the group of patients who received conventional chemotherapy, there is a tendency towards reduced QoL in patients with HDCT in all of the three main categories of the EORTC-QLQ-C30. However, these differences were not statistically significant, with the exception of the subcategory of dyspnoea, which was worse in the group that was treated with BCNU containing high-dose protocols. We conclude that the negative impact of both HDCT and conventional therapy on the QoL of long-term survivors with Hodgkin lymphoma should not be underestimated and should lead to the development of less toxic therapy strategies.

  9. High-dose chemotherapy and autologous stem cell support followed by post-transplant doxorubicin and taxol as initial therapy for metastatic breast cancer: hematopoietic tolerance and efficacy.

    PubMed

    deMagalhaes-Silverman, M; Hammert, L; Lembersky, B; Lister, J; Rybka, W; Ball, E

    1998-06-01

    A multistep HDC regimen was designed as first-line chemotherapy for MBC. Twenty-four patients with MBC and no previous chemotherapy for metastatic disease were treated with high-dose cyclophosphamide (5000 mg/m2), and etoposide (1000 mg/m2) (CyVP16), followed by granulocyte colony-stimulating factor (G-CSF). Peripheral blood stem cells (PBSCs) were collected. Subsequently patients received cyclophosphamide (6000 mg/m2), thiotepa (500 mg/m2) and carboplatin (800 mg/m2) (CTCb) with hematopoietic rescue. Upon recovery from hematopoietic and gastrointestinal toxicity three cycles of doxorubicin (50 mg/m2) and taxol (150 mg/m2) were delivered. After CyVP16 42% of patients developed neutropenic fevers. There was one documented episode of bacteremia. Patients received CTCb 32 days after starting CyVP16. After CTCb the median number of days to ANC >5 x 10(9)/l was 10 and to a platelet count >20 x 10(9)/l was 14. Neutropenic fevers developed in 16 patients. There were no hemorrhagic episodes. A total of 69 cycles of doxorubicin and taxol were delivered (87% of planned). The median time from PBSC infusion to the first cycle was 38 days. The median time to the second cycle was 27 days and to the last cycle was 24 days. One patient developed congestive heart failure. Two episodes of neutropenic fevers were observed. No toxicity-related deaths were observed. Grafts are stable at 6 months post transplantation. This multistep regimen is feasible with acceptable toxicity. PMID:9674853

  10. Repair of Segmental Load-Bearing Bone Defect by Autologous Mesenchymal Stem Cells and Plasma-Derived Fibrin Impregnated Ceramic Block Results in Early Recovery of Limb Function

    PubMed Central

    Ng, Min Hwei; Duski, Suryasmi; Tan, Kok Keong; Yusof, Mohd Reusmaazran; Low, Kiat Cheong; Mohamed Rose, Isa; Mohamed, Zahiah; Bin Saim, Aminuddin; Idrus, Ruszymah Bt Hj

    2014-01-01

    Calcium phosphate-based bone substitutes have not been used to repair load-bearing bone defects due to their weak mechanical property. In this study, we reevaluated the functional outcomes of combining ceramic block with osteogenic-induced mesenchymal stem cells and platelet-rich plasma (TEB) to repair critical-sized segmental tibial defect. Comparisons were made with fresh marrow-impregnated ceramic block (MIC) and partially demineralized allogeneic bone block (ALLO). Six New Zealand White female rabbits were used in each study group and three rabbits with no implants were used as negative controls. By Day 90, 4/6 rabbits in TEB group and 2/6 in ALLO and MIC groups resumed normal gait pattern. Union was achieved significantly faster in TEB group with a radiological score of 4.50 ± 0.78 versus ALLO (1.06 ± 0.32), MIC (1.28 ± 0.24), and negative controls (0). Histologically, TEB group scored the highest percentage of new bone (82% ± 5.1%) compared to ALLO (5% ± 2.5%) and MIC (26% ± 5.2%). Biomechanically, TEB-treated tibiae achieved the highest compressive strength (43.50 ± 12.72 MPa) compared to those treated with ALLO (15.15 ± 3.57 MPa) and MIC (23.28 ± 6.14 MPa). In conclusion, TEB can repair critical-sized segmental load-bearing bone defects and restore limb function. PMID:25165699

  11. Bone formation following lenalidomide-dexamethasone combination therapy in cases of multiple myeloma refractory to high-dose chemotherapy with bortezomib and autologous peripheral blood stem cell transplantation: report of a case and review of the literature

    PubMed Central

    Sekiguchi, Yasunobu; Ichikawa, Kunimoto; Wakabayashi, Mutsumi; Sugimoto, Keiji; Tomita, Shigeki; Izumi, Hiroshi; Nakamura, Noriko; Sawada, Tomohiro; Ohta, Yasunori; Komatsu, Norio; Noguchi, Masaaki

    2015-01-01

    A 41-year-old man presented with the chief complaint of right hip pain that had persisted for 6 months. F18-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging showed FDG accumulation in the right pubic bone. A bone biopsy specimen from the site revealed findings suggestive of a plasma cell tumor. Bone marrow examination and serum and urine immunofixation tests showed no abnormalities. Based on these findings, the patient was diagnosed as having non-secretory multiple myeloma. FDG accumulation in the right pubic bone diminished following four cycles of weekly bortezomib and concomitant dexamethasone therapy. Tandem autologous peripheral blood stem cell transplantation was performed, followed by monthly bortezomib/dexamethasone maintenance therapy. A further FDG-PET/CT scan 9 months after the start of therapy indicated that FDG accumulation in the right pubic bone had worsened. Consequently, the therapy was switched to twice-weekly bortezomib/dexamethasone as remission re-induction therapy. New FDG uptake in the right hip bone was noted after six cycles of the therapy, and plain X-ray examination revealed osteolytic changes. The patient was then administered eight cycles of combined lenalidomide-dexamethasone therapy, which resulted in a marked decrease of the FDG accumulation in the right pubic bone and disappearance of uptake in the right hip bone. There was radiographic evidence of bone formation at these sites. This is only the second reported case in which treatment with the immunomodulatory drug lenalidomide and concomitant dexamethasone has been found to induce bone formation. PMID:26464727

  12. Stem cell therapy without the cells

    PubMed Central

    Maguire, Greg

    2013-01-01

    As an example of the burgeoning importance of stem cell therapy, this past month the California Institute for Regenerative Medicine (CIRM) has approved $70 million to create a new network of stem cell clinical trial centers. Much work in the last decade has been devoted to developing the use of autologous and allogeneic adult stem cell transplants to treat a number of conditions, including heart attack, dementia, wounds, and immune system-related diseases. The standard model teaches us that adult stem cells exists throughout most of the body and provide a means to regenerate and repair most tissues through replication and differentiation. Although we have often witnessed the medical cart placed in front of the scientific horse in the development of stem cell therapies outside of academic circles, great strides have been made, such as the use of purified stem cells1 instead of whole bone marrow transplants in cancer patients, where physicians avoid re-injecting the patients with their own cancer cells.2 We most often think of stem cell therapy acting to regenerate tissue through replication and then differentiation, but recent studies point to the dramatic effects adult stem cells exert in the repair of various tissues through the release of paracrine and autocrine substances, and not simply through differentiation. Indeed, up to 80% of the therapeutic effect of adult stem cells has been shown to be through paracrine mediated actions.3 That is, the collected types of molecules released by the stem cells, called the secretome, or stem cell released molecules (SRM), number in the 100s, including proteins, microRNA, growth factors, antioxidants, proteasomes, and exosomes, and target a multitude of biological pathways through paracrine actions. The composition of the different molecule types in SRM is state dependent, and varies with cell type and conditions such as age and environment. PMID:24567776

  13. Iodine I 131 Monoclonal Antibody BC8 Before Autologous Stem Cell Transplant in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma or Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2016-06-10

    Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Hodgkin Lymphoma; Refractory T-Cell Non-Hodgkin Lymphoma

  14. High incidence of post-transplant cytomegalovirus reactivations in myeloma patients undergoing autologous stem cell transplantation after treatment with bortezomib-based regimens: a survey from the Rome transplant network.

    PubMed

    Marchesi, F; Mengarelli, A; Giannotti, F; Tendas, A; Anaclerico, B; Porrini, R; Picardi, A; Cerchiara, E; Dentamaro, T; Chierichini, A; Romeo, A; Cudillo, L; Montefusco, E; Tirindelli, M C; De Fabritiis, P; Annino, L; Petti, M C; Monarca, B; Arcese, W; Avvisati, G

    2014-02-01

    The incidence of cytomegalovirus (CMV) reactivations in patients with multiple myeloma (MM) receiving autologous stem cell transplantation (ASCT) is relatively low. However, the recent increased use of novel agents, such as bortezomib and/or immunomodulators, before transplant, has led to an increasing incidence of Herpesviridae family virus infections. The aim of the study was to establish the incidence of post-engraftment symptomatic CMV reactivations in MM patients receiving ASCT, and to compare this incidence with that of patients treated with novel agents or with conventional chemotherapy before transplant. The study was a survey of 80 consecutive patients who underwent ASCT after treatment with novel agents (Group A). These patients were compared with a cohort of 89 patients treated with VAD regimen (vincristine, doxorubicin, and dexamethasone) before ASCT (Group B). Overall, 7 patients (4.1%) received an antiviral treatment for a symptomatic CMV reactivation and 1 died. The incidence of CMV reactivations was significantly higher in Group A than in Group B (7.5% vs. 1.1%; P = 0.048). When compared with Group B, the CMV reactivations observed in Group A were significantly more frequent in patients who received bortezomib, whether or not associated with immunomodulators (9.4% vs. 1.1%; P = 0.019), but not in those treated with immunomodulators only (3.7% vs. 1.1%; P = 0.396). These results suggest that MM patients treated with bortezomib-based regimens are at higher risk of developing a symptomatic CMV reactivation after ASCT. PMID:24215479

  15. Magnetic resonance imaging pattern of bone marrow involvement as a new predictive parameter of disease progression in newly diagnosed patients with multiple myeloma eligible for autologous stem cell transplantation.

    PubMed

    Song, Moo-Kon; Chung, Joo-Seop; Lee, Je-Jung; Min, Chang-Ki; Ahn, Jae-Sook; Lee, Sang-Min; Shin, Dong-Yeop; Bae, Sung-Hwa; Hong, Junshik; Lee, Gyeong-Won; Lee, In-Sook; Shin, Ho-Jin

    2014-06-01

    We investigated the prognostic value of the magnetic resonance imaging (MRI) pattern of bone marrow involvement in patients with multiple myeloma (MM) eligible for autologous stem cell transplantation (ASCT). 126 patients with untreated MM indicated for ASCT underwent spine MRI and cytogenetic analysis at diagnosis. All patients received ASCT after induction therapy of VAD (vincristine, doxorubicin, dexamethasone; n = 55) or a thalidomide-based regimen (TCD; n = 71). Thalidomide maintenance therapy was performed in 68 patients. The MRI pattern was normal in 27, focal in 47, and diffuse/variegated in 52 patients. Patients with the diffuse/variegated pattern showed significantly higher stage (P = 0·038), higher β-2 microglobulin level (P = 0·001) and severe anaemia (P = 0·015). However, the cytogenetics were not different among the MRI patterns (P = 0·890). Progression-free survival (PFS) was lower in the diffuse/variegated pattern (P = 0·002) than other patterns, but not overall survival (OS) (P = 0·058). Thalidomide maintenance therapy was correlated only with PFS (P = 0·001). High-risk cytogenetics were associated with both poorer PFS (P < 0·001) and OS (P = 0·003). In a multivariate analysis, the diffuse/variegated MRI pattern was an independent predictor of disease progression (Hazard Ratio, 1·922; 95% confidence interval, 1·185-3·118; P = 0·008). The diffuse/variegated MRI pattern is a novel prognostic factor for disease progression in MM patients eligible for ASCT.

  16. Results of a retrospective single institution analysis of targeted skeletal radiotherapy with (166)Holmium-DOTMP as conditioning regimen for autologous stem cell transplant for patients with multiple myeloma. Impact on transplant outcomes.

    PubMed

    Christoforidou, Anna V; Saliba, Rima M; Williams, Patricia; Qazilbash, Muzaffar; Roden, Linda; Aleman, Ana; Weber, Donna; Mendoza, Floralyn; Podoloff, Donald; Wendt, Richard; Breitz, Hazel; Alexanian, Raymond; Champlin, Richard; Giralt, Sergio

    2007-05-01

    (166)Holmium-DOTMP is a beta-emitting radiophosphonate that localizes specifically to the bone surfaces and can deliver high-dose radiation to the bone marrow. Phase I/II trials showed feasibility and tolerability when combined with high-dose melphalan with or without total-body irradiation (TBI) in patients with multiple myeloma (MM) undergoing autologous stem cell transplantation (ASCT). The purpose of this study was to define the potential impact of (166)Holmium-DOTMP on outcomes in patients with MM undergoing ASCT. Retrospective review of transplant outcomes among patients with MM who received an ASCT between January 1998 to December 2001 with either melphalan 200 mg/m(2) or a (166)Holmium-DOTMP containing regimen as part of their initial therapy. Univariate analysis was performed for response, overall survival (OS), and event free survival (EFS). One hundred four patients were identified, of which 41 received a (166)Holmium-DOTMP containing regimen and 63 received melphalan alone. The (166)Holmium-DOTMP patients were divided into 2 groups according to the dose received (<2400 mCi versus > or = 2400 mCi). The (166)Holmium-DOTMP group had a trend towards a higher complete remission (CR) rate compared to patients receiving melphalan alone (51% versus 32%). The median EFS for the low-dose (166)Holmium-DOTMP, the high-dose (166)Holmium-DOTMP, and melphalan alone was 30, 23, and 19 months, respectively; the OS rate at 5 years for the 3 groups was 61%, 40%, and 43%, respectively. (166)Holmium-DOTMP, in combination with high-dose melphalan, can result in higher CR rates when given in optimal doses (<2400 mCi) when compared to melphalan alone, and should be further tested in phase III trials in patients with MM undergoing ASCT.

  17. Serum after autologous transplantation stimulates proliferation and expansion of human hematopoietic progenitor cells.

    PubMed

    Walenda, Thomas; Bokermann, Gudrun; Jost, Edgar; Galm, Oliver; Schellenberg, Anne; Koch, Carmen M; Piroth, Daniela M; Drescher, Wolf; Brümmendorf, Tim H; Wagner, Wolfgang

    2011-01-01

    Regeneration after hematopoietic stem cell transplantation (HSCT) depends on enormous activation of the stem cell pool. So far, it is hardly understood how these cells are recruited into proliferation and self-renewal. In this study, we have addressed the question if systemically released factors are involved in activation of hematopoietic stem and progenitor cells (HPC) after autologous HSCT. Serum was taken from patients before chemotherapy, during neutropenia and after hematopoietic recovery. Subsequently, it was used as supplement for in vitro culture of CD34(+) cord blood HPC. Serum taken under hematopoietic stress (4 to 11 days after HSCT) significantly enhanced proliferation, maintained primitive immunophenotype (CD34(+), CD133(+), CD45(-)) for more cell divisions and increased colony forming units (CFU) as well as the number of cobblestone area-forming cells (CAFC). The stimulatory effect decays to normal levels after hematopoietic recovery (more than 2 weeks after HSCT). Chemokine profiling revealed a decline of several growth-factors during neutropenia, including platelet-derived growth factors PDGF-AA, PDGF-AB and PDGF-BB, whereas expression of monocyte chemotactic protein-1 (MCP-1) increased. These results demonstrate that systemically released factors play an important role for stimulation of hematopoietic regeneration after autologous HSCT. This feedback mechanism opens new perspectives for in vivo stimulation of the stem cell pool. PMID:21437259

  18. Iodine I 131 Tositumomab, Etoposide and Cyclophosphamide Followed by Autologous Stem Cell Transplant in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2014-08-04

    Anaplastic Large Cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  19. High-Dose Chemotherapy, Total-Body Irradiation, and Autologous Stem Cell Transplantation or Bone Marrow Transplantation in Treating Patients With Hematologic Cancer or Solid Tumors

    ClinicalTrials.gov

    2013-05-07

    Breast Cancer; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Testicular Germ Cell Tumor; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific

  20. Stem Cells in the Cornea.

    PubMed

    Hertsenberg, Andrew J; Funderburgh, James L

    2015-01-01

    The cornea is the tough, transparent tissue through which light first enters the eye and functions as a barrier to debris and infection as well as two-thirds of the refractive power of the eye. Corneal damage that is not promptly treated will often lead to scarring and vision impairment. Due to the limited options currently available to treat corneal scars, the identification and isolation of stem cells in the cornea has received much attention, as they may have potential for autologous, cell-based approaches to the treatment of damaged corneal tissue.

  1. Recovery of autologous reticulocytes by microhematocrit cell separation.

    PubMed

    Hall, Christy W

    2015-01-01

    Reticulocytes can be separated from more mature red blood cells based on differences in density. A method for obtaining autologous reticulocytes in ethylenediaminetetraacetic acid (EDTA) whole blood samples containing both autologous and transfused cells uses a microhematocrit centrifuge. The less dense reticulocytes harvested from the top 5 mm of microhematocrit tubes can be used to determine the patient's phenotype or assess whether a transfusion reaction is taking place. This method can be performed using equipment, reagents, and supplies readily available in most laboratories. PMID:27187194

  2. Autologous bone-marrow mesenchymal cell induced chondrogenesis (MCIC).

    PubMed

    Huh, Sung Woo; Shetty, Asode Ananthram; Ahmed, Saif; Lee, Dong Hwan; Kim, Seok Jung

    2016-01-01

    Degenerative and traumatic articular cartilage defects are common, difficult to treat, and progressive lesions that cause significant morbidity in the general population. There have been multiple approaches to treat such lesions, including arthroscopic debridement, microfracture, multiple drilling, osteochondral transplantation and autologous chondrocyte implantation (ACI) that are currently being used in clinical practice. Autologous bone-marrow mesenchymal cell induced chondrogenesis (MCIC) is a single-staged arthroscopic procedure. This method combines a modified microfracture technique with the application of a bone marrow aspirate concentrate (BMAC), hyaluronic acid and fibrin gel to treat articular cartilage defects. We reviewed the current literatures and surgical techniques for mesenchymal cell induced chondrogenesis. PMID:27489409

  3. The Power and the Promise of Cell Reprogramming: Personalized Autologous Body Organ and Cell Transplantation.

    PubMed

    Palomo, Ana Belen Alvarez; Lucas, Michaela; Dilley, Rodney J; McLenachan, Samuel; Chen, Fred Kuanfu; Requena, Jordi; Sal, Marti Farrera; Lucas, Andrew; Alvarez, Inaki; Jaraquemada, Dolores; Edel, Michael J

    2014-04-04

    Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) or direct reprogramming to desired cell types are powerful and new in vitro methods for the study of human disease, cell replacement therapy, and drug development. Both methods to reprogram cells are unconstrained by the ethical and social questions raised by embryonic stem cells. iPSC technology promises to enable personalized autologous cell therapy and has the potential to revolutionize cell replacement therapy and regenerative medicine. Potential applications of iPSC technology are rapidly increasing in ambition from discrete cell replacement applications to the iPSC assisted bioengineering of body organs for personalized autologous body organ transplant. Recent work has demonstrated that the generation of organs from iPSCs is a future possibility. The development of embryonic-like organ structures bioengineered from iPSCs has been achieved, such as an early brain structure (cerebral organoids), bone, optic vesicle-like structures (eye), cardiac muscle tissue (heart), primitive pancreas islet cells, a tooth-like structure (teeth), and functional liver buds (liver). Thus, iPSC technology offers, in the future, the powerful and unique possibility to make body organs for transplantation removing the need for organ donation and immune suppressing drugs. Whilst it is clear that iPSCs are rapidly becoming the lead cell type for research into cell replacement therapy and body organ transplantation strategies in humans, it is not known whether (1) such transplants will stimulate host immune responses; and (2) whether this technology will be capable of the bioengineering of a complete and fully functional human organ. This review will not focus on reprogramming to iPSCs, of which a plethora of reviews can be found, but instead focus on the latest developments in direct reprogramming of cells, the bioengineering of body organs from iPSCs, and an analysis of the immune response induced by i

  4. Differentiation of human endometrial stem cells into urothelial cells on a three-dimensional nanofibrous silk-collagen scaffold: an autologous cell resource for reconstruction of the urinary bladder wall.

    PubMed

    Shoae-Hassani, Alireza; Mortazavi-Tabatabaei, Seyed Abdolreza; Sharif, Shiva; Seifalian, Alexander Marcus; Azimi, Alireza; Samadikuchaksaraei, Ali; Verdi, Javad

    2015-11-01

    Reconstruction of the bladder wall via in vitro differentiated stem cells on an appropriate scaffold could be used in such conditions as cancer and neurogenic urinary bladder. This study aimed to examine the potential of human endometrial stem cells (EnSCs) to form urinary bladder epithelial cells (urothelium) on nanofibrous silk-collagen scaffolds, for construction of the urinary bladder wall. After passage 4, EnSCs were induced by keratinocyte growth factor (KGF) and epidermal growth factor (EGF) and seeded on electrospun collagen-V, silk and silk-collagen nanofibres. Later we tested urothelium-specific genes and proteins (uroplakin-Ia, uroplakin-Ib, uroplakin-II, uroplakin-III and cytokeratin 20) by immunocytochemistry, RT-PCR and western blot analyses. Scanning electron microscopy (SEM) and histology were used to detect cell-matrix interactions. DMEM/F12 supplemented by KGF and EGF induced EnSCs to express urothelial cell-specific genes and proteins. Either collagen, silk or silk-collagen scaffolds promoted cell proliferation. The nanofibrous silk-collagen scaffolds provided a three-dimensional (3D) structure to maximize cell-matrix penetration and increase differentiation of the EnSCs. Human EnSCs seeded on 3D nanofibrous silk-collagen scaffolds and differentiated to urothelial cells provide a suitable source for potential use in bladder wall reconstruction in women.

  5. High-Dose Chemotherapy With or Without Total-Body Irradiation Followed by Autologous Stem Cell Transplant in Treating Patients With Hematologic Cancer or Solid Tumors

    ClinicalTrials.gov

    2016-08-17

    Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor (PNET); Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Plasma Cell Neoplasm; Primary Systemic Amyloidosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2

  6. Regeneration of Tissues and Organs Using Autologous Cells

    SciTech Connect

    Anthony Atala, M D

    2012-10-11

    The proposed work aims to address three major challenges to the field of regenerative medicine: 1) the growth and expansion of regenerative cells outside the body in controlled in vitro environments, 2) supportive vascular supply for large tissue engineered constructs, and 3) interactive biomaterials that can orchestrate tissue development in vivo. Toward this goal, we have engaged a team of scientists with expertise in cell and molecular biology, physiology, biomaterials, controlled release, nanomaterials, tissue engineering, bioengineering, and clinical medicine to address all three challenges. This combination of resources, combined with the vast infrastructure of the WFIRM, have brought to bear on projects to discover and test new sources of autologous cells that can be used therapeutically, novel methods to improve vascular support for engineered tissues in vivo, and to develop intelligent biomaterials and bioreactor systems that interact favorably with stem and progenitor cells to drive tissue maturation. The Institute's ongoing programs are aimed at developing regenerative medicine technologies that employ a patient's own cells to help restore or replace tissue and organ function. This DOE program has provided a means to solve some of the vexing problems that are germane to many tissue engineering applications, regardless of tissue type or target disease. By providing new methods that are the underpinning of tissue engineering, this program facilitated advances that can be applied to conditions including heart disease, diabetes, renal failure, nerve damage, vascular disease, and cancer, to name a few. These types of conditions affect millions of Americans at a cost of more than $400 billion annually. Regenerative medicine holds the promise of harnessing the body's own power to heal itself. By addressing the fundamental challenges of this field in a comprehensive and focused fashion, this DOE program has opened new opportunities to treat conditions where

  7. Stem Cell Sciences plc.

    PubMed

    Daniels, Sebnem

    2006-09-01

    Stem Cell Sciences' core objective is to develop safe and effective stem cell-based therapies for currently incurable diseases. In order to achieve this goal, Stem Cell Sciences recognizes the need for multiple technologies and a globally integrated stem cell initiative. The key challenges for the successful application of stem cells in the clinic is the need for a reproducible supply of pure, fully characterized stem cells that have been grown in suitable conditions for use in the clinic.

  8. Study of Redirected Autologous T Cells Engineered to Contain Anti-CD19 Attached to TCR and 4-1BB Signaling Domains in Patients With Chemotherapy Resistant or Refractory Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2016-09-27

    Patients With B Cell ALL, Relapsed or Refractory, With no Available; Curative Treatment Options (Such as Autologous or Allogeneic Stem Cell; Transplantation) Who Have Limited Prognosis (> 12 Weeks Survival Expectancy); With Currently Available Therapies.

  9. Regeneration of Tissues and Organs Using Autologous Cells

    SciTech Connect

    Anthony Atala

    2010-04-28

    The Joint Commission for Health Care Organizations recently declared the shortage of transplantable organs and tissues a public health crisis. As such, there is about one death every 30 seconds due to organ failure. Complications and rejection are still significant albeit underappreciated problems. It is often overlooked that organ transplantation results in the patient being placed on an immune suppression regimen that will ultimate shorten their life span. Patients facing reconstruction often find that surgery is difficult or impossible due to the shortage of healthy autologous tissue. In many cases, autografting is a compromise between the condition and the cure that can result in substantial diminution of quality of life. The national cost of caring for persons who might benefit from engineered tissues or organs has reached $600 billion annually. Autologous tissue technologies have been developed as an alternative to transplantation or reconstructive surgery. Autologous tissues derived from the patient's own cells are capable of correcting numerous pathologies and injuries. The use of autologous cells eliminates the risks of rejection and immunological reactions, drastically reduces the time that patients must wait for lifesaving surgery, and negates the need for autologous tissue harvest, thereby eliminating the associated morbidities. In fact, the use of autologous tissues to create functional organs is one of the most important and groundbreaking steps ever taken in medicine. Although the basic premise of creating tissues in the laboratory has progressed dramatically, only a limited number of tissue developments have reached the patients to date. This is due, in part, to the several major technological challenges that require solutions. To that end, we have been in pursuit of more efficient ways to expand cells in vitro, methods to improve vascular support so that relevant volumes of engineered tissues can be grown, and constructs that can mimic the native

  10. Translational research of adult stem cell therapy.

    PubMed

    Suzuki, Gen

    2015-11-26

    Congestive heart failure (CHF) secondary to chronic coronary artery disease is a major cause of morbidity and mortality world-wide. Its prevalence is increasing despite advances in medical and device therapies. Cell based therapies generating new cardiomyocytes and vessels have emerged as a promising treatment to reverse functional deterioration and prevent the progression to CHF. Functional efficacy of progenitor cells isolated from the bone marrow and the heart have been evaluated in preclinical large animal models. Furthermore, several clinical trials using autologous and allogeneic stem cells and progenitor cells have demonstrated their safety in humans yet their clinical relevance is inconclusive. This review will discuss the clinical therapeutic applications of three specific adult stem cells that have shown particularly promising regenerative effects in preclinical studies, bone marrow derived mesenchymal stem cell, heart derived cardiosphere-derived cell and cardiac stem cell. We will also discuss future therapeutic approaches.

  11. Stem cells supporting other stem cells

    PubMed Central

    Leatherman, Judith

    2013-01-01

    Adult stem cell therapies are increasingly prevalent for the treatment of damaged or diseased tissues, but most of the improvements observed to date are attributed to the ability of stem cells to produce paracrine factors that have a trophic effect on existing tissue cells, improving their functional capacity. It is now clear that this ability to produce trophic factors is a normal and necessary function for some stem cell populations. In vivo adult stem cells are thought to self-renew due to local signals from the microenvironment where they live, the niche. Several niches have now been identified which harbor multiple stem cell populations. In three of these niches – the Drosophila testis, the bulge of the mammalian hair follicle, and the mammalian bone marrow – one type of stem cell has been found to produce factors that contribute to the maintenance of a second stem cell population in the shared niche. In this review, I will examine the architecture of these three niches and discuss the molecular signals involved. Together, these examples establish a new paradigm for stem cell behavior, that stem cells can promote the maintenance of other stem cells. PMID:24348512

  12. [Therapeutic use of stem cells. II. Adult stem cells].

    PubMed

    Uzan, Georges

    2004-09-30

    Many degenerative diseases are not curable by means of classical medicine. The long term objective of cell therapy is to treat the patients with their own stem cells that could be either purified from the diseased organ or from "reservoirs" of stem cells such as that constituted by the bone marrow. The existence of stem cells in the organs or reservoirs is now established in vitro and in some cases, in animal models. Numbers of technical problems linked to the scarcity of these cells still delay the clinical use of purified stem cells. However, clinical protocols using heterogeneous cell populations have already started to treat a growing number of diseases. In some case, autologous cells can be used, as it is the case for bone marrow transplantation in blood diseases. Mesenchymal cells, also purified from the bone marrow are currently used in orthopaedic diseases. Because these cells reveal a broad differentiation potential, active research programs explore their possible use for treatment of other diseases. Bone marrow also contains vascular stem cells that could be active in reappearing defective vessels responsible for ischaemic diseases. Indeed, clinical trials in which bone marrow cells are injected in the cardiac muscle of patients with myocardial infarction or in the leg muscle (gastrocnemius) of patients with hind limb ischaemia have already started. Artificial skin prepared from skin biopsies is used for the reconstitution of the derma of severely burned patients. Clinical trials have also started, using allogenic cells. The patients must be treated by immunosuppressive drugs. Neurodegenerative diseases such as Parkinson have been successfully treated by intra-cerebral injection of foetal neurones. Pancreatic islets implanted in the liver have shown to re-establish a normal glycaemia in diabetic patients. However, all these clinical trials use differentiated cells or at least progenitors which display differentiation potential and lifetime much more

  13. Stem cell biobanks.

    PubMed

    Bardelli, Silvana

    2010-04-01

    Stem cells contribute to innate healing and harbor a promising role for regenerative medicine. Stem cell banking through long-term storage of different stem cell platforms represents a fundamental source to preserve original features of stem cells for patient-specific clinical applications. Stem cell research and clinical translation constitute fundamental and indivisible modules catalyzed through biobanking activity, generating a return of investment. PMID:20560026

  14. Stem cells for the treatment of neurodegenerative diseases.

    PubMed

    Dantuma, Elise; Merchant, Stephanie; Sugaya, Kiminobu

    2010-12-10

    Stem cells offer an enormous pool of resources for the understanding of the human body. One proposed use of stem cells has been as an autologous therapy. The use of stem cells for neurodegenerative diseases has become of interest. Clinical applications of stem cells for Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, and multiple sclerosis will increase in the coming years, and although great care will need to be taken when moving forward with prospective treatments, the application of stem cells is highly promising.

  15. Autologous Graft-versus-Tumor Effect: Reality or Fiction?

    PubMed Central

    2016-01-01

    In contrast to allogeneic hematopoietic stem cell transplantation, the current dogma is not an evidence of graft-versus-tumor effect in autologous hematopoietic stem cell transplantation; thus, it is assumed that autologous hematopoietic stem cell transplantation only relies on the high-dose chemotherapy to improve clinical outcomes. However, recent studies argue in favor of the existence of an autologous graft-versus-tumor without the detrimental complications of graft-versus-host disease due to the nonspecific immune response from the infused donor alloreactive immune effector cells in allogeneic hematopoietic stem cell transplantation. Herein, this paper reviews the clinical evidence of an autologous graft-versus-tumor effect based on the autograft collected and infused host immune effector cells and host immunity recovery after autologous hematopoietic stem cell transplantation affecting clinical outcomes in cancer patients.

  16. Autologous Graft-versus-Tumor Effect: Reality or Fiction?

    PubMed Central

    2016-01-01

    In contrast to allogeneic hematopoietic stem cell transplantation, the current dogma is not an evidence of graft-versus-tumor effect in autologous hematopoietic stem cell transplantation; thus, it is assumed that autologous hematopoietic stem cell transplantation only relies on the high-dose chemotherapy to improve clinical outcomes. However, recent studies argue in favor of the existence of an autologous graft-versus-tumor without the detrimental complications of graft-versus-host disease due to the nonspecific immune response from the infused donor alloreactive immune effector cells in allogeneic hematopoietic stem cell transplantation. Herein, this paper reviews the clinical evidence of an autologous graft-versus-tumor effect based on the autograft collected and infused host immune effector cells and host immunity recovery after autologous hematopoietic stem cell transplantation affecting clinical outcomes in cancer patients. PMID:27635143

  17. Cell manipulation in autologous chondrocyte implantation: from research to cleanroom.

    PubMed

    Roseti, Livia; Serra, Marta; Tigani, Domenico; Brognara, Irene; Lopriore, Annamaria; Bassi, Alessandra; Fornasari, Pier Maria

    2008-04-01

    In the field of orthopaedics, autologous chondrocyte implantation is a technique currently used for the regeneration of damaged articular cartilage. There is evidence of the neo-formation of tissue displaying characteristics similar to hyaline cartilage. In vitro chondrocyte manipulation is a crucial phase of this therapeutic treatment consisting of different steps: cell isolation from a cartilage biopsy, expansion in monolayer culture and growth onto a three-dimensional biomaterial to implant in the damaged area. To minimise the risk of in vitro cell contamination, the manipulation must be performed in a controlled environment such as a cleanroom. Moreover, the choice of reagents and raw material suitable for clinical use in humans and the translation of research protocols into standardised production processes are important. In this study we describe the preliminary results obtained by the development of chondrocyte manipulation protocols (isolation and monolayer expansion) in cleanrooms for the application of autologous implantation.

  18. Evolutionarily stable anti-cancer therapies by autologous cell defection

    PubMed Central

    Archetti, Marco

    2013-01-01

    Game theory suggests an anti-cancer treatment based on the use of modified cancer cells that disrupt cooperation within the tumor. Cancer cells are harvested from the patient, the genes for the production of essential growth factors are knocked out in vitro and the cells are then reinserted in the tumor, where they lead to its collapse. Background and objectives: Current anti-cancer drugs and treatments based on gene therapy are prone to the evolution of resistance, because cancer is a process of clonal selection: resistant cell lines have a selective advantage and therefore increase in frequency, eventually conferring resistance to the whole tumor and leading to relapse. An effective treatment must be evolutionarily stable, that is, immune to the invasion of resistant mutant cells. This study shows how such a treatment can be achieved by autologous cell therapy using modified cancer cells, knocked out for genes coding for diffusible factors like growth factors. Methodology: The evolutionary dynamics of a population of cells producing diffusible factors are analyzed using a nonlinear public goods game in a structured population in which the interaction neighborhood and the update neighborhood are decoupled. The analysis of the dynamics of the system reveals what interventions can drive the population to a stable equilibrium in which no diffusible factors are produced. Results: A treatment based on autologous knockout cell therapy can be designed to lead to the spontaneous collapse of a tumor, without targeting directly the cancer cells, their growth factors or their receptors. Critical parameters that can make the therapy effective are identified. Concepts from evolutionary game theory and mechanism design, some of which are counterintuitive, can be adopted to optimize the treatment. Conclusions and implications: Although it shares similarities with other approaches based on gene therapy and RNA interference, the method suggested here is evolutionarily stable under

  19. Virgin birth: engineered heart muscle from parthenogenetic stem cells.

    PubMed

    McSweeney, Sara J; Schneider, Michael D

    2013-03-01

    Cardiac muscle restitution, or true regeneration, is an unmet need in the treatment of myocardial infarction (MI), prompting a decade of study with stem cells of many kinds. Among key obstacles to effective cardiac cell grafting are the cost of autologous stem cell-derived cardiomyocytes, the ethical implications of using embryonic stem cell (ESC) products, immunological barriers to allogeneic cells, functional maturation beyond just the correct lineage decision, and the lack of durable engraftment. In this issue of the JCI, Didié and colleagues show that cardiomyocytes made from parthenogenetic stem cells (PSCs) and deployed as engineered heart muscle (EHM) may overcome all of these formidable barriers.

  20. Parasitic Infections in Hematopoietic Stem Cell Transplantation.

    PubMed

    Jarque, Isidro; Salavert, Miguel; Pemán, Javier

    2016-01-01

    Parasitic infections are rarely documented in hematopoietic stem cell transplant recipients. However they may be responsible for fatal complications that are only diagnosed at autopsy. Increased awareness of the possibility of parasitic diseases both in autologous and allogeneic stem cell transplant patients is relevant not only for implementing preventive measures but also for performing an early diagnosis and starting appropriate therapy for these unrecognized but fatal infectious complications in hematopoietic transplant recipients. In this review, we will focus on parasitic diseases occurring in this population especially those with major clinical relevance including toxoplasmosis, American trypanosomiasis, leishmaniasis, malaria, and strongyloidiasis, among others, highlighting the diagnosis and management in hematopoietic transplant recipients. PMID:27413527

  1. Parasitic Infections in Hematopoietic Stem Cell Transplantation

    PubMed Central

    Jarque, Isidro; Salavert, Miguel; Pemán, Javier

    2016-01-01

    Parasitic infections are rarely documented in hematopoietic stem cell transplant recipients. However they may be responsible for fatal complications that are only diagnosed at autopsy. Increased awareness of the possibility of parasitic diseases both in autologous and allogeneic stem cell transplant patients is relevant not only for implementing preventive measures but also for performing an early diagnosis and starting appropriate therapy for these unrecognized but fatal infectious complications in hematopoietic transplant recipients. In this review, we will focus on parasitic diseases occurring in this population especially those with major clinical relevance including toxoplasmosis, American trypanosomiasis, leishmaniasis, malaria, and strongyloidiasis, among others, highlighting the diagnosis and management in hematopoietic transplant recipients. PMID:27413527

  2. Ventricular fibrillation following autologous intramyocardial cell therapy for inherited cardiomyopathy.

    PubMed

    Pytel, Peter; Husain, Aliya; Moskowitz, Ivan; Raman, Jai; MacLeod, Heather; Anderson, Allen S; Burke, Martin; McNally, Elizabeth M

    2010-01-01

    A 41-year-old male with cardiomyopathy from an inherited beta myosin heavy-chain mutation underwent treatment for heart failure with intramyocardial cell transplantation. He received direct injections into his heart of autologous precursor cells isolated from his blood. He immediately suffered ventricular fibrillation. Although he was resuscitated, he experienced a prolonged downward course that prohibited his undergoing transplantation. His autopsy revealed marked fibrosis throughout the myocardium with areas of mononuclear cell infiltrate. This case highlights the potential adverse effects associated with intramyocardial therapy in the cardiomyopathic heart.

  3. Ventricular fibrillation following autologous intramyocardial cell therapy for inherited cardiomyopathy

    PubMed Central

    Pytel, Peter; Husain, Aliya; Moskowitz, Ivan; Raman, Jai; MacLeod, Heather; Anderson, Allen S.; Burke, Martin; McNally, Elizabeth M.

    2010-01-01

    A 41 year old male with cardiomyopathy from an inherited β myosin heavy chain mutation underwent treatment for heart failure with intramyocardial cell transplantation. He received direct injections into his heart of autologous precursor cells isolated from his blood. He immediately suffered ventricular fibrillation. Although he was resuscitated, he experienced a prolonged downward course that prohibited his undergoing transplantation. His autopsy revealed marked fibrosis throughout the myocardium with areas of mononuclear cell infiltrate. This case highlights the potential adverse effects associated with intramyocardial therapy in the cardiomyopathic heart. PMID:19026577

  4. Treatment of pressure ulcers with autologous bone marrow nuclear cells in patients with spinal cord injury

    PubMed Central

    Sarasúa, J González; López, S Pérez; Viejo, M Álvarez; Basterrechea, M Pérez; Rodríguez, A Fernández; Gutiérrez, A Ferrero; Gala, J García; Menéndez, Y Menéndez; Augusto, D Escudero; Arias, A Pérez; Hernández, J Otero

    2011-01-01

    Context Pressure ulcers are especially difficult to treat in patients with spinal cord injury (SCI) and recurrence rates are high. Prompted by encouraging results obtained using bone marrow stem cells to treat several diseases including chronic wounds, this study examines the use of autologous stem cells from bone marrow to promote the healing of pressure ulcers in patients with SCI. Objective To obtain preliminary data on the use of bone marrow mononuclear cells (BM-MNCs) to treat pressure ulcers in terms of clinical outcome, procedure safety, and treatment time. Participants Twenty-two patients with SCI (19 men, 3 women; mean age 56.41 years) with single type IV pressure ulcers of more than 4 months duration. Interventions By minimally invasive surgery, the ulcers were debrided and treated with BM-MNCs obtained by Ficoll density gradient separation of autologous bone marrow aspirates drawn from the iliac crest. Results In 19 patients (86.36%), the pressure ulcers treated with BM-MNCs had fully healed after a mean time of 21 days. The number of MNCs isolated was patient dependent, although similar clinical outcomes were observed in each case. Compared to conventional surgical treatment, mean intra-hospital stay was reduced from 85.16 to 43.06 days. Following treatment, 5 minutes of daily wound care was required per patient compared to 20 minutes for conventional surgery. During a mean follow-up of 19 months, none of the resolved ulcers recurred. Conclusions Our data indicate that cell therapy using autologous BM-MNCs could be an option to treat type IV pressure ulcers in patients with SCI, avoiding major surgical intervention. PMID:21756569

  5. Stem Cell Research.

    PubMed

    Trounson, Alan; Kolaja, Kyle; Petersen, Thomas; Weber, Klaus; McVean, Maralee; Funk, Kathleen A

    2015-01-01

    Stem cells have great potential in basic research and are being slowly integrated into toxicological research. This symposium provided an overview of the state of the field, stem cell models, described allogenic stem cell treatments and issues of immunogenicity associated with protein therapeutics, and tehn concentrated on stem cell uses in regenerative medicine focusing on lung and testing strategies on engineered tissues from a pathologist's perspective.

  6. Fat, Stem Cells, and Platelet-Rich Plasma.

    PubMed

    James, Isaac B; Coleman, Sydney R; Rubin, J Peter

    2016-07-01

    The ideal filler for aesthetic surgery is inexpensive and easy to obtain, natural in appearance and texture, immunologically compatible, and long lasting without risk of infection. By most metrics, autologous fat grafts meet these criteria perfectly. Although facial fat grafting is now a commonly accepted surgical procedure, there has been a wave of activity applying stem cells and platelet-rich plasma (PRP) therapies to aesthetic practice. This article addresses technical considerations in the use of autologous fat transfer for facial rejuvenation, and also explores the current evidence for these stem cell and PRP therapies in aesthetic practice.

  7. Information on Stem Cell Research

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS Information on Stem Cell Research Research @ NINDS Stem Cell Highlights Submit a hESC ... found here: Human Induced Pluripotent Stem Cells NINDS Stem Cell Research on Campus The Intramural Research Program of NINDS ...

  8. The effect of autologous bone marrow stromal cells differentiated on scaffolds for canine tibial bone reconstruction.

    PubMed

    Özdal-Kurt, F; Tuğlu, I; Vatansever, H S; Tong, S; Deliloğlu-Gürhan, S I

    2015-01-01

    Bone marrow contains mesenchymal stem cells that form many tissues. Various scaffolds are available for bone reconstruction by tissue engineering. Osteoblastic differentiated bone marrow stromal cells (BMSC) promote osteogenesis on scaffolds and stimulate bone regeneration. We investigated the use of cultured autologous BMSC on different scaffolds for healing defects in tibias of adult male canines. BMSC were isolated from canine humerus bone marrow, differentiated into osteoblasts in culture and loaded onto porous ceramic scaffolds including hydroxyapatite 1, hydroxyapatite gel and calcium phosphate. Osteoblast differentiation was verified by osteonectine and osteocalcine immunocytochemistry. The scaffolds with stromal cells were implanted in the tibial defect. Scaffolds without stromal cells were used as controls. Sections from the defects were processed for histological, ultrastructural, immunohistochemical and histomorphometric analyses to analyze the healing of the defects. BMSC were spread, allowed to proliferate and differentiate to osteoblasts as shown by alizarin red histochemistry, and osteocalcine and osteonectine immunostaining. Scanning electron microscopy showed that BMSC on the scaffolds were more active and adhesive to the calcium phosphate scaffold compared to the others. Macroscopic bone formation was observed in all groups, but scaffolds with stromal cells produced significantly better results. Bone healing occurred earlier and faster with stromal cells on the calcium phosphate scaffold and produced more callus compared to other scaffolds. Tissue healing and osteoblastic marker expression also were better with stromal cells on the scaffolds. Increased trabecula formation, cell density and decreased fibrosis were observed in the calcium phosphate scaffold with stromal cells. Autologous cultured stromal cells on the scaffolds were useful for healing of canine tibial bone defects. The calcium phosphate scaffold was the best for both cell

  9. Plant stem cell niches.

    PubMed

    Aichinger, Ernst; Kornet, Noortje; Friedrich, Thomas; Laux, Thomas

    2012-01-01

    Multicellular organisms possess pluripotent stem cells to form new organs, replenish the daily loss of cells, or regenerate organs after injury. Stem cells are maintained in specific environments, the stem cell niches, that provide signals to block differentiation. In plants, stem cell niches are situated in the shoot, root, and vascular meristems-self-perpetuating units of organ formation. Plants' lifelong activity-which, as in the case of trees, can extend over more than a thousand years-requires that a robust regulatory network keep the balance between pluripotent stem cells and differentiating descendants. In this review, we focus on current models in plant stem cell research elaborated during the past two decades, mainly in the model plant Arabidopsis thaliana. We address the roles of mobile signals on transcriptional modules involved in balancing cell fates. In addition, we discuss shared features of and differences between the distinct stem cell niches of Arabidopsis.

  10. Artificial Stem Cell Niches

    PubMed Central

    Lutolf, Matthias P.; Blau, Helen M.

    2011-01-01

    Stem cells are characterized by their dual ability to reproduce themselves (self-renew) and specialize (differentiate), yielding a plethora of daughter cells that maintain and regenerate tissues. In contrast to their embryonic counterparts, adult stem cells retain their unique functions only if they are in intimate contact with an instructive microenvironment, termed stem cell niche. In these niches, stem cells integrate a complex array of molecular signals that, in concert with induced cell-intrinsic regulatory networks, control their function and balance their numbers in response to physiologic demands. This progress report provides a perspective on how advanced materials technologies could be used (i) to engineer and systematically analyze specific aspects of functional stem cells niches in a controlled fashion in vitro and (ii) to target stem cell niches in vivo. Such “artificial niches” constitute potent tools for elucidating stem cell regulatory mechanisms with the capacity to directly impact the development of novel therapeutic strategies for tissue regeneration. PMID:20882496

  11. Poor ex vivo induction of T-cell responses to idiotype or tumor cell lysate-pulsed autologous dendritic cells in advanced pre-treated multiple myeloma.

    PubMed

    Garderet, Laurent; Mazurier, Christelle; Pellat-Deceunynck, Catherine; Karim, Abdul; Baudin, Bruno; Funck-Brentano, Christian; Bouchet, Sandrine; Geffroy, Alexandrine; Bataille, Régis; Gorin, Norbert-Claude; Lopez, Manuel

    2006-07-01

    This study evaluated the feasibility of using dendritic cells (DCs) to generate, ex vivo, anti-tumor cytotoxic T lymphocytes (CTL) in patients with stage III multiple myeloma (MM). Nucleated cells from eight patients who had received chemotherapy (three of whom had undergone autologous hemopoeitic stem cell transplantation) were collected by apheresis. Their monocytes were enriched using counter-current centrifugation, differentiated into DCs which were further co-cultured with autologous CD8 lymphocytes to induce CTL. The DCs were pulsed either with the idiotypic paraprotein (regarded as a tumor-specific antigen) or with autologous MM cell lysate before co-culture. Specific T-cell responses were measured in IFNgamma enzyme-linked immunospot and chromium release assays of autologous plasmocyte targets. A slight increase in IFNgamma secretion by T-cells was observed for two patients (DCs pulsed with idiotypic paraprotein for one, MM cell lysate for the other). No or weak specific lysis of plasmocyte targets was observed in the chromium release assays. In conclusion, the T-cell response to pulsed DCs was very weak or absent. There are clinical and technical reasons that could explain, in part, this lack of response.

  12. Stem Cell Information: Glossary

    MedlinePlus

    ... based therapies Cell culture Cell division Chromosome Clone Cloning Cord blood stem cells Culture medium Differentiation Directed ... Pluripotent Polar body Preimplantation Proliferation Regenerative medicine Reproductive cloning Signals Somatic cell Somatic cell nuclear transfer (SCNT) ...

  13. Adipose tissue-derived mesenchymal stem cells and platelet-rich plasma: stem cell transplantation methods that enhance stemness.

    PubMed

    Tobita, Morikuni; Tajima, Satoshi; Mizuno, Hiroshi

    2015-11-05

    Because of their ease of isolation and relative abundance, adipose-derived mesenchymal stem cells (ASCs) are a particularly attractive autologous cell source for various therapeutic purposes. ASCs retain a high proliferation capacity in vitro and have the ability to undergo extensive differentiation into multiple cell lineages. Moreover, ASCs secrete a wide range of growth factors that can stimulate tissue regeneration. Therefore, the clinical use of ASCs is feasible. However, the potential of ASCs differs depending on the donor's medical condition, including diseases such as diabetes. Recent studies demonstrated that ASCs from diabetic donors exhibit reduced proliferative potential and a smaller proportion of stem cell marker-positive cells. Therefore, to ensure the success of regenerative medicine, tissue engineering methods must be improved by the incorporation of factors that increase the proliferation and differentiation of stem/progenitor cells when autologous cells are used. Platelet-rich plasma (PRP), which contains high levels of diverse growth factors that can stimulate stem cell proliferation and cell differentiation in the context of tissue regeneration, has recently been identified as a biological material that could be applied to tissue regeneration. Thus, co-transplantation of ASCs and PRP represents a promising novel approach for cell therapy in regenerative medicine. In this review, we describe the potential benefits of adding PRP to ASCs and preclinical and clinical studies of this approach in various medical fields. We also discuss the mechanisms of PRP action and future cell-based therapies using co-transplantation of ASCs and PRP.

  14. [Stem cell perspectives in myocardial infarctions].

    PubMed

    Aceves, José Luis; Archundia, Abel; Díaz, Guillermo; Páez, Araceli; Masso, Felipe; Alvarado, Martha; López, Manuel; Aceves, Rocío; Ixcamparij, Carlos; Puente, Adriana; Vilchis, Rafael; Montaño, Luis Felipe

    2005-01-01

    Myocardial infarction is the leading cause of congestive heart failure and death in industrializated countries. The cellular cardiomyoplasty has emerged as an alternative treatment in the regeneration of infarted myocardial tissue. In animals' models, different cellular lines such as cardiomyocites, skeletal myoblasts, embryonic stem cells and adult mesenchymal stem cells have been used, resulting in an improvement in ventricular function and decrease in amount of infarcted tissue. The first three cells lines have disvantages as they are allogenics and are difficult to obtain. The adult mesenchymal stem cells are autologous and can be obtained throught the aspiration of bone marrow or from peripherical circulation, after stimulating with cytokines (G-CSF). The implantation in humans with recent and old myocardial infarction have shown improvements similar to those shown in animal models. These findings encourage the continued investigation in the mechanism of cellular differentiation and implantation methods in infarcted myocardial tissue.

  15. Application of stem cells for articular cartilage regeneration.

    PubMed

    Hwang, Nathaniel S; Elisseeff, Jennifer

    2009-01-01

    Articular cartilage is a highly organized tissue lacking self-regeneration capacity upon lesion. Current surgical intervention by application of in vitro-expanded autologous chondrocytes transplantation procedure is associated with several disadvantages, including donor-site morbidity and inferior fibrocartilage formation at the defect site. However, recent advancements in tissue engineering have provided notable strategies for stem cell-based therapies and articular cartilage tissue engineering. In this review, we discuss the current strategies to engineer cartilage tissues from adult stem cells and human embryonic stem cell-derived cells. The characteristics of adult stem cells, the microenvironmental control of cell fate determination, and the limitation imposed by the intrinsic nature of stem cells are discussed. The strategy to commit the stem cells for functional cartilage tissues in vivo is also discussed.

  16. Hurdles to clinical translation of human induced pluripotent stem cells.

    PubMed

    Neofytou, Evgenios; O'Brien, Connor Galen; Couture, Larry A; Wu, Joseph C

    2015-07-01

    Human pluripotent stem cells are known to have the capacity to renew indefinitely, being intrinsically able to differentiate into many different cell types. These characteristics have generated tremendous enthusiasm about the potential applications of these cells in regenerative medicine. However, major challenges remain with the development and testing of novel experimental stem cell therapeutics in the field. In this Review, we focus on the nature of the preclinical challenges and discuss potential solutions that could help overcome them. Furthermore, we discuss the use of allogeneic versus autologous stem cell products, including a review of their respective advantages and disadvantages, major clinical requirements, quality standards, time lines, and costs of clinical grade development.

  17. Stem cells and reproduction

    PubMed Central

    Du, Hongling; Taylor, Hugh S.

    2011-01-01

    Purpose of review To review the latest developments in reproductive tract stem cell biology. Recent findings In 2004, two studies indicated that ovaries contain stem cells which form oocytes in adults and that can be cultured in vitro into mature oocytes. A live birth after orthotopic transplantation of cyropreserved ovarian tissue in a woman whose ovaries were damaged by chemotherapy demonstrates the clinical potential of these cells. In the same year, another study provided novel evidence of endometrial regeneration by stem cells in women who received bone marrow transplants. This finding has potential for the use in treatment of uterine disorders. It also supports a new theory for the cause of endometriosis, which may have its origin in ectopic transdifferentiation of stem cells. Several recent studies have demonstrated that fetal cells enter the maternal circulation and generate microchimerism in the mother. The uterus is a dynamic organ permeable to fetal stem cells, capable of transdifferentiation and an end organ in which bone marrow stem cells may differentiate. Finally stem cell transformation can be an underlying cause of ovarian cancer. Summary Whereas we are just beginning to understand stem cells, the potential implications of stem cells to reproductive biology and medicine are apparent. PMID:20305558

  18. Stem cells in urology.

    PubMed

    Aboushwareb, Tamer; Atala, Anthony

    2008-11-01

    The shortage of donors for organ transplantation has stimulated research on stem cells as a potential resource for cell-based therapy in all human tissues. Stem cells have been used for regenerative medicine applications in many organ systems, including the genitourinary system. The potential applications for stem cell therapy have, however, been restricted by the ethical issues associated with embryonic stem cell research. Instead, scientists have explored other cell sources, including progenitor and stem cells derived from adult tissues and stem cells derived from the amniotic fluid and placenta. In addition, novel techniques for generating stem cells in the laboratory are being developed. These techniques include somatic cell nuclear transfer, in which the nucleus of an adult somatic cell is placed into an oocyte, and reprogramming of adult cells to induce stem-cell-like behavior. Such techniques are now being used in tissue engineering applications, and some of the most successful experiments have been in the field of urology. Techniques to regenerate bladder tissue have reached the clinic, and exciting progress is being made in other areas, such as regeneration of the kidney and urethra. Cell therapy as a treatment for incontinence and infertility might soon become a reality. Physicians should be optimistic that regenerative medicine and tissue engineering will one day provide mainstream treatment options for urologic disorders.

  19. PHENOTYPE AND POLARIZATION OF AUTOLOGOUS T CELLS BY BIOMATERIAL-TREATED DENDRITIC CELLS

    PubMed Central

    Park, Jaehyung; Gerber, Michael H.; Babensee, Julia E.

    2014-01-01

    Given the central role of dendritic cells (DCs) in directing T cell phenotypes, the ability of biomaterial-treated DCs to dictate autologous T cell phenotype was investigated. Here, we demonstrate that differentially biomaterial-treated DCs differentially directed autologous T cell phenotype and polarization, depending on the biomaterial used to pre-treat the DCs. Immature DCs (iDCs) were derived from human peripheral blood monocytes, and treated with biomaterial films of alginate, agarose, chitosan, hyaluronic acid, or 75:25 poly(lactic-co-glycolic acid) (PLGA), followed by co-culture of these biomaterial-treated DCs and autologous T cells. When autologous T cells were co-cultured with DCs treated with biomaterial film/antigen (ovalbumin, OVA) combinations, different biomaterial films induced differential levels of T cell marker (CD4, CD8, CD25, CD69) expression, as well as differential cytokine profiles [interferon (IFN)-γ, interleukin (IL)-12p70, IL-10, IL-4] in the polarization of T helper types. Dendritic cells treated with agarose films/OVA induced CD4+CD25+FoxP3+ (T regulatory cells) expression, comparable to untreated iDCs, on autologous T cells in the DC-T co-culture system. Furthermore, in this co-culture, agarose treatment induced release of IL-12p70 and IL-10 at higher levels, as compared to DC treatment with other biomaterial films/OVA, suggesting Th1 and Th2 polarization, respectively. Dendritic cells treated with PLGA film/OVA treatment induced release of IFN-γ at higher levels compared to that observed for co-cultures with iDCs or DCs treated with all other biomaterial films. These results indicate that DC treatment with different biomaterial films has potential as a tool for immunomodulation by directing autologous T cell responses. PMID:24616366

  20. Direct-to-Consumer Stem Cell Marketing and Regulatory Responses

    PubMed Central

    2013-01-01

    Summary There is a large, poorly regulated international market of putative stem cell products, including transplants of processed autologous stem cells from various tissues, cell processing devices, cosmetics, and nutritional supplements. Despite the absence of rigorous scientific research in the form of randomized clinical trials to support the routine use of such products, the market appears to be growing and diversifying. Very few stem cell biologics have passed regulatory scrutiny, and authorities in many countries, including the United States, have begun to step up their enforcement activities to protect patients and the integrity of health care markets. PMID:23934911

  1. Direct-to-consumer stem cell marketing and regulatory responses.

    PubMed

    Sipp, Douglas

    2013-09-01

    There is a large, poorly regulated international market of putative stem cell products, including transplants of processed autologous stem cells from various tissues, cell processing devices, cosmetics, and nutritional supplements. Despite the absence of rigorous scientific research in the form of randomized clinical trials to support the routine use of such products, the market appears to be growing and diversifying. Very few stem cell biologics have passed regulatory scrutiny, and authorities in many countries, including the United States, have begun to step up their enforcement activities to protect patients and the integrity of health care markets.

  2. Stem and progenitor cells: advancing bone tissue engineering.

    PubMed

    Tevlin, R; Walmsley, G G; Marecic, O; Hu, Michael S; Wan, D C; Longaker, M T

    2016-04-01

    Unlike many other postnatal tissues, bone can regenerate and repair itself; nevertheless, this capacity can be overcome. Traditionally, surgical reconstructive strategies have implemented autologous, allogeneic, and prosthetic materials. Autologous bone--the best option--is limited in supply and also mandates an additional surgical procedure. In regenerative tissue engineering, there are myriad issues to consider in the creation of a functional, implantable replacement tissue. Importantly, there must exist an easily accessible, abundant cell source with the capacity to express the phenotype of the desired tissue, and a biocompatible scaffold to deliver the cells to the damaged region. A literature review was performed using PubMed; peer-reviewed publications were screened for relevance in order to identify key advances in stem and progenitor cell contribution to the field of bone tissue engineering. In this review, we briefly introduce various adult stem cells implemented in bone tissue engineering such as mesenchymal stem cells (including bone marrow- and adipose-derived stem cells), endothelial progenitor cells, and induced pluripotent stem cells. We then discuss numerous advances associated with their application and subsequently focus on technological advances in the field, before addressing key regenerative strategies currently used in clinical practice. Stem and progenitor cell implementation in bone tissue engineering strategies have the ability to make a major impact on regenerative medicine and reduce patient morbidity. As the field of regenerative medicine endeavors to harness the body's own cells for treatment, scientific innovation has led to great advances in stem cell-based therapies in the past decade.

  3. Hematopoietic stem cell transplantation for non-Hodgkin lymphoma.

    PubMed

    Bhatt, Vijaya Raj; Vose, Julie M

    2014-12-01

    Up-front rituximab-based chemotherapy has improved outcomes in non-Hodgkin lymphoma (NHL); refractory or relapsed NHL still accounts for approximately 18,000 deaths in the United States. Autologous hematopoietic stem cell transplantation (SCT) can improve survival in primary refractory or relapsed aggressive NHL and mantle cell lymphoma and in relapsed follicular or peripheral T-cell lymphoma. Autologous SCT as a consolidation therapy after first complete or partial remission in high-risk aggressive NHL, mantle cell lymphoma, and peripheral T-cell lymphoma may improve progression-free survival. Allogeneic SCT offers a lower relapse rate but a higher nonrelapse mortality resulting in overall survival similar to autologous SCT. PMID:25459180

  4. Brain tumor stem cells.

    PubMed

    Palm, Thomas; Schwamborn, Jens C

    2010-06-01

    Since the end of the 'no-new-neuron' theory, emerging evidence from multiple studies has supported the existence of stem cells in neurogenic areas of the adult brain. Along with this discovery, neural stem cells became candidate cells being at the origin of brain tumors. In fact, it has been demonstrated that molecular mechanisms controlling self-renewal and differentiation are shared between brain tumor stem cells and neural stem cells and that corruption of genes implicated in these pathways can direct tumor growth. In this regard, future anticancer approaches could be inspired by uncovering such redundancies and setting up treatments leading to exhaustion of the cancer stem cell pool. However, deleterious effects on (normal) neural stem cells should be minimized. Such therapeutic models underline the importance to study the cellular mechanisms implicated in fate decisions of neural stem cells and the oncogenic derivation of adult brain cells. In this review, we discuss the putative origins of brain tumor stem cells and their possible implications on future therapies.

  5. Fetal stem cell transplantation: Past, present, and future.

    PubMed

    Ishii, Tetsuya; Eto, Koji

    2014-09-26

    Since 1928, human fetal tissues and stem cells have been used worldwide to treat various conditions. Although the transplantation of the fetal midbrain substantia nigra and dopaminergic neurons in patients suffering from Parkinson's disease is particularly noteworthy, the history of other types of grafts, such as those of the fetal liver, thymus, and pancreas, should be addressed as there are many lessons to be learnt for future stem cell transplantation. This report describes previous practices and complications that led to current clinical trials of isolated fetal stem cells and embryonic stem (ES) cells. Moreover, strategies for transplantation are considered, with a particular focus on donor cells, cell processing, and the therapeutic cell niche, in addition to ethical issues associated with fetal origin. With the advent of autologous induced pluripotent stem cells and ES cells, clinical dependence on fetal transplantation is expected to gradually decline due to lasting ethical controversies, despite landmark achievements.

  6. Fetal stem cell transplantation: Past, present, and future

    PubMed Central

    Ishii, Tetsuya; Eto, Koji

    2014-01-01

    Since 1928, human fetal tissues and stem cells have been used worldwide to treat various conditions. Although the transplantation of the fetal midbrain substantia nigra and dopaminergic neurons in patients suffering from Parkinson’s disease is particularly noteworthy, the history of other types of grafts, such as those of the fetal liver, thymus, and pancreas, should be addressed as there are many lessons to be learnt for future stem cell transplantation. This report describes previous practices and complications that led to current clinical trials of isolated fetal stem cells and embryonic stem (ES) cells. Moreover, strategies for transplantation are considered, with a particular focus on donor cells, cell processing, and the therapeutic cell niche, in addition to ethical issues associated with fetal origin. With the advent of autologous induced pluripotent stem cells and ES cells, clinical dependence on fetal transplantation is expected to gradually decline due to lasting ethical controversies, despite landmark achievements. PMID:25258662

  7. Fish stem cell cultures.

    PubMed

    Hong, Ni; Li, Zhendong; Hong, Yunhan

    2011-04-13

    Stem cells have the potential for self-renewal and differentiation. First stem cell cultures were derived 30 years ago from early developing mouse embryos. These are pluripotent embryonic stem (ES) cells. Efforts towards ES cell derivation have been attempted in other mammalian and non-mammalian species. Work with stem cell culture in fish started 20 years ago. Laboratory fish species, in particular zebrafish and medaka, have been the focus of research towards stem cell cultures. Medaka is the second organism that generated ES cells and the first that gave rise to a spermatogonial stem cell line capable of test-tube sperm production. Most recently, the first haploid stem cells capable of producing whole animals have also been generated from medaka. ES-like cells have been reported also in zebrafish and several marine species. Attempts for germline transmission of ES cell cultures and gene targeting have been reported in zebrafish. Recent years have witnessed the progress in markers and procedures for ES cell characterization. These include the identification of fish homologs/paralogs of mammalian pluripotency genes and parameters for optimal chimera formation. In addition, fish germ cell cultures and transplantation have attracted considerable interest for germline transmission and surrogate production. Haploid ES cell nuclear transfer has proven in medaka the feasibility of semi-cloning as a novel assisted reproductive technology. In this special issue on "Fish Stem Cells and Nuclear Transfer", we will focus our review on medaka to illustrate the current status and perspective of fish stem cells in research and application. We will also mention semi-cloning as a new development to conventional nuclear transfer.

  8. Stem cells in dermatology.

    PubMed

    Ogliari, Karolyn Sassi; Marinowic, Daniel; Brum, Dario Eduardo; Loth, Fabrizio

    2014-01-01

    Preclinical and clinical research have shown that stem cell therapy could be a promising therapeutic option for many diseases in which current medical treatments do not achieve satisfying results or cure. This article describes stem cells sources and their therapeutic applications in dermatology today.

  9. Stem Cell Transplants (For Teens)

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Stem Cell Transplants KidsHealth > For Teens > Stem Cell Transplants Print ... Does it Take to Recover? Coping What Are Stem Cells? As you probably remember from biology class, every ...

  10. Spinal fluid lymphocytes responsive to autologous and allogeneic cells in multiple sclerosis and control individuals.

    PubMed Central

    Birnbaum, G; Kotilinek, L; Schwartz, M; Sternad, M

    1984-01-01

    Spinal fluid lymphocytes from multiple sclerosis (MS) patients and controls were stimulated with either autologous non-T cells or with allogeneic non-T cells followed by stimulation with autologous non-T lymphocytes. Cells responding to these stimuli were cloned and their proliferative responses to autologous and allogeneic MS and normal non-T cells were measured. Large numbers of clones with specific patterns of reaction to both autologous and allogeneic cells were obtained from lymphocytes in MS cerebrospinal fluid (CSF), but only occasionally from cells in control CSF. Patterns of responses among clones from a particular CSF were similar and often identical, which suggested that cells in MS CSF were relatively restricted in their specificities. Surface antigen phenotyping of the clones showed them to be predominantly OKT4+, with 13% OKT8+ and 11% OKT4+8+. Peripheral T cells that were stimulated and cultured in parallel with CSF cells were different in that they usually did not give rise to as many clones nor were their patterns of response similar. Many CSF clones were heteroclitic, that is they responded to particular allogeneic cells but not autologous cells. Lymphocytes in MS CSF thus appear to represent a selected population of cells with a high frequency of responsiveness to autologous and allogeneic antigens. Such responses may be evidence for immune regulation within the central nervous system or could represent responses to altered-self antigens. PMID:6237121

  11. Autophagy in stem cells

    PubMed Central

    Guan, Jun-Lin; Simon, Anna Katharina; Prescott, Mark; Menendez, Javier A.; Liu, Fei; Wang, Fen; Wang, Chenran; Wolvetang, Ernst; Vazquez-Martin, Alejandro; Zhang, Jue

    2013-01-01

    Autophagy is a highly conserved cellular process by which cytoplasmic components are sequestered in autophagosomes and delivered to lysosomes for degradation. As a major intracellular degradation and recycling pathway, autophagy is crucial for maintaining cellular homeostasis as well as remodeling during normal development, and dysfunctions in autophagy have been associated with a variety of pathologies including cancer, inflammatory bowel disease and neurodegenerative disease. Stem cells are unique in their ability to self-renew and differentiate into various cells in the body, which are important in development, tissue renewal and a range of disease processes. Therefore, it is predicted that autophagy would be crucial for the quality control mechanisms and maintenance of cellular homeostasis in various stem cells given their relatively long life in the organisms. In contrast to the extensive body of knowledge available for somatic cells, the role of autophagy in the maintenance and function of stem cells is only beginning to be revealed as a result of recent studies. Here we provide a comprehensive review of the current understanding of the mechanisms and regulation of autophagy in embryonic stem cells, several tissue stem cells (particularly hematopoietic stem cells), as well as a number of cancer stem cells. We discuss how recent studies of different knockout mice models have defined the roles of various autophagy genes and related pathways in the regulation of the maintenance, expansion and differentiation of various stem cells. We also highlight the many unanswered questions that will help to drive further research at the intersection of autophagy and stem cell biology in the near future. PMID:23486312

  12. Synovium-derived stem cells: a tissue-specific stem cell for cartilage engineering and regeneration.

    PubMed

    Jones, Brendan A; Pei, Ming

    2012-08-01

    Articular cartilage is difficult to heal once injury or disease occurs. Autologous chondrocyte transplantation is a biological treatment with good prognosis, but donor site morbidity and limited cell source are disadvantages. Currently, mesenchymal stem cells (MSCs) are a promising approach for cartilage regeneration. Despite there being various sources, the best candidate for cartilage regeneration is the one with the greatest chondrogenic potential and the least hypertrophic differentiation. These properties are able to insure that the regenerated tissue is hyaline cartilage of high quality. This review article will summarize relevant literature to justify synovium-derived stem cells (SDSCs) as a tissue-specific stem cell for chondrogenesis by comparing synovium and cartilage with respect to anatomical location and functional structure, comparing the growth characterization and chondrogenic capacity of SDSCs and MSCs, evaluating the application of SDSCs in regenerative medicine and diseases, and discussing potential future directions.

  13. Limbal stem cell transplantation: current perspectives

    PubMed Central

    Atallah, Marwan Raymond; Palioura, Sotiria; Perez, Victor L; Amescua, Guillermo

    2016-01-01

    Regeneration of the corneal surface after an epithelial insult involves division, migration, and maturation of a specialized group of stem cells located in the limbus. Several insults, both intrinsic and extrinsic, can precipitate destruction of the delicate microenvironment of these cells, resulting in limbal stem cell deficiency (LSCD). In such cases, reepithelialization fails and conjunctival epithelium extends across the limbus, leading to vascularization, persistent epithelial defects, and chronic inflammation. In partial LSCD, conjunctival epitheliectomy, coupled with amniotic membrane transplantation, could be sufficient to restore a healthy surface. In more severe cases and in total LSCD, stem cell transplantation is currently the best curative option. Before any attempts are considered to perform a limbal stem cell transplantation procedure, the ocular surface must be optimized by controlling causative factors and comorbid conditions. These factors include adequate eyelid function or exposure, control of the ocular surface inflammatory status, and a well-lubricated ocular surface. In cases of unilateral LSCD, stem cells can be obtained from the contralateral eye. Newer techniques aim at expanding cells in vitro or in vivo in order to decrease the need for large limbal resection that may jeopardize the “healthy” eye. Patients with bilateral disease can be treated using allogeneic tissue in combination with systemic immunosuppressive therapy. Another emerging option for this subset of patients is the use of noncorneal cells such as mucosal grafts. Finally, the use of keratoprosthesis is reserved for patients who are not candidates for any of the aforementioned options, wherein the choice of the type of keratoprosthesis depends on the severity of the disease. In summary, limbal stem cell transplantation improves both vision and quality-of-life in patients with ocular surface disorders associated with LSCD, and overall, the use of autologous tissue offers

  14. Generating Cartilage Repair from Pluripotent Stem Cells

    PubMed Central

    Cheng, Aixin; Hardingham, Timothy E.

    2014-01-01

    The treatment of degeneration and injury of articular cartilage has been very challenging for scientists and surgeons. As an avascular and hypocellular tissue, cartilage has a very limited capacity for self-repair. Chondrocytes are the only cell type in cartilage, in which they are surrounded by the extracellular matrix that they secrete and assemble. Autologous chondrocyte implantation for cartilage defects has achieved good results, but the limited resources and complexity of the procedure have hindered wider application. Stem cells form an alternative to chondrocytes as a source of chondrogenic cells due to their ability to proliferate extensively while retaining the potential for differentiation. Adult stem cells such as mesenchymal stem cells have been differentiated into chondrocytes, but the limitations in their proliferative ability and the heterogeneous cell population hinder their adoption as a prime alternative source for generating chondrocytes. Human embryonic stem cells (hESCs) are attractive as candidates for cell replacement therapy because of their unlimited self-renewal and ability for differentiation into mesodermal derivatives as well as other lineages. In this review, we focus on current protocols for chondrogenic differentiation of ESCs, in particular the chemically defined culture system developed in our lab that could potentially be adapted for clinical application. PMID:23957872

  15. Articular cartilage repair with autologous bone marrow mesenchymal cells.

    PubMed

    Matsumoto, Tomiya; Okabe, Takahiro; Ikawa, Tesshu; Iida, Takahiro; Yasuda, Hiroyuki; Nakamura, Hiroaki; Wakitani, Shigeyuki

    2010-11-01

    Articular cartilage defects that do not repair spontaneously induce osteoarthritic changes in joints over a long period of observation. In this study, we examined the usefulness of transplanting culture-expanded bone marrow mesenchymal cells into osteochondral defects of joints with cartilage defects. First, we performed experiments on rabbits and up on obtaining good results proceeded to perform the experiments on humans. Macroscopic and histological repair with this method was good, and good clinical results were obtained although there was no significant difference with the control group. Recent reports have indicated that this procedure is comparable to autologous chondrocyte implantation, and concluded that it was a good procedure because it required one step less than that required by surgery, reduced costs for patients, and minimized donor site morbidity. Although some reports have previously shown that progenitor cells formed a tumor when implanted into immune-deficient mice after long term in vitro culture, the safety of the cell transplantation was confirmed by our clinical experience. Thus, this procedure is useful, effective, and safe, but the repaired tissues were not always hyaline cartilage. To obtain better repair with this procedure, treatment approaches using some growth factors during in vitro culture or gene transfection are being explored.

  16. Prevention of limb amputation in patients with limbs ulcers by autologous peripheral blood mononuclear cell implantation.

    PubMed

    Kawamura, Akio; Horie, Takashi; Tsuda, Ichirou; Ikeda, Atushi; Egawa, Hirotoshi; Imamura, Emi; Iida, Jun-Ichi; Sakata, Hiromi; Tamaki, Tohru; Kukita, Kazutaka; Meguro, Jun-ichi; Yonekawa, Motoki; Kasai, Masaharu

    2005-02-01

    There are many cases of amputation of ischemic limbs of dialysis patients due to diabetes, despite the availability of medicine therapy and vascular by-pass operations. As there is extensive ruin of the vascular bed due to diabetes, vascular regeneration therapy by stem cell implantation is effective. Thirty patients with ischemic limbs due to diabetes (not including type-I) and on dialysis for chronic renal failure (19 cases), diabetes (5 cases), dialysis patients without diabetes (4 cases), and arteriosclerosis obliterans (ASO, 2 cases) were treated by autologous peripheral blood stem cell (PBSC) implantation where imminent amputation was under consideration. Granulocyte Colony Stimulate Factor (G-CSF: 5 microg/kg/day) was administered subcutaneously for 4 days before PBSC collection, that was carried out using a centrifuge (Spectra and/or CS3000) via the vein. The collected PBSC, containing 4.2 x 10(7) of CD 34 positive cells, was divided into units of 0.5-1.0 mL and implanted, without any purification, to the ischemic area of the limbs in about 65 points. In 21 cases, normalization of limb temperature was observed by thermograph, and symptoms also improved. The result of this first attempt of PBSC implantation is that we were able to save 22 ischemic limbs. This is the first large report of the application of regenerative medicine to peripheral ischemic limbs. PMID:15828908

  17. SMOOTH MUSCLE STEM CELLS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vascular smooth muscle cells (SMCs) originate from multiple types of progenitor cells. In the embryo, the most well-studied SMC progenitor is the cardiac neural crest stem cell. Smooth muscle differentiation in the neural crest lineage is controlled by a combination of cell intrinsic factors, includ...

  18. Comparison of human adipose-derived stem cells and bone marrow-derived stem cells in a myocardial infarction model.

    PubMed

    Rasmussen, Jeppe Grøndahl; Frøbert, Ole; Holst-Hansen, Claus; Kastrup, Jens; Baandrup, Ulrik; Zachar, Vladimir; Fink, Trine; Simonsen, Ulf

    2014-02-01

    Treatment of myocardial infarction (MI) with bone marrow-derived mesenchymal stem cells and recently also adipose-derived stem cells has shown promising results. In contrast to clinical trials and their use of autologous bone marrow-derived cells from the ischemic patient, the animal MI models are often using young donors and young, often immune-compromised, recipient animals. Our objective was to compare bone marrow-derived mesenchymal stem cells with adipose-derived stem cells from an elderly ischemic patient in the treatment of MI using a fully grown non-immune-compromised rat model. Mesenchymal stem cells were isolated from adipose tissue and bone marrow and compared with respect to surface markers and proliferative capability. To compare the regenerative potential of the two stem cell populations, male Sprague-Dawley rats were randomized to receive intramyocardial injections of adipose-derived stem cells, bone marrow-derived mesenchymal stem cells, or phosphate-buffered saline 1 week following induction of MI. After 4 weeks, left ventricular ejection fraction (LVEF) was improved in the adipose-derived stem cell group, and scar wall thickness was greater compared with the saline group. Adipose-derived as well as bone marrow-derived mesenchymal stem cells prevented left ventricular end diastolic dilation. Neither of the cell groups displayed increased angiogenesis in the myocardium compared with the saline group. Adipose-derived stem cells from a human ischemic patient preserved cardiac function following MI, whereas this could not be demonstrated for bone marrow-derived mesenchymal stem cells, with only adipose-derived stem cells leading to an improvement in LVEF. Neither of the stem cell types induced myocardial angiogenesis, raising the question whether donor age and health have an effect on the efficacy of stem cells used in the treatment of MI.

  19. Comparison of human adipose-derived stem cells and bone marrow-derived stem cells in a myocardial infarction model.

    PubMed

    Rasmussen, Jeppe Grøndahl; Frøbert, Ole; Holst-Hansen, Claus; Kastrup, Jens; Baandrup, Ulrik; Zachar, Vladimir; Fink, Trine; Simonsen, Ulf

    2014-02-01

    Treatment of myocardial infarction (MI) with bone marrow-derived mesenchymal stem cells and recently also adipose-derived stem cells has shown promising results. In contrast to clinical trials and their use of autologous bone marrow-derived cells from the ischemic patient, the animal MI models are often using young donors and young, often immune-compromised, recipient animals. Our objective was to compare bone marrow-derived mesenchymal stem cells with adipose-derived stem cells from an elderly ischemic patient in the treatment of MI using a fully grown non-immune-compromised rat model. Mesenchymal stem cells were isolated from adipose tissue and bone marrow and compared with respect to surface markers and proliferative capability. To compare the regenerative potential of the two stem cell populations, male Sprague-Dawley rats were randomized to receive intramyocardial injections of adipose-derived stem cells, bone marrow-derived mesenchymal stem cells, or phosphate-buffered saline 1 week following induction of MI. After 4 weeks, left ventricular ejection fraction (LVEF) was improved in the adipose-derived stem cell group, and scar wall thickness was greater compared with the saline group. Adipose-derived as well as bone marrow-derived mesenchymal stem cells prevented left ventricular end diastolic dilation. Neither of the cell groups displayed increased angiogenesis in the myocardium compared with the saline group. Adipose-derived stem cells from a human ischemic patient preserved cardiac function following MI, whereas this could not be demonstrated for bone marrow-derived mesenchymal stem cells, with only adipose-derived stem cells leading to an improvement in LVEF. Neither of the stem cell types induced myocardial angiogenesis, raising the question whether donor age and health have an effect on the efficacy of stem cells used in the treatment of MI. PMID:23211469

  20. Plant Stem Cells.

    PubMed

    Greb, Thomas; Lohmann, Jan U

    2016-09-12

    Among the trending topics in the life sciences, stem cells have received a fair share of attention in the public debate - mostly in connection with their potential for biomedical application and therapies. While the promise of organ regeneration and the end of cancer have captured our imagination, it has gone almost unnoticed that plant stem cells represent the ultimate origin of much of the food we eat, the oxygen we breathe, as well the fuels we burn. Thus, plant stem cells may be ranked among the most important cells for human well-being. Research by many labs in the last decades has uncovered a set of independent stem cell systems that fulfill the specialized needs of plant development and growth in four dimensions. Surprisingly, the cellular and molecular design of these systems is remarkably similar, even across diverse species. In some long-lived plants, such as trees, plant stem cells remain active over hundreds or even thousands of years, revealing the exquisite precision in the underlying control of proliferation, self-renewal and differentiation. In this minireview, we introduce the basic features of the three major plant stem cell systems building on these facts, highlight their modular design at the level of cellular layout and regulatory underpinnings and briefly compare them with their animal counterparts. PMID:27623267

  1. Indoor air pollution: impact on health and stem cells.

    PubMed

    Ghosh, Shyamasree; Ansar, Waliza

    2014-01-01

    Nearly 2 million people annually die prematurely from various illness contributed by indoor air pollutants (IAP). Such pollutants affect the lungs leading to diseases ranging from bronchial diseases to malignant lung cancer. Stem cells (SC) with the property of self-renewal, pluripotency, and capability of homing into tumors and metastases, have been reported to be promising in treatment of lung cancer. In this review, we have tried to understand the role of components of IAP affect the SC. Although very few studies have been conducted in these lines, existing reports suggest that IAP causes damage to stem cells and their niches thereby reducing successful chances of autologous stem cell transplantation and therapy. The mechanism by which components of IAP affects the functioning of stem cells thus conferring toxicity remains unexplored. The future scope of this review lies in revealing answer to underlying questions of repair and modulation of stem cells in therapeutic treatment of lung diseases.

  2. Hematopoietic stem cell transplantation for HIV cure.

    PubMed

    Kuritzkes, Daniel R

    2016-02-01

    The apparent cure of an HIV-infected person following hematopoietic stem cell transplantation (HSCT) from an allogeneic donor homozygous for the ccr5Δ32 mutation has stimulated the search for strategies to eradicate HIV or to induce long-term remission without requiring ongoing antiretroviral therapy. A variety of approaches, including allogeneic HSCT from CCR5-deficient donors and autologous transplantation of genetically modified hematopoietic stem cells, are currently under investigation. This Review covers the experience with HSCT in HIV infection to date and provides a survey of ongoing work in the field. The challenges of developing HSCT for HIV cure in the context of safe, effective, and convenient once-daily antiretroviral therapy are also discussed.

  3. [Stem cells and cancer].

    PubMed

    Arvelo, Francisco; Cotte, Carlos; Sojo, Felipe

    2014-12-01

    Surgery, radiotherapy and chemotherapy are universally recognized as the most effective anti-cancer therapies. Despite significant advances directed towards elucidating molecular mechanisms and developing clinical trials, cancer still remains a major public health issue. Cancer stem cells are a subpopulation of the cells that form the tumor. The discovery of these human cancer cells opens a perspective for understanding tumor recurrence, drug resistance and metastasis; and opens up new research directions on how cancer cells are capable of switching from dormancy to malignancy. Therapeutic alternatives emerge from a better understanding of the biology and the environment of tumor stem cells. The present paper aims to summarize the characteristics and properties of cancer stem cells, the ongoing research, as well as the best strategies for prevention and control of the mechanisms of tumor recurrence.

  4. Aneuploidy in stem cells

    PubMed Central

    Garcia-Martinez, Jorge; Bakker, Bjorn; Schukken, Klaske M; Simon, Judith E; Foijer, Floris

    2016-01-01

    Stem cells hold enormous promise for regenerative medicine as well as for engineering of model systems to study diseases and develop new drugs. The discovery of protocols that allow for generating induced pluripotent stem cells (IPSCs) from somatic cells has brought this promise steps closer to reality. However, as somatic cells might have accumulated various chromosomal abnormalities, including aneuploidies throughout their lives, the resulting IPSCs might no longer carry the perfect blueprint for the tissue to be generated, or worse, become at risk of adopting a malignant fate. In this review, we discuss the contribution of aneuploidy to healthy tissues and how aneuploidy can lead to disease. Furthermore, we review the differences between how somatic cells and stem cells respond to aneuploidy. PMID:27354891

  5. Prospects for clinical use of reprogrammed cells for autologous treatment of macular degeneration.

    PubMed

    Alvarez Palomo, Ana Belen; McLenachan, Samuel; Chen, Fred K; Da Cruz, Lyndon; Dilley, Rodney J; Requena, Jordi; Lucas, Michaela; Lucas, Andrew; Drukker, Micha; Edel, Michael J

    2015-01-01

    Since the discovery of induced pluripotent stem cells (iPSC) in 2006, the symptoms of many human diseases have been reversed in animal models with iPSC therapy, setting the stage for future clinical development. From the animal data it is clear that iPSC are rapidly becoming the lead cell type for cell replacement therapy and for the newly developing field of iPSC-derived body organ transplantation. The first human pathology that might be treated in the near future with iPSC is age-related macular degeneration (AMD), which has recently passed the criteria set down by regulators for phase I clinical trials with allogeneic human embryonic stem cell-derived cell transplantation in humans. Given that iPSC are currently in clinical trial in Japan (RIKEN) to treat AMD, the establishment of a set of international criteria to make clinical-grade iPSC and their differentiated progeny is the next step in order to prepare for future autologous cell therapy clinical trials. Armed with clinical-grade iPSC, we can then specifically test for their threat of cancer, for proper and efficient differentiation to the correct cell type to treat human disease and then to determine their immunogenicity. Such a rigorous approach sets a far more relevant paradigm for their intended future use than non-clinical-grade iPSC. This review focuses on the latest developments regarding the first possible use of iPSC-derived retinal pigment epithelial cells in treating human disease, covers data gathered on animal models to date and methods to make clinical-grade iPSC, suggests techniques to ensure quality control and discusses possible clinical immune responses.

  6. Strategies for bioengineered scaffolds that support adipose stem cells in regenerative therapies.

    PubMed

    Clevenger, Tracy N; Luna, Gabriel; Fisher, Steven K; Clegg, Dennis O

    2016-09-01

    Regenerative medicine possesses the potential to ameliorate damage to tissue that results from a vast range of conditions, including traumatic injury, tumor resection and inherited tissue defects. Adult stem cells, while more limited in their potential than pluripotent stem cells, are still capable of differentiating into numerous lineages and provide feasible allogeneic and autologous treatment options for many conditions. Adipose stem cells are one of the most abundant types of stem cell in the adult human. Here, we review recent advances in the development of synthetic scaffolding systems used in concert with adipose stem cells and assess their potential use for clinical applications.

  7. Advanced Properties of Urine Derived Stem Cells Compared to Adipose Tissue Derived Stem Cells in Terms of Cell Proliferation, Immune Modulation and Multi Differentiation.

    PubMed

    Kang, Hye Suk; Choi, Seock Hwan; Kim, Bum Soo; Choi, Jae Young; Park, Gang-Baek; Kwon, Tae Gyun; Chun, So Young

    2015-12-01

    Adipose tissue stem cells (ADSCs) would be an attractive autologous cell source. However, ADSCs require invasive procedures, and has potential complications. Recently, urine stem cells (USCs) have been proposed as an alternative stem cell source. In this study, we compared USCs and ADSCs collected from the same patients on stem cell characteristics and capacity to differentiate into various cell lineages to provide a useful guideline for selecting the appropriate type of cell source for use in clinical application. The urine samples were collected via urethral catheterization, and adipose tissue was obtained from subcutaneous fat tissue during elective laparoscopic kidney surgery from the same patient (n = 10). Both cells were plated for primary culture. Cell proliferation, colony formation, cell surface markers, immune modulation, chromosome stability and multi-lineage differentiation were analyzed for each USCs and ADSCs at cell passage 3, 5, and 7. USCs showed high cell proliferation rate, enhanced colony forming ability, strong positive for stem cell markers expression, high efficiency for inhibition of immune cell activation compared to ADSCs at cell passage 3, 5, and 7. In chromosome stability analysis, both cells showed normal karyotype through all passages. In analysis of multi-lineage capability, USCs showed higher myogenic, neurogenic, and endogenic differentiation rate, and lower osteogenic, adipogenic, and chondrogenic differentiation rate compared to ADSCs. Therefore, we expect that USC can be an alternative autologous stem cell source for muscle, neuron and endothelial tissue reconstruction instead of ADSCs.

  8. Advanced Properties of Urine Derived Stem Cells Compared to Adipose Tissue Derived Stem Cells in Terms of Cell Proliferation, Immune Modulation and Multi Differentiation

    PubMed Central

    2015-01-01

    Adipose tissue stem cells (ADSCs) would be an attractive autologous cell source. However, ADSCs require invasive procedures, and has potential complications. Recently, urine stem cells (USCs) have been proposed as an alternative stem cell source. In this study, we compared USCs and ADSCs collected from the same patients on stem cell characteristics and capacity to differentiate into various cell lineages to provide a useful guideline for selecting the appropriate type of cell source for use in clinical application. The urine samples were collected via urethral catheterization, and adipose tissue was obtained from subcutaneous fat tissue during elective laparoscopic kidney surgery from the same patient (n = 10). Both cells were plated for primary culture. Cell proliferation, colony formation, cell surface markers, immune modulation, chromosome stability and multi-lineage differentiation were analyzed for each USCs and ADSCs at cell passage 3, 5, and 7. USCs showed high cell proliferation rate, enhanced colony forming ability, strong positive for stem cell markers expression, high efficiency for inhibition of immune cell activation compared to ADSCs at cell passage 3, 5, and 7. In chromosome stability analysis, both cells showed normal karyotype through all passages. In analysis of multi-lineage capability, USCs showed higher myogenic, neurogenic, and endogenic differentiation rate, and lower osteogenic, adipogenic, and chondrogenic differentiation rate compared to ADSCs. Therefore, we expect that USC can be an alternative autologous stem cell source for muscle, neuron and endothelial tissue reconstruction instead of ADSCs. PMID:26713051

  9. Dental pulp stem cells

    PubMed Central

    Ashri, Nahid Y.; Ajlan, Sumaiah A.; Aldahmash, Abdullah M.

    2015-01-01

    Inflammatory periodontal disease is a major cause of loss of tooth-supporting structures. Novel approaches for regeneration of periodontal apparatus is an area of intensive research. Periodontal tissue engineering implies the use of appropriate regenerative cells, delivered through a suitable scaffold, and guided through signaling molecules. Dental pulp stem cells have been used in an increasing number of studies in dental tissue engineering. Those cells show mesenchymal (stromal) stem cell-like properties including self-renewal and multilineage differentiation potentials, aside from their relative accessibility and pleasant handling properties. The purpose of this article is to review the biological principles of periodontal tissue engineering, along with the challenges facing the development of a consistent and clinically relevant tissue regeneration platform. This article includes an updated review on dental pulp stem cells and their applications in periodontal regeneration, in combination with different scaffolds and growth factors. PMID:26620980

  10. Autologous red blood cells potentiate antibody synthesis by unfractionated human mononuclear cell cultures.

    PubMed

    Rugeles, M T; La Via, M; Goust, J M; Kilpatrick, J M; Hyman, B; Virella, G

    1987-08-01

    We have tried to determine the most favourable conditions for the in vitro induction of specific antibody (Ab) responses to tetanus toxoid (TT) and keyhole limpet haemocyanin (KLH). Human peripheral blood mononuclear cells (PBMNC) were obtained from normal volunteers and stimulated with PWM, TT, KLH, and mixtures of PWM and antigens in the presence or absence of autologous red blood cells (RBC) (1:50 ratio of PBMNC/RBC). The cultures were harvested on day 11; immunoglobulins were determined immunonephelometrically and Ab levels by ELISA with human antibodies used for calibration. While anti-TT responses were easy to induce with PBMNC from recently boosted individuals, the production of anti-TT from PBMNC obtained from non-recently boosted individuals was only possible when PBMNC were stimulated with TT and PWM in the presence of autologous RBC. Similarly, anti-KLH responses were easier to induce with PBMNC from an immune donor; maximal response was observed after stimulation with PWM + KLH in the presence of autologous RBC. Stimulation of primary anti-KLH responses with PBMNC from non-immune donors was only successful when the cells were stimulated with KLH + PWM in the presence of autologous RBC. The potentiation of human B-cell responses with autologous RBC can be abrogated by pretreatment of PBMNC with anti-CD2 antibodies and is associated with increased expression of IL-2 receptors and increased production of gamma interferon (IFN-gamma). However, addition of IFN-gamma in different doses and at different times to PWM-stimulated PBMNC cultures was not as effective as addition of RBC in enhancing the production of immunoglobulin and antibody. PMID:3114872

  11. Induced pluripotent stem cells and neurodegenerative diseases.

    PubMed

    Chen, Chao; Xiao, Shi-Fu

    2011-04-01

    Neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease and Amyotrophic Lateral Sclerosis, are characterized by idiopathic neuron loss in different regions of the central nervous system, which contributes to the relevant dysfunctions in the patients. The application of cell replacement therapy using human embryonic stem (hES) cells, though having attracted much attention, has been hampered by the intrinsic ethical problems. It has been demonstrated that adult somatic cells can be reprogrammed into the embryonic state, called induced pluripotent stem (iPS) cells. It is soon realized that iPS cells may be an alternative source for cell replacement therapy, because it raises no ethical problems and using patient-specific iPS cells for autologous transplantation will not lead to immunological rejection. What's more, certain types of neurons derived from patient-specific iPS cells may display disease-relevant phenotypes. Thus, patient-specific iPS cells can provide a unique opportunity to directly investigate the pathological properties of relevant neural cells in individual patient, and to study the vulnerability of neural cells to pathogenic factors in vitro, which may help reveal the pathogenesis of many neurodegenerative diseases. In this review, the recent development in cellular treatment of neurodegenerative diseases using iPS cells was summarized, and the potential value of iPS cells in the modeling of neurodegenerative disease was discussed.

  12. Pluripotent Stem Cells for Gene Therapy of Degenerative Muscle Diseases.

    PubMed

    Loperfido, Mariana; Steele-Stallard, Heather B; Tedesco, Francesco Saverio; VandenDriessche, Thierry

    2015-01-01

    Human pluripotent stem cells represent a unique source for cell-based therapies and regenerative medicine. The intrinsic features of these cells such as their easy accessibility and their capacity to be expanded indefinitely overcome some limitations of conventional adult stem cells. Furthermore, the possibility to derive patient-specific induced pluripotent stem (iPS) cells in combination with the current development of gene modification methods could be used for autologous cell therapies of some genetic diseases. In particular, muscular dystrophies are considered to be a good candidate due to the lack of efficacious therapeutic treatments for patients to date, and in view of the encouraging results arising from recent preclinical studies. Some hurdles, including possible genetic instability and their efficient differentiation into muscle progenitors through vector/transgene-free methods have still to be overcome or need further optimization. Additionally, engraftment and functional contribution to muscle regeneration in pre-clinical models need to be carefully assessed before clinical translation. This review offers a summary of the advanced methods recently developed to derive muscle progenitors from pluripotent stem cells, as well as gene therapy by gene addition and gene editing methods using ZFNs, TALENs or CRISPR/Cas9. We have also discussed the main issues that need to be addressed for successful clinical translation of genetically corrected patient-specific pluripotent stem cells in autologous transplantation trials for skeletal muscle disorders.

  13. Thrombosis in stem cell transplantation.

    PubMed

    Kansu, Emin

    2012-04-01

    Hemostatic changes and thrombotic events are frequent in patients undergoing stem cell transplantation. Arterial and venous thromboses are major causes of morbidity and mortality. Thrombotic complications can be classified into four groups including: catheter-related thrombosis, venous thromboembolic (VTE) events, sinusoidal obstructive syndrome (SOS)/veno-occlusive disease, and transplant-associated thrombotic microangiopathy (TAM). The incidence of catheter-related thrombosis is 8-20% in patients undergoing autologous hematopoietic stem cell transplantation (HSCT), and the incidence is low in syngeneic and allogeneic transplant patients. Venous duplex Doppler ultrasound, venogram, and computed tomography scan are required to visualize the venous thrombus. The treatment should be aimed at the prevention of pulmonary embolism, the avoidance of thrombus extension, and the preservation of catheter patency. Patients undergoing HSCT may have risk factors for VTE including underlying malignancy, traumatic brain injury, prolonged hospitalization, administration of conditioning regimens, and central venous catheters. Important risk factors are presence of history of VTE and graft-versus-host disease. One-year incidence of symptomatic VTE is 3.7%. SOS, also known as veno-occlusive disease, is a serious liver disease, seen in approximately 50-60% of HSCT patients. The mortality rate from the severe form of SOS is 84.3% and majority of the patients have multi-organ failure. The frequency is quite low after autologous transplantation. Risk factors for SOS include pre-existing hepatic damage, previous high-dose chemotherapy and abdominal irradiation, female gender and donor-recipient human leukocyte antigen disparity. Cyclophosphamide and busulphan are the most common agents with the highest incidence and fatal SOS. Histopathologic features of SOS include dilatation of sinusoids, necrosis of perivenular hepatocytes, and obstruction of small intrahepatic central venules by

  14. Stem cells in microfluidics

    PubMed Central

    Wu, Huei-Wen; Lin, Chun-Che; Lee, Gwo-Bin

    2011-01-01

    Microfluidic techniques have been recently developed for cell-based assays. In microfluidic systems, the objective is for these microenvironments to mimic in vivo surroundings. With advantageous characteristics such as optical transparency and the capability for automating protocols, different types of cells can be cultured, screened, and monitored in real time to systematically investigate their morphology and functions under well-controlled microenvironments in response to various stimuli. Recently, the study of stem cells using microfluidic platforms has attracted considerable interest. Even though stem cells have been studied extensively using bench-top systems, an understanding of their behavior in in vivo-like microenvironments which stimulate cell proliferation and differentiation is still lacking. In this paper, recent cell studies using microfluidic systems are first introduced. The various miniature systems for cell culture, sorting and isolation, and stimulation are then systematically reviewed. The main focus of this review is on papers published in recent years studying stem cells by using microfluidic technology. This review aims to provide experts in microfluidics an overview of various microfluidic systems for stem cell research. PMID:21522491

  15. Stem Cell Research

    SciTech Connect

    Verfaillie, Catherine

    2009-01-23

    We have identified a population of primitive cells in normal human post-natal bone marrow that can, at the single cell level, differentiate in many ways and also proliferate extensively. These cells can differentiate in vitro into most mesodermal cell types (for example, bone cells, and others), as well as cells into cells of the nervous system. The finding that stem cells exist in post-natal tissues with previously unknown proliferation and differentiation potential opens up the possibility of using them to treat a host of degenerative, traumatic or congenital diseases.

  16. Stem Cell Research

    SciTech Connect

    Verfaillie, Catherine

    2002-01-23

    We have identified a population of primitive cells in normal human post-natal bone marrow that can, at the single cell level, differentiate in many ways and also proliferate extensively. These cells can differentiate in vitro into most mesodermal cell types (for example, bone cells, and others), as well as cells into cells of the nervous system. The finding that stem cells exist in post-natal tissues with previously unknown proliferation and differentiation potential opens up the possibility of using them to treat a host of degenerative, traumatic or congenital diseases.

  17. Cryopreservation of Autologous Blood (Red Blood Cells, Platelets and Plasma)

    NASA Astrophysics Data System (ADS)

    Ebine, Kunio

    Prevention of post-transfusion hepatitis is still a problem in cardiovascular surgery. We initiated the cryopreservation of autologous blood for the transfusion in elective cardiovascular surgery since 1981. This study includes 152 surgical cases in which autologous frozen, allogeneic frozen, and/or allogeneic non-frozen blood were used. In the 152 surgical cases, there were 69 cases in which autologous blood only (Group I) was used; 12 cases with autologous and allogeneic frozen blood (Group II); 46 cases with autologous and allgeneic frozen plus allogeneic non-frozen blood (Group III); and 25 cases with allogeneic frozen plus allogeneic non-frozen blood (Group IV). No hepatitis developed in Groups I (0%) and II (0%), but there was positive hepatitis in Groups III (4.3%) and IV (8.0%) . In 357 cases of those who underwent surgery with allogeneic non-frozen whole blood during the same period, the incidence rate of hepatitis was 13.7% (49/357). Patients awaiting elective surgery can store their own blood in the frozen state. Patients who undergo surgery with the cryoautotransfusion will not produce any infections or immunologic reactions as opposed to those who undergo surgery with the allogeneic non-frozen blood.

  18. Catalyzing stem cell research.

    PubMed

    Willemse, Lisa; Lyall, Drew; Rudnicki, Michael

    2008-09-01

    In 2001, the Stem Cell Network was the first of its kind, a bold initiative to forge and nurture pan-Canadian collaborations involving researchers, engineers, clinicians and private and public sector partners. Canada's broad and deep pool of stem cell talent proved to be a fertile ground for such an initiative, giving rise to a strong, thriving network that, 7 years later, can list innovative cell expansion and screening technologies, early-phase clinical trials for stroke, pulmonary hypertension, muscular dystrophy and cornea replacement, and leading discourse on ethical, legal and social issues among its accomplishments. As it moves into its second and final phase of funding, the Stem Cell Network continues to push boundaries and has set its sights on overcoming the obstacles that impede the transfer of research findings to clinical applications, commercial products and public policy. PMID:18729799

  19. Catalyzing stem cell research.

    PubMed

    Willemse, Lisa; Lyall, Drew; Rudnicki, Michael

    2008-09-01

    In 2001, the Stem Cell Network was the first of its kind, a bold initiative to forge and nurture pan-Canadian collaborations involving researchers, engineers, clinicians and private and public sector partners. Canada's broad and deep pool of stem cell talent proved to be a fertile ground for such an initiative, giving rise to a strong, thriving network that, 7 years later, can list innovative cell expansion and screening technologies, early-phase clinical trials for stroke, pulmonary hypertension, muscular dystrophy and cornea replacement, and leading discourse on ethical, legal and social issues among its accomplishments. As it moves into its second and final phase of funding, the Stem Cell Network continues to push boundaries and has set its sights on overcoming the obstacles that impede the transfer of research findings to clinical applications, commercial products and public policy.

  20. Application of Stem Cell Technology in Dental Regenerative Medicine

    PubMed Central

    Feng, Ruoxue; Lengner, Chistopher

    2013-01-01

    Significance In this review, we summarize the current literature regarding the isolation and characterization of dental tissue-derived stem cells and address the potential of these cell types for use in regenerative cell transplantation therapy. Recent Advances Looking forward, platforms for the delivery of stem cells via scaffolds and the use of growth factors and cytokines for enhancing dental stem cell self-renewal and differentiation are discussed. Critical Issues We aim to understand the developmental origins of dental tissues in an effort to elucidate the molecular pathways governing the genesis of somatic dental stem cells. The advantages and disadvantages of several dental stem cells are discussed, including the developmental stage and specific locations from which these cells can be purified. In particular, stem cells from human exfoliated deciduous teeth may act as a very practical and easily accessibly reservoir for autologous stem cells and hold the most value in stem cell therapy. Dental pulp stem cells and periodontal ligament stem cells should also be considered for their triple lineage differentiation ability and relative ease of isolation. Further, we address the potentials and limitations of induced pluripotent stem cells as a cell source in dental regenerative. Future Directions From an economical and a practical standpoint, dental stem cell therapy would be most easily applied in the prevention of periodontal ligament detachment and bone atrophy, as well as in the regeneration of dentin-pulp complex. In contrast, cell-based tooth replacement due to decay or other oral pathology seems, at the current time, an untenable approach. PMID:24527351

  1. Cryopreservation of hematopoietic stem/progenitor cells for therapeutic use.

    PubMed

    Watt, Suzanne M; Austin, Eric; Armitage, Sue

    2007-01-01

    To date, more than 25,000 hematopoietic transplants have been carried out across Europe for hematological disorders, the majority being for hematological malignancies. At least 70% of these are autologous transplants, the remaining 30% being allogeneic, which are sourced from related (70% of the allogeneic) or unrelated donors. Peripheral blood mobilized with granulocyte colony stimulating factor is the major source of stem cells for transplantation, being used in approx 95% of autologous transplants and in approx 65% of allogeneic transplants. Other cell sources used for transplantation are bone marrow and umbilical cord blood. One crucial advance in the treatment of these disorders has been the development of the ability to cryopreserve hematopoietic stem cells for future transplantation. For bone marrow and mobilized peripheral blood, the majority of cryopreserved harvests come from autologous collections that are stored prior to a planned infusion following further treatment of the patient or at the time of a subsequent relapse. Other autologous harvests are stored as backup or "rainy day" harvests, the former specifically being intended to rescue patients who develop graft failure following an allogeneic transplant or who may require this transplant at a later date. Allogeneic bone marrow and mobilized peripheral blood are less often cryopreserved than autologous harvests. This is in contrast to umbilical cord blood that may be banked for directed or sibling (related) hematopoietic stem cell transplants, for allogeneic unrelated donations, and for autologous donations. Allogeneic unrelated donations are of particular use for providing a source of hematopoietic stem cells for ethnic minorities, patients with rare human leukocyte antigen types, or where the patient urgently requires a transplant and cannot wait for the weeks to months required to prepare a bone marrow donor. There are currently more than 200,000 banked umbilical cord blood units registered with

  2. Human T-Cell Clones from Autoimmune Thyroid Glands: Specific Recognition of Autologous Thyroid Cells

    NASA Astrophysics Data System (ADS)

    Londei, Marco; Bottazzo, G. Franco; Feldmann, Marc

    1985-04-01

    The thyroid glands of patients with autoimmune diseases such as Graves' disease and certain forms of goiter contain infiltrating activated T lymphocytes and, unlike cells of normal glands, the epithelial follicular cells strongly express histocompatability antigens of the HLA-DR type. In a study of such autoimmune disorders, the infiltrating T cells from the thyroid glands of two patients with Graves' disease were cloned in mitogen-free interleukin-2 (T-cell growth factor). The clones were expanded and their specificity was tested. Three types of clones were found. One group, of T4 phenotype, specifically recognized autologous thyroid cells. Another, also of T4 phenotype, recognized autologous thyroid or blood cells and thus responded positively in the autologous mixed lymphocyte reaction. Other clones derived from cells that were activated in vivo were of no known specificity. These clones provide a model of a human autoimmune disease and their analysis should clarify mechanisms of pathogenesis and provide clues to abrogating these undesirable immune responses.

  3. Chemotherapy targeting cancer stem cells.

    PubMed

    Liu, Haiguang; Lv, Lin; Yang, Kai

    2015-01-01

    Conventional chemotherapy is the main treatment for cancer and benefits patients in the form of decreased relapse and metastasis and longer overall survival. However, as the target therapy drugs and delivery systems are not wholly precise, it also results in quite a few side effects, and is less efficient in many cancers due to the spared cancer stem cells, which are considered the reason for chemotherapy resistance, relapse, and metastasis. Conventional chemotherapy limitations and the cancer stem cell hypothesis inspired our search for a novel chemotherapy targeting cancer stem cells. In this review, we summarize cancer stem cell enrichment methods, the search for new efficient drugs, and the delivery of drugs targeting cancer stem cells. We also discuss cancer stem cell hierarchy complexity and the corresponding combination therapy for both cancer stem and non-stem cells. Learning from cancer stem cells may reveal novel strategies for chemotherapy in the future.

  4. Chemotherapy targeting cancer stem cells

    PubMed Central

    Liu, Haiguang; Lv, Lin; Yang, Kai

    2015-01-01

    Conventional chemotherapy is the main treatment for cancer and benefits patients in the form of decreased relapse and metastasis and longer overall survival. However, as the target therapy drugs and delivery systems are not wholly precise, it also results in quite a few side effects, and is less efficient in many cancers due to the spared cancer stem cells, which are considered the reason for chemotherapy resistance, relapse, and metastasis. Conventional chemotherapy limitations and the cancer stem cell hypothesis inspired our search for a novel chemotherapy targeting cancer stem cells. In this review, we summarize cancer stem cell enrichment methods, the search for new efficient drugs, and the delivery of drugs targeting cancer stem cells. We also discuss cancer stem cell hierarchy complexity and the corresponding combination therapy for both cancer stem and non-stem cells. Learning from cancer stem cells may reveal novel strategies for chemotherapy in the future. PMID:26045975

  5. Introduction to Hair-Follicle-Associated Pluripotent Stem Cells.

    PubMed

    Hoffman, Robert M

    2016-01-01

    Nestin-expressing stem cells of the hair follicle, discovered by our laboratory, have been shown to be able to form outer-root sheaths of the follicle as well as neurons and many other non-follicle cell types. We have termed the nestin-expressing stem cells of the hair follicle as hair-follicle-associated pluripotent (HAP) stem cells. We have shown that the HAP stem cells from the hair follicle can effect the repair of peripheral nerve and spinal cord injury. The hair follicle stem cells differentiate into neuronal and glial cells after transplantation to the injured peripheral nerve and spinal cord, and enhance injury repair and locomotor recovery. When the excised hair follicle with its nerve stump was placed in Gelfoam(®) 3D histoculture, HAP stem cells grew and extended the hair follicle nerve which consisted of βIII-tubulin-positive fibers with F-actin expression at the tip. These findings indicate that βIII-tubulin-positive fibers elongating from the whisker follicle sensory nerve stump were growing axons. The growing whisker sensory nerve was highly enriched in HAP stem cells, which appeared to play a major role in its elongation and interaction with other nerves in 3D Gelfoam(®) histoculture, including the sciatic nerve, the trigeminal nerve, and the trigeminal nerve ganglion. These results suggest that a major function of the HAP stem cells in the hair follicle is for growth of the follicle sensory nerve. Recently, we have shown that HAP stem cells can differentiate into beating cardiac muscle cells. HAP stem cells have critical advantages for regenerative medicine over embryonic stem (ES) cells and induced pluripotent stem (iPS) cells in that they are highly accessible from each patient, thereby eliminating immunological issues since they are autologous, require no genetic manipulation, are non-tumorigenic, and do not present ethical issues.

  6. Electrolyte and acid/base changes in dogs undergoing autologous blood transfusion via a cell salvage device.

    PubMed

    Lamb, Jodie L; Thieman Mankin, Kelley M; Levine, Gwendolyn J; Thompson, James

    2015-09-01

    This study reports electrolyte and acid/base disturbances observed in clinical cases receiving autologous transfusion of blood processed by a cell salvage device. The records of 12 client-owned dogs that received an autologous transfusion via a cell salvage device with pre- and post-autologous transfusion blood work available were reviewed. Blood work from the 12 case dogs was compared to blood work from 12 control dogs with similar diseases. Control dogs received similar surgical treatment and were administered a similar volume per kg of packed red blood cells as case dogs, but did not undergo autologous transfusion. Case dogs that received autologous transfusion via a cell salvage device were significantly more likely to experience a decrease in ionized calcium and magnesium levels post-transfusion than were control dogs. Calcium and magnesium levels should be closely monitored during and after autologous transfusion. Calcium and/or magnesium supplementation may be required.

  7. Monitoring stem cells in phase contrast imaging

    NASA Astrophysics Data System (ADS)

    Lam, K. P.; Dempsey, K. P.; Collins, D. J.; Richardson, J. B.

    2016-04-01

    Understanding the mechanisms behind the proliferation of Mesenchymal Stem cells (MSCs) can offer a greater insight into the behaviour of these cells throughout their life cycles. Traditional methods of determining the rate of MSC differentiation rely on population based studies over an extended time period. However, such methods can be inadequate as they are unable to track cells as they interact; for example, in autologous cell therapies for osteoarthritis, the development of biological assays that could predict in vivo functional activity and biological action are particularly challenging. Here further research is required to determine non-histochemical biomarkers which provide correlations between cell survival and predictive functional outcome. This paper proposes using a (previously developed) advanced texture-based analysis algorithm to facilitate in vitro cells tracking using time-lapsed microscopy. The technique was adopted to monitor stem cells in the context of unlabelled, phase contrast imaging, with the goal of examining the cell to cell interactions in both monoculture and co-culture systems. The results obtained are analysed using established exploratory procedures developed for time series data and compared with the typical fluorescent-based approach of cell labelling. A review of the progress and the lessons learned are also presented.

  8. Emerging restorative treatments for Parkinson's disease: manipulation and inducement of dopaminergic neurons from adult stem cells.

    PubMed

    Zhao, Junpeng; Xu, Qunyuan

    2011-06-01

    Parkinson's disease (PD) is a common neurodegenerative disease, characterized by a selective loss of midbrain Dopaminergic (DA) neurons. To address this problem, various types of stem cells that have potential to differentiate into DA neurons are being investigated as cellular therapies for PD, including cells derived from embryonic or adult donor tissue, and embryonic stem cells. These cell sources, however, have raised certain questions with regard to ethical and rejection issues. Recent progress in adult stems has further proved that the cells derived from adult tissue could be expanded and differentiated into DA precursor cells in vitro, and cell therapy with adult stem cells could produce a clear improvement for PD models. Using adult stem cells for clinic application may not only overcome the ethical problem inherent in using human fetal tissue or embryonic stem cells, but also open the possibility for autologous transplantation. The patient-specific adult stem cell is therefore a potential and prospective candidate for PD treatment.

  9. Stem cells and transplant arteriosclerosis.

    PubMed

    Xu, Qingbo

    2008-05-01

    Stem cells can differentiate into a variety of cells to replace dead cells or to repair damaged tissues. Recent evidence indicates that stem cells are involved in the pathogenesis of transplant arteriosclerosis, an alloimmune initiated vascular stenosis that often results in transplant organ failure. Although the pathogenesis of transplant arteriosclerosis is not yet fully understood, recent developments in stem cell research have suggested novel mechanisms of vascular remodeling in allografts. For example, stem cells derived from the recipient may repair damaged endothelial cells of arteries in transplant organs. Further evidence suggests that stem cells or endothelial progenitor cells may be released from both bone marrow and non-bone marrow tissues. Vascular stem cells appear to replenish cells that died in donor vessels. Concomitantly, stem/progenitor cells may also accumulate in the intima, where they differentiate into smooth muscle cells. However, several issues concerning the contribution of stem cells to the pathogenesis of transplant arteriosclerosis are controversial, eg, whether bone marrow-derived stem cells can differentiate into smooth muscle cells that form neointimal lesions of the vessel wall. This review summarizes recent research on the role of stem cells in transplant arteriosclerosis, discusses the mechanisms of stem cell homing and differentiation into mature endothelial and smooth muscle cells, and highlights the controversial issues in the field.

  10. Techniques of Human Embryonic Stem Cell and Induced Pluripotent Stem Cell Derivation.

    PubMed

    Lewandowski, Jarosław; Kurpisz, Maciej

    2016-10-01

    Developing procedures for the derivation of human pluripotent stem cells (PSCs) gave rise to novel pathways into regenerative medicine research. For many years, stem cells have attracted attention as a potentially unlimited cell source for cellular therapy in neurodegenerative disorders, cardiovascular diseases, and spinal cord injuries, for example. In these studies, adult stem cells were insufficient; therefore, many attempts were made to obtain PSCs by other means. This review discusses key issues concerning the techniques of pluripotent cell acquisition. Technical and ethical issues hindered the medical use of somatic cell nuclear transfer and embryonic stem cells. Therefore, induced PSCs (iPSCs) emerged as a powerful technique with great potential for clinical applications, patient-specific disease modelling and pharmaceutical studies. The replacement of viral vectors or the administration of analogous proteins or chemical compounds during cell reprogramming are modifications designed to reduce tumorigenesis risk and to augment the procedure efficiency. Intensified analysis of new PSC lines revealed other barriers to overcome, such as epigenetic memory, disparity between human and mouse pluripotency, and variable response to differentiation of some iPSC lines. Thus, multidimensional verification must be conducted to fulfil strict clinical-grade requirements. Nevertheless, the first clinical trials in patients with spinal cord injury and macular dystrophy were recently carried out with differentiated iPSCs, encouraging alternative strategies for potential autologous cellular therapies.

  11. Laser biomodulation on stem cells

    NASA Astrophysics Data System (ADS)

    Liu, Timon C.; Duan, Rui; Li, Yan; Li, Xue-Feng; Tan, Li-Ling; Liu, Songhao

    2001-08-01

    Stem cells are views from the perspectives of their function, evolution, development, and cause. Counterintuitively, most stem cells may arise late in development, to act principally in tissue renewal, thus ensuring an organisms long-term survival. Surprisingly, recent reports suggest that tissue-specific adult stem cells have the potential to contribute to replenishment of multiple adult tissues. Stem cells are currently in the news for two reasons: the successful cultivation of human embryonic stem cell lines and reports that adult stem cells can differentiate into developmentally unrelated cell types, such as nerve cells into blood cells. The spotlight on stem cells has revealed gaps in our knowledge that must be filled if we are to take advantage of their full potential for treating devastating degenerative diseases such as Parkinsons's disease and muscular dystrophy. We need to know more about the intrinsic controls that keep stem cells as stem cells or direct them along particular differentiation pathways. Such intrinsic regulators are, in turn, sensitive to the influences of the microenvironment, or niche, where stem cells normally reside. Both intrinsic and extrinsic signals regular stem cell fate and some of these signals have now been identified. Vacek et al and Wang et al have studied the effect of low intensity laser on the haemopoietic stem cells in vitro. There experiments show there is indeed the effect of low intensity laser on the haemopoietic stem cells in vitro, and the present effect is the promotion of haemopoietic stem cells proliferation. In other words, low intensity laser irradiation can act as an extrinsic signal regulating stem cell fate. In this paper, we study how low intensity laser can be used to regulate stem cell fate from the viewpoint of collective phototransduction.

  12. Role of hematopoietic stem cell transplantation in multiple myeloma.

    PubMed

    Garcia, Ima N

    2015-02-01

    High-dose therapy followed by autologous stem cell transplantation (ASCT) has been the standard frontline consolidative therapy for patients with newly diagnosed multiple myeloma (MM) for > 2 decades. This approach has resulted in higher complete response (CR) rates and increased event-free survival and overall survival (OS) compared with conventional chemotherapy. The emergence of novel agent-based therapy combined with ASCT has revolutionized MM therapy by improving the CR rates and OS, raising questions concerning the role of hematopoietic stem cell transplantation in this setting.

  13. Adult stem cells therapy for urine incontinence in women.

    PubMed

    Stangel-Wójcikiewicz, Klaudia; Majka, Marcin; Basta, Antoni; Stec, Małgorzata; Pabian, Wojciech; Piwowar, Monika; Chancellor, Michael B

    2010-05-01

    The past few years brought high development in obtaining and culturing autologous adult stem cells. In this paper we review publications of experimental investigations and clinical trials of the muscle-derived cells and the application in the treatment of stress urinary incontinence among women. Mesenchymal stem cells (MSCs) can be obtained from bone marrow but it is associated with a painful biopsy procedure. Collection of muscle-derived stem cells (MDSCs) is less harmful because the skeletal muscle biopsy is performed with a small caliber needle in local anesthesia. The stem-based therapy could be the next step in the treatment of urinary incontinence. There are still many elements of therapy such as effectiveness or long-term side effects which need to be researched.

  14. Stem cell therapy after myocardial infarction: ready for clinical application?

    PubMed

    Engelmann, Markus G; Franz, Wolfgang M

    2006-10-01

    The discovery of stem cells capable of generating angiogenic or contractile cells and structures might offer new treatment options for patients suffering from heart disease. In particular, embryonic stem cells are considered to have great potential for regenerative medicine and tissue engineering. Studies suggest that delivery or mobilization of stem and progenitor cells might improve tissue perfusion and contractile performance of the damaged heart; however, the underlying mechanisms are poorly understood. Fusion or trans-differentiation into cardiomyocytes or vascular cells are considered rare events of cellular engraftment, and adult stem cells are now considered as 'regenerator cells', acting via paracrine effects of cytokines, or by activation of resident stent cells, thereby supporting the myocardial healing mechanisms after injury. Administration of autologous hematopoietic stem cells or mobilization of endogenous stem cells has been shown to be safe after myocardial infarction or cardiomyopathies, whereas skeletal myoblasts are considered to be hazardous due to the occurrence of life-threatening arrhythmias. This review focuses on the use of adult human stem cells for treating myocardial infarction and cardiomyopathy, and discusses recent preliminary efficacy data, which suggest that 'regenerator cells' might have the potential to improve myocardial perfusion and contractile performance in patients suffering from myocardial infarction, severe ischemic heart disease and chronic heart failure. PMID:17078382