Ethical issues relating the the banking of umbilical cord blood in Mexico.

PubMed

Serrano-Delgado, V Moises; Novello-Garza, Barbara; Valdez-Martinez, Edith

2009-08-14

Umbilical cord banks are a central component, as umbilical cord tissue providers, in both medical treatment and scientific research with stem cells. But, whereas the creation of umbilical cord banks is seen as successful practice, it is perceived as a risky style of play by others. This article examines and discusses the ethical, medical and legal considerations that arise from the operation of umbilical cord banks in Mexico. A number of experts have stated that the use of umbilical cord goes beyond the mere utilization of human tissues for the purpose of treatment. This tissue is also used in research studies: genetic studies, studies to evaluate the effectiveness of new antibiotics, studies to identify new proteins, etc. Meanwhile, others claim that the law and other norms for the functioning of cord banks are not consistent and are poorly defined. Some of these critics point out that the confidentiality of donor information is handled differently in different places. The fact that private cord banks offer their services as "biological insurance" in order to obtain informed consent by promising the parents that the tissue that will be stored insures the health of their child in the future raises the issue of whether the consent is freely given or given under coercion. Another consideration that must be made in relation to privately owned cord banks has to do with the ownership of the stored umbilical cord. Conflicts between moral principles and economic interests (non-moral principles) cause dilemmas in the clinical practice of umbilical cord blood storage and use especially in privately owned banks. This article presents a reflection and some of the guidelines that must be followed by umbilical cord banks in order to deal with these conflicts. This reflection is based on the fundamental notions of ethics and public health and seeks to be a contribution towards the improvement of umbilical cord banks' performance.

Ethical issues relating to the banking of umbilical cord blood in Mexico

PubMed Central

2009-01-01

Background Umbilical cord banks are a central component, as umbilical cord tissue providers, in both medical treatment and scientific research with stem cells. But, whereas the creation of umbilical cord banks is seen as successful practice, it is perceived as a risky style of play by others. This article examines and discusses the ethical, medical and legal considerations that arise from the operation of umbilical cord banks in Mexico. Discussion A number of experts have stated that the use of umbilical cord goes beyond the mere utilization of human tissues for the purpose of treatment. This tissue is also used in research studies: genetic studies, studies to evaluate the effectiveness of new antibiotics, studies to identify new proteins, etc. Meanwhile, others claim that the law and other norms for the functioning of cord banks are not consistent and are poorly defined. Some of these critics point out that the confidentiality of donor information is handled differently in different places. The fact that private cord banks offer their services as "biological insurance" in order to obtain informed consent by promising the parents that the tissue that will be stored insures the health of their child in the future raises the issue of whether the consent is freely given or given under coercion. Another consideration that must be made in relation to privately owned cord banks has to do with the ownership of the stored umbilical cord. Summary Conflicts between moral principles and economic interests (non-moral principles) cause dilemmas in the clinical practice of umbilical cord blood storage and use especially in privately owned banks. This article presents a reflection and some of the guidelines that must be followed by umbilical cord banks in order to deal with these conflicts. This reflection is based on the fundamental notions of ethics and public health and seeks to be a contribution towards the improvement of umbilical cord banks' performance. PMID:19678958

Applications of human umbilical cord blood cells in central nervous system regeneration.

PubMed

Herranz, Antonio S; Gonzalo-Gobernado, Rafael; Reimers, Diana; Asensio, Maria J; Rodríguez-Serrano, Macarena; Bazán, Eulalia

2010-03-01

In recent decades, there has been considerable amount of information about embryonic stem cells (ES). The dilemma facing scientists interested in the development and use of human stem cells in replacement therapies is the source of these cells, i.e. the human embryo. There are many ethical and moral problems related to the use of these cells. Hematopoietic stem cells from umbilical cord blood have been proposed as an alternative source of embryonic stem cells. After exposure to different agents, these cells are able to express antigens of diverse cellular lineages, including the neural type. The In vitro manipulation of human umbilical cord blood (hUCB) cells has shown their stem capacity and plasticity. These cells are easily accessible, In vitro amplifiable, well tolerated by the host, and with more primitive molecular characteristics that give them great flexibility. Overall, these properties open a promising future for the use of hUCB in regenerative therapies for the Central Nervous System (CNS). This review will focus on the available literature concerning umbilical cord blood cells as a therapeutic tool for the treatment of neurodegenerative diseases.

Delayed clamping of the umbilical cord after delivery and implications for public cord blood banking.

PubMed

Allan, David S; Scrivens, Nicholas; Lawless, Tiffany; Mostert, Karen; Oppenheimer, Lawrence; Walker, Mark; Petraszko, Tanya; Elmoazzen, Heidi

2016-03-01

Public banking of umbilical cord blood units (CBUs) containing higher numbers of cells ensures timely engraftment after transplantation for increasing numbers of patients. Delayed clamping of the umbilical cord after birth may benefit some infants by preventing iron deficiency. Implications of delayed cord clamping for public cord blood banking remains unclear. CBUs collected by Canadian Blood Services at one collection site between November 1, 2014, and March 17, 2015, were analyzed. The delay in cord clamping after birth was timed and classified as "no delay," 20 to 60 seconds, more than 60 seconds, or more than 120 seconds. Of 367 collections, 100 reported no delay in clamping while clamping was delayed by 20 to 60 seconds (n = 69), more than 60 seconds (n = 98), or more than 120 seconds (n = 100) in the remaining cases. The mean volume and total nucleated cells (TNCs) in units with no delay in clamping were significantly greater than mean volumes for all categories of delayed clamping (Tukey's test, p < 0.05 for each comparison). The proportion of units with more than 1.5 × 10(9) TNCs was significantly reduced when clamping was delayed (p = 5.5 × 10(-8) ). The difference was most marked for cords that were clamped more than 120 seconds after delivery (6.2% compared with 39%). Delayed cord clamping greatly diminishes the volume and TNC count of units collected for a public cord blood bank. Creating an inventory of CBUs with high TNC content may take more time than expected. © 2015 AABB.

Ex vivo expansion of human umbilical cord blood-derived T-lymphocytes with homologous cord blood plasma.

PubMed

Kim, Yong-Man; Jung, Min-Hyung; Song, Ha-Young; Yang, Hyun Ok; Lee, Sung-Tae; Kim, Jong-Hyeok; Kim, Young-Tak; Nam, Joo-Hyun; Mok, Jung-Eun

2005-02-01

This study was designed to establish a more effective and safe culture system for adoptive immunotherapy by investigating the use of homologous cord blood plasma (HCBP) instead of fetal bovine serum (FBS), which has various limitations including ethical problems for the ex vivo expansion of human umbilical T lymphocytes. Fresh human umbilical mononuclear cell fractions were isolated by Ficoll-Hypaque density centrifugation. Nonadherent mononuclear cell fractions were cultured with anti-CD3 antibody (5 microg/ml), IL-2 (175 U/ml), and either 10% FBS or 10% HCBP. On day 8, the cellular proliferation rate and cell surface markers were assessed. There was no significant difference in proliferation when human umbilical cord blood T lymphocytes were grown in medium supplemented with FBS or HCBP (p > 0.05). In medium containing FBS, the proportion of CD3(+)CD4(+) (markers for helper T cell), CD3(+)CD8(+) (cytotoxic T cell), CD3(+)CD25(+) (activated T cell), CD3(+)CD38(+) (immature T cell), and CD3(+)CD45RO(+) (memory T cell) cells was significantly increased (p < 0.05), whereas proportion of CD3(+)CD45RA(+) (naive T cell) and CD16(+)CD56(+) (NK cell) cells was significantly decreased (p < 0.05). In HCBP supplemented medium, the proportion of CD3(+)CD8(+), CD3(+)CD25(+), CD3(+)CD45RA(+), and CD3(+)CD45RO(+) cells was significantly increased (p < 0.05). The proportion of CD3(+)CD4(+), CD3(+)CD45RO(+) and CD3(+)CD38(+) cells was significantly higher, but proportion of CD3(+)CD45RA(+) and CD3(+)CD8(+) cells was significantly lower in FBS compared with HCBP supplemented medium (p < 0.05). Our results support the feasibility of ex vivo expansion of human umbilical cord blood T lymphocytes in medium supplemented with HCBP for future adoptive cellular immunotherapy.

Release from quiescence of CD34+ CD38- human umbilical cord blood cells reveals their potentiality to engraft adults.

PubMed Central

Cardoso, A A; Li, M L; Batard, P; Hatzfeld, A; Brown, E L; Levesque, J P; Sookdeo, H; Panterne, B; Sansilvestri, P; Clark, S C

1993-01-01

Using optimal culture conditions in which the transforming growth factor beta 1 (TGF-beta 1) inhibitory loop has been interrupted by antisense TGF-beta 1 oligonucleotides or anti-TGF-beta serum, we have compared the proliferative capacities and the abilities of the CD34+ CD38- cell populations from bone marrow and umbilical cord blood to generate early progenitors in long-term cultures. The CD34+ CD38- fraction of umbilical cord blood accounts for 4% of the CD34+ fraction compared to only 1% in bone marrow, indicating that umbilical cord blood may be relatively enriched in stem cells. We estimate that the CD34+ CD38- cells from a typical umbilical cord blood sample produce equivalent numbers of colony-forming units (CFU)-granulocyte/erythrocyte/macrophage/megakaryocyte, twice as many CFU-granulocyte/macrophage (GM) and 3 times as many burst-forming units-erythroid as the same population from an average bone marrow sample used in adult transplantation. In addition, the colonies resulting from the umbilical cord blood samples were significantly larger than those from bone marrow, indicating a greater growth potential. However, the content of later progenitors, which may be important for short-term reconstitution, was less in umbilical cord blood-derived than in bone marrow-derived cell preparations, as estimated by a 4-fold lower production of CFU-GM in long-term cultures of CD34+ CD38+ cells. This deficit is partially compensated by the higher growth capacity of the resulting CFU-GM. These studies suggest that umbilical cord blood is a suitable source of cells for adult transplantation. PMID:7690969

Engineered living blood vessels: functional endothelia generated from human umbilical cord-derived progenitors.

PubMed

Schmidt, Dörthe; Asmis, Lars M; Odermatt, Bernhard; Kelm, Jens; Breymann, Christian; Gössi, Matthias; Genoni, Michele; Zund, Gregor; Hoerstrup, Simon P

2006-10-01

Tissue-engineered living blood vessels (TEBV) with growth capacity represent a promising new option for the repair of congenital malformations. We investigate the functionality of TEBV with endothelia generated from human umbilical cord blood-derived endothelial progenitor cells. Tissue-engineered living blood vessels were generated from human umbilical cord-derived myofibroblasts seeded on biodegradable vascular scaffolds, followed by endothelialization with differentiated cord blood-derived endothelial progenitor cells. During in vitro maturation the TEBV were exposed to physiologic conditioning in a flow bioreactor. For functional assessment, a subgroup of TEBV was stimulated with tumor necrosis factor-alpha. Control vessels endothelialized with standard vascular endothelial cells were treated in parallel. Analysis of the TEBV included histology, immunohistochemistry, biochemistry (extracellular matrix analysis, DNA), and biomechanical testing. Endothelia were analyzed by flow cytometry and immunohistochemistry (CD31, von Willebrand factor, thrombomodulin, tissue factor, endothelial nitric oxide synthase). Histologically, a three-layered tissue organization of the TEBV analogous to native vessels was observed, and biochemistry revealed the major matrix constituents (collagen, proteoglycans) of blood vessels. Biomechanical properties (Young's modulus, 2.03 +/- 0.65 MPa) showed profiles resembling those of native tissue. Endothelial progenitor cells expressed typical endothelial cell markers CD31, von Willebrand factor, and endothelial nitric oxide synthase comparable to standard vascular endothelial cells. Stimulation with tumor necrosis factor-alpha resulted in physiologic upregulation of tissue factor and downregulation of thrombomodulin expression. These results indicate that TEBV with tissue architecture and functional endothelia similar to native blood vessels can be successfully generated from human umbilical cord progenitor cells. Thus, blood

The effects of compound danshen dripping pills and human umbilical cord blood mononuclear cell transplant after acute myocardial infarction.

PubMed

Jun, Yi; Chunju, Yuan; Qi, Ai; Liuxia, Deng; Guolong, Yu

2014-04-01

The low frequency of survival of stem cells implanted in the myocardium after acute myocardial infarction may be caused by inflammation and oxidative stress in the myocardial microenvironment. We evaluated the effects of a traditional Chinese medicine, Compound Danshen Dripping Pills, on the cardiac microenvironment and cardiac function when used alone or in combination with human umbilical cord blood mononuclear cell transplant after acute myocardial infarction. After surgically induced acute myocardial infarction, rabbits were treated with Compound Danshen Dripping Pills alone or in combination with human umbilical cord blood mononuclear cell transplant. Evaluation included histology, measurement of left ventricular ejection fraction and fractional shortening, leukocyte count, count of green fluorescent protein positive cells, superoxide dismutase activity, and malondialdehyde content. Combination treatment with Compound Danshen Dripping Pills and human umbilical cord blood mononuclear cell transplant significantly increased the survival of implanted cells, inhibited cardiac cell apoptosis, decreased oxidative stress, decreased the inflammatory response, and improved cardiac function. Rabbits treated with either Compound Danshen Dripping Pills or human umbilical cord blood mononuclear cells alone had improvement in these effects compared with untreated control rabbits. Combination therapy with Compound Danshen Dripping Pills and human umbilical cord blood mononuclear cells may improve cardiac function and morphology after acute myocardial infarction.

[Correlation analysis of the pre-pregnant body mass index, the gestational weight gain and umbilical cord blood C peptide].

PubMed

Chen, X L; Han, Y; Zhao, X M; Liu, Y; Lü, J J

2017-01-03

Objective: To explore the correlation among the pre-pregnant body mass index (BMI), gestational weight gain (GWG) and umbilical cord blood C peptide, and to investigate the influence of maternal weight management on the incidence of baby long-term metabolic syndrome. Methods: During May to Aug.2015, 485 pregnant women in Zhejiang Taizhou first people's hospital and Taizhou Huangyan maternal &child care service centre were selected in random and divided into four groups according to pre-pregnant BMI: low body mass, normal body mass, over body mass and obese group, and also divided into two groups for getting gestational diabetes mellitus (GDM) or not. According to the gestational weight gain (GWG), all the cases were divided into two groups: above the Institute Of Medicine (IMO) 2009 recommendations or not. According to the outcome, the GDM group which had received weight control treatment, was divided into successful treat group or not. At last, we tested the umbilical cord blood C peptide and birth weight of each newborn and compared the difference in all subgroups. The correlation between the umbilical cord blood C peptide and birth weight were analysed. Results: (1) In the pre-pregnant BMI groups, there were significant differences of incidence of GDM ( P <0.05). But, there were no significant differences of incidence of GWG in four groups ( P >0.05). (2) Newborn birth weight and the umbilical cord blood C peptide were positively correlated ( r =0.673, P <0.05). (3) Umbilical cord blood C peptide showed the correlation in all subgroups for different pre-pregnant BMI, GDM or not, overweight or not ( P <0.05), but only the GDM or not group had relation to newborn birth weight in all subgroups. (4) All groups showed correlations with neonatal umbilical cord blood C peptide, the GDM mostly (β=0.58), pre-pregnant BMI secondly (β: 0.36, 0.38) , and GWG weakly (β=0.17). (5) By stratification analysis, in GDM group, low body mass was negatively correlated with

Regulation of malonyl-CoA-acyl carrier protein transacylase network in umbilical cord blood affected by intrauterine hyperglycemia.

PubMed

Zhang, Yong; Ye, Jianping; Fan, Jianxia

2017-09-26

Gestational diabetes mellitus (GDM) has been shown to be associated with high risk of diabetes in offspring. However, the mechanisms involved in the insulin resistance in offspring are still unclear. Mitochondrial dysfunction is related with insulin resistance. In mitochondria, malonyl-CoA-acyl carrier protein transacylase (MCAT) is the key enzyme of mitochondrial fatty acid synthesis and is estimated to contribute to insulin resistance. In this study, we aimed to examine the role of MCAT and its network in the umbilical cord blood in GDM-induced offspring insulin resistance. We isolated lymphocytes from umbilical cord vein blood in 6 GDM patients and 6 controls and examined the differences of RNA by RNA sequencing. qRT-PCR and western blot were used to measure mRNA and protein changes. Bisulfite genomic sequencing PCR was applied to detect DNA methylation. We found more than 400 genes were differentially regulated in the lymphocytes of umbilical cord blood from GDM patients and these genes were mainly enriched in immune system and endocrine system, which relate to mitochondrial dysfunction and insulin resistance. MCAT closely related with PTPN1 (Protein Tyrosine Phosphatase, Non-Receptor Type1) and STAT5A (Signal Transducer And Activator of Transcription 5A), which were all increased in umbilical cord blood from GDM patients. Increase in MCAT may be due to decreased MCAT DNA methylation. MCAT and its network with PTPN1, STAT5A are regulated in umbilical cord blood affected by maternal intrauterine hyperglycemia.

Neural cells derived from adult bone marrow and umbilical cord blood.

PubMed

Sanchez-Ramos, Juan R

2002-09-15

Under experimental conditions, tissue-specific stem cells have been shown to give rise to cell lineages not normally found in the organ or tissue of residence. Neural stem cells from fetal brain have been shown to give rise to blood cell lines and conversely, bone marrow stromal cells have been reported to generate skeletal and cardiac muscle, oval hepatocytes, as well as glia and neuron-like cells. This article reviews studies in which cells from postnatal bone marrow or umbilical cord blood were induced to proliferate and differentiate into glia and neurons, cellular lineages that are not their normal destiny. The review encompasses in vitro and in vivo studies with focus on experimental variables, such as the source and characterization of cells, cell-tracking methods, and markers of neural differentiation. The existence of stem/progenitor cells with previously unappreciated proliferation and differentiation potential in postnatal bone marrow and in umbilical cord blood opens up the possibility of using stem cells found in these tissues to treat degenerative, post-traumatic and hereditary diseases of the central nervous system. Copyright 2002 Wiley-Liss, Inc.

Umbilical cord blood banking and the next generation of human tissue regulation: an agenda for research.

PubMed

Stewart, Cameron; Kerridge, Ian

2012-03-01

The transformation of umbilical cord blood from being a waste product to being a valuable source of stem cells has led to the emergence of significant legal, ethical and social issues. This editorial proposes an agenda for research into the regulation of umbilical cord blood banking which focuses on issues of characterisation, consent, the interplay of public and private services, and the importance of applying property concepts. It concludes by stressing the need for reform to be based on well-informed public debate.

Effect of Cord Blood Processing on Transplant Outcomes after Single Myeloablative Umbilical Cord Blood Transplantation

PubMed Central

Ballen, Karen K.; Logan, Brent R.; Laughlin, Mary J.; He, Wensheng; Ambruso, Daniel R.; Armitage, Susan E.; Beddard, Rachel L.; Bhatla, Deepika; Hwang, William Y.K.; Kiss, Joseph E.; Koegler, Gesine; Kurtzberg, Joanne; Nagler, Arnon; Oh, David; Petz, Lawrence D.; Price, Thomas H.; Quinones, Ralph R.; Ratanatharathorn, Voravit; Rizzo, J. Douglas; Sazama, Kathleen; Scaradavou, Andromachi; Schuster, Michael W.; Sender, Leonard S.; Shpall, Elizabeth J.; Spellman, Stephen R.; Sutton, Millicent; Weitekamp, Lee Ann; Wingard, John R.; Eapen, Mary

2015-01-01

Variations in cord blood manufacturing and administration are common, and the optimal practice, not known. We compared processing and banking practices at 16 public cord blood banks (CBB) in the United States, and assessed transplant outcomes on 530 single umbilical cord blood (UCB) myeloablative transplantations for hematologic malignancies, facilitated by these banks. UCB banking practices were separated into three mutually exclusive groups based on whether processing was automated or manual; units were plasma and red blood cell reduced or buffy coat production method or plasma reduced. Compared to the automated processing system for units, the day-28 neutrophil recovery was significantly lower after transplantation of units that were manually processed and plasma reduced (red cell replete) (odds ratio [OR] 0.19 p=0.001) or plasma and red cell reduced (OR 0.54, p=0.05). Day-100 survival did not differ by CBB. However, day-100 survival was better with units that were thawed with the dextran-albumin wash method compared to the “no wash” or “dilution only” techniques (OR 1.82, p=0.04). In conclusion, CBB processing has no significant effect on early (day 100) survival despite differences in kinetics of neutrophil recovery. PMID:25543094

Organochlorine pesticide levels in umbilical cord blood of newborn in Veracruz, Mexico.

PubMed

Herrero-Mercado, Margarita; Waliszewski, S M; Caba, M; Martínez-Valenzuela, C; Hernández-Chalate, F

2010-10-01

Organochlorine pesticides accumulate in lipid rich compartments of organisms. During pregnancy, the compounds pass through the placental barrier appear in cord blood. The aim of this study was to monitor the levels of organochlorine pesticides in 70 umbilical cord blood samples taken during deliveries in Veracruz in 2009. For organochlorine pesticides, only the presence β-HCH (4%, 3.9 μg/L median concentration on wet weight), pp'DDE (100%, 0.7 μg/L) and pp'DDT (4%, 1.4 μg/L) were detected. The total pool of samples divided according to sex of new born babies, showed no statistical differences among median concentrations. The number of deliveries considered as a determinant contamination factor affirmed there were no statistical differences among median concentrations; however pp'DDE levels increased from the one to two childbirth groups. Age of pregnant women as a discriminate factor manifests in a significant increase in contamination levels among first, second and third tertile. In general, umbilical cord blood samples in Veracruz contained organochlorine pesticides, especially pp'DDE, confirming the presence of these compounds in the environment and their transfer from the mother to the developing fetus.

Regulation of malonyl-CoA-acyl carrier protein transacylase network in umbilical cord blood affected by intrauterine hyperglycemia

PubMed Central

Zhang, Yong; Ye, Jianping; Fan, Jianxia

2017-01-01

Background Gestational diabetes mellitus (GDM) has been shown to be associated with high risk of diabetes in offspring. However, the mechanisms involved in the insulin resistance in offspring are still unclear. Mitochondrial dysfunction is related with insulin resistance. In mitochondria, malonyl-CoA-acyl carrier protein transacylase (MCAT) is the key enzyme of mitochondrial fatty acid synthesis and is estimated to contribute to insulin resistance. In this study, we aimed to examine the role of MCAT and its network in the umbilical cord blood in GDM-induced offspring insulin resistance. Methods We isolated lymphocytes from umbilical cord vein blood in 6 GDM patients and 6 controls and examined the differences of RNA by RNA sequencing. qRT-PCR and western blot were used to measure mRNA and protein changes. Bisulfite genomic sequencing PCR was applied to detect DNA methylation. Results We found more than 400 genes were differentially regulated in the lymphocytes of umbilical cord blood from GDM patients and these genes were mainly enriched in immune system and endocrine system, which relate to mitochondrial dysfunction and insulin resistance. MCAT closely related with PTPN1 (Protein Tyrosine Phosphatase, Non-Receptor Type1) and STAT5A (Signal Transducer And Activator of Transcription 5A), which were all increased in umbilical cord blood from GDM patients. Increase in MCAT may be due to decreased MCAT DNA methylation. Conclusion MCAT and its network with PTPN1, STAT5A are regulated in umbilical cord blood affected by maternal intrauterine hyperglycemia. PMID:29088862

Untying the Gordian knot: policies, practices, and ethical issues related to banking of umbilical cord blood

PubMed Central

Kurtzberg, Joanne; Lyerly, Anne Drapkin; Sugarman, Jeremy

2005-01-01

Since the first successful transplantation of umbilical cord blood in 1988, cord blood has become an important source of hematopoietic stem and progenitor cells for the treatment of blood and genetic disorders. Significant progress has been accompanied by challenges for scientists, ethicists, and health policy makers. With the recent recognition of the need for a national system for the collection, banking, distribution, and use of cord blood and the increasing focus on cord blood as an alternative to embryos as a source of tissue for regenerative medicine, cord blood has garnered significant attention. We review the development of cord blood banking and transplantation and then discuss the scientific and ethical issues influencing both established and investigational practices surrounding cord blood collection, banking, and use. PMID:16200191

Umbilical Cord Blood Banking for Transplantation in Morocco: Problems and opportunities

PubMed Central

Mazini, Loubna; Matar, Nourredine; Bouhya, Said; Marzouk, Diaa; Anwar, Wagida; Khyatti, Meriem

2014-01-01

Since the success of the first umbilical cord blood (UCB) transplantation in a child with Fanconi anaemia in 1989, great interests have emerged for this source of stem cells. UCB provides an unlimited source of ethnically diverse stem cells and is an alternative for bone marrow (BM) and peripheral blood (PB) haematopoietic stem cell transplantation (HSCT). Thus, UCB and manipulated stem cells are now collected and banked according to international accreditation standards for listing on registries allowing rapid search and accessibility worldwide. This work aims to identify problems limiting the creation of a Moroccan cord blood bank and to highlight opportunities and issues of a new legislation promoting additional applications of cell therapy. PMID:25705096

Effects of umbilical cord blood stem cells on healing factors for diabetic foot injuries.

PubMed

Çil, N; Oğuz, E O; Mete, E; Çetinkaya, A; Mete, G A

2017-01-01

The use of stem or progenitor cells from bone marrow, or peripheral or umbilical cord blood is becoming more common for treatment of diabetic foot problems. These cells promote neovascularization by angiogenic factors and they promote epithelium formation by stimulating cell replication and migration under certain pathological conditions. We investigated the role of CD34 + stem cells from human umbilical cord blood in wound healing using a rat model. Rats were randomly divided into a control group and two groups with diabetes induced by a single dose of 55 mg/kg intraperitoneal streptozocin. Scarred areas 5 mm in diameter were created on the feet of all rats. The diabetic rats constituted the diabetes control group and a diabetes + stem cell group with local injection into the wound site of 0.5 × 106 CD34 + stem cells from human umbilical cord blood. The newly formed skin in the foot wounds following CD34 + stem cell treatment showed significantly improvement by immunohistochemistry and TUNEL staining, and were closer to the wound healing of the control group than the untreated diabetic animals. The increase in FGF expression that accompanied the local injection of CD34 + stem cells indicates that FGF stimulation helped prevent apoptosis. Our findings suggest a promising new treatment approach to diabetic wound healing.

Cord blood units collected at a remote site: a collaborative endeavor to collect umbilical cord blood through the Hawaii Cord Blood Bank and store the units at the Puget Sound Blood Center.

PubMed

Wada, Randal K; Bradford, Andrea; Moogk, Margery; Yim, Robyn; Strong, D Michael; Drachman, Jonathan; Reems, Jo Anna

2004-01-01

Umbilical cord blood is a useful source of hematopoietic stem cells, especially because compared to equivalent HLA-matched stem cells from unrelated adult donors. A network of community collection sites targeted at particular ethnic groups and serviced by a central processing and storage facility can maximize the genetic diversity of banked cord blood units (CBUs) in a cost-effective fashion. The present study compared CBUs collected near the Puget Sound Blood Center in Seattle, WA, with those collected in Honolulu, HI, and processed in Seattle. Evaluated variables include collection volume, total nucleated cell count, cellular viability, CD34+ cell count, clonogenic activity, and donor race for a total of 1646 CBUs received from July 1998 through November 2002. CBUs from the two sites did not differ with regard to volume or total nucleated cells. Those from Hawaii had significantly longer transit times (p < 0.001) and lower whole cord blood cell viability. However, the numbers of CFU and viable CD34+ cells were not affected by remote collection. CBUs screened from Seattle were largely from Caucasian donors, whereas over 85 percent of those from Honolulu were from donors of Asian-Pacific Islander or mixed ethnicity. These studies demonstrate the feasibility of long-distance umbilical cord blood banking. Arrangements such as those described here could be used to help target cost-effective collection from minority populations and increase the HLA and ethnic diversity for CBUs.

Mesenchymal stem cells from the Wharton's jelly of umbilical cord segments provide stromal support for the maintenance of cord blood hematopoietic stem cells during long-term ex vivo culture.

PubMed

Bakhshi, Tiki; Zabriskie, Ryan C; Bodie, Shamanique; Kidd, Shannon; Ramin, Susan; Paganessi, Laura A; Gregory, Stephanie A; Fung, Henry C; Christopherson, Kent W

2008-12-01

Hematopoietic stem cells (HSCs) are routinely obtained from marrow, mobilized peripheral blood, and umbilical cord blood. Mesenchymal stem cells (MSCs) are traditionally isolated from marrow. Bone marrow-derived MSCs (BM-MSCs) have previously demonstrated their ability to act as a feeder layer in support of ex vivo cord blood expansion. However, the use of BM-MSCs to support the growth, differentiation, and engraftment of cord blood may not be ideal for transplant purposes. Therefore, the potential of MSCs from a novel source, the Wharton's jelly of umbilical cords, to act as stromal support for the long-term culture of cord blood HSC was evaluated. Umbilical cord-derived MSCs (UC-MSCs) were cultured from the Wharton's jelly of umbilical cord segments. The UC-MSCs were then profiled for expression of 12 cell surface receptors and tested for their ability to support cord blood HSCs in a long-term culture-initiating cell (LTC-IC) assay. Upon culture, UC-MSCs express a defined set of cell surface markers (CD29, CD44, CD73, CD90, CD105, CD166, and HLA-A) and lack other markers (CD45, CD34, CD38, CD117, and HLA-DR) similar to BM-MSCs. Like BM-MSCs, UC-MSCs effectively support the growth of CD34+ cord blood cells in LTC-IC assays. These data suggest the potential therapeutic application of Wharton's jelly-derived UC-MSCs to provide stromal support structure for the long-term culture of cord blood HSCs as well as the possibility of cotransplantation of genetically identical, HLA-matched, or unmatched cord blood HSCs and UC-MSCs in the setting of HSC transplantation.

Signs of fetal brain sparing are not related to umbilical cord blood gases at birth.

PubMed

Cheema, Riffat; Dubiel, Mariusz; Gudmundsson, Saemundur

2009-07-01

Fetal chronic hypoxia leads to centralization of circulation in order to spare the vital organs brain, adrenals and the heart. This can be documented by Doppler ultrasound. Increased blood velocity in the fetal middle cerebral artery (MCA) is an acknowledged sign of centralization of circulation in chronic hypoxia, and is called brain sparing. Our aim was to assess the relationship between signs of brain sparing in the MCA and umbilical cord blood gases at birth. A prospective study. Singleton 57 high-risk pregnancies (outcome was compared with 21 normal pregnancies). MCA Doppler was performed within 24 h of elective caesarean section in high-risk pregnancies. Umbilical cord blood gases were analysed at birth. Cord blood gases were related to signs of centralization of fetal circulation in the MCA. No correlation between signs of brain sparing in the MCA and cord blood gases. Apgar score at 5'<7 was seen in three newborns, but only one of these had antenatal signs of brain sparing. Newborns with antenatal brain sparing were admitted more often (p<0.04) and had a longer duration of stay in NICU (p<0.03) compared to newborns without brain sparing. Decreased pulsatility index in MCA is an acknowledged sign of fetal centralization of circulation during chronic hypoxia. However, signs of brain sparing are not related to cord blood gases at birth, which might suggest that redistribution of fetal circulation can maintain normal blood gases for a long time during chronic hypoxia.

[Effect of different cryopreservation time on quality of umbilical cord blood cells].

PubMed

Huang, Lu; Song, Gui-Qi; Wu, Yun; Wang, Jian

2013-02-01

This study was aimed to explore the effect of different cryopreservation time on recovery rate of cord blood stem cells, and analyze the influence of cord blood cells after thawing on the engraftment speed of cord blood cells in patients. 20 cord blood units were stored at -196°C for 1 - 10 years. The cell viability, content of total nucleated cell (TNC), CD34(+) cells and the colony forming units of granulocyte/macrophage (CFU-GM) were assessed after thawing, the impact of cell recovery on engraftment speed in patients was analyzed. The results showed that as compared with data provided by Umbilical Cord Blood Bark, the different cryopreservation time had no effect on yield of cord blood stem cells after thawing. The cell viability was (92.75 ± 2.55)% after thawing, the yields of TNC, CD34(+) cells and CFU-GM were 89.9%, 84.8% and 84.3%, compared with that of pre-freezing, their differences were statistically significant (P = 0.000), however, loss of cells had no effect on the time of neutrophils and platelets engraftment. The TNC and CD34(+)cell count after thawing correlated closely with that of pre-freezing (r = 0.954 and r = 0.931, P = 0.000), but CFU-GM content poorly correlated with that (r = 0.285, P = 0.223). It is concluded that cryopreservation and thawing process can damage the cord blood stem cells, leading to cell loss, but not affect transplant results.

Transient spontaneous engraftment of CD34 hematopoietic cord blood stem cells as seen in peripheral blood: treatment of leprosy patients with anemia by placental umbilical cord whole blood transfusion.

PubMed

Bhattacharya, N

2006-01-01

Cord blood, because of its rich mix of fetal and adult hemoglobin, high platelet and white blood cell (WBC) counts, and a plasma filled with cytokine and growth factors, as well as its hypoantigenic nature and altered metabolic profile, has all the potential of a real and safe alternative to adult blood transfusion. Our experience of 74 units (50 ml-146 ml mean, 86 ml +/- 7.6 ml SD, median 80 ml, mean packed cell volume 48 +/- 4.1 SD, mean percent hemoglobin concentration 16.2 g/dl +/- 1.8 g/dl of placental umbilical cord whole blood collection (from 1 April 1999) after lower uterine cesarean section (LUCS) from consenting mothers and transfusion of the same to 16 informed, consenting patients with percent plasma hemoglobin 8 g/dl or less, is presented here. After collection the blood was immediately preserved in the refrigerator and transfused within 72 hours of collection. Fifteen males and one female, aged 12-72 yrs (mean 48.4 yrs) participated: five cases were pausibacillary type (PB) and 11 cases were multibacillary type (MB). The clinical spectrum of the cases varied widely from the tuberculoid to the lepromatous type and one patient presented with gangrene of the leg preceding an auto amputation which was infested with maggots. Each case was approved by the institutional ethical committee and received two to eight units of freshly collected placental umbilical cord blood in one transfusion without encountering any clinical, immunological or non-immunological reaction. Seven days after completion of the placental umbilical cord blood transfusion, the peripheral blood hematopoietic stem cell (CD34) estimation revealed a rise from the pretransfusion base level (.09%), varying from 3.6% to 16.2%, in 75% of the cases, without provoking any clinical graft vs host reaction in any of the leprosy victims. This value returned to normal within three months in most cases.

Design guidelines for an umbilical cord blood stem cell therapy quality assessment model

NASA Astrophysics Data System (ADS)

Januszewski, Witold S.; Michałek, Krzysztof; Yagensky, Oleksandr; Wardzińska, Marta

The paper enlists the pivotal guidelines for producing an empirical umbilical cord blood stem cell therapy quality assessment model. The methodology adapted was single equation linear model with domain knowledge derived from MEDAFAR classification. The resulting model is ready for therapeutical application.

Concentrations of pentosidine, an advanced glycation end-product, in umbilical cord blood.

PubMed

Tsukahara, Hirokazu; Ohta, Naoko; Sato, Shuko; Hiraoka, Masahiro; Shukunami, Ken-Ichi; Uchiyama, Mayumi; Kawakami, Hisako; Sekine, Kyouichi; Mayumi, Mitsufumi

2004-07-01

Advanced glycation end-products (AGEs) are formed over several weeks to months by non-enzymatic glycation and oxidation ("glycoxidation") reactions between carbohydrate-derived carbonyl groups and protein amino groups, known as the Maillard reaction. Pentosidine is one of the best-characterized AGEs and is accepted as a satisfactory marker for glycoxidation in vivo. The present study was intended to measure pentosidine concentrations in umbilical cord blood from newborns with various gestational ages using our recently established high-performance liquid chromatography method [Tsukahara, H. et al. (2003) Pediatr. Res. 54, 419-424]. Our study demonstrates, for the first time, that pentosidine is detected in most of the umbilical blood samples. This study also shows that the umbilical blood concentrations of pentosidine are considerably lower than normal adult values, but that they increase with gestation progression and fetal growth. Umbilical pentosidine concentrations were significantly elevated in newborns of mothers with preeclampsia compared to those of mothers without preeclampsia. We conclude that accumulation of AGEs and oxidative stress occurs in fetal tissues and organs in utero at the early stage of human life and that their accumulation is augmented in the maternal preeclampsic condition.

Mesenchymal stem cells from the Wharton’s jelly of umbilical cord segments provide stromal support for the maintenance of cord blood hematopoietic stem cells during long-term ex vivo culture

PubMed Central

Bakhshi, Tiki; Zabriskie, Ryan C.; Bodie, Shamanique; Kidd, Shannon; Ramin, Susan; Paganessi, Laura A.; Gregory, Stephanie A.; Fung, Henry C.; Christopherson, Kent W.

2012-01-01

BACKGROUND Hematopoietic stem cells (HSCs) are routinely obtained from marrow, mobilized peripheral blood, and umbilical cord blood. Mesenchymal stem cells (MSCs) are traditionally isolated from marrow. Bone marrow–derived MSCs (BM-MSCs) have previously demonstrated their ability to act as a feeder layer in support of ex vivo cord blood expansion. However, the use of BM-MSCs to support the growth, differentiation, and engraftment of cord blood may not be ideal for transplant purposes. Therefore, the potential of MSCs from a novel source, the Wharton’s jelly of umbilical cords, to act as stromal support for the long-term culture of cord blood HSC was evaluated. STUDY DESIGN AND METHODS Umbilical cord–derived MSCs (UC-MSCs) were cultured from the Wharton’s jelly of umbilical cord segments. The UC-MSCs were then profiled for expression of 12 cell surface receptors and tested for their ability to support cord blood HSCs in a long-term culture-initiating cell (LTC-IC) assay. RESULTS Upon culture, UC-MSCs express a defined set of cell surface markers (CD29, CD44, CD73, CD90, CD105, CD166, and HLA-A) and lack other markers (CD45, CD34, CD38, CD117, and HLA-DR) similar to BM-MSCs. Like BM-MSCs, UC-MSCs effectively support the growth of CD34+ cord blood cells in LTC-IC assays. CONCLUSION These data suggest the potential therapeutic application of Wharton’s jelly–derived UC-MSCs to provide stromal support structure for the long-term culture of cord blood HSCs as well as the possibility of cotransplantation of genetically identical, HLA-matched, or unmatched cord blood HSCs and UC-MSCs in the setting of HSC transplantation. PMID:18798803

Generation of mesenchymal stromal cells in the presence of platelet lysate: a phenotypic and functional comparison of umbilical cord blood- and bone marrow-derived progenitors

PubMed Central

Avanzini, Maria Antonietta; Bernardo, Maria Ester; Cometa, Angela Maria; Perotti, Cesare; Zaffaroni, Nadia; Novara, Francesca; Visai, Livia; Moretta, Antonia; Del Fante, Claudia; Villa, Raffaella; Ball, Lynne M.; Fibbe, Willem E.; Maccario, Rita; Locatelli, Franco

2009-01-01

Background Mesenchymal stromal cells are employed in various different clinical settings in order to modulate immune response. However, relatively little is known about the mechanisms responsible for their immunomodulatory effects, which could be influenced by both the cell source and culture conditions. Design and Methods We tested the ability of a 5% platelet lysate-supplemented medium to support isolation and ex vivo expansion of mesenchymal stromal cells from full-term umbilical-cord blood. We also investigated the biological/functional properties of umbilical cord blood mesenchymal stromal cells, in comparison with platelet lysate-expanded bone marrow mesenchymal stromal cells. Results The success rate of isolation of mesenchymal stromal cells from umbilical cord blood was in the order of 20%. These cells exhibited typical morphology, immunophenotype and differentiation capacity. Although they have a low clonogenic efficiency, umbilical cord blood mesenchymal stromal cells may possess high proliferative potential. The genetic stability of these cells from umbilical cord blood was demonstrated by a normal molecular karyotype; in addition, these cells do not express hTERT and telomerase activity, do express p16ink4a protein and do not show anchorage-independent cell growth. Concerning alloantigen-specific immune responses, umbilical cord blood mesenchymal stromal cells were able to: (i) suppress T- and NK-lymphocyte proliferation, (ii) decrease cytotoxic activity and (iii) only slightly increase interleukin-10, while decreasing interferon-γ secretion, in mixed lymphocyte culture supernatants. While an indoleamine 2,3-dioxygenase-specific inhibitor did not reverse mesenchymal stromal cell-induced suppressive effects, a prostaglandin E2-specific inhibitor hampered the suppressive effect of both umbilical cord blood- and bone marrow-mesenchymal stromal cells on alloantigen-induced cytotoxic activity. Mesenchymal stromal cells from both sources expressed HLA

Time related variations in stem cell harvesting of umbilical cord blood

NASA Astrophysics Data System (ADS)

Mazzoccoli, Gianluigi; Miscio, Giuseppe; Fontana, Andrea; Copetti, Massimiliano; Francavilla, Massimo; Bosi, Alberto; Perfetto, Federico; Valoriani, Alice; de Cata, Angelo; Santodirocco, Michele; Totaro, Angela; Rubino, Rosa; di Mauro, Lazzaro; Tarquini, Roberto

2016-02-01

Umbilical cord blood (UCB) contains hematopoietic stem cells and multipotent mesenchymal cells useful for treatment in malignant/nonmalignant hematologic-immunologic diseases and regenerative medicine. Transplantation outcome is correlated with cord blood volume (CBV), number of total nucleated cells (TNC), CD34+ progenitor cells and colony forming units in UCB donations. Several studies have addressed the role of maternal/neonatal factors associated with the hematopoietic reconstruction potential of UCB, including: gestational age, maternal parity, newborn sex and birth weight, placental weight, labor duration and mode of delivery. Few data exist regarding as to how time influences UCB collection and banking patterns. We retrospectively analyzed 17.936 cord blood donations collected from 1999 to 2011 from Tuscany and Apulia Cord Blood Banks. Results from generalized multivariable linear mixed models showed that CBV, TNC and CD34+ cell were associated with known obstetric and neonatal parameters and showed rhythmic patterns in different time domains and frequency ranges. The present findings confirm that volume, total nucleated cells and stem cells of the UCB donations are hallmarked by rhythmic patterns in different time domains and frequency ranges and suggest that temporal rhythms in addition to known obstetric and neonatal parameters influence CBV, TNC and CD34+ cell content in UBC units.

Safety and Tolerability of HSC835 in Patients With Hematological Malignancies Undergoing Single Umbilical Cord Blood Transplant

ClinicalTrials.gov

2017-08-31

Single Umbilical Cord Blood Transplantation; Non-myeloablative Conditioning; Acute Lymphocytic Leukemia; Myelodysplastic Syndrome; Non-Hodgkin's Lymphoma; Multiple Myeloma; Chronic Lymphocytic Leukemia

Mercury in the Umbilical Cord: Implications for Risk Assessment for Minamata Disease.

PubMed Central

Dalgard, C; Grandjean, P; Jorgensen, PJ; Weihe, P

1994-01-01

Umbilical cord tissue was obtained from 50 births in the Faroe Islands, where high mercury intake is due to ingestion of pilot whale meat. The mercury concentration correlated significantly with the frequency of maternal whale meat dinners during pregnancy and with mercury concentrations in umbilical cord blood and in maternal hair. The results were compared with published values for mercury in umbilical cord tissue from 12 infants diagnosed with congenital methylmercury poisoning in Minamata, Japan. From the regression coefficients obtained in the Faroese samples, the median umbilical cord mercury concentration of 4.95 nmol/g dry weight in Minamata would correspond to 668 nmol/l cord blood and 114 nmol/g maternal hair. These levels agree well with other evidence of susceptibility of the fetus to increased exposure to methylmercury. Images Figure 1. Figure 2. PMID:9679113

Post-test probability for neonatal hyperbilirubinemia based on umbilical cord blood bilirubin, direct antiglobulin test, and ABO compatibility results.

PubMed

Peeters, Bart; Geerts, Inge; Van Mullem, Mia; Micalessi, Isabel; Saegeman, Veroniek; Moerman, Jan

2016-05-01

Many hospitals opt for early postnatal discharge of newborns with a potential risk of readmission for neonatal hyperbilirubinemia. Assays/algorithms with the possibility to improve prediction of significant neonatal hyperbilirubinemia are needed to optimize screening protocols and safe discharge of neonates. This study investigated the predictive value of umbilical cord blood (UCB) testing for significant hyperbilirubinemia. Neonatal UCB bilirubin, UCB direct antiglobulin test (DAT), and blood group were determined, as well as the maternal blood group and the red blood cell antibody status. Moreover, in newborns with clinically apparent jaundice after visual assessment, plasma total bilirubin (TB) was measured. Clinical factors positively associated with UCB bilirubin were ABO incompatibility, positive DAT, presence of maternal red cell antibodies, alarming visual assessment and significant hyperbilirubinemia in the first 6 days of life. UCB bilirubin performed clinically well with an area under the receiver-operating characteristic curve (AUC) of 0.82 (95 % CI 0.80-0.84). The combined UCB bilirubin, DAT, and blood group analysis outperformed results of these parameters considered separately to detect significant hyperbilirubinemia and correlated exponentially with hyperbilirubinemia post-test probability. Post-test probabilities for neonatal hyperbilirubinemia can be calculated using exponential functions defined by UCB bilirubin, DAT, and ABO compatibility results. • The diagnostic value of the triad umbilical cord blood bilirubin measurement, direct antiglobulin testing and blood group analysis for neonatal hyperbilirubinemia remains unclear in literature. • Currently no guideline recommends screening for hyperbilirubinemia using umbilical cord blood. What is New: • Post-test probability for hyperbilirubinemia correlated exponentially with umbilical cord blood bilirubin in different risk groups defined by direct antiglobulin test and ABO blood group

Study of Umbilical Cord Blood Culture in Diagnosis of Early-onset Sepsis Among Newborns with High-risk Factors.

PubMed

Kalathia, Mitul Babubhai; Shingala, Prakash Ashokbhai; Parmar, Parin Niranjanbhai; Parikh, Yogesh Narenedrabhai; Kalathia, Ila Mitulkumar

2013-10-01

Blood culture is gold standard for diagnosis of neonatal sepsis. Low sensitivity of blood culture is usually due to small volume of blood sample, intrapartum antibiotics, and antibiotics given to newborn before sampling. We evaluated use of Umbilical cord blood culture (UCBC) in diagnosis of neonatal sepsis as compared to peripheral venous blood culture. This study was done in tertiary care teaching hospital during May-June 2012. A total of 45 newborns with presence of two or more risk factors of sepsis were included. Blood sample from placental end of umbilical cord was collected and cultured. Primary outcome was diagnosis of neonatal sepsis by use of umbilical cord blood sample as compared with venous blood sample. Secondary outcome was to compare organisms identified by UCBC and venous blood culture. Sensitivity, specificity, positive and negative predictive values of UCBC were calculated. A total of 24.44% (11 out of 45) high-risk newborns had positive UCBC. A total of 17.8% (8 out of 45) newborns had positive blood culture report. Organisms grown in UCBC were Pseudomonas (45%, 5 out of 11), Acinetobacter (27.27%, 3 out of 11), Escherichia coli (18.18%, 2 out of 11), and Klebsiella (9%, 1 out of 11). UCBC is a good method for diagnosis of neonatal sepsis among high-risk newborns as compared to venous blood culture with a sensitivity of 80% and specificity of 91.43%. Organisms grown are comparable to blood culture samples.

Autologus or allogenic uses of umbilical cord blood whole or RBC transfusion - a review.

PubMed

Chakrabarty, P; Rudra, S

2013-01-01

Once Umbilical Cord with Placenta considered a biological waste product and generally discarded after delivery but now cord blood has emerged as a viable source of hematopoietic stem cell transplantation. High-risk premature infants require red cell transfusions for anemia. A unique property of cord blood (CB) for its high content of immature hematopoietic progenitor cells (HPCs). Placental blood for autologous transfusions can be collected with aseptic precaution/sterilely into citrate-phosphate-dextrose and stored at 4°C. During storage for 8 days, the placental red cell content of adenosine triphosphate remained normal. The 2,3,-diphosphoglycerate concentration of cells stored beyond 8 days declined sharply. So we have to store umbilical cord blood (UCB) within 7 days for its best result. During storage, placental blood underwent an exchange of extra-cellular Na+ and K+, but no change in glutathione content. Hemolysis was less than 1 percent. Bacteriologic and fungal cultures remained sterile. These suggest that human placental blood can be collected safely and preserved effectively for autologous/allogenic transfusion therapy. In neonatal transfusion practice, efforts have been made to provide premature infants with autologous red blood cell (RBC), especially those born before 32 gestational weeks. In India no adverse transfusion effects were seen in a wide variety of patients that received (pooled) allogeneic fresh whole blood / UCB transfusions. The use of UCB for small volume allogeneic transfusions in anaemic children in Africa or in malaria endemic areas has also been proposed. A preclinical study showed that donation and transfusion of UCB would be acceptable to women living in Mombasa, Kenya. In view of the small volumes RBC per unit that can be collected, it is most likely that anaemic children need of a small volume of transfusions. In resource-restricted countries would benefit most from this easily available transfusion product.

PP032. Apolipoprotein profiling in umbilical cord blood of intrauterine growth restricted (IUGR) neonates.

PubMed

Pecks, Ulrich; Wölter, Manja; Borchers, Christoph; Smith, Derek; Maass, Nicolai; Glocker, Michael; Rath, Werner

2013-04-01

Fetal umbilical cord HDL concentration is lower in IUGR neonates as compared to gestational age matched controls (CTRL). The causes by now are unknown. A full apolipoprotein analysis of cord blood might help in understanding the changes in lipid metabolism seen in IUGR. To characterize cord blood apolipoprotein profile of IUGR neonates. Serum of venous umbilical cord blood (15 IUGR vs. 15 CTRL) was analyzed by Multiple Reaction Monitoring (MRM). 15 different known apolipoproteins were profiled. HDL and LDL were measured by colorimetric methods in fetal cord blood and their corresponding mothers. Fetal HDL (p<0.0001), ApoC1 (p<0.0001), and ApoE (p=0.0001) levels were lower in IUGR as compared to CTRL. Fetal HDL levels were positive correlated to ApoE, ApoC1, and ApoA2 (r=0.79, r=0.74, r=0.56). Fetal LDL levels were positive correlated to ApoB, ApoE, ApoA2, and ApoC3 (r=0.74, r=0.67, r=0.57, r=0.55). Maternal LDL concentrations correlated positive to fetal ApoC1, ApoC2, and LCAT-concentration (r=0.54, r=0.52, r=0.52). The results underlines the relevance of ApoE in fetal development. Moreover, we speculate that maternal lipid profile has an impact on fetal lipid metabolisms as evidenced by the association of maternal LDL levels and fetal ApoC1, ApoC2, and LCAT concentrations. This observation requires further confirmation and is worth to be analyzed since it provides a mechanistic link for therapeutic options. Copyright © 2013. Published by Elsevier B.V.

Potential substitution of cord blood for infant blood in the neonatal sepsis evaluation.

PubMed

Hansen, Anne; Forbes, Peter; Buck, Rosanne

2005-01-01

Evaluation of sepsis accounts for one third of all nursery triage admissions. If umbilical cord blood could be accurately substituted for infant blood, it would spare infants the discomfort of an invasive procedure and save both time and resources. While awaiting 48-hour blood culture results, we decide on clinical management based on whether the white blood cell (WBC) immature to total (I:T) granulocyte ratio is >or=0.2. Our goal was to assess the correlation of complete blood count (CBC), I:T ratio and blood culture results between umbilical cord and infant blood. We conducted a prospective cohort study comparing CBC/differential and blood culture results of paired samples of umbilical cord and infant blood from term newborns. We sent 113 paired samples of cord and infant venous blood for CBC/differential and blood culture. All 113 umbilical cord and infant blood cultures were negative, yielding a false-positive blood culture rate of zero. For 92% of babies, both the cord and infant blood I:T ratio were <0.2 or both were >or=0.2. Cord and infant WBC, hematocrit and platelet counts were moderately to highly correlated. We conclude that cord blood can be safely substituted for infant blood in routine sepsis evaluations of asymptomatic, term infants based on both the low false-positive cord blood culture rate and the significant association between high I:T ratios in cord and infant blood. Copyright (c) 2005 S. Karger AG, Basel.

Umbilical cord vitamin D, ionized calcium and myocardial oxygen demand.

PubMed

Reeves, Inez; Liang, Willie; Asadi, M Sadegh; Millis, Richard M

2014-07-01

Systemic blood vitamin D and total calcium are correlates of birthweight and cardiovascular disease but whether umbilical cord blood vitamin D and ionized calcium are correlates of birthweight and cardiovascular function is not known. This cross-sectional study correlates umbilical cord vitamin D, ionized calcium and birthweight with the heart rate-systolic pressure product (RPP), an indicator of myocardial oxygen demand. Cord blood vitamin D and ionized calcium concentrations were compared for vitamin D normal (≥50 nM, 20 ng/mL) and vitamin D deficiency (<50 nM, 20 ng/mL) in normal weight (≥2500 g) and low birthweight (LBW, <2500 g) newborns. Heart rate and blood pressure were measured during postnatal transition and RPP was computed. RPP was positively correlated with birthweight (r = +0.52, p < 0.001) and with cord ionized calcium level (r = +0.42, p < 0.01) in the normal and LBW newborns. RPP was positively correlated with cord vitamin D level in the LBW newborns (raw r = +0.50, p < 0.05, normalized for birthweight r = +0.73, p < 0.01). Small RPP, an indicator of low myocardial oxygen demand, in LBW newborns appears to correlate with low umbilical cord vitamin D and ionized calcium levels, suggestive of pathological heart development.

Maternal hemochromatosis gene H63D single-nucleotide polymorphism and lead levels of placental tissue, maternal and umbilical cord blood

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kayaalti, Zeliha, E-mail: kayaalti@ankara.edu.tr; Kaya-Akyüzlü, Dilek; Söylemez, Esma

Human hemochromatosis protein (HFE), a major histocompatibility complex class I-like integral membrane protein, participates in the down regulation of intestinal iron absorption by binding to transferrin receptor (TR). HFE competes with transferrin-bound iron for the TR and thus reduces uptake of iron into cells. On the other hand, a lack of HFE increases the intestinal absorption of iron similarly to iron deficiency associated with increasing in absorption and deposition of lead. During pregnancy, placenta cannot prevent transfer lead to the fetus; even low-level lead poisoning causes neurodevelopmental toxicity in children. The aim of this study was to determine the associationmore » between the maternal HFE H63D single-nucleotide polymorphism and lead levels in placental tissue, maternal blood and umbilical cord bloods. The study population comprised 93 mother–placenta pairs. Venous blood from mother was collected to investigate lead levels and HFE polymorphism that was detected by standard PCR–RFLP technique. Cord bloods and placentas were collected for lead levels which were analyzed by dual atomic absorption spectrometer system. The HFE H63D genotype frequencies of mothers were found as 75.3% homozygote typical (HH), 23.6% heterozygote (HD) and 1.1% homozygote atypical (DD). Our study results showed that the placental tissue, umbilical cord and maternal blood lead levels of mothers with HD+DD genotypes were significantly higher than those with HH genotype (p<0.05). The present study indicated for the first time that mothers with H63D gene variants have higher lead levels of their newborn's placentas and umbilical cord bloods. - Highlights: • Mothers with H63D gene variants have higher lead levels of their newborn's umbilical cord blood. • Unborn child of women with HD+DD genotypes may be at increased risk of internal exposure to lead. • Maternal HFE status may have an effect on increased placenta, maternal and cord blood lead levels. • Maternal

Trace of heavy metals in maternal and umbilical cord blood samples in association with birth outcomes in Baghdad, Iraq

NASA Astrophysics Data System (ADS)

Hasan Rhaif Al-Sahlanee, Mayyadah; Maizan Ramli, Ramzun; Abdul Hassan Ali, Miami; Fadhil Tawfiq, Nada; Zahirah Noor Azman, Nurul; Abdul Rahman, Azhar; Shahrim Mustafa, Iskandar; Noor Ashikin Nik Abdul Razak, Nik; Zakiah Yahaya, Nor; Mohammed Al-Marri, Hana; Syuhada Ayob, Nur; Zakaria, Nabela

2017-10-01

Trace elements are essential nutritional components in humans and inconvenient tissue content that have a significant influence on infant size. The aim of this study is to evaluate the effects of concentration of elements (uranium (U), lead (Pb) and iron (Fe)) and absorption of Pb and Fe on maternal and umbilical cord blood samples. The concentration and absorption of Pb and Fe in blood samples were determined by using atomic absorption spectrophotometry device, while the uranium concentration was determined by using CR-39 detector. Fifty women of age 16-44 years are involved in this study. Results show that the maximum and minimum values of both concentration and absorption in the maternal samples were for Pb and Fe, respectively. In addition, for umbilical cord, the maximum values of concentration and absorption were for Fe and the minimum concentration and absorption were for U and Pb, respectively. A significant correlation between maternal and umbilical cord blood samples was found. This indicates that the Pb, U and Fe elements can easily transfer from maternal to the fetal body which impacts the growth of fetus.

Androgen Concentrations in Umbilical Cord Blood and Their Association with Maternal, Fetal and Obstetric Factors

PubMed Central

Keelan, Jeffrey A.; Mattes, Eugen; Tan, HaiWei; Dinan, Andrew; Newnham, John P.; Whitehouse, Andrew J. O.; Jacoby, Peter; Hickey, Martha

2012-01-01

The aim of this study was to measure umbilical blood androgen concentrations in a birth cohort using a highly specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay and assesses the effects of sex, labor, and gestational age on fetal androgen levels at birth. We performed a prospective cohort study of androgen concentrations in mixed arterial and venous umbilical cord serum from 803 unselected singleton pregnancies from a general obstetric population in Western Australia. Total testosterone (TT), Δ4-androstenedione, and dehydroepiandrosterone were extracted from archived cord serum samples and measured using LC-MS/MS. SHBG was measured by ELISA; free testosterone (FT) and bioavailable testosterone (BioT) values were also calculated. Median values for all three androgens were generally lower than previously published values. Levels of TT, FT, BioT, and SHBG were significantly higher in male verses female neonates (P<0.0001), while dehydroepiandrosterone levels were higher in females (P<0.0001). Labor was associated with a significant (∼15–26%) decrease in median cord blood TT and FT levels (both sexes combined), but a modest (∼16–31%) increase in SHBG, Δ4-androstenedione, and dehydroepiandrosterone concentrations. TT and FT were significantly negatively correlated with gestational age at delivery, while SHBG, Δ4-androstenedione, and dehydroepiandrosterone were positively correlated. Antenatal glucocorticoid administration also had a significant effect in the multiple regression models. This is the first study to report umbilical cord androgen levels in a large unselected population of neonates using LC-MS/MS. Our findings suggest that previous studies have over-estimated cord androgen levels, and that fetal, maternal, and obstetric factors influence cord androgen levels differentially. Caution should be exercised when interpreting previously-published data that have not taken all of these factors into account. PMID:22916165

The comparison of umbilical cord arterial blood lactate and pH values for predicting short-term neonatal outcomes.

PubMed

Einikyte, Ruta; Snieckuviene, Vilija; Ramasauskaite, Diana; Panaviene, Jurate; Paliulyte, Virginija; Opolskiene, Gina; Kazenaite, Edita

2017-12-01

Current clinical practice of assessing neonatal condition is based on evaluation of umbilical cord arterial blood pH value rather than lactate. However, evidence shows that lactate is direct and more predictive measurement than pH or at least of equal importance. This study is to assess and compare umbilical cord arterial lactate and pH values for predicting short-term neonatal outcomes. A retrospective cohort study was conducted at the tertiary level hospital, were arterial umbilical cord blood sampling was collected according to the standard procedures. Neonatal morbidity was registered if at least one of the following conditions was noted: Apgar score at 1 min after delivery was 6 or lower, resuscitation performed, including assisted ventilation and requirement of admission to neonatal intensive care unit. Mothers-newborns pairs were allocated into two groups: newborns exposed to perinatal hypoxia (group 1) and observed as healthy newborns (group 2). Receiver operating characteristics curves (ROC) were generated to assess the predictive ability of pH and lactate for the short-term neonatal outcomes. 901 neonates born at ≥37 weeks of gestation were included. Newborns exposed to perinatal hypoxia (group 1) encompassed 39 (4.3%) patients, and observed as healthy (group 2) - 862 (95.7%). Arterial umbilical cord blood pH in group 1 was 7.160 ± 0.126 as compared to 7.314 ± 0.083 in group 2; p < 0.001. Mean arterial lactate was significantly higher in group 1 than group 2 (6.423 ± 2.335 as compared to 3.600 ± 1.833; p < 0.001). The difference between areas under ROC curves representing pH and lactate was not significant (0.848 and 0.831 respectively; p = 0.6132). Umbilical cord arterial lactate and pH predicted short-term neonatal outcomes with similar efficacies. Copyright © 2017. Published by Elsevier B.V.

Effect of body position and ventilation on umbilical artery and venous blood flows during delayed umbilical cord clamping in preterm lambs.

PubMed

Hooper, Stuart B; Crossley, Kelly J; Zahra, Valerie A; van Vonderen, Jeroen; Moxham, Alison; Gill, Andrew W; Kluckow, Martin; Te Pas, Arjan B; Wallace, Euan M; Polglase, Graeme R

2017-07-01

While delayed umbilical cord clamping (UCC) is thought to facilitate placental to infant blood transfusion, the physiological factors regulating flow in the umbilical arteries and veins during delayed UCC is unknown. We investigated the effects of gravity, by changing fetal height relative to the placenta, and ventilation on umbilical blood flows and the cardiovascular transition during delayed UCC at birth. Catheters and flow probes were implanted into preterm lambs (128 days) prior to delivery to measure pulmonary, carotid, umbilical artery (UaBF) and umbilical venous (UvBF) blood flows. Lambs were placed either 10 cm below or 10 cm above the ewe. Ventilation commenced 2-3 min before UCC and continued for 30 min after UCC. Gravity reduced umbilical and cerebral flows when lambs were placed below the midline, but the reduction in UaBF and UvBF was similar. Ventilation during delayed UCC reduced UvBF and UaBF by similar amounts, irrespective of the lamb's position, such that flows into and out of the placenta remained balanced. The effects of ventilation on umbilical flows were much greater than the effects of gravity, but no net placental to lamb blood transfusion could be detected under any condition. Cardiovascular parameters, cerebral oxygen kinetics and final blood volumes were similar in both groups 5 min after UCC. Gravity caused small transient effects on umbilical and cerebral flow, but given changes were similar in umbilical arteries and veins, no net placental transfusion was detected. Ventilation during delayed UCC has a markedly greater influence on cardiovascular function in the newborn. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

A great lack of knowledge regarding umbilical cord blood banking among pregnant women in Berlin, Germany.

PubMed

Palten, Patricia E; Dudenhausen, Joachim W

2010-11-01

we evaluated what German-speaking women in Berlin know about umbilical cord blood banking (UCBB) and whether a correlation exists between women's knowledge about UCBB and level of education. we used the anonymous questionnaire given to German-speaking women in Berlin, Germany. a total of 300 questionnaires could be evaluated. Although three quarters of our population heard of UCBB, most had no further knowledge about the method. Only about one-third of the interviewed women were informed about whether certain diseases had been treated with umbilical cord blood (UCB) by the time the survey was being conducted, whereas 50-65% did not know how to answer these questions. women in Berlin were poorly educated about the usefulness, the costs and the methods of cryopreservation. To some extent there is a correlation between women's level of education and their knowledge regarding UCB.

Umbilical cord care in newborns

MedlinePlus

... the stump clean with gauze and water only. Sponge bathe the rest of your baby, as well. ... Neonatal care - umbilical cord Images Umbilical cord healing Sponge bath References Carlo WA, Ambalavanan N. The umbilicus. ...

Sex-Specific Associations between Umbilical Cord Blood Testosterone Levels and Language Delay in Early Childhood

ERIC Educational Resources Information Center

Whitehouse, Andrew J. O.; Mattes, Eugen; Maybery, Murray T.; Sawyer, Michael G.; Jacoby, Peter; Keelan, Jeffrey A.; Hickey, Martha

2012-01-01

Background: Preliminary evidence suggests that prenatal testosterone exposure may be associated with language delay. However, no study has examined a large sample of children at multiple time-points. Methods: Umbilical cord blood samples were obtained at 861 births and analysed for bioavailable testosterone (BioT) concentrations. When…

[Intestinal polyp of the umbilical cord].

PubMed

Guschmann, M; Janda, J; Wenzelides, K; Vogel, M

2002-02-01

The morphology, pathogenesis, complications and differential diagnosis of an intestinal polyp of the umbilical cord are presented. The polyp were detected postnatal on the umbilical cord in an healthy male newborn. The presents of intestinal tissue upon the umbilical cord ist possible about the persistence from remnants of the ductus omphalomesentericus with prolapse and differentiation of the intestinal cells. The ductus omphalomesentericus is a tubular structure, a communication between the developing embryonic gut and the yolk sac, forming during the early embryonic life. Obliteration of the omphalomesenteric duct is usually complete by the 10(th) week of gestation. Various portions of the duct may persist, however, giving rise to polyps, fistulas or cysts of the umbilical cord with potentially dangerous clinical consequences. Other tumors of the umbilical cord are myxoma, angioma and teratoma are differential diagnosis.

Biobanks between common good and private interest: the example of umbilical cord blood private biobanks.

PubMed

Onisto, Maurizio; Ananian, Viviana; Caenazzo, Luciana

2011-12-01

Storage of human biological samples and personal data associated with them is organised in Biobanks. In spite of expectation given by biobanks in medicine, their management involved some ethical questions, for example, the need for policies to regulate economic interests, potential commercial use of data (including patents), private sector financing, ownership of samples and benefit sharing. In the context of contributing to the general public interest, we can consider the act of giving biological material to biobanks as a donation, in which the donation constitutes part of a generalised form of reciprocity in which the act of donation contributes to society's common good. Starting from this perspective, we move into a different situation represented by the biobanking of umbilical cord blood for personal use. We used the example of the private biobanking of umbilical cords to demonstrate the restrictive utility of the collection and preservation of cord blood for personal use in private biobanks, in the context of society's common good. In summary, a system based on solidarity seems to be able to guarantee necessary levels of supply for the donation of biological material to biobanks.

Clinical Use and Patentability of Cord Blood

PubMed

Cavusoglu, Turker; Kilic, Kubilay Dogan; Yigitturk, Gurkan; Tomruk, Canberk; Turgut, Mehmet; Uyanikgil, Yigit

2018-03-14

The blood in the umbilical cord that provides the connection between mother and fetus during pregnancy is called cord blood. The blood of umbilical cord which is usually got rid of following birth, is a very rich stem cell source. Cord blood collection gives no harm to the mother and baby. Besides, its allogeneic and au-tologous usage, the most important disadvantage is that the number of cells is insufficient in adults. Today, it is predominantly used for therapeutic purposes for many diseases. The aim of this review is giving a detailed information about groups of stem cells in cord blood and determining the point of clinical use. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Delivery route determines the presence of immune complexes on umbilical cord erythrocytes.

PubMed

de Lima, Andrés; Franco, Luis C; Sarmiento, Andrés; González, John M

2017-11-01

Umbilical cord blood offers a unique opportunity to study the basal level of immunoglobulin complexes. This study aims to determine the presence of immune complexes and complement deposition on erythrocytes from umbilical cord blood from normal, full-term pregnancies. In vitro pre-formed IgA, IgG, and IgM complexes were used as positive control for flow cytometry detection, and for C3d deposition. Blood samples (34) of umbilical cord blood taken from vaginal and cesarean deliveries were tested for the presence of immunoglobulin complexes. Fourteen samples from vaginal deliveries and 20 samples from cesarean deliveries were assessed. IgG and IgM complexes were detected on erythrocytes, whereas no IgA complexes or complement deposition was observed. Interestingly, the percentage of IgG complexes was higher on erythrocytes from vaginal delivery samples compared to those from cesarean deliveries. No other associations between immune complexes and other maternal or newborn variables were found. IgG and IgM complexes seem to be normally present on umbilical cord erythrocytes. Erythrocytes from vaginal deliveries have a higher percentage of IgG complexes present compared to that from cesarean deliveries. Since no C3d activity was detected, these complexes are non-pathological and should be part of the newborn's initial innate immune response.

A study report of 174 units of placental umbilical cord whole blood transfusion in 62 patients as a rich source of fetal hemoglobin supply in different indications of blood transfusion.

PubMed

Bhattacharya, N; Mukherijee, K; Chettri, M K; Banerjee, T; Mani, U; Bhattacharya, S

2001-01-01

In the animal kingdom, even herbivorous animals swallow the placenta after the birth of the baby (for example, the cow). In the human system, we do not know about the proper utilization of the placenta and membranes although there are suggestions regarding this on the basis of research on placental umbilical cord blood stem cells as an alternative to bone marrow transplantation. In this present series of placental umbilical cord whole blood transfusions, we wanted to examine the safety aspect of other components of cord blood transfusion, e.g., fetal RBC, growth factors and cytokine filled plasma, etc., in different indications of blood transfusion, from the pediatric to the geriatric age group, in malignant and non-malignant disorders affecting our patients. One hundred and seventy-four units of umbilical cord whole blood were collected aseptically from the umbilical vein after caesarean section in standard pediatric blood transfusion bags, after the removal of the baby from the operative field and after confirming the stable condition of the mother. The volume of cord blood varied from 50 ml to 140 ml with a mean of 86 ml+/-16 ml. The cord blood was transfused immediately (within three days of collection) to 62 patients from nine years to 78 years of age, of whom 32 were suffering from varying stages and grades of malignancy from 1 April 1999 till date i.e., 11 Aug 2000, after obtaining adequate consent and following the precautions of standard blood transfusion protocol. The remaining 30 patients included patients suffering from thalassemia major, aplastic anemia, systemic lupus erythematosus, chronic renal failure, rheumatoid arthritis, ankylosing spondylitis and a geriatric group of patients with benign prostatic hypertrophy. All have tolerated the procedure without any immunological or non-immunological reactions. On the basis of our experience with 174 units of placental umbilical cord whole blood transfusion in malignant and non-malignant conditions (within

A new strategy for umbilical cord blood collection developed at the first Colombian public cord blood bank increases total nucleated cell content.

PubMed

Vanegas, Diana; Triviño, Lady; Galindo, Cristian; Franco, Leidy; Salguero, Gustavo; Camacho, Bernardo; Perdomo-Arciniegas, Ana-María

2017-09-01

The total nucleated cell dosage of umbilical cord blood (UCB) is an important factor in determining successful allogeneic hematopoietic stem cell transplantation after a minimum human leukocyte antigen donor-recipient match. The northern South American population is in need of a new-generation cord blood bank that cryopreserves only units with high total nucleated cell content, thereby increasing the likelihood of use. Colombia set up a public cord blood bank in 2014; and, as a result of its research for improving high total nucleated cell content, a new strategy for UCB collection was developed. Data from 2933 collected and 759 cryopreserved cord blood units between 2014 and 2015 were analyzed. The correlation of donor and collection variables with cellularity was evaluated. Moreover, blood volume, cell content, CD34+ count, clonogenic capacity, and microbial contamination were assessed comparing the new method, which combines in utero and ex utero techniques, with the conventional strategies. Multivariate analysis confirmed a correlation between neonatal birth weight and cell content. The new collection method increased total nucleated cell content in approximately 26% and did not alter pre-cryopreservation and post-thaw cell recovery, viability, or clonogenic ability. Furthermore, it showed a remarkably low microbial contamination rate (1.2%). The strategy for UCB collection developed at the first Colombian public cord blood bank increases total nucleated cell content and does not affect unit quality. The existence of this bank is a remarkable breakthrough for Latin-American patients in need of this kind of transplantation. © 2017 The Authors Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.

Establishing a public umbilical cord blood stem cell bank for South Africa: an enquiry into public acceptability.

PubMed

Meissner-Roloff, Madelein; Pepper, Michael S

2013-12-01

South Africa (SA) faces a large unmet need for bone marrow (BM) transplantation, which could be alleviated in part by establishing a public umbilical cord blood stem cell bank (UCB SCB). Umbilical cord blood is an increasingly utilised source of hematopoietic stem cells for BM transplantation in addition to BM or mobilized peripheral blood stem cells. Establishing a public UCB SCB would therefore be a positive step towards improving the quality of health care in SA by providing for an important unmet need. This study takes the form of an enquiry into the acceptability of establishing a public bank through an interview with and questionnaire completed by mothers-to-be in the antenatal clinic of a large public hospital in SA. Initial results are positive, with 85 % of the participants in favour of establishing a public UCB SCB in SA. This initial probe will serve as a model for a more comprehensive national enquiry into public support and acceptability in different clinics, hospitals and provinces in SA.

Umbilical cord blood donation: public or private?

PubMed

Ballen, K K; Verter, F; Kurtzberg, J

2015-10-01

Umbilical cord blood (UCB) is a graft source for patients with malignant or genetic diseases who can be cured by allogeneic hematopoietic cell transplantation (HCT), but who do not have an appropriately HLA-matched family or volunteer unrelated adult donor. Starting in the 1990s, unrelated UCB banks were established, accepting donations from term deliveries and storing UCB units for public use. An estimated 730 000 UCB units have been donated and stored to date and ~35 000 UCB transplants have been performed worldwide. Over the past 20 years, private and family banks have grown rapidly, storing ~4 million UCB units for a particular patient or family, usually charging an up-front and yearly storage fee; therefore, these banks are able to be financially sustainable without releasing UCB units. Private banks are not obligated to fulfill the same regulatory requirements of the public banks. The public banks have released ~30 times more UCB units for therapy. Some countries have transitioned to an integrated banking model, a hybrid of public and family banking. Today, pregnant women, their families, obstetrical providers and pediatricians are faced with multiple choices about the disposition of their newborn's cord blood. In this commentary, we review the progress of UCB banking technology; we also analyze the current data on pediatric and adult unrelated UCB, including the recent expansion of interest in transplantation for hemoglobinopathies, and discuss emerging studies on the use of autologous UCB for neurologic diseases and regenerative medicine. We will review worldwide approaches to UCB banking, ethical considerations, criteria for public and family banking, integrated banking ideas and future strategies for UCB banking.

Fetal demise by umbilical cord around abdomen and stricture.

PubMed

Tan, Shun-Jen; Chen, Chi-Huang; Wu, Gwo-Jang; Chen, Wei-Hwa; Chang, Cheng-Chang

2010-01-01

Umbilical cord abnormalities are accepted as conditions associated with intrauterine fetal demise (IUFD), and umbilical cord stricture is most frequently encountered. In addition, although cord entanglement with multiple loops rarely increases the perinatal mortality, it is associated with a significant increase in variable kind of morbidity such as growth restriction. We describe a 27-year-old woman, with a missed abortion history at about 10 weeks' gestation in her first pregnancy, who presented to our outpatient department at 34 4/7 weeks of gestation due to decreased fetal activity during the preceding week. No fetal heart activity and blood flow had been detected by ultrasonography and pulsed-wave Doppler. A demised fetus with umbilical cord stricture and three loops around abdomen was delivered and was weighted 1,830 g that was below the tenth percentile for the gestational age. Either umbilical cord stricture or entanglement around the body can affect the development of the fetus and even be lethal. The former might play a more important role in this case. Their etiology and the sequence of the events are still undetermined, and additional evaluation such as autopsy and further research may be needed. In addition, counsel and frequent fetal surveillance should be done in patients with previous IUFD attributed to cord stricture during next pregnancy because of undetermined risk of recurrence.

Prenatal Arsenic Exposure and DNA Methylation in Maternal and Umbilical Cord Blood Leukocytes

PubMed Central

Baccarelli, Andrea; Hoffman, Elaine; Tarantini, Letizia; Quamruzzaman, Quazi; Rahman, Mahmuder; Mahiuddin, Golam; Mostofa, Golam; Hsueh, Yu-Mei; Wright, Robert O.; Christiani, David C.

2012-01-01

Background: Arsenic is an epigenetic toxicant and could influence fetal developmental programming. Objectives: We evaluated the association between arsenic exposure and DNA methylation in maternal and umbilical cord leukocytes. Methods: Drinking-water and urine samples were collected when women were at ≤ 28 weeks gestation; the samples were analyzed for arsenic using inductively coupled plasma mass spectrometry. DNA methylation at CpG sites in p16 (n = 7) and p53 (n = 4), and in LINE-1 and Alu repetitive elements (3 CpG sites in each), was quantified using pyrosequencing in 113 pairs of maternal and umbilical blood samples. We used general linear models to evaluate the relationship between DNA methylation and tertiles of arsenic exposure. Results: Mean (± SD) drinking-water arsenic concentration was 14.8 ± 36.2 μg/L (range: < 1–230 μg/L). Methylation in LINE-1 increased by 1.36% [95% confidence interval (CI): 0.52, 2.21%] and 1.08% (95% CI: 0.07, 2.10%) in umbilical cord and maternal leukocytes, respectively, in association with the highest versus lowest tertile of total urinary arsenic per gram creatinine. Arsenic exposure was also associated with higher methylation of some of the tested CpG sites in the promoter region of p16 in umbilical cord and maternal leukocytes. No associations were observed for Alu or p53 methylation. Conclusions: Exposure to higher levels of arsenic was positively associated with DNA methylation in LINE-1 repeated elements, and to a lesser degree at CpG sites within the promoter region of the tumor suppressor gene p16. Associations were observed in both maternal and fetal leukocytes. Future research is needed to confirm these results and determine if these small increases in methylation are associated with any health effects. PMID:22466225

Correlation between maternal and umbilical cord blood in pregnant women of Pokhara Valley: a cross sectional study.

PubMed

Timilsina, Sameer; Karki, Sirisa; Gautam, Aajeevan; Bhusal, Pujan; Paudel, Gita; Sharma, Deepak

2018-03-21

Complete blood count is one of the routinely advised blood investigation during pregnancy. It is also utilized as a diagnostic tool for neonatal anemia, sepsis and determining hemostatic status of the newborn. The present study aims at estimating the complete blood count of maternal and umbilical cord blood at the time of delivery and to establish its correlation. This cross sectional study included 114 mothers and their healthy neonates born through normal vaginal delivery. Complete blood count of umbilical cord blood and maternal blood was estimated using automatic hematology analyzer. The mean maternal and neonatal hemoglobin concentration was 11.14 ± 1.39 g/dL and 16.34 ± 2.01 g/dL respectively. A significant positive correlation was found between maternal and fetal hemoglobin concentration (p < 0.001 and Pearson R = 0.496). The correlation between maternal and fetal WBC, RBC and Platelet count was not statistically significant. A significant positive correlation was found between maternal and fetal MCV and MCH while PCV showed a non-significant positive correlation. There was moderately positive correlation between maternal and fetal hemoglobin, MCV and MCH. The cord blood hemoglobin was lower in babies born to anemic mothers. The decrease in hemoglobin followed the severity of anemia, however, the correlation did not exist in anemic mothers. It suggested that fetal hematological parameters are not reflective of maternal hemogram.

Reasons for exclusion of 6820 umbilical cord blood donations in a public cord blood bank.

PubMed

Wang, Tso-Fu; Wen, Shu-Hui; Yang, Kuo-Liang; Yang, Shang-Hsien; Yang, Yun-Fan; Chang, Chu-Yu; Wu, Yi-Feng; Chen, Shu-Huey

2014-01-01

To provide information for umbilical cord blood (UCB) banks to adopt optimal collection strategies and to make UCB banks operate efficiently, we investigated the reasons for exclusion of UCB units in a 3-year recruitment period. We analyzed records of the reasons for exclusion of the potential UCB donation from 2004 to 2006 in the Tzu-Chi Cord Blood Bank and compared the results over 3 years. We grouped these reasons for exclusion into five phases, before collection, during delivery, before processing, during processing, and after freezing according to the time sequence and analyzed the reasons at each phase. Between 2004 and 2006, there were 10,685 deliveries with the intention of UCB donation. In total, 41.2% of the UCB units were considered eligible for transplantation. The exclusion rates were 93.1, 48.4, and 54.1% in 2004, 2005, and 2006, respectively. We excluded 612 donations from women before their child birth, 133 UCB units during delivery, 80 units before processing, 5010 units during processing, and 421 units after freezing. There were 24 UCB units with unknown reasons of ineligibility. Low UCB weight and low cell count were the first two leading causes of exclusion (48.6 and 30.9%). The prevalence of artificial errors, holiday or transportation problem, low weight, and infant problems decreased year after year. The exclusion rate was high at the beginning of our study as in previous studies. Understanding the reasons for UCB exclusion may help to improve the efficiency of UCB banking programs in the future. © 2013 American Association of Blood Banks.

Free testosterone levels in umbilical-cord blood predict infant head circumference in females.

PubMed

Whitehouse, Andrew J O; Maybery, Murray T; Hart, Roger; Sloboda, Deborah M; Stanley, Fiona J; Newnham, John P; Hickey, Martha

2010-03-01

Fetal androgens influence fetal growth as well as postnatal neurocognitive ability. However, to our knowledge, no published study has prospectively examined the impact of early-life androgens on infant brain growth. We report the association between circulating fetal androgen levels, measured from umbilical-cord blood at birth, and a proxy measure of brain growth: head circumference. Participants were 82 unselected female infants from a large representative birth cohort (mean gestational age 39.4 wks, SD 1.7). Umbilical-cord blood was obtained at birth and analysed for androgen concentrations (total testosterone, androstenedione, dehyrdroepiandrosterone, and its sulphated metabolite). Head circumference and two other measures of growth - weight (mean 3311.4 g, SD 461.3) and length - were measured within 3 days of birth and again at approximately 1 year of age (mean age 13.1 mo, SD 1.1). Multivariate linear regressions found an inverse association between levels of free testosterone and growth in head circumference (correlation=-.24), even when adjusting for sociodemographic/obstetric covariates and head size at birth. Growth in weight and length could not be predicted by free testosterone concentration. This is the first report of an association between prenatal androgen levels and postnatal growth in head circumference. These findings suggest that early-life androgens may impact brain development during infancy.

Umbilical Cord Blood-Derived Mononuclear Cells Exhibit Pericyte-Like Phenotype and Support Network Formation of Endothelial Progenitor Cells In Vitro

PubMed Central

Peters, Erica B.; Liu, Betty; Christoforou, Nicolas; West, Jennifer L.; Truskey, George A.

2015-01-01

Umbilical cord blood represents a promising cell source for pro-angiogenic therapies. The present study examined the potential of mononuclear cells (MNCs) from umbilical cord blood to support endothelial progenitor cell (EPC) microvessel formation. MNCs were isolated from the cord blood of 20 separate donors and selected for further characterization based upon their proliferation potential and morphological resemblance to human vascular pericytes (HVPs). MNCs were screened for their ability to support EPC network formation using an in vitro assay (Matrigel™) as well as a reductionist, coculture system consisting of no additional angiogenic cytokines beyond those present in serum. In less than 15% of the isolations, we identified a population of highly proliferative MNCs that phenotypically resembled HVPs as assessed by expression of PDGFR-β, NG2, α-SMA, and ephrin-B2. Within a Matrigel™ system, MNCs demonstrated pericyte-like function through colocalization to EPC networks and similar effects as HVPs upon total EPC tubule length (p = 0.95) and number of branch points (p = 0.93). In a reductionist coculture system, MNCs served as pro-angiogenic mural cells by supporting EPC network formation to a significantly greater extent than HVP cocultures, by day 14 of coculture, as evidenced through EPC total tubule length (p <0.0001) and number of branch points (p < 0.0001). Our findings are significant as we demonstrate mural cell progenitors can be isolated from umbilical cord blood and develop culture conditions to support their use in microvascular tissue engineering applications. PMID:25777295

Human umbilical cord blood-derived f-macrophages retain pluripotentiality after thrombopoietin expansion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao Yong; Mazzone, Theodore

2005-11-01

We have previously characterized a new type of stem cell from human peripheral blood, termed fibroblast-like macrophage (f-M{phi}). Here, using umbilical cord blood as a source, we identified cells with similar characteristics including expression of surface markers (CD14, CD34, CD45, CD117, and CD163), phagocytosis, and proliferative capacity. Further, thrombopoietin (TPO) significantly stimulated the proliferation of cord blood-derived f-M{phi} (CB f-M{phi}) at low dosage without inducing a megakaryocytic phenotype. Additional experiments demonstrated that TPO-expanded cord blood-derived f-M{phi} (TCB f-M{phi}) retained their surface markers and differentiation ability. Treatment with vascular endothelial cell growth factor (VEGF) gave rise to endothelial-like cells, expressing Flt-1,more » Flk-1, von Willebrand Factor (vWF), CD31, acetylated low density lipoprotein internalization, and the ability to form endothelial-like cell chains. In the presence of lipopolyssacharide (LPS) and 25 mM glucose, the TCB f-M{phi} differentiated to express insulin mRNA, C-peptide, and insulin. In vitro functional analysis demonstrated that these insulin-positive cells could release insulin in response to glucose and other secretagogues. These findings demonstrate a potential use of CB f-M{phi} and may lead to develop new therapeutic strategy for treating dominant disease.« less

Engraftment kinetics and graft failure after single umbilical cord blood transplantation using a myeloablative conditioning regimen.

PubMed

Ruggeri, Annalisa; Labopin, Myriam; Sormani, Maria Pia; Sanz, Guillermo; Sanz, Jaime; Volt, Fernanda; Michel, Gerard; Locatelli, Franco; Diaz De Heredia, Cristina; O'Brien, Tracey; Arcese, William; Iori, Anna Paola; Querol, Sergi; Kogler, Gesine; Lecchi, Lucilla; Pouthier, Fabienne; Garnier, Federico; Navarrete, Cristina; Baudoux, Etienne; Fernandes, Juliana; Kenzey, Chantal; Eapen, Mary; Gluckman, Eliane; Rocha, Vanderson; Saccardi, Riccardo

2014-09-01

Umbilical cord blood transplant recipients are exposed to an increased risk of graft failure, a complication leading to a higher rate of transplant-related mortality. The decision and timing to offer a second transplant after graft failure is challenging. With the aim of addressing this issue, we analyzed engraftment kinetics and outcomes of 1268 patients (73% children) with acute leukemia (64% acute lymphoblastic leukemia, 36% acute myeloid leukemia) in remission who underwent single-unit umbilical cord blood transplantation after a myeloablative conditioning regimen. The median follow-up was 31 months. The overall survival rate at 3 years was 47%; the 100-day cumulative incidence of transplant-related mortality was 16%. Longer time to engraftment was associated with increased transplant-related mortality and shorter overall survival. The cumulative incidence of neutrophil engraftment at day 60 was 86%, while the median time to achieve engraftment was 24 days. Probability density analysis showed that the likelihood of engraftment after umbilical cord blood transplantation increased after day 10, peaked on day 21 and slowly decreased to 21% by day 31. Beyond day 31, the probability of engraftment dropped rapidly, and the residual probability of engrafting after day 42 was 5%. Graft failure was reported in 166 patients, and 66 of them received a second graft (allogeneic, n=45). Rescue actions, such as the search for another graft, should be considered starting after day 21. A diagnosis of graft failure can be established in patients who have not achieved neutrophil recovery by day 42. Moreover, subsequent transplants should not be postponed after day 42. Copyright© Ferrata Storti Foundation.

Transplantation of Ex Vivo Expanded Umbilical Cord Blood (NiCord) Decreases Early Infection and Hospitalization.

PubMed

Anand, Sarah; Thomas, Samantha; Hyslop, Terry; Adcock, Janet; Corbet, Kelly; Gasparetto, Cristina; Lopez, Richard; Long, Gwynn D; Morris, Ashley K; Rizzieri, David A; Sullivan, Keith M; Sung, Anthony D; Sarantopoulos, Stefanie; Chao, Nelson J; Horwitz, Mitchell E

2017-07-01

Delayed hematopoietic recovery contributes to increased infection risk following umbilical cord blood (UCB) transplantation. In a Phase 1 study, adult recipients of UCB stem cells cultured ex vivo for 3 weeks with nicotinamide (NiCord) had earlier median neutrophil recovery compared with historical controls. To evaluate the impact of faster neutrophil recovery on clinically relevant early outcomes, we reviewed infection episodes and hospitalization during the first 100 days in an enlarged cohort of 18 NiCord recipients compared with 86 standard UCB recipients at our institution. The median time to neutrophil engraftment was shorter in NiCord recipients compared with standard UCB recipients (12.5 days versus 26 days; P < .001). Compared with standard UCB recipients, NiCord recipients had a significantly reduced risk for total infection (RR, 0.69; P = .01), grade 2-3 (moderate to severe) infection (RR, 0.36; P < .001), bacterial infection (RR, 0.39; P = .003), and grade 2-3 bacterial infection (RR, 0.21; P = .003) by Poisson regression analysis; this effect persisted after adjustment for age, disease stage, and grade II-IV acute GVHD. NiCord recipients also had significantly more time out of the hospital in the first 100 days post-transplantation after adjustment for age and Karnofsky Performance Status (69.9 days versus 49.7 days; P = .005). Overall, transplantation of NiCord was associated with faster neutrophil engraftment, fewer total and bacterial infections, and shorter hospitalization in the first 100 days compared with standard UCB transplantation. In conclusion, rapid hematopoietic recovery from an ex vivo expanded UCB transplantation approach is associated with early clinical benefit. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Cord blood clinical processing, cryopreservation, and storage.

PubMed

Elmoazzen, Heidi; Holovati, Jelena L

2015-01-01

Allogeneic umbilical cord blood (UCB) hematopoietic stem cell transplantation has become a crucial advancement in the treatment for a variety of diseases including hematopoietic and non-hematopoietic malignancies, BM failure syndromes, hemoglobinopathies, and metabolic and immunodeficiency disorders. It has been well documented that the success of UCB engraftment is tied to UCB banking processes, and now there are established guidelines for standardization of collection, banking, processing, and cryopreservation for unrelated UCB units with purpose of achieving consistent production of high quality placental and UCB units for administration. In 2011, Canada's Ministry of Health has announced Canada's first national, publicly funded umbilical cord blood bank, which aims to provide altruistic donations for unrelated allogeneic hematopoietic stem cell transplant. In this chapter, we describe specific protocols for clinical processing, cryopreservation, and storage of UCB used by the Canadian Blood Services National Public Umbilical Cord Blood Bank.

Association between ambient air pollution and proliferation of umbilical cord blood cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Novack, L., E-mail: novack@bgu.ac.il

It has been established as a common knowledge that ambient air pollution (AAP) has an adverse effect on human health. The pathophysiological mechanism of this impact is likely to be related to the oxidative stress. In the current study we estimate the association between AAP and cell proliferation (CP) of umbilical cord blood cells, representing maternal organism most proximal to the fetal body. Blood samples were tested for proliferation in 292 enrolled Arab-Bedouin women at delivery (July 2012–March 2013). The estimates of AAP were defined by a hybrid satellite based model predicting both PM{sub 2.5} (particles<2.5 µm in diameter) andmore » PM{sub 10} (particles<10 µm in diameter) as well as monitoring stations for gaseous air pollutants. Risk estimates of pollution exposure were adjusted to medical history, household risk factors and meteorological factors on the day of delivery or one week prior. Ambient ozone (O{sub 3}) levels on 1, 2, 3and 4 days prior to delivery were associated with lower CP (Prevalence ratio (PR)=0.92, 0.92, 0.93, 0.93, respectively). Increase in inter-quartile range (IOR) of PM{sub 2.5} one day before delivery was associated with 9% increase in CP levels (PR=1.09). The positive direction in association was changed to negative association with CP for PM{sub 2.5} levels measured at more distant time periods (PR=0.90 and 0.93 for lags 5 and 6 days, respectively). Investigation of PM{sub 10} levels indicated a similar pattern (PR=1.05 for pollution values recorded one day before delivery and 0.93 and 0.95 for lags of 5 and 6 days, respectively). Carbon monoxide (CO) levels were associated with lower CP on the day of delivery and 1 day prior (PR=0.92 and PR=0.94). To conclude, the levels of cell proliferation of umbilical cord blood cells appear to be associated with the AAP. More studies are needed to support our findings. - Highlights: • Ambient air pollutants were suggested to have an impact on cell proliferation (CP) of umbilical

Umbilical Cord Blood-Derived Mononuclear Cells Exhibit Pericyte-Like Phenotype and Support Network Formation of Endothelial Progenitor Cells In Vitro.

PubMed

Peters, Erica B; Liu, Betty; Christoforou, Nicolas; West, Jennifer L; Truskey, George A

2015-10-01

Umbilical cord blood represents a promising cell source for pro-angiogenic therapies. The present study examined the potential of mononuclear cells (MNCs) from umbilical cord blood to support endothelial progenitor cell (EPC) microvessel formation. MNCs were isolated from the cord blood of 20 separate donors and selected for further characterization based upon their proliferation potential and morphological resemblance to human vascular pericytes (HVPs). MNCs were screened for their ability to support EPC network formation using an in vitro assay (Matrigel™) as well as a reductionist, coculture system consisting of no additional angiogenic cytokines beyond those present in serum. In less than 15% of the isolations, we identified a population of highly proliferative MNCs that phenotypically resembled HVPs as assessed by expression of PDGFR-β, NG2, α-SMA, and ephrin-B2. Within a Matrigel™ system, MNCs demonstrated pericyte-like function through colocalization to EPC networks and similar effects as HVPs upon total EPC tubule length (p = 0.95) and number of branch points (p = 0.93). In a reductionist coculture system, MNCs served as pro-angiogenic mural cells by supporting EPC network formation to a significantly greater extent than HVP cocultures, by day 14 of coculture, as evidenced through EPC total tubule length (p < 0.0001) and number of branch points (p < 0.0001). Our findings are significant as we demonstrate mural cell progenitors can be isolated from umbilical cord blood and develop culture conditions to support their use in microvascular tissue engineering applications.

The acceptability to women in Mombasa, Kenya, of the donation and transfusion of umbilical cord blood for severe anaemia in young children

PubMed Central

Hassall, O; Ngina, L; Kongo, W; Othigo, J; Mandaliya, K; Maitland, K; Bates, I

2008-01-01

Background and Objectives Severe anaemia, for which a blood transfusion can be life saving, is common in hospitalized children in sub-Saharan Africa but blood for transfusion is often in short supply. Umbilical cord blood is usually thrown away but could be a useful source of red cells for small volume transfusions in young children in this setting. The objective of this study was to evaluate the attitudes of women using the maternity services of the provincial hospital in Mombasa, Kenya, towards cord blood donation and transfusion, and essential aspects of this process including informed consent and the acceptability of screening for human immunodeficiency virus (HIV) infection. Materials and Methods A structured questionnaire was developed based on data provided by focus group discussions with women attending the hospital's maternity unit and administered to women who had recently delivered at the hospital. Results Of the 180 women who completed a questionnaire, the donation and transfusion of cord blood were acceptable to 81% and 78%, respectively. Ninety per cent of women who supported cord blood donation were willing to undergo further HIV testing at the time of delivery. Seventy-seven per cent of women wanted informed consent to be sought for cord blood donation and 66% of these felt they could make this decision alone. Conclusion The donation of umbilical cord blood and its transfusion are acceptable to the majority of women delivering at Coast Provincial General Hospital, Mombasa. Findings from the study will benefit the planned cord blood donation programme at this facility. PMID:18067489

Study on the relationship between the expression of IGF-1 in umbilical cord blood and abnormal glucose metabolism during pregnancy.

PubMed

Liu, K; Wu, H-Y; Xu, Y-H

2017-02-01

To explore the relationship between the expression of insulin-like growth factor-1 (IGF-1) in neonatal umbilical cord blood and abnormal glucose metabolism during pregnancy. We have selected 63 cases of delivery randomly, term birth and maternal from January 2015 to January 2016 in our hospital, gestational diabetes mellitus for Group A, abnormal gestational glucose tolerance for Group B and normal for Group C with 21 cases in each group. The venous blood samples were collected from all the pregnant females 2 weeks before delivery, and the levels of HbA1c in serum were detected by Elisa method. During the delivery, the umbilical cord blood was collected and the levels of IGF-1 were measured by double site immune enzyme analysis. The neonatal weight was recorded and the correlation analysis was made in respect of the measurement results. The level of HbA1c in Group A was significantly higher than that in Group C (p < 0.05); IGF-1 level and neonatal weight of Group B were significantly higher than that of Group C (p < 0.05), IGF-1 has a significant correlation with neonatal weight in Group C, and HbA1c and IGF-1 were positively correlated (p < 0.05); IGF-1 was positively correlated with neonatal weight in Group A and Group B (p < 0.05). There was a significant positive correlation between the IGF-1 level of neonatal umbilical cord blood and the neonatal weight (p < 0.05). Also, the level of HbA1c was positively correlated with the level of IGF-1 in neonatal umbilical cord blood at the end of pregnancy (p < 0.05). The expression level of IGF-1 in the final stage of pregnant females can be detected to predict the expression level of IGF-1 in newborn infants and then the growth status of the fetus can be obtained.

Gross umbilical cord complications are associated with placental lesions of circulatory stasis and fetal hypoxia.

PubMed

Chan, Joanna S Y; Baergen, Rebecca N

2012-01-01

Umbilical cord complications (UCC), such as true knots (TK), velamentous (VEL) insertion, marginal umbilical cord (MUC) insertion, umbilical cord entanglement (UCE) (both nuchal and non-nuchal), excessively long umbilical cord (ELUC), and excessively twisted umbilical cord (ETUC), can lead to decreased UC blood flow and have been associated with adverse fetal outcome and intrauterine fetal demise (IUFD). Few large series exist that correlate UCC with specific pathologic findings of the placenta. We present the largest series of UCC at this time. Eight hundred forty-one 3rd-trimester placentas with UCC were identified, as well as 858 randomly selected gestational age-matched placentas with grossly unremarkable UC. Lesions associated with circulatory stasis and thrombosis, including villous capillary congestion (VC), umbilical vessel distension (UVD), chorionic plate vessel distension (CPD), umbilical vessel thrombosis (UVT), fetal vascular thrombosis (FVT), intimal fibrin cushions (IFC), and avascular villi (AV), were noted, as well as other pathologic lesions. Data were analyzed by analysis of variance and Fisher exact tests, with P < 0.05 statistically significant. Umbilical cord complications as a group was associated with a significant increase in placental circulatory stasis lesions. Lesions associated with hypoxia, namely nucleated red blood cells and chorangiosis, were also increased. Finally, the presence of any UCC was significantly associated with IUFD. We also found that multiple UCC are associated with nonreassuring fetal heart rate and chorangiosis but that the presence of a single UCC was not. This indicates that UCC may lead to intrauterine hypoxia and subsequent adverse fetal outcome and that multiple UCC may be cumulative in effect.

Transplantation of canine umbilical cord blood-derived mesenchymal stem cells in experimentally induced spinal cord injured dogs.

PubMed

Lim, Ji Hey; Byeon, Ye Eun; Ryu, Hak Hyun; Jeong, Yun Hyeok; Lee, Young Won; Kim, Wan Hee; Kang, Kyung Sun; Kweon, Oh Kyeong

2007-09-01

This study was to determine the effects of allogenic umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) and recombinant methionyl human granulocyte colony-stimulating factor (rmhGCSF) on a canine spinal cord injury model after balloon compression at the first lumbar vertebra. Twenty-five adult mongrel dogs were assigned to five groups according to treatment after a spinal cord injury: no treatment (CN); saline treatment (CP); rmhGCSF treatment (G); UCB-MSCs treatment (UCB-MSC); co-treatment (UCBG). The UCBMSCs isolated from cord blood of canine fetuses were prepared as 10(6) cells/150 microl saline. The UCB-MSCs were directly injected into the injured site of the spinal cord and rmhGCSF was administered subcutaneously 1 week after the induction of spinal cord injury. The Olby score, magnetic resonance imaging, somatosensory evoked potentials and histopathological examinations were used to evaluate the functional recovery after transplantation. The Olby scores of all groups were zero at the 0-week evaluation. At 2 week after the transplantation, the Olby scores in the groups with the UCB-MSC and UCBG were significantly higher than in the CN and CP groups. However, there were no significant differences between the UCB-MSC and UCBG groups, and between the CN and CP groups. These comparisons remained stable at 4 and 8 week after transplantation. There was significant improvement in the nerve conduction velocity based on the somatosensory evoked potentials. In addition, a distinct structural consistency of the nerve cell bodies was noted in the lesion of the spinal cord of the UCB-MSC and UCBG groups. These results suggest that transplantation of the UCB-MSCs resulted in recovery of nerve function in dogs with a spinal cord injury and may be considered as a therapeutic modality for spinal cord injury.

Transplantation of canine umbilical cord blood-derived mesenchymal stem cells in experimentally induced spinal cord injured dogs

PubMed Central

Lim, Ji-Hey; Byeon, Ye-Eun; Ryu, Hak-Hyun; Jeong, Yun-Hyeok; Lee, Young-Won; Kim, Wan Hee

2007-01-01

This study was to determine the effects of allogenic umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) and recombinant methionyl human granulocyte colony-stimulating factor (rmhGCSF) on a canine spinal cord injury model after balloon compression at the first lumbar vertebra. Twenty-five adult mongrel dogs were assigned to five groups according to treatment after a spinal cord injury: no treatment (CN); saline treatment (CP); rmhGCSF treatment (G); UCB-MSCs treatment (UCB-MSC); co-treatment (UCBG). The UCB-MSCs isolated from cord blood of canine fetuses were prepared as 106 cells/150 µl saline. The UCB-MSCs were directly injected into the injured site of the spinal cord and rmhGCSF was administered subcutaneously 1 week after the induction of spinal cord injury. The Olby score, magnetic resonance imaging, somatosensory evoked potentials and histopathological examinations were used to evaluate the functional recovery after transplantation. The Olby scores of all groups were zero at the 0-week evaluation. At 2 week after the transplantation, the Olby scores in the groups with the UCB-MSC and UCBG were significantly higher than in the CN and CP groups. However, there were no significant differences between the UCB-MSC and UCBG groups, and between the CN and CP groups. These comparisons remained stable at 4 and 8 week after transplantation. There was significant improvement in the nerve conduction velocity based on the somatosensory evoked potentials. In addition, a distinct structural consistency of the nerve cell bodies was noted in the lesion of the spinal cord of the UCB-MSC and UCBG groups. These results suggest that transplantation of the UCB-MSCs resulted in recovery of nerve function in dogs with a spinal cord injury and may be considered as a therapeutic modality for spinal cord injury. PMID:17679775

Evaluation of the impact of banking umbilical cord blood units with high cell dose for ethnically diverse patients.

PubMed

Stritesky, Gretta; Wadsworth, Kimberly; Duffy, Merry; Buck, Kelly; Dehn, Jason

2018-02-01

Umbilical cord blood units provide an important stem cell source for transplantation, particularly for patients of ethnic diversity who may not have suitably matched available, adult-unrelated donors. However, with the cost of cord blood unit acquisition from public banks significantly higher than that for adult-unrelated donors, attention is focused on decreasing cost yet still providing cord blood units to patients in need. Historical practices of banking units with low total nucleated cell counts, including units with approximately 90 × 10 7 total nucleated cells, indicates that most banked cord blood units have much lower total nucleated cell counts than are required for transplant. The objective of this study was to determine the impact on the ability to identify suitable cord blood units for transplantation if the minimum total nucleated cell count for banking were increased from 90 × 10 7 to 124 or 149 × 10 7 . We analyzed ethnically diverse patients (median age, 3 years) who underwent transplantation of a single cord blood unit in 2005 to 2016. A cord blood unit search was evaluated to identify units with equal or greater human leukocyte antigen matching and a greater total nucleated cell count than that of the transplanted cord blood unit (the replacement cord blood unit). If the minimum total nucleated cell count for banking increased to 124 or 149 × 10 7 , then from 75 to 80% of patients would still have at least 1 replacement cord blood unit in the current (2016) cord blood unit inventory. The best replacement cord blood units were often found among cords with the same ethnic background as the patient. The current data suggest that, if the minimum total nucleated cell count were increased for banking, then it would likely lead to an inventory of more desirable cord blood units while having minimal impact on the identification of suitable cord blood units for transplantation. © 2017 AABB.

Ethical considerations in umbilical cord blood banking.

PubMed

Fox, Nathan S; Chervenak, Frank A; McCullough, Laurence B

2008-01-01

Pregnant patients have the option at delivery of having their cord blood collected and stored for future use. At many hospitals, they have the option of donating their cord blood to the public banking system for future use by anyone who is an appropriate match (public banking). Patients also have the option of having their cord blood stored for a fee with a commercial/private company for future use within their family (private banking). Currently, private banking is not recommended by major obstetric and pediatric professional organizations. We applied current evidence of the risks and benefits of private and public cord blood banking and accepted ethical principles to answer the following two related questions: 1) Do obstetricians have an ethical obligation to comply with a request for private banking? and 2) Do obstetricians have an ethical obligation to routinely offer private banking to women who do not request it? The only situation where there is a known benefit to private banking is when public banking is not available and the patient currently has an affected family member who may benefit from cord blood therapy. We conclude that when presented with a request for private banking, obstetricians have an ethical obligation to explain the lack of proven benefit of this procedure. If the patient still requests private banking, it would be appropriate to comply, because there is minimal or no risk to the procedure. However, obstetricians are not ethically obligated to offer private banking, even when public banking is not available, except in the limited circumstance when the patient currently has an affected family member who may benefit from cord blood therapy.

Associations of Maternal Prenatal Smoking with Umbilical Cord Blood Hormones: The Project Viva Cohort

PubMed Central

Fleisch, Abby F.; Rifas-Shiman, Sheryl L.; Rokoff, Lisa B.; Hivert, Marie-France; Mantzoros, Christos S.; Oken, Emily

2017-01-01

Background Maternal smoking during pregnancy is associated with low fetal growth and adverse cardiometabolic health in offspring. However, hormonal pathways underlying these associations are unclear. Therefore, we examined maternal smoking habits and umbilical cord blood hormone profiles in a large, prospective cohort. Methods We studied 978 mother/infant pairs in Project Viva, a Boston-area cohort recruited 1999–2002. We categorized mothers as early pregnancy smokers, former smokers, or never smokers. Outcomes were cord blood concentrations of IGF-1, IGF-2, IGFBP-3, leptin, adiponectin, insulin, and C-peptide. We used linear regression models adjusted for maternal pre-pregnancy body mass index (BMI), race/ethnicity, parity, education, and infant sex. We conducted analyses in the full cohort and stratified by infant sex. Results Thirteen percent of women were early pregnancy smokers, 20% former smokers, and 68% never smokers. Infants of early pregnancy smokers had lower IGF-1 adjusted for IGFBP-3 [−5.2 ng/mL (95% CI: −8.6, −1.7)], with more pronounced associations in girls [−10.7 ng/mL (95% CI: −18.5, −2.9) vs. −4.0 ng/mL (95% CI: −8.4, 0.4) for boys]. Early pregnancy smoking was not associated with cord blood hormones other than IGF-1. Infants of former smokers had a cord blood hormone profile similar to infants of never smokers. Conclusions As compared to mothers who never smoked, early pregnancy smokers had infants with lower cord blood IGF-1 which could prime adverse metabolic outcomes. This provides further reason to support smoking cessation programs in women of reproductive age. PMID:28641780

Associations of maternal prenatal smoking with umbilical cord blood hormones: the Project Viva cohort.

PubMed

Fleisch, Abby F; Rifas-Shiman, Sheryl L; Rokoff, Lisa B; Hivert, Marie-France; Mantzoros, Christos S; Oken, Emily

2017-07-01

Maternal smoking during pregnancy is associated with low fetal growth and adverse cardiometabolic health in offspring. However, hormonal pathways underlying these associations are unclear. Therefore, we examined maternal smoking habits and umbilical cord blood hormone profiles in a large, prospective cohort. We studied 978 mother/infant pairs in Project Viva, a Boston-area cohort recruited 1999-2002. We categorized mothers as early pregnancy smokers, former smokers, or never smokers. Outcomes were cord blood concentrations of IGF-1, IGF-2, IGFBP-3, leptin, adiponectin, insulin, and C-peptide. We used linear regression models adjusted for maternal pre-pregnancy body mass index (BMI), race/ethnicity, parity, education, and infant sex. We conducted analyses in the full cohort and stratified by infant sex. Thirteen percent of women were early pregnancy smokers, 20% former smokers, and 68% never smokers. Infants of early pregnancy smokers had lower IGF-1 adjusted for IGFBP-3 [-5.2ng/mL (95% CI: -8.6, -1.7)], with more pronounced associations in girls [-10.7ng/mL (95% CI: -18.5, -2.9) vs. -4.0ng/mL (95% CI: -8.4, 0.4) for boys]. Early pregnancy smoking was not associated with cord blood hormones other than IGF-1. Infants of former smokers had a cord blood hormone profile similar to infants of never smokers. As compared to mothers who never smoked, early pregnancy smokers had infants with lower cord blood IGF-1 which could prime adverse metabolic outcomes. This provides further reason to support smoking cessation programs in women of reproductive age. Copyright © 2017 Elsevier Inc. All rights reserved.

Experimental studies on the tensile properties of human umbilical cords.

PubMed

Tantius, Britta; Rothschild, Markus A; Valter, Markus; Michael, Joern; Banaschak, Sibylle

2014-03-01

When tried in court, mothers accused of neonaticide may claim that the umbilical cord just broke during birth and the newborn child bled to death accordingly. To evaluate the possibility of a breakage of the umbilical cord is the goal of this work. Therefore 25 umbilical cords from neonates of both sexes born at term were stretched using an electrically operated material testing machine and the energy necessary to break them was measured. This experimental set-up equals a static strain, not a dynamic one. The maximum force endured (F max) ranged from 37.24 N to 150.04 N. The average force endured was 79.87 N with a standard deviation of 27.39. The elongation at break varied from 13.24% to a maximum of 119.93%. We found no relationship between the force endured and any of the following parameters: birth weight, pH of the venous umbilical blood, diameter of cord, free length under testing, duration of pregnancy or the mother's age. We performed a literature research and tried to define the circumstances in which a break is more likely to occur, these being malformations, entanglement or disease, e.g. inflammation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Global Methylation in the Placenta and Umbilical Cord Blood From Pregnancies With Maternal Gestational Diabetes, Preeclampsia, and Obesity

PubMed Central

Lambertini, Luca; Rialdi, Alexander; Lee, MenJean; Mystal, Elana Ying; Grabie, Mordy; Manaster, Isaac; Huynh, Nancy; Finik, Jackie; Davey, Mia; Davey, Kei; Ly, Jenny; Stone, Joanne; Loudon, Holly; Eglinton, Gary; Hurd, Yasmin; Newcorn, Jeffrey H.; Chen, Jia

2014-01-01

Emerging evidence indicates that maternal medical risk during pregnancy, such as gestational diabetes mellitus (GDM), preeclampsia, and obesity, predisposes the offspring to suboptimal development. However, the underlying biological/epigenetic mechanism in utero is still unknown. The current pilot study (N = 50) compared the levels of global methylation in the placenta and umbilical cord blood among women with and without each risk condition (GDM, preeclampsia, and obesity) and explored whether the levels of global methylation were associated with fetal/infant growth. Results show that global methylation levels in the placenta were lower in patients with gestational diabetes (P = .003) and preeclampsia (P = .05) but higher with obesity (P = .01). Suggestive negative associations were found between global methylation level in the placenta and infant body length and head circumference. While preliminary, it is possible that the placenta tissue, but not umbilical cord blood, may be epigenetically programmed by maternal GDM, preeclampsia, and obesity to carry out its own specific functions that influence fetal growth. PMID:23765376

Umbilical cord blood expansion with nicotinamide provides long-term multilineage engraftment.

PubMed

Horwitz, Mitchell E; Chao, Nelson J; Rizzieri, David A; Long, Gwynn D; Sullivan, Keith M; Gasparetto, Cristina; Chute, John P; Morris, Ashley; McDonald, Carolyn; Waters-Pick, Barbara; Stiff, Patrick; Wease, Steven; Peled, Amnon; Snyder, David; Cohen, Einat Galamidi; Shoham, Hadas; Landau, Efrat; Friend, Etty; Peleg, Iddo; Aschengrau, Dorit; Yackoubov, Dima; Kurtzberg, Joanne; Peled, Tony

2014-07-01

Delayed hematopoietic recovery is a major drawback of umbilical cord blood (UCB) transplantation. Transplantation of ex vivo-expanded UCB shortens time to hematopoietic recovery, but long-term, robust engraftment by the expanded unit has yet to be demonstrated. We tested the hypothesis that a UCB-derived cell product consisting of stem cells expanded for 21 days in the presence of nicotinamide and a noncultured T cell fraction (NiCord) can accelerate hematopoietic recovery and provide long-term engraftment. In a phase I trial, 11 adults with hematologic malignancies received myeloablative bone marrow conditioning followed by transplantation with NiCord and a second unmanipulated UCB unit. Safety, hematopoietic recovery, and donor engraftment were assessed and compared with historical controls. No adverse events were attributable to the infusion of NiCord. Complete or partial neutrophil and T cell engraftment derived from NiCord was observed in 8 patients, and NiCord engraftment remained stable in all patients, with a median follow-up of 21 months. Two patients achieved long-term engraftment with the unmanipulated unit. Patients transplanted with NiCord achieved earlier median neutrophil recovery (13 vs. 25 days, P < 0.001) compared with that seen in historical controls. The 1-year overall and progression-free survival rates were 82% and 73%, respectively. UCB-derived hematopoietic stem and progenitor cells expanded in the presence of nicotinamide and transplanted with a T cell-containing fraction contain both short-term and long-term repopulating cells. The results justify further study of NiCord transplantation as a single UCB graft. If long-term safety is confirmed, NiCord has the potential to broaden accessibility and reduce the toxicity of UCB transplantation. Clinicaltrials.gov NCT01221857. Gamida Cell Ltd.

[Transformation of attached cells derived from fetal umbilical cord blood induced by conditional medium of hepatoma cells].

PubMed

Zhang, Xiao-Dong; Cai, Na; Wang, Hong-Hui; Guo, Shi-Yi; Ye, Li-Hong

2006-01-01

Stem cells derived from fetal umbilical cord blood are of undifferentiated at early stage. They are sensitive to stimulations from the environment, and may be transformed under the effects of carcinogenic factors. This study was to explore the sensitivity of stem cells derived from fetal umbilical cord blood to carcinogenic factors. Mononuclear cells were isolated from fetal umbilical cord blood, and the attached cells were cultured in the medium containing 10% conditional medium of HepG2 hepatoma cells. A new cell line was gained, termed H-UCB. The biological features of H-UCB cells were detected by electron microscopy, karyotype analysis, cell cytometry, Western blot, and colony formation assay. H-UCB cells proliferated faster after passage 3. The cells were fibroblast-like and hepatocyte-like, with the ratio of nucleus to cytoplasm increased. Under electron microscope, many microvilli on the surface and numbers of vacuoles in the cytoplasm of the cells were observed, the nuclei were large and irregular, endocytosis phenomena were noticed. Karyotype analysis indicated that the cells were heteroploid, and the number of chromosomes was between 50 and 70. Flow cytometry data indicated that the proliferation period was 22.9 h, and the karyotype was between diploid and tetraploid. Western blot showed that c-Myc protein and proliferating cell nuclear antigen (PCNA) were overexpressed in H-UCB cells. According to flow cytometry, the positive rates of surface markers of H-UCB cells were 79.0% for CD105, 1.2% for CD34, and 12.2% for CD106; those of control HepG2 cells were 15.0% for CO105, 9.8% for CD34, and 1.4% for CD106. The colony formation rate of H-UCB cells in soft agar was (13.2+/-2.6)%. H-UCB cells are derived from endothelial cells, and are transformed as malignant cells with tumor cell characteristics.

Amnioinfusion for umbilical cord compression in labour.

PubMed

Hofmeyr, G J

2000-01-01

Amnioinfusion aims to prevent or relieve umbilical cord compression during labour by infusing a solution into the uterine cavity. The objective of this review was to assess the effects of amnioinfusion on maternal and perinatal outcome for potential or suspected umbilical cord compression or potential amnionitis. The Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register were searched. Randomised trials of amnioinfusion compared with no amnioinfusion in women with babies at risk of umbilical cord compression; and women at risk of intrauterine infection. Eligibility and trial quality were assessed by the reviewer. Twelve studies were included. Transcervical amnioinfusion for potential or suspected umbilical cord compression was associated with the following reductions: fetal heart rate decelerations (relative risk 0.54, 95% confidence interval 0.43 to 0.68); caesarean section for suspected fetal distress (relative risk 0.35, 95% confidence interval 0.24 to 0.52); neonatal hospital stay greater than 3 days (relative risk 0.40, 95% confidence interval 0. 26 to 0.62); maternal hospital stay greater than 3 days (relative risk 0.46, 95% 0.29 to 0.74). Transabdominal amnioinfusion showed similar results. Transcervical amnioinfusion to prevent infection in women with membranes ruptured for more than 6 hours was associated with a reduction in puerperal infection (relative risk 0.50, 95% confidence interval 0.26 to 0.97). Amnioinfusion appears to reduce the occurrence of variable heart rate decelerations and lower the use of caesarean section. However the studies were done in settings where fetal distress was not confirmed by fetal blood sampling. The results may therefore only be relevant where caesarean sections are commonly done for abnormal fetal heart rate alone. The trials reviewed are too small to address the possibility of rare but serious maternal adverse effects of amnioinfusion.

Umbilical cord CD71+ erythroid cells are reduced in neonates born to women in spontaneous preterm labor.

PubMed

Gomez-Lopez, Nardhy; Romero, Roberto; Xu, Yi; Miller, Derek; Unkel, Ronald; C MacKenzie, Tippi; Frascoli, Michela; Hassan, Sonia S

2016-10-01

Preterm neonates are highly susceptible to infection. Neonatal host defense against infection seems to be maintained by the temporal presence of immunosuppressive CD71+ erythroid cells. The aim of this study was to investigate whether umbilical cord CD71+ erythroid cells are reduced in neonates born to women who undergo spontaneous preterm labor/birth. Umbilical cord blood samples (n=155) were collected from neonates born to women who delivered preterm with (n=39) and without (n=12) spontaneous labor or at term with (n=82) and without (n=22) spontaneous labor. Time-matched maternal peripheral blood samples were also included (n=111). Mononuclear cells were isolated from these samples, and CD71+ erythroid cells were identified and quantified as CD3-CD235a+CD71+ cells by flow cytometry. (i) The proportion of CD71+ erythroid cells was 50-fold higher in cord blood than in maternal blood; (ii) a reduced number and frequency of umbilical cord CD71+ erythroid cells were found in neonates born to women who underwent spontaneous preterm labor compared to those born to women who delivered preterm without labor; (iii) umbilical cord CD71+ erythroid cells were fewer in neonates born to term pregnancies, regardless of the process of labor, than in those born to women who delivered preterm without labor; and (iv) no differences were seen in umbilical cord CD71+ erythroid cells between neonates born to women who underwent spontaneous preterm labor and those born to women who delivered at term with labor. Umbilical cord CD71+ erythroid cells are reduced in neonates born to women who had undergone spontaneous preterm labor. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

[Predictive value of interleukin 6 from the umbilical cord blood in early neonatal infection].

PubMed

Cosićkić, Almira; Skokić, Fahrija

2009-01-01

We have analyzed diagnostic value of interleukin 6 (IL-6) from the umbilical cord blood in recognition of early neonatal infection (ENI) of newborns whose mothers have obstetrical risks. The study included 120 newborns with birth weight <2500 gr., gestational age from 37 to 42 weeks, which mothers had some of the obstetrical risks. We established three groups: group A (newborns with microbiological proof of ENI), group B (clinical signs and hematological parameters of ENI) and group C (newborns without ENI). Median of IL-6 value in group A was 48.5 pg/ml with sensitivity, specificity and diagnostic value in recognition of ENI 78%, 81% and 80%. In group B median of IL-6 was 49 pg/ml with sensitivity, specificity and diagnostic value 65%, 80% and 77%. In group C median of IL-6 was 9.7 pg/ml. We noticed significant connection between value of IL-6 and mother's urinary tract infection; group A (p=0.023), group B (p = 0.007). Also there was a remarkable relationship between mother's colpitis and level of IL-6 in newborn with ENI in group A (p=0.011) and group B (p = 0.012). High levels of IL-6 in umbilical cord blood can help us in recognition of newborns that are endangered by infection and they are clearly connected with some of mother's obstetrical risks.

Banking on cord blood stem cells.

PubMed

Sullivan, Michael J

2008-07-01

Umbilical cord blood gifted to non-profit public cord blood banks is now routinely used as an alternative source of haematopoietic stem cells for allogeneic transplantation for children and adults with cancer, bone marrow failure syndromes, haemoglobinopathies and many genetic metabolic disorders. Because of the success and outcomes of public cord banking, many companies now provide private cord banking services. However, in the absence of any published transplant evidence to support autologous and non-directed family banking, commercial cord banks currently offer a superfluous service.

Optoacoustic measurements of human placenta and umbilical blood oxygenation

NASA Astrophysics Data System (ADS)

Nanovskaya, T. N.; Petrov, I. Y.; Petrov, Y.; Patrikeeva, S. L.; Ahmed, M. S.; Hankins, G. D. V.; Prough, D. S.; Esenaliev, R. O.

2016-03-01

Adequate oxygenation is essential for normal embryogenesis and fetal growth. Perturbations in the intrauterine oxidative environment during pregnancy are associated with several pathophysiological disorders such as pregnancy loss, preeclampsia, and intrauterine growth restriction. We proposed to use optoacoustic technology for monitoring placental and fetal umbilical blood oxygenation. In this work, we studied optoacoustic monitoring of oxygenation in placenta and umbilical cord blood ex vivo using technique of placenta perfusion. We used a medical grade, nearinfrared, tunable, optoacoustic system developed and built for oxygenation monitoring in blood vessels and in tissues. First, we calibrated the system for cord blood oxygenation measurements by using a CO-Oximeter (gold standard). Then we performed validation in cord blood circulating through the catheters localized on the fetal side of an isolated placental lobule. Finally, the oxygenation measurements were performed in the perfused placental tissue. To increase or decrease blood oxygenation, we used infusion of a gas mixture of 95% O2 + 5% CO2 and 95% N2 + 5% CO2, respectively. In placental tissue, up to four cycles of changes in oxygenation were performed. The optoacoustically measured oxygenation in circulating cord blood and in placental lobule closely correlated with the actual oxygenation data measured by CO-Oximeter. We plan to further test the placental and cord blood oxygenation monitoring with optoacoustics in animal and clinical studies.

Evidence-based pathology: umbilical cord coiling.

PubMed

Khong, T Y

2010-12-01

The generation of a pathology test result must be based on criteria that are proven to be acceptably reproducible and clinically relevant to be evidence-based. This review de-constructs the umbilical cord coiling index to illustrate how it can stray from being evidence-based. Publications related to umbilical cord coiling were retrieved and analysed with regard to how the umbilical coiling index was calculated, abnormal coiling was defined and reference ranges were constructed. Errors and other influences that can occur with the measurement of the length of the umbilical cord or of the number of coils can compromise the generation of the coiling index. Definitions of abnormal coiling are not consistent in the literature. Reference ranges defining hypocoiling or hypercoiling have not taken those potential errors or the possible effect of gestational age into account. Even the way numerical test results in anatomical pathology are generated, as illustrated by the umbilical coiling index, warrants a critical analysis into its evidence base to ensure that they are reproducible or free from errors.

Discordant Umbilical Cord Drug Testing Results in Monozygotic Twins.

PubMed

Alexander, Amy; Abbas, Liaqat; Jones, Mary; Jones, Joseph; Lewis, Douglas; Negrusz, Adam

2018-06-01

Our laboratory received segments of umbilical cord that originated from identical twins for routine toxicology analysis. The specimens were analyzed multiple times by liquid chromatography tandem mass spectrometry. The umbilical cord from newborn #1 was positive for hydromorphone only (1.06 ng/g), and the umbilical cord from newborn #2 was positive for hydromorphone (0.81 ng/g) and benzoylecgonine (5.41 ng/g). The hydromorphone results are consistent with maternal administration of hydromorphone; however, the cause of the discrepant benzoylecgonine results in the umbilical cords from the identical twins is unknown.

Evaluation of motor neuron differentiation potential of human umbilical cord blood- derived mesenchymal stem cells, in vitro.

PubMed

Yousefi, Behnam; Sanooghi, Davood; Faghihi, Faezeh; Joghataei, Mohammad Taghi; Latifi, Nourahmad

2017-04-01

Many people suffer from spinal cord injuries annually. These deficits usually threaten the quality of life of patients. As a postpartum medically waste product, human Umbilical Cord Blood (UCB) is a rich source of stem cells with self- renewal properties and neural differentiation capacity which made it useful in regenerative medicine. Since there is no report on potential of human umbilical cord blood-derived mesenchymal stem cells into motor neurons, we set out to evaluate the differentiation properties of these cells into motor neuron-like cells through administration of Retinoic Acid(RA), Sonic Hedgehog(Shh) and BDNF using a three- step in vitro procedure. The results were evaluated using Real-time PCR, Flowcytometry and Immunocytochemistry for two weeks. Our data showed that the cells changed into bipolar morphology and could express markers related to motor neuron; including Hb-9, Pax-6, Islet-1, NF-H, ChAT at the level of mRNA and protein. We could also quantitatively evaluate the expression of Islet-1, ChAT and NF-H at 7 and 14days post- induction using flowcytometry. It is concluded that human UCB-MSCs is potent to express motor neuron- related markers in the presence of RA, Shh and BDNF through a three- step protocol; thus it could be a suitable cell candidate for regeneration of motor neurons in spinal cord injuries. Copyright © 2017. Published by Elsevier B.V.

Protein S100B in umbilical cord blood as a potential biomarker of hypoxic-ischemic encephalopathy in asphyxiated newborns.

PubMed

Zaigham, Mehreen; Lundberg, Fredrik; Olofsson, Per

2017-09-01

Neonatal hypoxic ischemic encephalopathy (HIE) is a devastating condition resulting from a sustained lack of oxygen during birth. The interest in identifying a relevant biomarker of HIE has thrown into limelight the role of protein S100B as a clinical diagnostic marker of hypoxic brain damage in neonates. To evaluate the diagnostic value of protein S100B, measured in umbilical cord blood immediately after birth, as a useful biomarker in the diagnosis of HIE Sarnat stages II-III as well as a marker for long-term mortality and morbidity. Protein S100B was analyzed in cord blood sampled at birth from 13 newborns later diagnosed with stage II-III HIE and compared with 21 healthy controls. S100B concentrations were related to cord artery pH, amplitude-integrated electroencephalography (aEEG), stage of HIE, and death/sequelae up to an age of 6years. Both parametric and non-parametric statistics were used with a two-sided P<0.05 considered significant. The difference in S100B concentration was marginally statistically significant between HIE cases and controls (P=0.056). Cord blood acidosis (P=0.046), aEEG pattern severity (P=0.030), HIE severity (P=0.027), and condition at 6-year follow-up (healthy/permanent sequelae/death; P=0.027) were all related to an increase in S100B concentration. Protein S100B in neonates suffering from HIE stages II-III appeared elevated in umbilical cord blood at birth. The S100B concentrations were positively associated to the severity of disease and the risk of suffering from neurodevelopmental sequelae and even death. Copyright © 2017. Published by Elsevier B.V.

Newborn umbilical cord and skin care in Sylhet District, Bangladesh: Implications for promotion of umbilical cord cleansing with topical chlorhexidine

PubMed Central

Alam, Ashraful; Ali, Nabeel Ashraf; Sultana, Nighat; Mullany, Luke C.; Teela, Katherine C.; Khan, Nazib Uz Zaman; Baqui, Abdullah H.; Arifeen, Shams El; Mannan, Ishtiaq; Darmstadt, Gary L.; Winch, Peter J.

2010-01-01

Background Newborn cord care practices may directly contribute to infections, which account for a large proportion of the 4 million annual global neonatal deaths. This formative research study assessed current umbilical and skin care knowledge and practices for neonates in Sylhet, Bangladesh in preparation for a cluster-randomised trial of the impact of topical chlorhexidine cord cleansing on neonatal mortality and omphalitis. Methodology Unstructured interviews (n=60), structured observations (n=20), rating and ranking exercises (n=40), and household surveys (n=400) were conducted to elicit specific behaviours regarding newborn cord and skin care practices. These included hand-washing, skin and cord care at the time of birth, persons engaged in cord care, cord cutting practices, topical applications to the cord at the time of birth, wrapping/dressing of the cord stump, and use of skin-to-skin care. Results Ninety percent of deliveries occurred at home. The umbilical cord was almost always (98%) cut after delivery of the placenta, and cut by mothers in more than half the cases (57%). Substances were commonly (52%) applied to the stump after cord cutting; turmeric was the most common application (83%). Umbilical stump care revolved around bathing, skin massage with mustard oil, and heat massage on the umbilical stump. Forty-two percent of newborns were bathed on the day of birth. Mothers were the principal provider for skin and cord care during the neonatal period and 9% reported umbilical infections in their infants. Discussion Unhygienic cord care practices are prevalent in the study area. Efforts to promote hand washing, cord cutting with clean instruments, and avoiding unclean home applications to the cord may reduce exposure and improve neonatal outcomes. Such efforts should broadly target a range of caregivers, including mothers and other female household members. PMID:19057570

Clearance of CMV viremia and survival after double umbilical cord blood transplantation in adults depends on reconstitution of thymopoiesis.

PubMed

Brown, Julia A; Stevenson, Kristen; Kim, Haesook T; Cutler, Corey; Ballen, Karen; McDonough, Sean; Reynolds, Carol; Herrera, Maria; Liney, Deborah; Ho, Vincent; Kao, Grace; Armand, Philippe; Koreth, John; Alyea, Edwin; McAfee, Steve; Attar, Eyal; Dey, Bimalangshu; Spitzer, Thomas; Soiffer, Robert; Ritz, Jerome; Antin, Joseph H; Boussiotis, Vassiliki A

2010-05-20

Umbilical cord blood grafts are increasingly used as sources of hematopoietic stem cells in adults. Data regarding the outcome of this approach in adults are consistent with delayed and insufficient immune reconstitution resulting in high infection-related morbidity and mortality. Using cytomegalovirus (CMV)-specific immunity as a paradigm, we evaluated the status, mechanism, and clinical implications of immune reconstitution in adults with hematologic malignancies undergoing unrelated double unit cord blood transplantation. Our data indicate that CD8(+) T cells capable of secreting interferon-gamma (IFN-gamma) in a CMV-specific enzyme-linked immunosorbent spot (ELISpot) assay are detectable at 8 weeks after transplantation, before reconstitution of thymopoiesis, but fail to clear CMV viremia. Clearance of CMV viremia occurs later and depends on the recovery of CD4(+)CD45RA(+) T cells, reconstitution of thymopoiesis, and attainment of T-cell receptor rearrangement excision circle (TREC) levels of 2000 or more copies/mug DNA. In addition, overall survival was significantly higher in patients who displayed thymic regeneration and attainment of TREC levels of 2000 or more copies/mug DNA (P = .005). These results indicate that reconstitution of thymopoiesis is critical for long-term clinical outcome in adult recipients of umbilical cord blood transplant. The trial was prospectively registered at http://www.clinicaltrials.gov (NCT00133367).

Umbilical cord blood: Current status & promise for the future

PubMed Central

McKenna, David; Sheth, Jayesh

2011-01-01

Umbilical cord blood (UCB) has been shown to be a suitable source of haematopoietic stem cells (HSCs) for haematopoietic reconstitution. An increase in the number of UCB transplants indicates an expansion of utility in a broad spectrum of disease conditions. Along with the advantages, UCB also has limitations, and hence several investigators are working to further optimize UCB for this use. Beyond haematopoietic transplantation, additional potential applications of UCB include immunotherapy, tissue engineering and regenerative medicine. UCB banking has improved with time largely due to involvement of professional organizations and their published standards. However, accreditation of these organizations remains voluntary, and in India three of ten banks are public with the remaining being private. Only one public and one private bank are American Association of Blood Banks (AABB) accredited in India. Government agencies need to provide regulatory and safety oversight, which is lacking in serveral countries. Public policy regarding UCB is in its infancy throughout most of the world. Ethical issues, including access to UCB banking and use as therapy for diseases other than haematological and metabolic disorders are in the early phase of trials and remain speculative. PMID:21985808

1H-NMR-Based Metabolic Profiling of Maternal and Umbilical Cord Blood Indicates Altered Materno-Foetal Nutrient Exchange in Preterm Infants

PubMed Central

Küster, Alice; Guignard, Nadia; Alexandre–Gouabau, Marie-Cécile; Darmaun, Dominique; Robins, Richard J.

2012-01-01

Background Adequate foetal growth is primarily determined by nutrient availability, which is dependent on placental nutrient transport and foetal metabolism. We have used 1H nuclear magnetic resonance (NMR) spectroscopy to probe the metabolic adaptations associated with premature birth. Methodology The metabolic profile in 1H NMR spectra of plasma taken immediately after birth from umbilical vein, umbilical artery and maternal blood were recorded for mothers delivering very-low-birth-weight (VLBW) or normo-ponderal full-term (FT) neonates. Principal Findings Clear distinctions between maternal and cord plasma of all samples were observed by principal component analysis (PCA). Levels of amino acids, glucose, and albumin-lysyl in cord plasma exceeded those in maternal plasma, whereas lipoproteins (notably low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) and lipid levels were lower in cord plasma from both VLBW and FT neonates. The metabolic signature of mothers delivering VLBW infants included decreased levels of acetate and increased levels of lipids, pyruvate, glutamine, valine and threonine. Decreased levels of lipoproteins glucose, pyruvate and albumin-lysyl and increased levels of glutamine were characteristic of cord blood (both arterial and venous) from VLBW infants, along with a decrease in levels of several amino acids in arterial cord blood. Conclusion These results show that, because of its characteristics and simple non-invasive mode of collection, cord plasma is particularly suited for metabolomic analysis even in VLBW infants and provides new insights into the materno-foetal nutrient exchange in preterm infants. PMID:22291897

Distribution and Predictors of Pesticides in the Umbilical Cord Blood of Chinese Newborns

PubMed Central

Silver, Monica K.; Shao, Jie; Chen, Minjian; Xia, Yankai; Lozoff, Betsy; Meeker, John D.

2015-01-01

Rates of pesticide use in Chinese agriculture are five times greater than the global average, leading to high exposure via the diet. Many are neurotoxic, making prenatal pesticide exposure a concern. Previous studies of prenatal exposure in China focused almost entirely on organochlorines. Here the study goals were to characterize the exposure of Chinese newborns to all classes of pesticides and identify predictors of those exposures. Eighty-four pesticides and 12 metabolites were measured in the umbilical cord plasma of 336 infants. Composite variables were created for totals detected overall and by class. Individual pesticides were analyzed as dichotomous or continuous, based on detection rates. Relationships between demographic characteristics and pesticides were evaluated using generalized linear regression. Seventy-five pesticides were detected. The mean number of detects per sample was 15.3. Increased pesticide detects were found in the cord blood of infants born in the summer (β = 2.2, p = 0.01), particularly in July (β = 4.0, p = 0.03). Similar trends were observed for individual insecticide classes. Thus, a summer birth was the strongest predictor of pesticide evidence in cord blood. Associations were more striking for overall pesticide exposure than for individual pesticides, highlighting the importance of considering exposure to mixtures of pesticides, rather than individual agents or classes. PMID:26729147

The timing of umbilical cord clamping at birth: physiological considerations.

PubMed

Hooper, Stuart B; Binder-Heschl, Corinna; Polglase, Graeme R; Gill, Andrew W; Kluckow, Martin; Wallace, Euan M; Blank, Douglas; Te Pas, Arjan B

2016-01-01

While it is now recognized that umbilical cord clamping (UCC) at birth is not necessarily an innocuous act, there is still much confusion concerning the potential benefits and harms of this common procedure. It is most commonly assumed that delaying UCC will automatically result in a time-dependent net placental-to-infant blood transfusion, irrespective of the infant's physiological state. Whether or not this occurs, will likely depend on the infant's physiological state and not on the amount of time that has elapsed between birth and umbilical cord clamping (UCC). However, we believe that this is an overly simplistic view of what can occur during delayed UCC and ignores the benefits associated with maintaining the infant's venous return and cardiac output during transition. Recent experimental evidence and observations in humans have provided compelling evidence to demonstrate that time is not a major factor influencing placental-to-infant blood transfusion after birth. Indeed, there are many factors that influence blood flow in the umbilical vessels after birth, which depending on the dominating factors could potentially result in infant-to-placental blood transfusion. The most dominant factors that influence umbilical artery and venous blood flows after birth are lung aeration, spontaneous inspirations, crying and uterine contractions. It is still not entirely clear whether gravity differentially alters umbilical artery and venous flows, although the available data suggests that its influence, if present, is minimal. While there is much support for delaying UCC at birth, much of the debate has focused on a time-based approach, which we believe is misguided. While a time-based approach is much easier and convenient for the caregiver, ignoring the infant's physiology during delayed UCC can potentially be counter-productive for the infant.

Comparison of human umbilical cord blood processing with or without hydroxyethyl starch.

PubMed

Souri, Milad; Nikougoftar Zarif, Mahin; Rasouli, Mahboobeh; Golzadeh, Khadijeh; Nakhlestani Hagh, Mozhdeh; Ezzati, Nasim; Atarodi, Kamran

2017-11-01

Umbilical cord blood (UCB) processing with hydroxyethyl starch (HES) is the most common protocol in the cord blood banks. The quality of UCB volume reduction was guaranteed by minimum manipulation of cord blood samples in the closed system. This study aimed to analyze and compare cell recovery and viability of UCB processed using the Sepax automated system in the presence and absence of HES. Thirty UCB bags with a total nucleated cell (TNC) count of more than 2.5 × 10 9 were divided in two bags with equal volume. HES solution was added to one bag and another was intact. Both bags were processed with the Sepax. To determine cell recovery, viability, and potential of colony-forming cells (CFCs), preprocessing, postprocessing, and thawing samples were analyzed. The mean TNC recovery after processing and after thaw was significantly better with the HES method (p < 0.01 for the postprocessing step and p < 0.05 for the postthaw step). There were no significant differences to mononucleated cells (MNCs) and CD34+ cell recovery between the two methods after processing and after thaw. TNC and MNC viability was significantly higher without HES after processing and after thaw (p < 0.01). The results of the CFC assay were similar for both methods after processing and after thaw. These results showed that processing of UCB using the Sepax system with the without-HES protocol due to the lower manipulation of samples could be used as an eligible protocol to reduce the volume of UCB. © 2017 AABB.

Cord Blood Chimerism And Relapse After Haplo-Cord Transplantation

PubMed Central

van Besien, Koen; Koshy, Nebu; Gergis, Usama; Mayer, Sebastian; Cushing, Melissa; Rennert, Hannah; Slotky, Ronit; Mark, Tomer; Pearse, Roger; Rossi, Adriana; Phillips, Adrienne; Vasovic, Liljana; Ferrante, Rosanna; Hsu, Michael; Shore, Tsiporah

2018-01-01

Haplo-cord stem cell transplantation combines the infusion of CD34 selected hematopoietic progenitors from a haplo-identical donor with an umbilical cord blood graft from an unrelated donor and allows faster count recovery, with low rates of disease recurrence and chronic GVHD. But the contribution of the umbilical cord blood graft to long-term transplant outcome remains unclear. We analyzed 39 recipients of haplo-cord transplants with AML and MDS, engrafted and in remission at 2 months. Median age was 66 (18-72) and all had intermediate, high, or very high risk disease. Less than 20% UCB chimerism in the CD33 lineage was associated with an increased rate of disease recurrence (54% vs 11% P<0.0001) and decrease in one year progression-free (20% vs 55%, P=0.004) and overall survival (30% vs 62%, P=0.02). Less than 100% UCB chimerism in the CD3 lineage was associated with increase rate of disease recurrence (46% vs 12%, P=0.007) Persistent haplo-chimerism in the CD3 lineage was associated with an increased rate of disease recurrence (40% vs 15%, P=0.009) Chimerism did not predict for treatment related mortality. The cumulative incidence of acute GVHD by day 100 was 43%. The cumulative incidence of moderate/severe chronic GVHD was only 5%. Engraftment of the umbilical cord blood grafts provides powerful GVL effects which protect against disease recurrence and is associated with low risk of chronic GVHD. Engraftment of CD34 selected haplo-identical cells can lead to rapid development of circulating T-cells, but when these cells dominate, GVL-effects are limited and rates of disease recurrence are high. PMID:27333804

Umbilical Cord Care in the Newborn Infant.

PubMed

Stewart, Dan; Benitz, William

2016-09-01

Postpartum infections remain a leading cause of neonatal morbidity and mortality worldwide. A high percentage of these infections may stem from bacterial colonization of the umbilicus, because cord care practices vary in reflection of cultural traditions within communities and disparities in health care practices globally. After birth, the devitalized umbilical cord often proves to be an ideal substrate for bacterial growth and also provides direct access to the bloodstream of the neonate. Bacterial colonization of the cord not infrequently leads to omphalitis and associated thrombophlebitis, cellulitis, or necrotizing fasciitis. Various topical substances continue to be used for cord care around the world to mitigate the risk of serious infection. More recently, particularly in high-resource countries, the treatment paradigm has shifted toward dry umbilical cord care. This clinical report reviews the evidence underlying recommendations for care of the umbilical cord in different clinical settings. Copyright © 2016 by the American Academy of Pediatrics.

DETERMINATION OF MATERNAL SERUM ZINC, IRON, CALCIUM AND MAGNESIUM DURING PREGNANCY IN PREGNANT WOMEN AND UMBILICAL CORD BLOOD AND THEIR ASSOCIATION WITH OUTCOME OF PREGNANCY

PubMed Central

Khoushabi, Fahimeh; Shadan, Mohammad Reza; Miri, Ali; Sharifi-Rad, Javad

2016-01-01

Background: Trace elements and specially minerals are critical for the development of fetus. Many minerals are transferred to the fetus for fetal stores in the latter part of the pregnancy. It has been shown that various trace elements such as Zinc, Iron, Calcium and Magnesium are metabolically interrelated and there is alteration in their concentration during pregnancy. Beyond pregnancy is associated with increased demand of all the nutrients and deficiency of any of these could affect pregnancy, delivery and outcome of pregnancy. Aim: To study the levels of trace elements namely zinc, iron, magnesium and calcium in maternal and umbilical cord blood and their association with pregnancy outcome. Methods: Sixty pregnant women in Zabol, Iran were selected from those who had registered their names for the prenatal care and who had followed up till the 3rd trimester of pregnancy ending in child birth. Biochemical parameters analyzed with help of the biochemical laboratory. Data were analyzed by SPSS software. Results: The mean biochemical profile such, serum calcium, magnesium, zinc and iron in the pregnant women were as follow: in the 1st trimester 8.3, 1.9, 74.9 and 74.4 µg/dl respectively; in the 2nd trimester 8.5, 1.9, 73.1 and 79.3 µg/dl, respectively; in the 3rd trimester 8.6, 1.9, 68.4, and 82.2 µg/dl, respectively. In the umbilical cord blood, the mean serum calcium, magnesium, zinc and iron were 8.5, 1.9, 84.1, and 89.8 µg/dl, respectively. The mean serum calcium and magnesium during the three trimesters of pregnancy were not significantly different from that in the umbilical cord blood, while the mean serum zinc and iron in the umbilical cord blood were significantly different (p<0.05) in the three trimester of pregnancy. The mean birth weight of neonates was 3.1 kg and 12% of neonates showed low birth weight. Our findings showed that, except magnesium, the profile of other biochemical variables, namely, calcium, zinc and iron in the umbilical cord blood

Lipidomics of human umbilical cord serum: identification of unique sterol sulfates.

PubMed

Wood, Paul L; Siljander, Heli; Knip, Mikael

2017-08-01

There are currently limited lipidomics data for human umbilical cord blood. Therefore, the lipidomes of cord sera from six newborns and sera from six nonpregnant females were compared. Sera lipidomics analyses were conducted using a high-resolution mass spectrometry analytical platform. Cord serum contained a diverse array of glycerophospholipids, albeit generally at lower concentrations than monitored in adult serum. The unexpected observations were that cord serum contained several neurosteroid sulfates and bile acid sulfates that were not detectable in adult serum. Our data are the first to demonstrate that cord serum contains bile acid sulfates that are synthesized early in the hydroxylase, neutral and acidic pathways of primary bile acid biosynthesis and support previous publications of cord blood perfluoralkyl toxins in newborns.

The meanings of consent to the donation of cord blood stem cells: perspectives from an interview-based study of a public cord blood bank in England

PubMed Central

Busby, Helen

2010-01-01

This paper explores the perspectives of women who have agreed that their umbilical cord blood may be collected for a public ‘cord blood bank’, for use in transplant medicine or research. Drawing on interview data from 27 mothers who agreed to the collection and use of their umbilical cord blood, these choices and the informed consent process are explored. It is shown that the needs of sick children requiring transplants are prominent in narrative accounts of cord blood banking, together with high expectations for future applications of stem cells. Given this dynamic, a concern arises that the complex and multiple uses of tissues and related data might be oversimplified in the consent process. In conclusion, the positive finding of a commitment to mutuality in cord blood banking among these women is underlined, and its implications for the wider debate on cord blood banking are discussed. PMID:21666742

The meanings of consent to the donation of cord blood stem cells: perspectives from an interview-based study of a public cord blood bank in England.

PubMed

Busby, Helen

2010-03-01

This paper explores the perspectives of women who have agreed that their umbilical cord blood may be collected for a public 'cord blood bank', for use in transplant medicine or research. Drawing on interview data from 27 mothers who agreed to the collection and use of their umbilical cord blood, these choices and the informed consent process are explored. It is shown that the needs of sick children requiring transplants are prominent in narrative accounts of cord blood banking, together with high expectations for future applications of stem cells. Given this dynamic, a concern arises that the complex and multiple uses of tissues and related data might be oversimplified in the consent process. In conclusion, the positive finding of a commitment to mutuality in cord blood banking among these women is underlined, and its implications for the wider debate on cord blood banking are discussed.

Expansion of Human Tregs from Cryopreserved Umbilical Cord Blood for GMP-Compliant Autologous Adoptive Cell Transfer Therapy.

PubMed

Seay, Howard R; Putnam, Amy L; Cserny, Judit; Posgai, Amanda L; Rosenau, Emma H; Wingard, John R; Girard, Kate F; Kraus, Morey; Lares, Angela P; Brown, Heather L; Brown, Katherine S; Balavage, Kristi T; Peters, Leeana D; Bushdorf, Ashley N; Atkinson, Mark A; Bluestone, Jeffrey A; Haller, Michael J; Brusko, Todd M

2017-03-17

Umbilical cord blood is a traditional and convenient source of cells for hematopoietic stem cell transplantation. Thymic regulatory T cells (Tregs) are also present in cord blood, and there is growing interest in the use of autologous Tregs to provide a low-risk, fully human leukocyte antigen (HLA)-matched cell product for treating autoimmune diseases, such as type 1 diabetes. Here, we describe a good manufacturing practice (GMP)-compatible Treg expansion protocol using fluorescence-activated cell sorting, resulting in a mean 2,092-fold expansion of Tregs over a 16-day culture for a median yield of 1.26 × 10 9 Tregs from single-donor cryopreserved units. The resulting Tregs passed prior clinical trial release criteria for Treg purity and sterility, including additional rigorous assessments of FOXP3 and Helios expression and epigenetic analysis of the FOXP3 Treg-specific demethylated region (TSDR). Compared with expanded adult peripheral blood Tregs, expanded cord blood Tregs remained more naive, as assessed by continued expression of CD45RA, produced reduced IFN-γ following activation, and effectively inhibited responder T cell proliferation. Immunosequencing of the T cell receptor revealed a remarkably diverse receptor repertoire within cord blood Tregs that was maintained following in vitro expansion. These data support the feasibility of generating GMP-compliant Tregs from cord blood for adoptive cell transfer therapies and highlight potential advantages in terms of safety, phenotypic stability, autoantigen specificity, and tissue distribution.

Umbilical cord blood banks. Ethical aspects. Public versus private banks.

PubMed

Aznar Lucea, Justo

2012-01-01

The creation of umbilical cord blood (UCB) banks raises interesting medical, social, economic and ethical issues. This paper reviews the ethical problems specifically. In this respect, it evaluates: a) whether there are advantages to the use of UCB compared to bone marrow, b) whether or not it is ethical to create UCB banks, c) whether their creation is ethically acceptable in terms of their clinical usefulness or d) the use made of them for therapeutic purposes, and finally e) whether their creation is ethically justified from a cost/profitability point of view. We focus primarily on evaluating the ethical controversy between public and private banks, particularly on whether it is ethical to bank autologous blood in private UCB banks, on the basis of its limited possibilities for use by the cord blood donor. We can conclude that, from an ethical point of view, autologous blood banks have limited acceptance among specialised researchers, scientific societies and other public institutions. Therefore, we believe that it is ethically more acceptable to support the creation of public UCB banks for medical and social reasons and, above all, based on the principle of justice and human solidarity. Nevertheless, there is no definitive ethical argument why a couple, according to their autonomy and freedom, cannot bank their child's UCB in a private bank. An equally acceptable solution could be the creation of mixed banks, such as that proposed by the Virgin Health Bank or like the Spanish system where autologous samples can be stored in public banks but with the proviso that if at any time the stored sample is required by any person other than the donor, it would have to be given to them.

Combination of a Haploidentical Stem Cell Transplant With Umbilical Cord Blood for Cerebral X-Linked Adrenoleukodystrophy.

PubMed

Jiang, Hua; Jiang, Min-Yan; Liu, Sha; Cai, Yan-Na; Liang, Cui-Li; Liu, Li

2015-08-01

Childhood cerebral X-linked adrenoleukodystrophy is a rapidly progressive neurodegenerative disorder that affects central nervous system myelin and the adrenal cortex. Hematopoietic stem cell transplantation is the best available curative therapy if performed during the early stages of disease. Only 30% of patients who might benefit from a hematopoietic stem cell transplant will have a full human leukocyte antigen-matched donor, which is considered to be the best choice. We present a 5-year-old boy with cerebral X-linked adrenoleukodystrophy whose brain magnetic resonance imaging severity score was 7 and who needed an immediate transplantation without an available full human leukocyte antigen-matched donor. We combined haploidentical and umbilical cord blood sources for transplantation and saw encouraging results. After transplantation, the patient showed neurological stability for 6 months and the level of very long chain fatty acids had decreased. By 1 year, the patient appeared to gradually develop cognition, motor, and visual disturbances resulting from possible mix chimerism. Transplantation of haploidentical stem cells combined with the infusion of umbilical cord blood is a novel approach for treating cerebral X-linked adrenoleukodystrophy. It is critical to monitor posttransplant chimerism and carry out antirejection therapy timely for a beneficial clinical outcome. Copyright © 2015 Elsevier Inc. All rights reserved.

Association between ambient air pollution and proliferation of umbilical cord blood cells.

PubMed

Novack, L; Yitshak-Sade, M; Landau, D; Kloog, I; Sarov, B; Karakis, I

2016-11-01

It has been established as a common knowledge that ambient air pollution (AAP) has an adverse effect on human health. The pathophysiological mechanism of this impact is likely to be related to the oxidative stress. In the current study we estimate the association between AAP and cell proliferation (CP) of umbilical cord blood cells, representing maternal organism most proximal to the fetal body. Blood samples were tested for proliferation in 292 enrolled Arab-Bedouin women at delivery (July 2012-March 2013). The estimates of AAP were defined by a hybrid satellite based model predicting both PM 2.5 (particles<2.5µm in diameter) and PM 10 (particles<10µm in diameter) as well as monitoring stations for gaseous air pollutants. Risk estimates of pollution exposure were adjusted to medical history, household risk factors and meteorological factors on the day of delivery or one week prior. Ambient ozone (O 3 ) levels on 1, 2, 3and 4 days prior to delivery were associated with lower CP (Prevalence ratio (PR)=0.92, 0.92, 0.93, 0.93, respectively). Increase in inter-quartile range (IOR) of PM 2.5 one day before delivery was associated with 9% increase in CP levels (PR=1.09). The positive direction in association was changed to negative association with CP for PM 2.5 levels measured at more distant time periods (PR=0.90 and 0.93 for lags 5 and 6 days, respectively). Investigation of PM 10 levels indicated a similar pattern (PR=1.05 for pollution values recorded one day before delivery and 0.93 and 0.95 for lags of 5 and 6 days, respectively). Carbon monoxide (CO) levels were associated with lower CP on the day of delivery and 1day prior (PR=0.92 and PR=0.94). To conclude, the levels of cell proliferation of umbilical cord blood cells appear to be associated with the AAP. More studies are needed to support our findings. Copyright © 2016. Published by Elsevier Inc.

Concepts, Utility and Limitations of Cord Blood Banking: What Clinicians Need to Know.

PubMed

Narayanan, Dhanya Lakshmi; Phadke, Shubha R

2018-03-20

Stem cell transplantation and cord blood banking have received much popularity among general public and medical professionals in the recent past. But information about the scientific aspects, its utility and limitations is incomplete amongst laypersons as well as many medical practitioners. Stem cells differ from all other types of cells in the human body because of their ability to multiply in order to self perpetuate and differentiate into specialized cells. Stems cells could be totipotent, multipotent, pluripotent, oligopotent or unipotent depending on the type of cells that can arise or differentiate from them. Umbilical cord blood serves as a potent source of hematopoeitic stem cells and is being used to treat various disorders like blood cancers, hemoglobinopathies and immunodeficiency disorders for which hematological stem cell transplantation is the standard of care. Cord blood can be collected at ease, without any major complications and has a lower incidence of graft vs. host reaction compared to bone marrow cells or peripheral blood cells. Both public and private banks have been established for collection and storage of umbilical cord blood. However, false claims and misleading commercial advertisements about the use of umbilical cord blood stem cells for the treatment of a variety of conditions ranging from neuromuscular disorders to cosmetic benefits are widespread and create unrealistic expectations in laypersons and clinicians. Many clinicians and laypersons are unaware of the limitations of cord blood banking, as in treating a genetic disorder by autologous cord blood transplant. Knowledge and awareness about the scientific indications of cord blood stem cell transplantation and realistic expectations about the utility of cord blood among medical practitioners are essential for providing accurate information to laypersons before they decide to preserve umbilical cord blood in private banks and thus prevent malpractice.

Rare Abdominal Wall Malformation: Case Report of Umbilical Cord Hernia.

PubMed

Gliha, Andro; Car, Andrija; Višnjić, Stjepan; Zupancic, Bozidar; Kondza, Karmen; Petracic, Ivan

The umbilical cord hernia is the rarest form of abdominal wall malformations, anatomically completely different from gastroschisis and omphalocele. It occurs due to the permanent physiological evisceration of abdominal organs into umbilical celom and persistence of a patent umbilical ring. The umbilical cord hernia is often mistaken for omphalocele and called "small omphalocele". Here we present a case of a female newborn with umbilical cord hernia treated in our Hospital. After preoperative examinations surgery was done on the second day of life. The abdominal wall was closed without tension. The aim of this article is to present the importance of the proper diagnose of these three entities and to stimulate academic community for the answer, is this umbilical cord hernia or small omphalocele.

Infectious Complications after Umbilical Cord-Blood Transplantation from Unrelated Donors

PubMed Central

Montoro, Juan; Piñana, José Luis; Moscardó, Federico; Sanz, Jaime

2016-01-01

Umbilical cord-blood (UCB) is a well-recognized alternative source of stem cells for unrelated donor hematopoietic stem cell transplantation (HSCT). As compared with other stem cell sources from adult donors, it has the advantages of immediate availability of cells, absence of risk to the donor and reduced risk of graft-versus-host disease despite donor-recipient HLA disparity. However, the use of UCB is limited by the delayed post-transplant hematologic recovery due, at least in part, to the reduced number of hematopoietic cells in the graft and the delayed or incomplete immune reconstitution. As a result, severe infectious complications continue to be a leading cause of morbidity and mortality following UCB transplantation (UCBT). We will address the complex differences in the immune properties of UCB and review the incidence, characteristics, risk factors, and severity of bacterial, fungal and viral infectious complications in patients undergoing UCBT. PMID:27872731

Umbilical cord blood for unrelated bone marrow replacement; Asia bank and Japan cord blood bank network update.

PubMed

Mugishima, Hideo; Takahashi, Tuneo; Nagamura, Tokiko; Asano, Sigetaka; Saito, Hidehiko

2002-08-01

Cord blood offers many advantages including a high concentration of hematopoietic stem cells, a large number of potential donors, and ease of harvest. Furthermore, since there is no risk for either the mother or baby, few people refuse to donate. There is thought to be a low risk for virus contamination and also probably a low incidence and severity of GVHD. Cord blood can be obtained quickly without the assistance of a coordinator and one or 2 locus-mismatched HLA is usually acceptable. In Japan, there are 10 cord blood banks supported by the government. Between 1996 and June 2002, 9,500 units were registered with the Japan cord blood bank network (JCBBN). 630 units were delivered and most of these were transplanted. The status of registered cord blood units worldwide is shown. 59,081 units have been registered by NETCORD. The Japan cord blood bank network accounts for 13% of these units. I will discuss the Tokyo cord blood tank (TCBB). The bank at Tokyo, to which we belong, is one of the largest banks in Japan. We helped to establish Asia CORD in 2000 and have held annual conferences and meetings in Tokyo to exchange information. So far, China, Korea, Taiwan, Thailand, Viet Nam and Japan have participated. We accepted three trainees from the Ho Chi Minh City Blood Transfusion and Hematology Center for training in cord blood transplantation in May 2001. In January 2002, a patient with ALL received cord blood and was successfully engrafted at Ho Chi Minh City Blood Transfusion and Hematology Center. We present here the clinical outcome of these patients through Tokyo cord blood bank and Japan cord blood bank network. First, the number of CB units stored and registered at JCBBN and TCBB has increased rapidly over the past two years. Second, the survival rate of acute leukemia patients in release was significantly lower than that in patients in CR. Third, the engraftment rate in patients with metabolic disease (50%) was lower than that in patients with leukemia

Outcomes after Unrelated Umbilical Cord Blood Transplantation for Children with Osteopetrosis.

PubMed

Chiesa, Robert; Ruggeri, Annalisa; Paviglianiti, Annalisa; Zecca, Marco; Gónzalez-Vicent, Marta; Bordon, Victoria; Stein, Jerry; Lawson, Sarah; Dupont, Sophie; Lanino, Edoardo; Abecasis, Manuel; Al-Seraihy, Amal; Kenzey, Chantal; Bierings, Marc; Locatelli, Franco; Gluckman, Eliane; Schulz, Ansgar; Gennery, Andrew; Page, Kristin; Kurtzberg, Joanne; Rocha, Vanderson

2016-11-01

Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for most children with osteopetrosis (OP). Timing of HSCT is critical; therefore, umbilical cord blood transplantation (UCBT) is an attractive option. We analyzed outcomes after UCBT in 51 OP children. Median age at UCBT was 6 months. Seventy-seven percent of the cord blood grafts had 0 or 1 HLA disparity with the recipient. Conditioning regimen was myeloablative (mostly busulfan-based in 84% and treosulfan-based in 10%). Antithymocyte globulin was given to 90% of patients. Median number of total nucleated and CD34 + cells infused was 14 × 10 7 /kg and 3.4 × 10 5 /kg, respectively. Median follow-up for survivors was 74 months. Cumulative incidence (CI) of neutrophil recovery was 67% with a median time to recovery of 23 days; 33% of patients had graft failure, 81% of engrafted patients had full donor engraftment, and 19% had mixed donor chimerism. Day 100 CI of acute graft-versus-host disease (grades II to IV) was 31% and 6-year CI of chronic graft-versus-host disease was 21%. Mechanical ventilation was required in 28%, and veno-occlusive disease was diagnosed in 16% of cases. Six-year overall survival rate was 46%. Comparative studies with other alternative donors should be performed to evaluate whether UCBT remains a valid alternative for children with OP without an HLA-matched donor. Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

A preliminary report of 123 units of placental umbilical cord whole blood transfusion in HIV-positive patients with anemia and emaciation.

PubMed

Bhattacharya, N

2006-01-01

Cord blood, because of its rich mix of fetal and adult hemoglobin, high platelet and WBC counts, and a plasma filled with cytokine and growth factors, as well as its hypo antigenic nature and altered metabolic profile, has all the potential of a real and safe alternative to adult blood transfusion. Our team's experience (from 1st April 1999 to 1st July 2005) with 123 units of placental umbilical cord whole blood (62 ml-154 ml mean 85 ml +/- 8.4 ml SD, median 82 ml, mean packed cell volume 48.8 +/- 4.2 SD, mean percent hemoglobin concentration 16.3 g/dl +/- 1.6 g/dl SD; after collection the blood was immediately preserved in a refrigerator and transfused within 72 hours of collection) collected after lower uterine cesarean section (LUCS), and the transfusion to 16 consenting HIV-positive patients (12 cases had full blown AIDS) with anemia and emaciation is presented here. On the basis of our preliminary experience of cord blood transfusion, we are of the opinion that umbilical cord whole blood transfusion is safe in HIV-positive patients. This blood has the potential to carry more oxygen than adult blood and it does not trigger any clinical, immunological or non-immunological reaction after its transfusion to an adult host with a HIV-positive status. Apart from the correction of anemia, there was also definite improvement in the energy and fatigue levels in individuals with HIV, i.e., physical functioning, a sense of well-being and weight gain from two to five pounds, within three to ten months of the commencement of transfusion. There was also an immediate rise in CD34 levels of peripheral blood in the HLA-randomized host after transfusion, without any clinical graft vs host reaction.

Identification of stem cells from human umbilical cord blood with embryonic and hematopoietic characteristics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao Yong; Wang Honglan; Mazzone, Theodore

2006-08-01

We identified stem cells from the umbilical cord blood, designated cord blood-stem cells (CB-SC). CB-SC displayed important embryonic stem (ES) cell characteristics including expression of ES-cell-specific molecular markers including transcription factors OCT-4 and Nanog, along with stage-specific embryonic antigen (SSEA)-3 and SSEA-4. CB-SC also expressed hematopoietic cell antigens including CD9, CD45 and CD117, but were negative for CD34. CB-SC displayed very low immunogenicity as indicated by expression of a very low level of major histocompatibility complex (MHC) antigens and failure to stimulate the proliferation of allogeneic lymphocytes. CB-SC could give rise to cells with endothelial-like and neuronal-like characteristics in vitro,more » as demonstrated by expression of lineage-associated markers. Notably, CB-SC could be stimulated to differentiate into functional insulin-producing cells in vivo and eliminated hyperglycemia after transplantation into a streptozotocin-induced diabetic mouse model. These findings may have significant potential to advance stem-cell-based therapeutics.« less

Allogeneic umbilical cord blood red cell concentrates: an innovative blood product for transfusion therapy of preterm infants.

PubMed

Bianchi, Maria; Giannantonio, Carmen; Spartano, Serena; Fioretti, Maria; Landini, Alessandra; Molisso, Anna; Tesfagabir, Ghennet Mikael; Tornesello, Assunta; Barbagallo, Ombretta; Valentini, Caterina Giovanna; Vento, Giovanni; Zini, Gina; Romagnoli, Costantino; Papacci, Patrizia; Teofili, Luciana

2015-01-01

Preterm infants often receive blood transfusions early in life. In this setting, umbilical cord blood (UCB) might be safer than adult blood (A) with respect to infectious and immunologic threats. To evaluate, as a first objective, the feasibility of fulfilling transfusion needs of preterm infants with allogeneic UCB red blood cell (RBC) concentrates and, as a secondary objective, to assess the safety of allogeneic cord blood transfusions. At the Neonatal Intensive Care Unit and the UNICATT Cord Blood Bank of 'A. Gemelli' Hospital in Rome, a prospective study was carried out over a 1-year period, enrolling newborns with gestational age ≤30 weeks and/or birth weight ≤1,500 g requiring RBC transfusions within the first 28 days of life. At first transfusion, patients were assigned to receive UCB-RBCs or A-RBCs depending on the availability of ABO-Rh(D)-matched UCB-RBC units. The same regimen (UCB-RBC or A-RBC units) was thereafter maintained, unless ABO-Rh(D)-matched UCB-RBC units were not available. Overall, 23 UCB-RBC units were transfused to 9 patients; the requests for UCB-RBC units were met in 45% of patients at the first transfusion and in 78% at the subsequent transfusions. At a median follow-up of 57 days (range 6-219), no acute or delayed transfusion-related adverse events occurred. Hematocrit gain after transfusion and time intervals between transfusions were similar in the UCB-RBC and A-RBC group, as well. Transfusing allogeneic UCB-RBC units in preterm infants appears a feasible and safe approach, although the transfusion needs of our study population were not completely covered. More data are necessary to validate this novel transfusion practice. © 2014 S. Karger AG, Basel.

Quality of red blood cells isolated from umbilical cord blood stored at room temperature.

PubMed

Zhurova, Mariia; Akabutu, John; Acker, Jason

2012-01-01

Red blood cells (RBCs) from cord blood contain fetal hemoglobin that is predominant in newborns and, therefore, may be more appropriate for neonatal transfusions than currently transfused adult RBCs. Post-collection, cord blood can be stored at room temperature for several days before it is processed for stem cells isolation, with little known about how these conditions affect currently discarded RBCs. The present study examined the effect of the duration cord blood spent at room temperature and other cord blood characteristics on cord RBC quality. RBCs were tested immediately after their isolation from cord blood using a broad panel of quality assays. No significant decrease in cord RBC quality was observed during the first 65 hours of storage at room temperature. The ratio of cord blood to anticoagulant was associated with RBC quality and needs to be optimized in future. This knowledge will assist in future development of cord RBC transfusion product.

Transplantation of cryopreserved human umbilical cord blood mononuclear cells does not induce sustained recovery after experimental stroke in spontaneously hypertensive rats

PubMed Central

Weise, Gesa; Lorenz, Marlene; Pösel, Claudia; Maria Riegelsberger, Ute; Störbeck, Veronika; Kamprad, Manja; Kranz, Alexander; Wagner, Daniel-Christoph; Boltze, Johannes

2014-01-01

Previous studies have highlighted the enormous potential of cell-based therapies for stroke not only to prevent ischemic brain damage, but also to amplify endogenous repair processes. Considering its widespread availability and low immunogenicity human umbilical cord blood (HUCB) is a particularly attractive stem cell source. Our goal was to investigate the neurorestorative potential of cryopreserved HUCB mononuclear cells (MNC) after permanent middle cerebral artery occlusion (MCAO) in spontaneously hypertensive rats (SHR). Human umbilical cord blood MNC or vehicle solution was administered intravenously 24 hours after MCAO. Experimental groups were as follows: (1) quantitative polymerase chain reaction (PCR) of host-derived growth factors up to 48 hours after stroke; (2) immunohistochemical analysis of astroglial scarring; (3) magnetic resonance imaging (MRI) and weekly behavioral tests for 2 months after stroke. Long-term functional outcome and lesion development on MRI were not beneficially influenced by HUCB MNC therapy. Furthermore, HUCB MNC treatment did not change local growth factor levels and glial scarring extent. In summary, we could not demonstrate neurorestorative properties of HUCB MNC after stroke in SHR. Our results advise caution regarding a prompt translation of cord blood therapy into clinical stroke trials as long as deepened knowledge about its precise modes of action is missing. PMID:24169850

Impact of delayed umbilical cord clamping on public cord blood donations: can we help future patients and benefit infant donors?

PubMed

Ciubotariu, Rodica; Scaradavou, Andromachi; Ciubotariu, Ilinca; Tarnawski, Michal; Lloyd, Sara; Albano, Maria; Dobrila, Ludy; Rubinstein, Pablo; Grunebaum, Amos

2018-03-25

Cord blood (CB) is a widely accepted stem cell source and its clinical utilization depends, to a great extent, on its cell content. Birth-to-clamping (BTC) time of umbilical cord determines placental transfusion to the newborn, and the remaining blood that can be collected and banked. The 2017 Committee Opinion of the American College of Obstetrics and Gynecologists (ACOG) recommends a delay of "at least 30-60 seconds" before clamping the cord for all newborns to ensure adequate iron stores. The impact of delayed cord clamping (DCC) on public CB banking can be substantial. Cord blood units (CBUs) collected from 1210 mothers at one hospital were evaluated for total nucleated cells (TNCs) and weight/volume based on time to clamping. Bank staff recorded BTC time in seconds as reported by obstetricians; collections were performed ex utero. Immediate clamping was defined as BTC of less than 30 seconds, whereas DCC was defined as BTC of 30 seconds or more. Cord clamping was immediate in 903 (75%) and delayed in 307 (25%) deliveries. Successful recovery (% clinical CBUs) decreased 10-fold with DCC of more than 60 seconds (22% vs. 2.4%, p < 0.001). CBUs collected after DCC of more than 60 seconds had significantly lower TNC counts than those after DCC of less than 60 seconds (p < 0.0001). Furthermore, 38% to 46% of CBUs after DCC of more than 60 seconds had volume of less than 40 mL. Our study indicates that DCC of 30 to 60 seconds has a small negative impact on collection of high-TNC-count CBUs. However, increasing BTC to more than 60 seconds decreases significantly both TNC content and volume, reducing drastically the chances of obtaining clinically useful CBUs. © 2018 AABB.

The Metabolomic Profile of Umbilical Cord Blood in Neonatal Hypoxic Ischaemic Encephalopathy

PubMed Central

Walsh, Brian H.; Broadhurst, David I.; Mandal, Rupasri; Wishart, David S.; Boylan, Geraldine B.; Kenny, Louise C.; Murray, Deirdre M.

2012-01-01

Background Hypoxic ischaemic encephalopathy (HIE) in newborns can cause significant long-term neurological disability. The insult is a complex injury characterised by energy failure and disruption of cellular homeostasis, leading to mitochondrial damage. The importance of individual metabolic pathways, and their interaction in the disease process is not fully understood. The aim of this study was to describe and quantify the metabolomic profile of umbilical cord blood samples in a carefully defined population of full-term infants with HIE. Methods and Findings The injury severity was defined using both the modified Sarnat score and continuous multichannel electroencephalogram. Using these classification systems, our population was divided into those with confirmed HIE (n = 31), asphyxiated infants without encephalopathy (n = 40) and matched controls (n = 71). All had umbilical cord blood drawn and biobanked at −80°C within 3 hours of delivery. A combined direct injection and LC-MS/MS assay (AbsolutIDQ p180 kit, Biocrates Life Sciences AG, Innsbruck, Austria) was used for the metabolomic analyses of the samples. Targeted metabolomic analysis showed a significant alteration between study groups in 29 metabolites from 3 distinct classes (Amino Acids, Acylcarnitines, and Glycerophospholipids). 9 of these metabolites were only significantly altered between neonates with Hypoxic ischaemic encephalopathy and matched controls, while 14 were significantly altered in both study groups. Multivariate Discriminant Analysis models developed showed clear multifactorial metabolite associations with both asphyxia and HIE. A logistic regression model using 5 metabolites clearly delineates severity of asphyxia and classifies HIE infants with AUC = 0.92. These data describe wide-spread disruption to not only energy pathways, but also nitrogen and lipid metabolism in both asphyxia and HIE. Conclusion This study shows that a multi-platform targeted approach to

Umbilical Cord Blood Transplantation Corrects Very Early-Onset Inflammatory Bowel Disease in Chinese Patients With IL10RA-Associated Immune Deficiency.

PubMed

Peng, Kaiyue; Qian, Xiaowen; Huang, Zhiheng; Lu, Junping; Wang, Yuhuan; Zhou, Ying; Wang, Huijun; Wu, Bingbing; Wang, Ying; Chen, Lingli; Zhai, Xiaowen; Huang, Ying

2018-05-18

Hematopoietic stem cell transplantation is considered the only curative therapy for very early-onset inflammatory bowel disease with specific immune defects, such as interleukin-10 receptor deficiency. We performed reduced-intensity conditioning before umbilical cord blood transplantation in patients with interleukin-10 receptor-A deficiency. We enrolled 9 very early-onset inflammatory bowel disease patients with typical manifestations. We diagnosed the patients with interleukin-10 receptor-A deficiency by whole-exome sequencing. Umbilical cord blood transplantation was performed in all 9 patients. Eight patients received the reduced-intensity conditioning regimen, and 1 patient received the myeloablative conditioning regimen. All 9 patients received transplantation between the ages of 6 months to 43 months (average, 16.8 months) with body weights ranging from 3 to 10.4 kg (average, 6.6 kg). The patients displayed complete chimerism at 2-8 weeks after transplantation; 6 patients achieved complete remission without evidence of graft-vs-host disease or infections; 1 patient died of chronic lung graft-vs-host disease at 6 months post-transplantation; and the other 2 patients died of sepsis post-transplantation because of unsuccessful engraftments. Severe malnutrition and growth retardation associated with interleukin-10 receptor-A deficiency were significantly improved post-transplantation. We recommend umbilical cord blood transplantation as a potential treatment for very early-onset inflammatory bowel disease with a defined monogenic immunodeficiency, and we suggest that reduced-intensity conditioning chemotherapy is more suitable than myeloablative conditioning for patients with severe malnutrition and bowel disease. We have demonstrated success with reduced-intensity conditioning for interleukin-10 receptor-A deficiency in pediatric patients with severe clinical conditions. 10.1093/ibd/izy028_video1izy028.video15786489183001.

[Recurrence of chronic active Epstein-Barr virus infection presenting with myelopathy after umbilical cord blood transplantation].

PubMed

Watanabe, Shohei; Okada, Masaya; Tokugawa, Tazuko; Sawada, Akihiro; Ogawa, Hiroyasu; Yoshikawa, Hiroo

2014-01-01

A 38-year-old man was admitted to our hospital with neck pain, dysesthesia of both hands, and weakness of the left upper limb. He had been diagnosed with a chronic active Epstein-Barr virus infection (CAEBV) at the age of 34 and had undergone umbilical cord blood transplantation at the age of 37. MRI of the spinal cord revealed an intramedullary hyperintense lesion on T₂-weighted images with gadolinium enhancement. Because his laboratory tests revealed proliferation of CD19(+) lymphocytes in the peripheral blood, and EBV DNA was detected in both peripheral blood and CSF, he was diagnosed as having post-transplant EBV associated lymphoproliferative disease. However, chemotherapy did not alleviate his symptoms. At a later time, quantitative chimerism analysis of his CSF showed a higher proportion of lymphocytes that had originated from the recipient. Finally, he was diagnosed as having a recurrence of CAEBV in the central nervous system, and his symptoms were restored by intrathecal chemotherapy (methotrexate, cytosine arabinoside, and prednisolone). Quantitative chimerism analysis of CSF was useful for diagnosing the recurrence of CAEBV in the central nervous system.

The crying sign: the winking umbilical cord

PubMed Central

Smith, Aisling M; Healy, David B; Ryan, C Anthony; Dempsey, Eugene M

2015-01-01

A preterm baby girl, born at 34 weeks gestation, with features of Beckwith-Wiedemann syndrome was noted to have a relatively large umbilical stump. No fetal abnormalities had been detected on anatomy scan at 28 weeks and only mild polyhydramnios and macrosomia were noted on a 32-week ultrasound scan. Although there was no obvious omphalocoele, clinical assessment of the umbilical cord revealed an abdominal wall defect through which bowel would protrude into the umbilicus when the infant was crying. In keeping with an abdominal wall defect α-fetoprotein was found to be elevated. Surgical consultation advised conservative management. Subsequently, detachment of the umbilical cord occurred 1 week postdischarge and a large umbilical hernia persists. Genetic analysis confirmed a diagnosis of Beckwith-Wiedemann syndrome. PMID:25820111

[The cord blood bank at the Instituto Mexicano del Seguro Social].

PubMed

Peñaflor-Juárez, Karina; Guillén-Chan, Sonia Marilyn; Romero-Juárez, Yanín; Luna-Bautista, Fernando; Franco-Gutiérrez, Elizabeth; Arellano-Ocampo, Jesús Salvador; Ibáñez-Sánchez, Rocío; de Lourdes Domínguez-Contreras, María; Guerra-Márquez, Angel

2015-01-01

Hematopoietic stem cells have been used for over 50 years in the treatment of diverse diseases. Umbilical cord blood (UCB) has proved to be a viable source of hematopoietic stem cells for transplantation purposes. The aim was to report the contribution of the umbilical cord blood bank over the past 9 years, in the treatment of various diseases. Since 2005 the number of units of blood from the umbilical cord and their use for transplantation in diverse disease were analyzed. A selection of volunteer pregnant women in labor was performed. Umbilical cord blood was obtained from them, which underwent processing, cryopreservation and validation, as well as compatibility test before using for transplantation. Ten thousand and ninety nine candidates to donation were assessed, from whom 2481 unit of UCB were collected. Of these, 893 unit were processed and cryopreserved for transplantation. In 65% of cases there was histocompatibility between the cord cell and the receptors. Transplantation was done in 87 patients, 67% had hematologic neoplasias, who have received 140 units of UCB in 102 transplants. This Bank of UCB ranks second in the world in productivity according to the rate of utility of units in transplantation (3.3%). Our bank of UCB has been able to develop a cell line (hematopoietic stem cells) with international quality standards and has been beneficial for patients served by our institution with need of a transplant mainly in hemato-oncologic patients.

Umbilical cord blood banking in the worldwide hematopoietic stem cell transplantation system: perspectives for Ukraine.

PubMed

Kalynychenko, T O

2017-09-01

Significant progress in the promotion of procedural technologies associated with the transplantation of hematopoietic stem cells caused a rapid increase in activity. The exchange of hematopoietic stem cells for unrelated donor transplantations is now much easier due to the relevant international professional structures and organizations established to support cooperation and standard setting, as well as rules for the functioning of both national donor registries and cord blood banks. These processes are increasing every year and are contributing to the outpacing rates of development in this area. Products within their country should be regulated by the competent government authorities. This study analyzes the work of international and national levels of support for transplantation activity in the field of unrelated hematopoietic stem cell transplantation, the standardization order of technologies, as well as data that justify the need to create a network of donated umbilical cord blood banks in Ukraine as a factor in the development of allogeneic transplantation. This will promote the accessibility of international standards for the treatment of serious diseases for Ukrainian citizens.

[Private umbilical cord blood banking does not reduce the number of samples for scientific stem cell research].

PubMed

Jacobs, V R; Niemeyer, M; Gottschalk, N; Schneider, K T; Kiechle, M

2005-12-01

Private umbilical cord blood (UCB) banking after delivery has increased over the last decade. For adult/somatic stem cell research UCB is an essential source of stem cells and researchers question if the number of UCB samples for research might be reduced by private banking. A survey among seven private blood banks in Germany and analysis and comparison of the number of UCB samples donated for research within the STEMMAT project with private blood banking were performed from 03/2003 to 06/2005 at the Frauenklinik (OB/GYN), Technical University Munich, Germany. Within 27.5 months 1,551 UCB samples were collected for research purposes; the effective recruitment rate was higher than expectations at an effective 66.2 %. Private UCB banking [n = 24] was distributed among three cord blood banks [n = 16, 6 and 4]. The rate of private blood banking was 0.99 % for all deliveries, thus reducing the effective rate for research purpose by only 1.5 %. Under the assumption of active and successful recruitment of scientific UCB samples, private blood banking does not significantly reduce this rate and therefore is a negligible rival in the competition for sufficient numbers of UCB samples for research.

The influence of active and passive smoking during pregnancy on umbilical cord blood levels of vitamins A and E and neonatal anthropometric indices.

PubMed

Titova, Olga E; Ayvazova, Elena A; Bichkaeva, Fatima A; Brooks, Samantha J; Chumakova, Galina N; Schiöth, Helgi B; Benedict, Christian

2012-10-28

Smoking during pregnancy has been shown to be detrimental for the developing fetus. The effects of active and passive maternal smoking on umbilical cord serum levels of vitamin A and vitamin E were examined. Secondary measures included anthropometric parameters in the newborn. Maternal and umbilical cord serum levels of vitamins A and E were measured at delivery. The mothers were assigned to three groups: non-smoking (n 12); passive smoking (n 13); active smoking (n 18). Based on multivariate linear regressions, active smoking during pregnancy was associated with increased umbilical cord serum levels of vitamin A and vitamin E. While enhanced circulating levels of vitamin A in cord blood were also found in non-smoking mothers exposed to tobacco smoke during pregnancy, those of vitamin E were not influenced. Further, an inverse association between smoking behaviour during pregnancy and birth length was observed, with shortest length in active smokers followed by passive smoking mothers. Active and passive maternal smoking behaviour during pregnancy increases the fetal demand for antioxidant compounds in order to counteract the oxidative burden by cigarette smoke. Against this background, the observed increase in umbilical cord serum levels of vitamins A and E may subserve antioxidative processes in response to tobacco smoke-induced oxidative stress. This would reduce the availability of vitamins A and E for fetal maturation, which is critical inasmuch as both compounds are indispensable for the developing fetus. However, due to the cross-sectional nature of our observation, this line of reasoning definitely requires validation in cause-effect experiments in the future.

Concentrations of Polychlorinated Biphenyls and Organochlorine Pesticides in Umbilical Cord Blood Serum of Newborns in Kingston, Jamaica

PubMed Central

Rahbar, Mohammad H.; Samms-Vaughan, Maureen; Hessabi, Manouchehr; Dickerson, Aisha S.; Lee, MinJae; Bressler, Jan; Tomechko, Sara E.; Moreno, Emily K.; Loveland, Katherine A.; Desai, Charlene Coore; Shakespeare-Pellington, Sydonnie; Reece, Jody-Ann; Morgan, Renee; Geiger, Matthew J.; O’Keefe, Michael E.; Grove, Megan L.; Boerwinkle, Eric

2016-01-01

To date much of the biomonitoring related to exposure to polychlorinated biphenyls (PCBs) and organochlorine (OC) pesticides is from middle to high income countries, including the U.S., Canada and Europe, but such data are lacking for the majority of low to middle income countries. Using data from 64 pregnant mothers who were enrolled in 2011, we aimed to assess the concentrations of the aforementioned toxins in umbilical cord blood serum of 67 Jamaican newborns. For 97 of the 100 PCB congeners and 16 of the 17 OC pesticides, all (100%) concentrations were below their respective limits of detection (LOD). Mean (standard deviation (SD)) lipid-adjusted concentrations in cord blood serum for congeners PCB-153, PCB-180, PCB-206 and total PCB were 14.25 (3.21), 7.16 (1.71), 7.30 (1.74) and 28.15 (6.03) ng/g-lipid, respectively. The means (SD) for the 4,4′-dichlorodiphenyldichloroethylene (DDE)-hexane fraction and total-DDE were 61.61 (70.78) and 61.60 (70.76) ng/g-lipid, respectively. Compared to the U.S. and Canada, the concentrations of these toxins were lower in cord-blood serum of Jamaican newborns. We discuss that these differences could be partly due to differences in dietary patterns in these countries. Despite limitations in our dataset, our results provide information on the investigated toxins in cord blood serum that could serve as a reference for Jamaican newborns. PMID:27775677

Umbilical cord rupture: a case report and review of literature.

PubMed

Naidu, Madhusudhan; Nama, Vivek; Karoshi, Mahantesh; Kakumani, Vijayasri; Worth, Richard

2007-01-01

The umbilical cord acts as a mechanical conduit between the fetus and placenta, allowing movement of water and nutrient substances between the fetal circulation and the amniotic fluid. Complications can occur antenatally or intranatally and are usually acute events that require immediate delivery to prevent intrauterine death. Even though the majority of the cord complications are unpreventable, significant improvement in perinatal mortality and morbidity can be achieved if such an event can be predicted. Umbilical cord rupture is not uncommon, but significantly underreported. We present an unusual cause of umbilical cord rupture and a review of literature.

Impact of Delayed Infusion Time in Umbilical Cord Blood Transplantation.

PubMed

Mitchell, Richard; Wagner, John E; Brunstein, Claudio; Cao, Qing; McKenna, David H; Verneris, Michael R

2017-05-01

In umbilical cord blood (UCB) transplantation, UCB units are typically thawed, washed, and infused into the patient as rapidly as possible. In some instances there is a delay in the time from the unit thaw and wash procedure to infusion into the patient. Therefore, we examined the effect of thaw duration time on engraftment outcomes in 567 patients undergoing UCB transplantation. With a range of 32 to 523 minutes, a prolonged thaw duration had no obvious effect on the incidence of neutrophil engraftment or time to recovery. This was true for recipients of single UCB transplantation (incidence: 97% versus 93%, P = .13; time to neutrophil recovery: 21 days versus 21 days, P = .32; and platelet recovery: 79% versus 78%, P = .48), and similar results were observed in double UCB transplantation (time to neutrophil engraftment: 20 days versus 19 days, P = .71). However, there was a trend toward better platelet recovery in recipients of double UCB transplants with prolonged thaw duration (HR, 1.28; P = .06). In conclusion, this study demonstrates prolonged thaw duration has no detrimental effect on engraftment after single or double UCB transplantation. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Attitudes of Swiss mothers toward unrelated umbilical cord blood banking 6 months after donation.

PubMed

Danzer, Enrico; Holzgreve, Wolfgang; Troeger, Carolyn; Kostka, Ulrike; Steimann, Sabine; Bitzer, Johanes; Gratwohl, Alois; Tichelli, André; Seelmann, Kurt; Surbek, Daniel V

2003-05-01

During the past decade, the use of umbilical cord blood (CB) as a source of transplantable hematopoietic stem cells has been increasing. Little is known about the psychosocial consequences that later affect parents after unrelated CB donation. The objective of this study was to evaluate the attitudes of mothers toward unrelated donation of umbilical CB for transplantation 6 months after giving birth. A prospective study was performed with a standardized, anonymous questionnaire distributed to 131 women 6 months after CB donation. The questionnaire included topics concerning views about the ethical accuracy of having donated CB, emotional responses after donation, concerns about genetic testing and research with CB samples, attitude toward anonymity between her child and possible unrelated CB recipient, and willingness to repeatedly donate umbilical CB in a next pregnancy. The vast majority (96.1%) stated that they would donate umbilical CB again, and all respondents were certain that their decision to have donated umbilical CB was ethical. With regard to the potential risks of genetic testing and "experimentation" of umbilical CB, a significant correlation (p = 0.01) was found between negative attitudes and the decision not to donate umbilical CB again. Additionally, it was observed that women who had a negative experience concerning the donation of CB would not donate again (p = 0.004). This study shows a high degree of satisfaction of unrelated umbilical CB donation for banking in women 6 months after delivery. Despite a well-performed and detailed informed consent procedure, one of the ongoing issues for the donators in CB banking involves the concern regarding of improper use of the cells, such as genetic testing or experimentation. Accurate and detailed counseling of pregnant women and their partners therefore maximizes the likelihood that they will donate CB for unrelated banking. These data provide a basis for the improvement of donor selection procedures

Poorly understood and often miscategorized congenital umbilical cord hernia: an alternative repair method.

PubMed

İnce, E; Temiz, A; Ezer, S S; Gezer, H Ö; Hiçsönmez, A

2017-06-01

Umbilical cord hernia is poorly understood and often miscategorized as "omphalocele minor". Careless clamping of the cord leads to iatrogenic gut injury in the situation of umbilical cord hernia. This study aimed to determine the characteristics and outcomes of umbilical cord hernias. We also highlight an alternative repair method for umbilical cord hernias. We recorded 15 cases of umbilical cord hernias over 10 years. The patients' data were retrospectively reviewed, and preoperative preparation of the newborn, gestational age, birth weight, other associated malformations, surgical technique used, enteral nutrition, and length of hospitalization were recorded. This study included 15 neonates with umbilical cord hernias. The mean gestational age at the time of referral was 38.2 ± 2.1 umbilical cord hernia, the body folds develop normally and form the umbilical ring. The double purse-string technique is easy to apply and produces satisfactory cosmetic results in neonates with umbilical cord hernias.

[Umbilical cord collision in the first trimester in a monoamniotic twin pregnancy--does it really matter?].

PubMed

Ropacka-Lesiak, Mariola; Lebioda, Anna; Breborowicz, Grzegorz

2012-09-01

A case of an umbilical cord collision diagnosed in the first trimester of a monochorionic monoamniotic twin pregnancy is presented. An intensive surveillance included ultrasound monitoring with color and spectral Doppler and fetal echocardiography. The first signs of fetal distress were observed at 31 weeks of gestation. The brain sparing effect as well as a periodic appearance of the "notch" in the wave forms obtained from the umbilical artery from the collision region were observed. In the first ultrasound scan there were no abnormalities in twin I. In contrast, in twin II a vascular resistance in the umbilical artery was at the upper limit for the gestational age. Five days later, decreased vascular resistance in the middle cerebral artery, which fluctuated at the lower limit, was noticed in twin II. After the next four days, PI in the middle cerebral artery decreased below the lower limit and tricuspid regurgitation appeared. In twin I the vascular resistance in the umbilical artery increased and remained at the upper limit of the reference ranges. Cardiotocographic records did not reveal signs of fetal distress. After a week the signs of brain sparing effect were visible in both fetuses. However, twin II showed features of umbilical cord clamping in the form of abnormal blood flow waveforms in the umbilical artery ("notch"). Therefore, despite the absence of signs of fetal distress in CTG in monochorionic monoamniotic twins with growth discordance of 20% and exponents of periodical clamping of the umbilical cord in twin II at 34 weeks, the decision to perform a caesarean section was made. The patient gave birth to two daughters (twin I: weight 1780g, Ap 10, pH 7.39, 7.40, BE -3.0, -2.6, and twin II: weight 1860g, Ap 10, pH 7.29, 7.35, BE -1.4, -2.4). During the delivery the umbilical cords collision was found at the region close to the body of twins. This case presents the possibility of using ultrasound and Doppler in the early diagnosis, monitoring and

Cost of umbilical cord blood units released for transplantation.

PubMed

Sirchia, G; Rebulla, P; Tibaldi, S; Lecchi, L

1999-06-01

A large number of institutions have started programs banking umbilical cord blood (UCB) for allogeneic unrelated-donor and related-donor transplantation. However, limited information is available on the financial issues surrounding these activities. The aim of this study was to determine the fee per UCB unit released for transplantation that would allow cost recovery after 10 years. Three organizational models were considered suitable to provide units for five UCB transplants per 1 million population per year, a figure that would translate into an annual need for 280 units in Italy. Models A, B, and C included, respectively, seven networked banks, each with an inventory of 1,500 units; two networked banks, each with an inventory of 5,000 units; and one bank with an inventory of 10,000 units. It was estimated that it would take 3 years to develop the cryopreserved inventory and that approximately 3 percent of the inventory could be released and replaced each year during the 7-year interval between the fourth and tenth years of activity. The data on the costs of labor, reagents and diagnostics, disposables, depreciation and maintenance, laboratory tests, and overhead, as well as the operational data used in the analysis were collected at the Milano Cord Blood Bank in 1996. Fees of US $15,061, $12,666, and $11,602 per unit released during the fourth through the tenth years of activity allow full cost recovery (principle and interest) under Models A, B, and C, respectively. Although UCB procurement costs compare favorably with those of other hematopoietic cell sources, these results and the current fee of US $15,300 used in some institutions show that UCB is an expensive resource. Therefore, judicious planning of banking programs with high quality standards is necessary to prevent economic losses. The advantages of lower fees associated with the centralized banking approach of Model C should be balanced with the more flexible collection offered by Model A.

[Expression and significance of adipocyte fatty acid-binding protein in placenta, serum and umbilical cord blood in preeclampsia].

PubMed

Yan, Jian-Ying; Wang, Xiao-Juan

2010-12-01

To investigate the change of adipocyte fatty acid-binding protein (FABP4) in maternal serum and umbilical cord blood and FABP4 mRNA placental expression in patients with preeclampsia (PE). A total of 60 women with PE and 60 normal pregnant women as control participated in this study.All are admitted to Fujian Maternity and Children Health Hospital for delivery from December 2008 to October 2009. Patients with PE were divided into early-onset group (n = 30, presented at ≤ 34 weeks of gestation) and late-onset group (n = 30, presented at > 34 weeks of gestation), with 30 normal pregnant women as early control group (≤ 34 weeks of gestation) and 30 as late control group (> 34 weeks of gestation). Enzyme-linked immunosorbent assay (ELISA) was used to detect FABP4, fasting serum glucose, fasting insulin (FINS) in maternal serum and FABP4 in umbilical cord blood. Real-time fluorescent quantitative reverse transcription PCR was used to detect placental FABP4 mRNA expression. Furthermore, clinical and biochemical parameters were recorded, such as body mass index (BMI), systolic pressure (SP), diastolic pressure (DP), mean arterial pressure (MAP), total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), high density lipoprotein (HDL), creatinine (Cr), uric acid (UA), glomerular filtration rate (GFR), 24 hours urine protein in pregnant women and neonatal weight. (1) Maternal serum FABP4 was (176 ± 9) ng/L in early-onset PE group and (170 ± 9) ng/L in late-onset PE group, significantly elevated as compared to (81 ± 13) ng/L in early control group and (94 ± 15) ng/L in late control group. (2) Mean maternal FINS, homeostasis model of assessment for insulin resistence index (HOMA-IR) were significantly elevated in the early-onset PE group and late-onset PE group as compared to control groups, respectively. (3) Mean placental FABP4 mRNA expression were significantly elevated in the early-onset PE group and late-onset PE group as compared to late control

Impact of long-term cryopreservation on single umbilical cord blood transplantation outcomes.

PubMed

Mitchell, Richard; Wagner, John E; Brunstein, Claudio G; Cao, Qing; McKenna, David H; Lund, Troy C; Verneris, Michael R

2015-01-01

Umbilical cord blood (UCB) may be collected and cryopreserved for years before use. In vitro and murine models suggest that the duration of storage does not affect UCB progenitor cell performance; however, the impact of UCB age on clinical outcomes has not been definitely defined. This study sought to determine the effect of UCB unit cryopreservation time on hematopoietic potency. We analyzed 288 single UCB units used for transplantation from 1992 to 2013, with unit cryopreservation time ranging from .08 to 11.07 years. UCB unit post-thaw characteristics were examined, including percent recovery of total nucleated cells (TNC). The number of years the UCB unit spent in cryopreservation had no impact on TNC recovery nor UCB unit post-thaw viability. Duration of cryopreservation also had no impact on neutrophil or platelet engraftment in single UCB transplantations. These results show that UCB units can undergo cryopreservation for at least 10 years with no impact on clinical outcomes. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Experiences of the Dresdner Cord Blood Bank, supported by the Deutsche Knochenmarkspenderdatei.

PubMed

Ordemann, R; Petzold, K; Hölig, K; Schaffer, B; Mauersberger, S; Ehninger, G; Ehminger, G

1999-01-01

Allogeneic bone marrow and peripheral blood stem cell transplantation is the treatment of choice for some malignant hematologic diseases, marrow failure syndromes, and severe congenital immunodeficiency states. Since Gluckman et al reported in 1988 the first successful human leukocyte antigen (HLA)-matched sibling umbilical cord blood stem cell transplantation, it has been known that cord blood is a valuable source of hematopoietic stem cells. The Cord Blood Bank at the University Hospital of Dresden was founded in 1997 and started collecting, processing, and cryoconserving umbilical cord blood in August 1997. The cord blood bank is supported by the largest German donor registry: Deutsche Knochenmarkspenderdatei (DKMS) in Tubingen, Germany. With the informed consent of the mothers, the collection is performed in collaboration with six hospitals in Dresden, Berlin, and Bautzen. We routinely perform a volume reduction by centrifuging the blood bag and expressing the leukocyte-rich supernatant. Routinely, sterility, total nucleated cells (TNC), CD34+ cell count, HLA class I and II, ABO/Rh blood group, and colony-forming units are evaluated. The maternal blood is screened for anti-immunodeficiency virus (anti-HIV), anti-hepatitis C virus (anti-HCV), anti-hepatitis B surface antigen (HBsAg), anti-hepatitis B surface (anti-HBs), anti-hepatitis B core (anti-HBc), anticytomegalovirus (anti-CMV), and toxoplasmosis and with Treponema pallidum hemagglutination assay (TPHA). More than 1,000 cord blood units could be collected. Because of the required volume and cell count and because of sterility, 50% of the collected units had to be discharged. Our results are comparable with data of other cord blood banks: mean volume 79 mL; cell count after volume reduction-TNC, 7.16 x 10(8); mononucleated cells (MNC), 3.75 x 10(8); CD34+ cells, 1.95 x 10(6); colony-forming units (CFU), 67.1 x 10(4). To increase the pool of potential umbilical cord blood units and in order to evaluate the

Carboxyhemoglobin levels in umbilical cord blood of women with pre-eclampsia and intrauterine growth restriction.

PubMed

Yusuf, Kamran; Kamaluddeen, Majeeda; Wilson, R Douglas; Akierman, Albert

2012-11-01

Pre-eclampsia (PE) and intrauterine growth restriction (IUGR) are associated with abnormal placentation. Heme oxygenase (HO) and carbon monoxide (CO) are involved in normal placental development and function and vasomotor control in the placenta. The objective of our study was to measure CO levels, as assessed by carboxyhemoglobin (COHb) levels in the umbilical cord arterial blood of women with PE, normotensive IUGR (<10th percentile for birth weight), and normotensive pregnancies with appropriate-for-gestational age (AGA) infants. We prospectively analyzed COHb levels in the umbilical arterial blood of women with PE, normotensive IUGR, and normotensive AGA pregnancies. Exclusion criteria included cigarette smoke exposure, hemolytic disorders, a positive direct anti-globulin test, chronic hypertension, fever, and any significant medical illness. COHb levels were measured using the ABL 725 blood gas analyzer. There were 41 women in the normotensive AGA group, 42 in the PE group, and 36 in the normotensive IUGR group. Maternal age, mode of delivery, gravidity, parity, and gender of the infants were similar in the three groups. Gestational age and birth weight were significantly higher in the normotensive AGA group compared with the other two groups. COHb levels were significantly lower in the PE group compared with the normotensive AGA group (0.38±0.06% vs. 0.77±0.11%, P<0.05). COHb levels, although lower in the normotensive IUGR group compared with the normotensive AGA group, did not reach statistical significance. Our data suggests the HO-CO system may have a role in the pathogenesis of PE. We also, for the first time, provide information on umbilical arterial COHb levels in normotensive IUGR pregnancies.

Can routine commercial cord blood banking be scientifically and ethically justified?

PubMed

Fisk, Nicholas M; Roberts, Irene A G; Markwald, Roger; Mironov, Vladimir

2005-02-01

Umbilical cord blood--the blood that remains in the placenta after birth--can be collected and stored frozen for years. A well-accepted use of cord blood is as an alternative to bone marrow as a source of hematopoietic stem cells for allogeneic transplantation to siblings or to unrelated recipients; women can donate cord blood for unrelated recipients to public banks. However, private banks are now open that offer expectant parents the option to pay a fee for the chance to store cord blood for possible future use by that same child (autologous transplantation).

Stem cell transplantation (cord blood transplants).

PubMed

Chao, Nelson J; Emerson, Stephen G; Weinberg, Kenneth I

2004-01-01

achieved by specific genetic pathways known or believed to support primitive HSC proliferation such as Notch-1 receptor activation, Wnt/LEF-1 pathway induction, telomerase or the Homeobox (Hox) gene products. The clinical experience with the use of expanded cord blood cells is also discussed. In Section III, Dr. Kenneth Weinberg describes immune reconstitution or lack thereof following cord blood transplantation. One of the hallmarks of successful hematopoietic stem cell transplantation is the ability to fully reconstitute the immune system of the recipient. Thus, the relationship between stem cell source and the development of T lymphocyte functions required for protection of the recipient from infection will be described, and cord blood recipients will be compared with those receiving other sources of stem cells. T cell development is described in detail, tracking from prethymic to postthymic lymphocytes with specific attention to umbilical cord blood as the source of stem cells. Moreover, a discussion of the placenta as a special microenvironment for umbilical cord blood is presented. Strategies to overcome the immunological defects are presented to improve the outcome of these recipients.

Maternal obesity alters immune cell frequencies and responses in umbilical cord blood samples.

PubMed

Wilson, Randall M; Marshall, Nicole E; Jeske, Daniel R; Purnell, Jonathan Q; Thornburg, Kent; Messaoudi, Ilhem

2015-06-01

Maternal obesity is one of the several key factors thought to modulate neonatal immune system development. Data from murine studies demonstrate worse outcomes in models of infection, autoimmunity, and allergic sensitization in offspring of obese dams. In humans, children born to obese mothers are at increased risk for asthma. These findings suggest a dysregulation of immune function in the children of obese mothers; however, the underlying mechanisms remain poorly understood. The aim of this study was to examine the relationship between maternal body weight and the human neonatal immune system. Umbilical cord blood samples were collected from infants born to lean, overweight, and obese mothers. Frequency and function of major innate and adaptive immune cell populations were quantified using flow cytometry and multiplex analysis of circulating factors. Compared to babies born to lean mothers, babies of obese mothers had fewer eosinophils and CD4 T helper cells, reduced monocyte and dendritic cell responses to Toll-like receptor ligands, and increased plasma levels of IFN-α2 and IL-6 in cord blood. These results support the hypothesis that maternal obesity influences programming of the neonatal immune system, providing a potential link to increased incidence of chronic inflammatory diseases such as asthma and cardiovascular disease in the offspring. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Local Perceptions, Cultural Beliefs and Practices That Shape Umbilical Cord Care: A Qualitative Study in Southern Province, Zambia

PubMed Central

Herlihy, Julie M.; Shaikh, Affan; Mazimba, Arthur; Gagne, Natalie; Grogan, Caroline; Mpamba, Chipo; Sooli, Bernadine; Simamvwa, Grace; Mabeta, Catherine; Shankoti, Peggy; Messersmith, Lisa; Semrau, Katherine; Hamer, Davidson H.

2013-01-01

Background Global policy regarding optimal umbilical cord care to prevent neonatal illness is an active discussion among researchers and policy makers. In preparation for a large cluster-randomized control trial to measure the impact of 4% chlorhexidine as an umbilical wash versus dry cord care on neonatal mortality in Southern Province, Zambia, we performed a qualitative study to determine local perceptions of cord health and illness and the cultural belief system that shapes umbilical cord care knowledge, attitudes, and practices. Methods and Findings This study consisted of 36 focus group discussions with breastfeeding mothers, grandmothers, and traditional birth attendants, and 42 in-depth interviews with key community informants. Semi-structured field guides were used to lead discussions and interviews at urban and rural sites. A wide variation in knowledge, beliefs, and practices surrounding cord care was discovered. For home deliveries, cords were cut with non-sterile razor blades or local grass. Cord applications included drying agents (e.g., charcoal, baby powder, dust), lubricating agents (e.g., Vaseline, cooking oil, used motor oil) and agents intended for medicinal/protective purposes (e.g., breast milk, cow dung, chicken feces). Concerns regarding the length of time until cord detachment were universally expressed. Blood clots in the umbilical cord, bulongo-longo, were perceived to foreshadow neonatal illness. Management of bulongo-longo or infected umbilical cords included multiple traditional remedies and treatment at government health centers. Conclusion Umbilical cord care practices and beliefs were diverse. Dry cord care, as recommended by the World Health Organization at the time of the study, is not widely practiced in Southern Province, Zambia. A cultural health systems model that depicts all stakeholders is proposed as an approach for policy makers and program implementers to work synergistically with existing cultural beliefs and practices

Knowledge, beliefs, and decisions of pregnant Australian women concerning donation and storage of umbilical cord blood: a population-based survey.

PubMed

Jordens, Christopher F C; Kerridge, Ian H; Stewart, Cameron L; O'Brien, Tracey A; Samuel, Gabrielle; Porter, Maree; O'Connor, Michelle A C; Nassar, Natasha

2014-12-01

Many women giving birth in Australian hospitals can choose to donate their child's umbilical cord blood to a public cord blood bank or pay to store it privately. We conducted a survey to determine the proportion and characteristics of pregnant women who are aware of umbilical cord blood (UCB) banking and who have considered and decided about this option. The survey also sought to ascertain information sources, knowledge, and beliefs about UCB banking, and the effect of basic information about UCB on decisions. Researchers and hospital maternity staff distributed a survey with basic information about UCB banking to 1,873 women of at least 24 weeks' gestation who were attending antenatal classes and hospital clinics in 14 public and private maternity hospitals in New South Wales. Most respondents (70.7%) were aware of UCB banking. Their main information sources were leaflets from hospital clinics, print media, antenatal classes, TV, radio, friends, and relatives. Knowledge about UCB banking was patchy, and respondents overestimated the likelihood their child would need or benefit from UCB. Women who were undecided about UCB banking were younger, less educated, or from ethnic or rural backgrounds. After providing basic information about UCB banking, the proportion of respondents who indicated they had decided whether or not to donate or store UCB more than doubled from 30.0 to 67.7 percent. Basic information for parents about UCB banking can affect planned decisions about UCB banking. Information should be accurate and balanced, should counter misconceptions, and should target specific groups. © 2014 Wiley Periodicals, Inc.

Manganese concentrations in maternal and umbilical cord blood: related to birth size and environmental factors.

PubMed

Guan, Huai; Wang, Man; Li, Xiaowei; Piao, Fengyuan; Li, Qiujuan; Xu, Lei; Kitamura, Fumihiko; Yokoyama, Kazuhito

2014-02-01

Manganese (Mn) is an essential element and a potential toxicant for developing organism. Deficiency and excess of it were both deleterious to fetal growth in experimental animals. However, literature on relationship between Mn status and birth outcome in humans is sparse. Mn concentrations were measured in mother whole blood (MWB) and umbilical cord blood (UCB) in 125 pairs of mother-infant; birth size was examined and relationship between them was analysed. Potentially environmental factors influencing Mn loads in maternal and fetal organisms were investigated through epidemiological method. Mn level in UCB was significantly higher than that in MWB (mean value: 54.98 vs. 78.75 µg/L), and a significant positive correlation was shown between them. There was a quadratic curvilinear (inverted U-shaped curve) relationship between MWB Mn and birth size, and between UCB Mn and birth size. Both univariate analysis and multiple linear regression analysis showed that exposure to harmful occupational factors during gestation remarkably increased maternal and fetal Mn levels. Living close to major transportation routes (<500 m) also increased the MWB Mn levels. Our results suggested that lower or higher Mn level in maternal and umbilical blood may induce adverse effect on birth size in humans. In addition, increased levels of Mn in MWB or UCB may be associated with exposure to some environmental hazard factors.

Are hybrid umbilical cord blood banks really the best of both worlds?

PubMed

Guilcher, Gregory M T; Fernandez, Conrad V; Joffe, Steven

2015-03-01

Since the first use of umbilical cord blood (UCB) as a medical therapy, the number of UCB banks worldwide has grown. Public UCB banks offer the option of altruistic donation, whereas private banks allow a product to be stored for the exclusive use of the paying client. With many more UCB products banked privately than publicly in countries such as the USA, hybrid models blending aspects of public and private banking have been proposed. One such bank is in operation in the UK. In this paper we review the hybrid UCB model and conclude that it offers limited benefit to the general public. Furthermore, compared with private banking, this model provides few advantages and potential disadvantages to private clients. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A risk factor analysis of outcomes after unrelated cord blood transplantation for children with Wiskott-Aldrich syndrome

PubMed Central

Shekhovtsova, Zhanna; Bonfim, Carmem; Ruggeri, Annalisa; Nichele, Samantha; Page, Kristin; AlSeraihy, Amal; Barriga, Francisco; de Toledo Codina, José Sánchez; Veys, Paul; Boelens, Jaap Jan; Mellgren, Karin; Bittencourt, Henrique; O’Brien, Tracey; Shaw, Peter J.; Chybicka, Alicja; Volt, Fernanda; Giannotti, Federica; Gluckman, Eliane; Kurtzberg, Joanne; Gennery, Andrew R.; Rocha, Vanderson

2017-01-01

Wiskott-Aldrich syndrome is a severe X-linked recessive immune deficiency disorder. A scoring system of Wiskott-Aldrich syndrome severity (0.5–5) distinguishes two phenotypes: X-linked thrombocytopenia and classic Wiskott-Aldrich syndrome. Hematopoietic cell transplantation is curative for Wiskott-Aldrich syndrome; however, the use of unrelated umbilical cord blood transplantation has seldom been described. We analyzed umbilical cord blood transplantation outcomes for 90 patients. The median age at umbilical cord blood transplantation was 1.5 years. Patients were classified according to clinical scores [2 (23%), 3 (30%), 4 (23%) and 5 (19%)]. Most patients underwent HLA-mismatched umbilical cord blood transplantation and myeloablative conditioning with anti-thymocyte globulin. The cumulative incidence of neutrophil recovery at day 60 was 89% and that of grade II–IV acute graft-versus-host disease at day 100 was 38%. The use of methotrexate for graft-versus-host disease prophylaxis delayed engraftment (P=0.02), but decreased acute graft-versus-host disease (P=0.03). At 5 years, overall survival and event-free survival rates were 75% and 70%, respectively. The estimated 5-year event-free survival rates were 83%, 73% and 55% for patients with a clinical score of 2, 4–5 and 3, respectively. In multivariate analysis, age <2 years at the time of the umbilical cord blood transplant and a clinical phenotype of X-linked thrombocytopenia were associated with improved event-free survival. Overall survival tended to be better in patients transplanted after 2007 (P=0.09). In conclusion, umbilical cord blood transplantation is a good alternative option for young children with Wiskott-Aldrich syndrome lacking an HLA identical stem cell donor. PMID:28255019

A risk factor analysis of outcomes after unrelated cord blood transplantation for children with Wiskott-Aldrich syndrome.

PubMed

Shekhovtsova, Zhanna; Bonfim, Carmem; Ruggeri, Annalisa; Nichele, Samantha; Page, Kristin; AlSeraihy, Amal; Barriga, Francisco; de Toledo Codina, José Sánchez; Veys, Paul; Boelens, Jaap Jan; Mellgren, Karin; Bittencourt, Henrique; O'Brien, Tracey; Shaw, Peter J; Chybicka, Alicja; Volt, Fernanda; Giannotti, Federica; Gluckman, Eliane; Kurtzberg, Joanne; Gennery, Andrew R; Rocha, Vanderson

2017-06-01

Wiskott-Aldrich syndrome is a severe X-linked recessive immune deficiency disorder. A scoring system of Wiskott-Aldrich syndrome severity (0.5-5) distinguishes two phenotypes: X-linked thrombocytopenia and classic Wiskott-Aldrich syndrome. Hematopoietic cell transplantation is curative for Wiskott-Aldrich syndrome; however, the use of unrelated umbilical cord blood transplantation has seldom been described. We analyzed umbilical cord blood transplantation outcomes for 90 patients. The median age at umbilical cord blood transplantation was 1.5 years. Patients were classified according to clinical scores [2 (23%), 3 (30%), 4 (23%) and 5 (19%)]. Most patients underwent HLA-mismatched umbilical cord blood transplantation and myeloablative conditioning with anti-thymocyte globulin. The cumulative incidence of neutrophil recovery at day 60 was 89% and that of grade II-IV acute graft- versus -host disease at day 100 was 38%. The use of methotrexate for graft- versus -host disease prophylaxis delayed engraftment ( P =0.02), but decreased acute graft- versus -host disease ( P =0.03). At 5 years, overall survival and event-free survival rates were 75% and 70%, respectively. The estimated 5-year event-free survival rates were 83%, 73% and 55% for patients with a clinical score of 2, 4-5 and 3, respectively. In multivariate analysis, age <2 years at the time of the umbilical cord blood transplant and a clinical phenotype of X-linked thrombocytopenia were associated with improved event-free survival. Overall survival tended to be better in patients transplanted after 2007 ( P =0.09). In conclusion, umbilical cord blood transplantation is a good alternative option for young children with Wiskott-Aldrich syndrome lacking an HLA identical stem cell donor. Copyright© Ferrata Storti Foundation.

Pregnant women's perspectives on umbilical cord blood banking.

PubMed

Sugarman, J; Kaplan, L; Cogswell, B; Olson, J

1998-08-01

Promising clinical results suggest that umbilical cord blood (UCB) collected after delivery of a child may have many advantages over bone marrow for transplantation. As there are an increasing number of options regarding the collection of UCB, including private and public banking, more pregnant women are likely to be asked to make decisions about UCB collection. We conducted three focus groups with pregnant women to learn about their perspectives on this emerging technology. All the women in these focus groups indicated that they would choose to have UCB collected. Reasons leading to this choice were that the UCB would otherwise be discarded and altruism. Participants indicated that possible reasons to decide not to have UCB collected include concerns about the safety of the mother and neonate, beliefs about the placenta, threats against confidentiality, rejection of UCB, and the influence of fathers. While feeling confident in making an anticipatory decision about UCB collection, women expressed a clear desire to learn much more about the collection, storage (including distinctions between public and private banking), and use of UCB. In addition, they believed that recruitment for UCB collection should occur after sufficient education about UCB and certainly not after delivery and collection. These data will be useful in guiding efforts to help women make decisions about having UCB collected and in developing an appropriate recruitment and informed consent process for donating UCB to a public bank.

Systemic treatment of focal brain injury in the rat by human umbilical cord blood cells being at different level of neural commitment.

PubMed

Gornicka-Pawlak, El Bieta; Janowski, Miroslaw; Habich, Aleksandra; Jablonska, Anna; Drela, Katarzyna; Kozlowska, Hanna; Lukomska, Barbara; Sypecka, Joanna; Domanska-Janik, Krystyna

2011-01-01

The aim of the study was to evaluate therapeutic effectiveness of intra-arterial infusion of human umbilical cord blood (HUCB) derived cells at different stages of their neural conversion. Freshly isolated mononuclear cells (D-0), neurally directed progenitors (D-3) and neural-like stem cells derived from umbilical cord blood (NSC) were compared. Focal brain damage was induced in rats by stereotactic injection of ouabain into dorsolateral striatum Three days later 10(7) of different subsets of HUCB cells were infused into the right internal carotid artery. Following surgery rats were housed in enriched environment for 30 days. Behavioral assessment consisted of tests for sensorimotor deficits (walking beam, rotarod, vibrissae elicited forelimb placing, apomorphine induced rotations), cognitive impairments (habit learning and object recognition) and exploratory behavior (open field). Thirty days after surgery the lesion volume was measured and the presence of donor cells was detected in the brain at mRNA level. At the same time immunohistochemical analysis of brain tissue was performed to estimate the local tissue response of ouabain injured rats and its modulation after HUCB cells systemic treatment. Functional effects of different subsets of cord blood cells shared substantial diversity in various behavioral tests. An additional analysis showed that D-0 HUCB cells were the most effective in functional restoration and reduction of brain lesion volume. None of transplanted cord blood derived cell fractions were detected in rat's brains at 30(th) day after treatment. This may suggest that the mechanism(s) underlying positive effects of HUCB derived cell may concern the other than direct neural cell supplementation. In addition increased immunoreactivity of markers indicating local cells proliferation and migration suggests stimulation of endogenous reparative processes by HUCB D-0 cell interarterial infusion.

Methylmercury dose estimation from umbilical cord concentrations in patients with Minamata disease.

PubMed

Akagi, H; Grandjean, P; Takizawa, Y; Weihe, P

1998-05-01

The methylmercury exposure of patients with congenital or infantile Minamata disease is known only from a small number of analyses of umbilical cords. Four laboratories in Japan have analyzed a total of 176 samples of umbilical cord tissue obtained from Minamata. The highest concentrations were seen in cord tissue from children born during 1950-1965, i.e., the peak period of acetaldehyde production in Minamata before installation of waste water treatment. Twenty-four samples from patients diagnosed with Minamata disease showed a median mercury concentration of 1.63 microg/g and differed significantly from levels seen in cord tissue from control children. However, children diagnosed with mental retardation had mercury concentrations in cord that were intermediate between the two other groups. Using regression coefficients obtained at a study conducted at the Faroe Islands, the median cord mercury concentration from the children with Minamata disease is estimated to correspond to about 216 microg/L cord blood and 41 microg/g in maternal hair. Based on correlations reported in the literature, the median daily mercury intake of the women whose children developed Minamata disease can then be estimated at about 225 microg. Although these children had fully developed Minamata disease, the estimates of median mercury levels are only four to five times higher than current mercury exposure limits. Copyright 1998 Academic Press.

Can Routine Commercial Cord Blood Banking Be Scientifically and Ethically Justified?

PubMed Central

Fisk, Nicholas M; Roberts, Irene A. G; Markwald, Roger; Mironov, Vladimir

2005-01-01

Background to the debate: Umbilical cord blood—the blood that remains in the placenta after birth—can be collected and stored frozen for years. A well-accepted use of cord blood is as an alternative to bone marrow as a source of hematopoietic stem cells for allogeneic transplantation to siblings or to unrelated recipients; women can donate cord blood for unrelated recipients to public banks. However, private banks are now open that offer expectant parents the option to pay a fee for the chance to store cord blood for possible future use by that same child (autologous transplantation.) PMID:15737000

Haemodynamic effects of umbilical cord milking in premature sheep during the neonatal transition.

PubMed

Blank, Douglas A; Polglase, Graeme R; Kluckow, Martin; Gill, Andrew William; Crossley, Kelly J; Moxham, Alison; Rodgers, Karyn; Zahra, Valerie; Inocencio, Ishmael; Stenning, Fiona; LaRosa, Domeic A; Davis, Peter G; Hooper, Stuart B

2017-12-05

Umbilical cord milking (UCM) at birth may benefit preterm infants, but the physiological effects of UCM are unknown. We compared the physiological effects of two UCM strategies with immediate umbilical cord clamping (UCC) and physiological-based cord clamping (PBCC) in preterm lambs. At 126 days' gestational age, fetal lambs were exteriorised, intubated and instrumented to measure umbilical, pulmonary and cerebral blood flows and arterial pressures. Lambs received either (1) UCM without placental refill (UCMwoPR); (2) UCM with placental refill (UCMwPR); (3) PBCC, whereby ventilation commenced prior to UCC; or (4) immediate UCC. UCM involved eight milks along a 10 cm length of cord, followed by UCC. A net volume of blood was transferred into the lamb during UCMwPR (8.8 mL/kg, IQR 8-10, P=0.01) but not during UCMwoPR (0 mL/kg, IQR -2.8 to 1.7) or PBCC (1.1 mL/kg, IQR -1.3 to 4.3). UCM had no effect on pulmonary blood flow, but caused large fluctuations in mean carotid artery pressures (MBP) and blood flows (CABF). In UCMwoPR and UCMwPR lambs, MBP increased by 12%±1% and 8%±1% and CABF increased by 32%±2% and 15%±2%, respectively, with each milk. Cerebral oxygenation decreased the least in PBCC lambs (17%, IQR 13-26) compared with UCMwoPR (26%, IQR 23-25, P=0.03), UCMwPR (35%, IQR 27-44, P=0.02) and immediate UCC (34%, IQR 28-41, P=0.02) lambs. UCMwoPR failed to provide placental transfusion, and UCM strategies caused considerable haemodynamic disturbance. UCM does not provide the same physiological benefits of PBCC. Further review of UCM is warranted before adoption into routine clinical practice. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Impact of long term cryopreservation on single umbilical cord blood transplant outcomes

PubMed Central

Mitchell, R.; Wagner, J.E.; Brunstein, C.G.; Cao, Q.; McKenna, D.H.; Lund, T.C.; Verneris, M.R.

2015-01-01

Umbilical cord blood (UCB) has the advantage of being collected and cryopreserved for years prior to use. In vitro or in murine models suggest that the duration of storage does not affect UCB progenitor cell performance, however the impact of UCB age on clinical outcomes has not been definitely defined. This study sought to determine the effect of UCB unit cryopreservation time on hematopoietic potency. We analyzed 288 single UCB units used for transplantation from 1992–2013, with unit cryopreservation time ranging from 0.08 to 11.07 years. UCB unit post thaw characteristics were examined, including percent recovery of total nucleated cells (TNC). The number of years the UCB unit spent in cryopreservation had no impact on TNC recovery nor UCB unit post-thaw viability. Duration of cryopreservation also had no impact on neutrophil or platelet engraftment in single UCB transplants. These results show that UCB units can undergo cryopreservation for at least 10 years with no impact on clinical outcomes. PMID:25262882

Serum levels of perfluoroalkyl compounds in human maternal and umbilical cord blood samples

DOE Office of Scientific and Technical Information (OSTI.GOV)

Monroy, Rocio; Morrison, Katherine; Teo, Koon

2008-09-15

Perfluoroalkyl compounds (PFCs) are end-stage metabolic products from industrial flourochemicals used in the manufacture of plastics, textiles, and electronics that are widely distributed in the environment. The objective of the present study was to quantify exposure to perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorodecanoic acid (PFDeA), perfluorohexane sulfonate (PFHxS), perfluoroheptanoic acid (PFHpA), and perfluorononanoic acid (PFNA) in serum samples collected from pregnant women and the umbilical cord at delivery. Pregnant women (n=101) presenting for second trimester ultrasound were recruited and PFC residue levels were quantified in maternal serum at 24-28 weeks of pregnancy, at delivery, and in umbilical cord blood (UCB;more » n=105) by liquid chromatography-mass spectrometry. Paired t-test and multiple regression analysis were performed to determine the relationship between the concentrations of each analyte at different sample collection time points. PFOA and PFOS were detectable in all serum samples analyzed including the UCB. PFOS serum levels (mean{+-}S.D.) were significantly higher (p<0.001) in second trimester maternal serum (18.1{+-}10.9 ng/mL) than maternal serum levels at delivery (16.2{+-}10.4 ng/mL), which were higher than the levels found in UCB (7.3{+-}5.8 ng/mL; p<0.001). PFHxS was quantifiable in 46/101 (45.5%) maternal and 21/105 (20%) UCB samples with a mean concentration of 4.05{+-}12.3 and 5.05{+-}12.9 ng/mL, respectively. There was no association between serum PFCs at any time point studied and birth weight. Taken together our data demonstrate that although there is widespread exposure to PFCs during development, these exposures do not affect birth weight.« less

Prioritization of biomarker targets in human umbilical cord blood: identification of proteins in infant blood serving as validated biomarkers in adults.

PubMed

Hansmeier, Nicole; Chao, Tzu-Chiao; Goldman, Lynn R; Witter, Frank R; Halden, Rolf U

2012-05-01

Early diagnosis represents one of the best lines of defense in the fight against a wide array of human diseases. Umbilical cord blood (UCB) is one of the first easily available diagnostic biofluids and can inform about the health status of newborns. However, compared with adult blood, its diagnostic potential remains largely untapped. Our goal was to accelerate biomarker research on UCB by exploring its detectable protein content and providing a priority list of potential biomarkers based on known proteins involved in disease pathways. We explored cord blood serum proteins by profiling a UCB pool of 12 neonates with different backgrounds using a combination of isoelectric focusing and liquid chromatography coupled with matrix-assisted laser desorption/ionization tandem mass spectrometry (MALDI-MS/MS) and by comparing results with information contained in metabolic and disease databases available for adult blood. A total of 1,210 UCB proteins were identified with a protein-level false discovery rate of ~ 5% as estimated by naïve target-decoy and MAYU approaches, signifying a 6-fold increase in the number of UCB proteins described to date. Identified proteins correspond to 138 different metabolic and disease pathways and provide a platform of mechanistically linked biomarker candidates for tracking disruptions in cellular processes. Moreover, among the identified proteins, 38 were found to be approved biomarkers for adult blood. The results of this study advance current knowledge of the human cord blood serum proteome. They showcase the potential of UCB as a diagnostic medium for assessing infant health by detection and identification of candidate biomarkers for known disease pathways using a global, nontargeted approach. These biomarkers may inform about mechanisms of exposure-disease relationships. Furthermore, biomarkers approved by the U.S. Food and Drug Administration for screening in adult blood were detected in UCB and represent high-priority targets for

Feasibility of trialling cord blood stem cell treatments for cerebral palsy in Australia.

PubMed

Crompton, Kylie E; Elwood, Ngaire; Kirkland, Mark; Clark, Pamela; Novak, Iona; Reddihough, Dinah

2014-07-01

Umbilical cord blood may have therapeutic benefit in children with cerebral palsy (CP), but further studies are required. On first appearance it seems that Australia is well placed for such a trial because we have excellence in CP research backed by extensive CP registers, and both public and private cord blood banks. We aimed to examine the possibilities of conducting a trial of autologous umbilical cord blood cells (UCBCs) as a treatment for children with CP in Australia. Data linkages between CP registers and cord blood banks were used to estimate potential participant numbers for a trial of autologous UCBCs for children with CP. As of early 2013, one Victorian child with CP had cord blood stored in the public bank, and between 1 and 3 children had their cord blood stored at Cell Care Australia (private cord blood bank). In New South Wales, we counted two children on the CP register who had their stored cord blood available in early 2013. We estimate that there are between 10 and 24 children with CP of any type who have autologous cord blood available across Australia. In nations with small populations like Australia, combined with Australia's relatively low per capita cord blood storage to date, it is not currently feasible to conduct trials of autologous UCBCs for children with CP. Other options must be explored, such as allogeneic UCBCs or prospective trials for neonates at risk of CP. © 2014 The Authors. Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Current and historical perspectives on methodological flaws in processing umbilical cord blood.

PubMed

Mehrishi, J N

2013-11-01

Umbilical cord blood (UCB) hematopoietic stem cells (HSC-CD34+) are valuable for treating malignant or nonmalignant disease. Processing UCB by HESPAN-6% and anti-CD34-Miltenyi particles provides insufficient cells for treating adults. Physicochemical-electrokinetic studies on UCB-mononuclear cells (MNCs) under conditions of delayed processing, ice or very low temperatures, and some cell separation media identified artifacts introduced by procedures. Adsorption of biomaterials from cell damage by temperature, degradation products after using enzymes, harsh reagents, dithiothreitol, and HESPAN affect cell properties and distribution. Miltenyi particles internalized by cells could release iron that accumulating in liver or spleen would then risk toxicity. Summary topics included the effects of temperature, HESPAN (fast sedimenting agent), glycoproteases, DNase, and dithiothreitol risk affecting cell receptors in recognition, "homing," leading to possible unintended iatrogenic bioeffects should such cells be transfused into humans. The loss of undetectable and uncaptured low CD34 antigen-bearing cells by Miltenyi particles seems to occur when the current methods of isolation of CD34+ cells and other cells are critically assessed. The purpose here is to highlight and suggest avoiding the procedural flaws involved. Preventing ice temperatures avoids ice-damaged platelets releasing biomaterials that are adsorbed on cells altering UBC-MNCs/HSC properties and cell loss. Omitting the positive selection with antibody-linked Miltenyi particles obviates the use of harsh reagents to release the cells. Internalized Miltenyi particles are a toxicity hazard that needs investigations. Achieving approximately 5% yields of CD34+ cells (153 × 10(5) /110 mL cord-placenta blood) is a major advance holding great promise, for the first time increasing the prospect of stem cell therapy of 70-kg adults, using a single UCB donation (with dose of 1.5 × 10(5) cells/kg) and

Ethnicity, equity and public benefit: a critical evaluation of public umbilical cord blood banking in Australia.

PubMed

Samuel, G N; Kerridge, I H; Vowels, M; Trickett, A; Chapman, J; Dobbins, T

2007-10-01

Over the past decade umbilical cord blood (UCB) has been increasingly used as a source of haematopoietic stem cells (HSCs) for patients who require a HSC transplant but do not have an HLA-matched donor. It was anticipated that using UCB as an alternative source of HSCs would increase the chance of finding a donor, particularly for the otherwise underrepresented ethnic minority groups. To evaluate the effectiveness of the Australian public UCB banks to increase the ethnic diversity of available HSC donations, this paper analyses the ethnic diversity of the Sydney Cord Blood Bank (SCBB), comparing this diversity to that of the Australian Bone Marrow Donor Registry (ABMDR). It also examines the ethnic diversity of those patients who, after requesting a haematopoietic stem cell transplantation in the 2-year period between 2003 and 2005, managed to find a suitably matched bone marrow or UCB donor. We show that the ethnic mix of donors to the SCBB has remained generally broad in source, is comparative to the Australian population, and is more diverse than the ABMDR. This, however, may still not be sufficient to substantially increase the likelihood of finding a donor for some ethnic minority groups.

Establishment of an unrelated umbilical cord blood bank qualification program: ensuring quality while meeting Food and Drug Administration vendor qualification requirements.

PubMed

Rabe, Fran; Kadidlo, Diane; Van Orsow, Lisa; McKenna, David

2013-10-01

Qualification of a cord blood bank (CBB) is a complex process that includes evaluation of multiple aspects of donor screening and testing, processing, accreditation and approval by professional cell therapy groups, and results of received cord blood units. The University of Minnesota Medical Center Cell Therapy Laboratory has established a CBB vendor qualification process to ensure the CBB meets established regulatory and quality requirements. The deployed qualification of CBBs is based on retrospective and prospective review of the CBB. Forty-one CBBs were evaluated retrospectively: seven CBBs were disqualified based on failed quality control (QC) results. Eight CBBs did not meet the criteria for retrospective qualification because fewer than 3 cord blood units were received and the CBB was not accredited. As of March 2012, three US and one non-US CBBs have been qualified prospectively. One CBB withdrew from the qualification process after successful completion of the comprehensive survey and subsequent failure of the provided QC unit to pass the minimum criteria. One CBB failed the prospective qualification process based on processing methods that were revealed during the paper portion of the evaluation. A CBB qualification process is necessary for a transplant center to manage the qualification of the large number of CBBs needed to support a umbilical cord blood transplantation program. A transplant center that has utilized cord blood for a number of years before implementation of a qualification process should use a retrospective qualification process along with a prospective process. © 2013 American Association of Blood Banks.

Umbilical cord blood banking: from personal donation to international public registries to global bioeconomy

PubMed Central

Petrini, Carlo

2014-01-01

The procedures for collecting voluntarily and freely donated umbilical cord blood (UCB) units and processing them for use in transplants are extremely costly, and the capital flows thus generated form part of an increasingly pervasive global bioeconomy. To place the issue in perspective, this article first examines the different types of UCB biobank, the organization of international registries of public UCB biobanks, the optimal size of national inventories, and the possibility of obtaining commercial products from donated units. The fees generally applied for the acquisition of UCB units for transplantation are then discussed, and some considerations are proposed regarding the social and ethical implications raised by the international network for the importation and exportation of UCB, with a particular emphasis on the globalized bioeconomy of UCB and its commerciality or lack thereof. PMID:24971040

The relation between umbilical cord characteristics and the outcome of external cephalic version.

PubMed

Kuppens, Simone M I; Waerenburgh, Evelyne R; Kooistra, Libbe; van der Donk, Riet W P; Hasaart, Tom H M; Pop, Victor J M

2011-05-01

Umbilical cords of fetuses in breech presentation differ in length and coiling from their cephalic counterparts and it might be hypothesised that these cord characteristics may in turn affect ECV outcome. To investigate the relation between umbilical cord characteristics and the outcome of external cephalic version (ECV). Prospective cohort study. Women (>35 weeks gestation) with a singleton fetus in breech presentation, suitable for external cephalic version. Demographic, lifestyle and obstetrical parameters were assessed at intake. ECV success was based on cephalic presentation on ultrasound post-ECV. Umbilical cord length (UCL) and umbilical coiling index (UCI) were measured after birth. The relation between umbilical cord characteristics (cord length and coiling) and the success of external cephalic version. ECV success rate was overall 79/146 (54%), for multiparas 37/46(80%) and for nulliparas 42/100 (42%). Multiple logistic regression showed that UCL (OR: 1.04, CI: 1.01-1.07), nulliparity (OR: 0.20, CI: 0.08-0.51), frank breech (OR: 0.37, 95% CI: 0.15-0.90), body mass index (OR: 0.85, CI: 0.76-0.95), placenta anterior (OR: 0.27, CI: 0.12-0.63) and birth weight (OR: 1.002, CI: 1.001-1.003) were all independently related to ECV success. Umbilical cord length is independently related to the outcome of ECV, whereas umbilical coiling index is not. Copyright © 2011 Elsevier Ltd. All rights reserved.

Safety and efficacy of allogeneic umbilical cord red blood cell transfusion for children with severe anaemia in a Kenyan hospital: an open-label single-arm trial.

PubMed

Hassall, Oliver W; Thitiri, Johnstone; Fegan, Greg; Hamid, Fauzat; Mwarumba, Salim; Denje, Douglas; Wambua, Kongo; Mandaliya, Kishor; Maitland, Kathryn; Bates, Imelda

2015-03-01

In sub-Saharan Africa, children are frequently admitted with severe anaemia needing an urgent blood transfusion, but blood is often unavailable. When conventional blood supplies are inadequate, allogeneic umbilical cord blood could be a feasible alternative. The aim of this study was to assess the safety and efficacy of cord blood transfusion in children with severe anaemia. Between June 26, 2007, and May 20, 2008, 413 children needing an urgent blood transfusion were admitted to Kilifi District Hospital in Kenya. Of these, 87 children were eligible for our study--ie, younger than 12 years, no signs of critical illness, and haemoglobin 100 g/L or lower (if aged 3 months or younger) or 40 g/L or lower (if older than 3 months). Cord blood was donated at Coast Provincial General Hospital, Mombasa, and screened for transfusion-transmitted infections and bacterial contamination. Red blood cells were stored vertically at 2-6°C to enable sedimentation. After transfusion, children were monitored closely for adverse events and followed up for 28 days. The primary outcome measure was the frequency and nature of adverse reactions associated with the transfusion. Secondary outcomes were the changes in haemoglobin concentrations 24 h and 28 days after transfusion, compared with pretransfusion levels. This trial is registered on ISRCTN.com, number ISRCTN66687527. Of the 87 children eligible for the study, cord blood was unavailable for 24, six caregivers declined consent, and two children were withdrawn before transfusion. Therefore, 55 children received umbilical cord red blood cells from 74 donations. Ten (18%) children had ten serious adverse events and 43 (78%) had 94 adverse events; the most frequent adverse events were anaemia (n=14), weight loss (n=12), and vomiting (n=10). An independent expert panel judged none of these adverse events to be probably or certainly caused by the cord blood transfusion (one-sided 97·5% CI 0-6·5). Haemoglobin increased by a median of 26 g

Safety and efficacy of allogeneic umbilical cord red blood cell transfusion for children with severe anaemia in a Kenyan hospital: an open-label single-arm trial

PubMed Central

Hassall, Oliver W; Thitiri, Johnstone; Fegan, Greg; Hamid, Fauzat; Mwarumba, Salim; Denje, Douglas; Wambua, Kongo; Mandaliya, Kishor; Maitland, Kathryn; Bates, Imelda

2015-01-01

Summary Background In sub-Saharan Africa, children are frequently admitted with severe anaemia needing an urgent blood transfusion, but blood is often unavailable. When conventional blood supplies are inadequate, allogeneic umbilical cord blood could be a feasible alternative. The aim of this study was to assess the safety and efficacy of cord blood transfusion in children with severe anaemia. Methods Between June 26, 2007, and May 20, 2008, 413 children needing an urgent blood transfusion were admitted to Kilifi District Hospital in Kenya. Of these, 87 children were eligible for our study—ie, younger than 12 years, no signs of critical illness, and haemoglobin 100 g/L or lower (if aged 3 months or younger) or 40 g/L or lower (if older than 3 months). Cord blood was donated at Coast Provincial General Hospital, Mombasa, and screened for transfusion-transmitted infections and bacterial contamination. Red blood cells were stored vertically at 2–6°C to enable sedimentation. After transfusion, children were monitored closely for adverse events and followed up for 28 days. The primary outcome measure was the frequency and nature of adverse reactions associated with the transfusion. Secondary outcomes were the changes in haemoglobin concentrations 24 h and 28 days after transfusion, compared with pretransfusion levels. This trial is registered on ISRCTN.com, number ISRCTN66687527. Findings Of the 87 children eligible for the study, cord blood was unavailable for 24, six caregivers declined consent, and two children were withdrawn before transfusion. Therefore, 55 children received umbilical cord red blood cells from 74 donations. Ten (18%) children had ten serious adverse events and 43 (78%) had 94 adverse events; the most frequent adverse events were anaemia (n=14), weight loss (n=12), and vomiting (n=10). An independent expert panel judged none of these adverse events to be probably or certainly caused by the cord blood transfusion (one-sided 97·5% CI 0–6·5

Current obstetrical practice and umbilical cord prolapse.

PubMed

Usta, I M; Mercer, B M; Sibai, B M

1999-01-01

The aim of this study was to assess the contribution of current obstetrical practice to the occurrence and complications of umbilical cord prolapse. Maternal and neonatal charts of 87 pregnancies complicated by true umbilical cord prolapse during a 5-year period were reviewed. Twin gestation and noncephalic presentations were common features (14 and 41%, respectively). Eighty-nine percent (77) of infants were delivered by cesarean section of which 29% were classical and 88% were primary. The mean gestational age at delivery was 34.0 +/- 6.0 weeks, and the mean birth weight was 2318 +/- 1159 g. Obstetrical intervention preceded 41 (47%) cases (the obstetrical intervention group): amniotomy (9), scalp electrode application (4), intrauterine pressure catheter insertion (6), attempted external cephalic version (7), expectant management of preterm premature rupture of membranes (14), manual rotation of the fetal head (1), and amnioreduction (1). There were 11 perinatal deaths. Thirty-three percent of the infants (32) had a 5-min Apgar score < 7 and 34% had a cord pH < 7.20. Neonatal seizures, intracerebral hemorrhage, necrotizing enterocolitis, hyaline membrane disease, persistent fetal circulation, sepsis, assisted ventilation, and perinatal mortality were comparable in the "obstetrical intervention" and "no-intervention" groups. Most of the neonatal complications occurred in infants < 32 weeks' gestation. We conclude that obstetrical intervention contributes to 47% of umbilical cord prolapse cases; however, it does not increase the associated perinatal morbidity and mortality.

Exploring opinions and beliefs about cord blood donation among Hispanic and non-Hispanic black women.

PubMed

Rucinski, Dianne; Jones, Risé; Reyes, Brenda; Tidwell, Lawon; Phillips, RoiAnn; Delves, Denise

2010-05-01

Despite higher birth rates among non-Hispanic blacks and Hispanics, the availability of umbilical cord blood from these groups is lower due to lower donation rates than that of non-Hispanic whites. Similar racial and ethnic disparities in donation rates have been found for blood and organ donation. This study is among the first to explore beliefs and attitudes toward umbilical cord blood donation among Hispanic and non-Hispanic black women. Five focus groups composed of Hispanic and non-Hispanic black women were conducted to explore how women conceptualize information needs about umbilical cord blood donation and from whom women want to receive information about donation. Participants were adult women who had given birth within the past year or were pregnant. Lack of basic information regarding umbilical cord blood, its harvesting and use, and the steps and conditions necessary to donate were primary barriers to donation. Women expressed confusion over the differences between "donation" and "banking." The social value of donation was explicitly weighed in terms of the cost of the donation effort. Doctors were viewed as critical sources for information about donation, although women expressed skepticism about doctors' ability to convey sufficient information during short office visits. Efforts to increase donation rates among Hispanic and non-Hispanic black women should include information about both the technical aspects and the social value of donation. The specific terms "umbilical" and "donation" should be used consistently to prevent misunderstanding. Information should be provided by physicians with follow-up by other health providers.

Placental umbilical cord whole blood transfusion to combat anemia in the background of tuberculosis and emaciation and its potential role as an immuno-adjuvant therapy for the under-resourced people of the world.

PubMed

Bhattacharya, N

2006-01-01

Tuberculosis causes approximately 1.5 billion latent infections, 8 million new clinical cases, and 3 million deaths annually, making it the most prevalent infectious disease in the world. Anemia and malnutrition are essential comorbidities with tuberculosis. Cord blood, because of its rich mix of fetal and adult hemoglobin, high platelet and WBC counts, and a plasma filled with cytokine and growth factors, as well as its hypo-antigenic nature and altered metabolic profile, has all the potential of a real and safe alternative to adult blood transfusion. We transfused 106 units (48 ml-148 ml mean 81 ml +/- 6.6 ml SD, median 82 ml, mean packed cell volume 49.4 +/- 3.1 SD, mean percent hemoglobin concentration 16.3 g/dl +/- 1.7 g/dl SD) of placental umbilical cord whole blood (from 1 April 1999 to 1st 2005) after lower uterine cesarean section from consenting mothers to 21 informed consenting patients with tuberculosis who had percent plasma hemoglobin of 8 g/dl or less. After collection, the blood was immediately transfused following the standard adult blood transfusion protocol. Each case was passed through the institutional ethical committee. The patients received 2-21 units of freshly collected placental umbilical cord blood without encountering any clinical, immunological or non-immunological reactions. Three days after completion of the placental umbilical cord blood transfusion, the peripheral blood hematopoietic stem cell (CD34) estimation revealed a rise from the pretransfusion base level (.09%), varying from 2.99% to 33%, which returned to base level in 66.66% at the three-month CD34 re-estimation, without provoking any clinical graft vs host reaction in any of the patients.

Maternal systemic or cord blood inflammation is associated with birth anthropometry in a Tanzanian prospective cohort.

PubMed

Wilkinson, A L; Pedersen, S H; Urassa, M; Michael, D; Andreasen, A; Todd, J; Kinung'hi, S M; Changalucha, J; McDermid, J M

2017-01-01

HIV infection is associated with chronic systemic inflammation, with or without antiretroviral therapy. Consequences for foetal growth are not understood, particularly in settings where multiple maternal infections and malnutrition are common. The study was designed to examine maternal systemic circulating and umbilical cord blood cytokine concentrations in relation to birth anthropometry in a Tanzanian prospective cohort. A 9-plex panel of maternal plasma cytokines in HIV-positive (n = 44) and HIV-negative (n = 70) mothers and the same cytokines in umbilical cord blood collected at delivery was assayed. Linear regression modelled associations between maternal or cord blood cytokines and birth anthropometry. Health indicators (haemoglobin, mid-upper-arm circumference, body mass index) in HIV-positive mothers without considerable immunosuppression did not differ from HIV-negative women. Despite this, HIV-exposed infants had lower birthweight and length. Subgroup analyses indicated that HIV management using HAART was associated with lower plasma TNF-α, as were longer durations of any antiretroviral therapy (≥2 months). Greater maternal plasma TNF-α was associated with earlier delivery (-1.7 weeks, P = 0.039) and lower birthweights (-287 g; P = 0.020), while greater umbilical cord TNF-α (-1.43 cm; P = 0.036) and IL-12p70 (-2.4 cm; P = 0.008) were associated with shorter birth length. Birthweight was inversely associated with cord IL-12p70 (-723 g; P = 0.001) and IFN-γ (-482 g, P = 0.007). Maternal cytokines during pregnancy did not correlate with umbilical cord cytokines at delivery. Systemic inflammation identified in maternal plasma or umbilical cord blood was associated with poorer birth anthropometrics in HIV-exposed and HIV-unexposed infants. Controlling maternal and/or foetal systemic inflammation may improve birth anthropometry. © 2016 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

Triple dye plus rubbing alcohol versus triple dye alone for umbilical cord care.

PubMed

Suliman, Alawia K; Watts, Heidi; Beiler, Jessica; King, Tonya S; Khan, Sana; Carnuccio, Marybeth; Paul, Ian M

2010-01-01

Current practices for umbilical cord care vary across centers, but the evidence regarding these practices and their impact on cord separation, complications, and health care use are limited. The objective of this study was to compare the effect of triple dye alone (brilliant green, crystal violet, and proflavine hemisulfate) versus triple dye plus rubbing alcohol (isopropyl alcohol) twice daily on time to umbilical cord separation, complications, and health care use. For the 90 newborns who completed the study, there were no significant differences between treatment groups for time to cord separation, cord-related morbidities, or cord-related urgent care. Based on these study results, there does not appear to be significant benefit to the addition of twice daily applications of rubbing alcohol to neonatal umbilical cords following triple dye treatment after birth.

Rapid induction of single donor chimerism after double umbilical cord blood transplantation preceded by reduced intensity conditioning: results of the HOVON 106 phase II study

PubMed Central

Somers, Judith A.E.; Braakman, Eric; van der Holt, Bronno; Petersen, Eefke J.; Marijt, Erik W.A.; Huisman, Cynthia; Sintnicolaas, Kees; Oudshoorn, Machteld; Groenendijk-Sijnke, Marlies E.; Brand, Anneke; Cornelissen, Jan J.

2014-01-01

Double umbilical cord blood transplantation is increasingly applied in the treatment of adult patients with high-risk hematological malignancies and has been associated with improved engraftment as compared to that provided by single unit cord blood transplantation. The mechanism of improved engraftment is, however, still incompletely understood as only one unit survives. In this multicenter phase II study we evaluated engraftment, early chimerism, recovery of different cell lineages and transplant outcome in 53 patients who underwent double cord blood transplantation preceded by a reduced intensity conditioning regimen. Primary graft failure occurred in one patient. Engraftment was observed in 92% of patients with a median time to neutrophil recovery of 36 days (range, 15–102). Ultimate single donor chimerism was established in 94% of patients. Unit predominance occurred by day 11 after transplantation and early CD4+ T-cell chimerism predicted for unit survival. Total nucleated cell viability was also associated with unit survival. With a median follow up of 35 months (range, 10–51), the cumulative incidence of relapse and non-relapse mortality rate at 2 years were 39% and 19%, respectively. Progressionfree survival and overall survival rates at 2 years were 42% (95% confidence interval, 28–56) and 57% (95% confidence interval, 43–70), respectively. Double umbilical cord blood transplantation preceded by a reduced intensity conditioning regimen using cyclophosphamide/fludarabine/4 Gy total body irradiation results in a high engraftment rate with low non-relapse mortality. Moreover, prediction of unit survival by early CD4+ lymphocyte chimerism might suggest a role for CD4+ lymphocyte mediated unit-versus-unit alloreactivity. www.trialregister.nl NTR1573. PMID:25107890

A preliminary study of placental umbilical cord whole blood transfusion in under resourced patients with malaria in the background of anaemia.

PubMed

Bhattacharya, Niranjan

2006-03-23

Malaria is an annual killer of over one million people globally and its essential co-morbidity is anaemia. Cord blood, because of its rich mix of foetal and adult haemoglobin, high platelet and WBC counts, hypo-antigenic nature, altered metabolic profile and high affinity for oxygen as well as its anti-malarial effect, is an ideal choice in malaria with anaemia, necessitating blood transfusion. This paper presents an alternative protocol for fresh whole blood/packed cell transfusion from the hospital's biological waste resources, i.e., the placenta, after the birth of a healthy baby from a healthy mother. This collected blood was routinely transfused to patients admitted in our hospital with severe anaemia in the background of confirmed malaria. 94 units of placental umbilical cord whole blood were collected after lower uterine caesarean section (LUCS) from consenting mothers (from 1st April 1999 to April 2005), and safely transfused to 39 informed, consenting patients (age varying from 8 to 72 years). The collected volume of cord blood from each placenta (Unit) varied from 52 ml to 143 ml, with a mean packed cell volume of 48.9 +/- 4.1 SD and a mean haemoglobin concentration of 16.4 Gm percent +/- 1.6 Gm percent SD. The blood was immediately transfused after following the standard adult blood transfusion protocol of screening and cross-matching between the donor and the recipient. On occasion, the collected cord blood was preserved in the refrigerator, if no volunteer was readily available, and transfused within 72 hours of collection. Cord blood transfusion was tested on twenty two patients infected with Plasmodium falciparum and 17 patients with Plasmodium vivax. For inclusion in this study, the patient's plasma haemoglobin had to be 8 gm percent or less (the pre-transfusion haemoglobin in the malaria-infected patients in this series varied from 5.4 gm/dl to 7.9 gm/dl). The rise of haemoglobin within 72 hours of two units of freshly collected cord blood

Death by Edible Mushroom: First Report of Volvariella volvacea as an Etiologic Agent of Invasive Disease in a Patient following Double Umbilical Cord Blood Transplantation▿

PubMed Central

Salit, R. B.; Shea, Y. R.; Gea-Banacloche, J.; Fahle, G. A.; Abu-Asab, M.; Sugui, J. A.; Carpenter, A. E.; Quezado, M. M.; Bishop, M. R.; Kwon-Chung, K. J.

2010-01-01

We describe a case of invasive fungal infection caused by Volvariella volvacea following double umbilical cord blood transplantation (UCBT). Although infections caused by several mushroom species have been documented, we believe this to be the first published report of invasive infection with Volvariella volvacea, an edible mushroom belonging to Agaricales. PMID:20826647

Hypoxic ischemic encephalopathy in newborns linked to placental and umbilical cord abnormalities.

PubMed

Nasiell, Josefine; Papadogiannakis, Nikos; Löf, Erika; Elofsson, Fanny; Hallberg, Boubou

2016-03-01

Birth asphyxia and hypoxic ischemic encephalopathy (HIE) of the newborn remain serious complications. We present a study investigating if placental or umbilical cord abnormalities in newborns at term are associated with HIE. A prospective cohort study of the placenta and umbilical cord of infants treated with hypothermia (HT) due to hypoxic brain injury and follow-up at 12 months of age has been carried out. The study population included 41 infants treated for HT whose placentas were submitted for histopathological analysis. Main outcome measures were infant development at 12 months, classified as normal, cerebral palsy, or death. A healthy group of 100 infants without HIE and normal follow-up at 12 months of age were used as controls. A velamentous or marginal umbilical cord insertion and histological abruption was associated with the risk of severe HIE, OR = 5.63, p = 0.006, respectively, OR = 20.3, p = 0.01 (multiple-logistic regression). Velamentous or marginal umbilical cord insertion was found in 39% among HIE cases compared to 7% in controls. Placental and umbilical cord abnormalities have a profound association with HIE. A prompt examination of the placentas of newborns suffering from asphyxia can provide important information on the pathogenesis behind the incident and contribute to make a better early prognosis.

Umbilical cord care in Ethiopia and implications for behavioral change: a qualitative study.

PubMed

Amare, Yared

2014-04-18

Infections account for up to a half of neonatal deaths in low income countries. The umbilicus is a common source of infection in such settings. This qualitative study investigates practices and perspectives related to umbilical cord care in Ethiopia. In-depth interviews (IDI) were conducted in a district in each of the four most populous regions in the country: Oromia, Amhara, Tigray and Southern Nations, Nationalities and Peoples Region (SNNPR). In each district, one community was purposively selected; and in each study community, IDIs were conducted with 6 mothers, 4 grandmothers, 2 Traditional Birth Attendants and 2 Health Extension Workers (HEWs). The two main questions in the interview guide related to cord care were: How was the umbilical cord cut and tied? Was anything applied to the cord stump immediately after cutting/in the first 7 days? Why was it applied/not applied? The study elucidates local cord care practices and the rational for these practices. Concepts underlying cord tying practices were how to stem blood flow and facilitate delivery of the placenta. Substances were applied on the cord to moisturize it, facilitate its separation and promote healing. Locally recognized cord problems were delayed healing, bleeding or swelling. Few respondents reported familiarity with redness of the cord - a sign of infection. Grandmothers, TBAs and HEWs were influential regarding cord care. This study highlights local rationale for cord practices, concerns about cord related problems and recognition of signs of infection. Behavioral change messages aimed at improving cord care including cleansing with CHX should address these local perspectives. It is suggested that HEWs and health facility staff target mothers, grandmothers, TBAs and other community women with messages and counseling.

Prioritization of Biomarker Targets in Human Umbilical Cord Blood: Identification of Proteins in Infant Blood Serving as Validated Biomarkers in Adults

PubMed Central

Hansmeier, Nicole; Chao, Tzu-Chiao; Goldman, Lynn R.; Witter, Frank R.

2012-01-01

Background: Early diagnosis represents one of the best lines of defense in the fight against a wide array of human diseases. Umbilical cord blood (UCB) is one of the first easily available diagnostic biofluids and can inform about the health status of newborns. However, compared with adult blood, its diagnostic potential remains largely untapped. Objectives: Our goal was to accelerate biomarker research on UCB by exploring its detectable protein content and providing a priority list of potential biomarkers based on known proteins involved in disease pathways. Methods: We explored cord blood serum proteins by profiling a UCB pool of 12 neonates with different backgrounds using a combination of isoelectric focusing and liquid chromatography coupled with matrix-assisted laser desorption/ionization tandem mass spectrometry (MALDI-MS/MS) and by comparing results with information contained in metabolic and disease databases available for adult blood. Results: A total of 1,210 UCB proteins were identified with a protein-level false discovery rate of ~ 5% as estimated by naïve target-decoy and MAYU approaches, signifying a 6-fold increase in the number of UCB proteins described to date. Identified proteins correspond to 138 different metabolic and disease pathways and provide a platform of mechanistically linked biomarker candidates for tracking disruptions in cellular processes. Moreover, among the identified proteins, 38 were found to be approved biomarkers for adult blood. Conclusions: The results of this study advance current knowledge of the human cord blood serum proteome. They showcase the potential of UCB as a diagnostic medium for assessing infant health by detection and identification of candidate biomarkers for known disease pathways using a global, nontargeted approach. These biomarkers may inform about mechanisms of exposure–disease relationships. Furthermore, biomarkers approved by the U.S. Food and Drug Administration for screening in adult blood were

HLA-A, HLA-B, HLA-DRB1 allele and haplotype frequencies in 6384 umbilical cord blood units and transplantation matching and engraftment statistics in the Zhejiang cord blood bank of China.

PubMed

Wang, F; He, J; Chen, S; Qin, F; Dai, B; Zhang, W; Zhu, F M; Lv, H J

2014-02-01

Umbilical cord blood (UCB) is a widely accepted source of progenitor cells, and now, many cord blood banks were established. Here, we analysed the HLA-A, HLA-B and HLA-DRB1 allele and haplotype frequencies, HLA matching possibilities for searching potential donors and outcome of UCB transplantations in Zhejiang cord blood bank of China. A total of 6384 UCB units were characterized for 17 HLA-A, 30 HLA-B and 13 HLA-DRB1 alleles at the first field resolution level. Additionally, B*14, B*15 and B*40 were typed to the second field level. A total of 1372 distinct A-B-DRB1 haplotypes were identified. The frequencies of 7 haplotypes were more than 1%, and 439 haplotypes were <0.01%. A*02-B*46-DRB1*09, A*33-B*58-DRB1*03 and A*30-B*13-DRB1*07 were the most common haplotypes, with frequencies of 4.4%, 3.3%, and 2.9%, respectively. Linkage disequilibrium(LD) analysis showed that there were 83 A-B, 106 B-DRB1, 54 A-DRB1 haplotypes with positive LD, in which 51 A-B, 60 B-DRB1, 32 A-DRB1 haplotypes exhibited a significant LD (P < 0.05). In 682 search requests, 12.9%, 40.0% and 42.7% of patients were found to have 6 of 6, 5 of 6 and 4 of 6 HLA-A, HLA-B and HLA-DRB1 matching donors, respectively. A total of 30 UCB units were transplanted to 24 patients (3 patients not evaluated due to early death); 14 of 21 patients (66.7%) engrafted. This study reveals the HLA distribution and its transplantation application in the cord blood bank of Zhejiang province. These data can help to select potential UCB donors for transplantation and used to assess the scale of new cord blood banking endeavours. © 2013 John Wiley & Sons Ltd.

Comparison of mesenchymal stem cells derived from fat, bone marrow, Wharton's jelly, and umbilical cord blood for treating spinal cord injuries in dogs.

PubMed

Ryu, Hak-Hyun; Kang, Byung-Jae; Park, Sung-Su; Kim, Yongsun; Sung, Gyu-Jin; Woo, Heung-Myong; Kim, Wan Hee; Kweon, Oh-Kyeong

2012-12-01

Previous animal studies have shown that transplantation of mesenchymal stem cells (MSCs) into spinal cord lesions enhances axonal regeneration and promotes functional recovery. We isolated the MSCs derived from fat, bone marrow, Wharton's jelly and umbilical cord blood (UCB) positive for MSC markers and negative for hematopoietic cell markers. Their effects on the regeneration of injured canine spinal cords were compared. Spinal cord injury was induced by balloon catheter compression. Dogs with injured spinal cords were treated with only matrigel or matrigel mixed with each type of MSCs. Olby and modified Tarlov scores, immunohistochemistry, ELISA and Western blot analysis were used to evaluate the therapeutic effects. The different MSC groups showed significant improvements in locomotion at 8 weeks after transplantation (P<0.05). This recovery was accompanied by increased numbers of surviving neuron and neurofilament-positive fibers in the lesion site. Compared to the control, the lesion sizes were smaller, and fewer microglia and reactive astrocytes were found in the spinal cord epicenter of all MSC groups. Although there were no significant differences in functional recovery among the MSCs groups, UCB-derived MSCs (UCSCs) induced more nerve regeneration and anti-inflammation activity (P<0.05). Transplanted MSCs survived for 8 weeks and reduced IL-6 and COX-2 levels, which may have promoted neuronal regeneration in the spinal cord. Our data suggest that transplantation of MSCs promotes functional recovery after SCI. Furthermore, application of UCSCs led to more nerve regeneration, neuroprotection and less inflammation compared to other MSCs.

[Concentration of pro-inflammatory interleukins in cervical secretions of women with PROM and in the umbilical cord blood of their newborns].

PubMed

Skrzypczak, Jana; Wirstlein, Przemysław K; Wróbel, Magdalena; Mikołajczyk, Mateusz

2015-06-01

The aim of the study was to analyze the levels of pro-inflammatory interleukins in cervical secretions of women with PROM, depending on Ureaplasma spp. infection and the time elapsed since the rupture of the membranes, and to correlate their concentration in cervical secretions and in cord blood of the newborns. The study included 30 women with PROM between 24 and 33+6 weeks of gestation. Cervical swabs from women with confirmed rupture of membranes taken at certain intervals and umbilical cord blood of their newborns constituted the study material. Cervical secretions were evaluated microbiologically and by the PCR method. Concentrations of IL-6, IL-19, IL-10 and TNF-α were analyzed by ELISA. Ureaplasma spp. were the most frequently isolated microorganisms in cervical secretions of women with PROM. Secretion of interleukins in the cervix was not influenced by time elapsed since the PROM. Comparison of interleukin levels in cord blood of newborns born to mothers with and without Ureaplasma spp infection revealed significantly higher levels of IL-6 in the case of Ureaplasma spp. A positive correlation between IL-6 and TNF-α levels in cervical secretions and in cord blood of mothers with PROM and Ureaplasma spp. was detected. 1. Cervical culture method appears to be sufficient for detecting Ureaplasma spp. 2. Pro-inflammatory interleukins, especially IL-6, obtained by non-invasive methods can be used to predict fetal inflammatory response.

Umbilical cord entanglement's frequency and its impact on the newborn.

PubMed

Walla, Tatjana; Rothschild, Markus A; Schmolling, Jan C; Banaschak, Sibylle

2018-05-01

Neonaticide is a serious allegation that needs a complete chain of criminal investigations. In this context, a nuchal cord is considered to be responsible for an infant's death, but there is a clear lack of evidence. The purpose of our study is to reveal if a nuchal cord can be responsible for stillbirth, poor perinatal outcome, or neonatal death in the forensic aspect. We conducted a prospective study in collaboration with the Augustinian Sisters' Hospital in Cologne, Germany in the period from February 2014 to May 2016. Four-hundred eighty-six children were enrolled. All births were assessed regarding the occurrence of an umbilical cord entanglement, and perinatal outcome was measured by arterial blood gas analysis, Apgar after 1, 5, and 10 min after birth as well as the general vitality. The prevalence of a nuchal cord was 16.87%. Apgar decrease and acidosis were significantly associated with a nuchal cord. No adverse perinatal outcome was recorded in this constellation. There was no child death regarding the first 24 h, and no mother experienced a syncope while giving birth. We can conclude that a nuchal cord is not associated with adverse perinatal outcome.

Intravenous human umbilical cord blood improves electrophysiological and metabolic properties in ISO induced myocardial necrosis in rats.

PubMed

Mohan, Mahalaxmi; Rokade, Rahul; Kasturet, Sanjay

2013-03-01

Rats treated with isoproterenol (ISO, 85 mg/kg, sc, twice at an interval of 24 h) showed a significant increase in heart rate, mean arterial blood pressure, pressure rate index, ST elevation on ECG, and a significant increase in the levels of cardiac marker enzymes- lactate dehydrogenase, and creatine kinase in serum and a significant reduction in superoxide dismutase, and catalase and increase in thiobarbituric acid reactive substance activity in heart tissue. Treatment with Human umbilical cord blood (hUCBC; 500 and 1000 microL, iv, via the tail vein; 2 h after the second dose of ISO) significantly restored back to normal levels and showed a lesser degree of cellular infiltration and infarct size in histopathological and planimetry studies respectively. Thus, hUCBC ameliorates cardiotoxic effects of isoproterenol and may be of value in the treatment of myocardial infarction.

Detection of in utero cannabis exposure by umbilical cord analysis.

PubMed

Kim, Jiyoung; de Castro, Ana; Lendoiro, Elena; Cruz-Landeira, Angelines; López-Rivadulla, Manuel; Concheiro, Marta

2018-04-01

According to the 2014 National Survey on Drug Use and Health, 5.3% of pregnant women smoked marijuana in the past month. This prevalence is expected to increase as a growing number of states and countries are now considering legalization. Although the umbilical cord is becoming a useful objective tool to detect in utero drug exposure, currently data about analytical methods and its utility to detect cannabis exposure are scarce. The objective of this work was to develop a method for the determination of Δ 9 -tetrahydrocannabinol (THC), 11-hydroxyTHC (THC-OH), 11-nor-9-carboxy-THC (THCCOOH), 8-β-11-dihydroxyTHC (THC-diOH), THC and THCCOOH glucuronides, and cannabidiol (CBD) in the umbilical cord by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with dual ionization source. Umbilical cord samples (0.5 g) were homogenized in methanol and extracted by solid-phase extraction. Reversed-phase chromatographic separation was performed in 14 minutes, and 2 transitions per analyte were monitored in multiple reaction monitoring mode. Method validation included linearity (1-10 to 20-200 ng/g), precision (4.1%-23.4%), accuracy (87.5%-111.4%), matrix effect (-54.8% to -5.8%), extraction efficiency (25%-45.6%), limits of detection and quantification (1-10 ng/g), and endogenous (n = 5) or exogenous interferences (not detected). The method was applied to 13 authentic samples from cannabis-exposed newborns, which meconium samples had tested positive for cannabis. Twelve cord specimens tested positive for THCCOOH-glucuronide (1.6-19.1 ng/g). We developed and validated a specific and sensitive method for the simultaneous determination of THC, its metabolites, including THC and THCCOOH glucuronides, and CBD in umbilical cord samples by LC-MS/MS. The analysis of authentic samples showed the usefulness of umbilical cord to detect cannabis in utero exposure. Copyright © 2017 John Wiley & Sons, Ltd.

Umbilical cord sparing technique for repair of congenital hernia into the cord and small omphalocele.

PubMed

Ceccanti, Silvia; Falconi, Ilaria; Frediani, Simone; Boscarelli, Alessandro; Musleh, Layla; Cozzi, Denis A

2017-01-01

Current repair of small omphaloceles and hernias into the umbilical cord is a straightforward procedure, whose repair may result in a suboptimal cosmetic outcome. We describe a novel repair technique retaining the umbilical cord elements in an attempt to improve the cosmetic appearance of the umbilicus. Eight neonates were consecutively treated more than a ten-year period. Size of the fascial defects ranged 1 to 3cm (median, 2). Present technique entails incision of the amniotic sac without its detachment from the skin, reduction of the extruded contents under direct vision, and closure of the abdominal wall defect by circumferential suturing of peritoneum and fascia around the base of the amniotic sac. The amniotic sac is then re-approximated and folded to create an umbilical stump, which is trimmed and left to shed naturally. All patients achieved a scarless abdomen with a normal appearing umbilicus in 6. The remaining 2 patients are awaiting surgery for persisting umbilical hernia repair and umbilicoplasty, respectively. Poor esthetic outcome was significantly associated with initial fascial defect ≥2.5cm in size (p=0.03). Present technique is a simple and cosmetically appealing repair for umbilical cord hernias and small omphaloceles, especially effective when the size of the fascial defect is less than 2.5cm. IV (Treatment Study). Copyright © 2017 Elsevier Inc. All rights reserved.

Incorporating placental tissue in cord blood banking for stem cell transplantation.

PubMed

Teofili, Luciana; Silini, Antonietta R; Bianchi, Maria; Valentini, Caterina Giovanna; Parolini, Ornella

2018-06-01

Human term placenta is comprised of various tissues from which different cell populations can be obtained, including hematopoietic stem cells and mesenchymal stem/stromal cells (MSCs). Areas covered: This review will discuss the possibility to incorporate placental tissue cells in cord blood banking. It will discuss general features of human placenta, with a brief review of the immune cells at the fetal-maternal interface and the different cell populations isolated from placenta, with a particular focus on MSCs. It will address the question as to why placenta-derived MSCs should be banked with their hematopoietic counterparts. It will discuss clinical trials which are studying safety and efficacy of placenta tissue-derived MSCs in selected diseases, and preclinical studies which have proven their therapeutic properties in other diseases. It will discuss banking of umbilical cord blood and raise several issues for improvement, and the applications of cord blood cells in non-malignant disorders. Expert Commentary: Umbilical cord blood banking saves lives worldwide. The concomitant banking of non-hematopoietic cells from placenta, which could be applied therapeutically in the future, alone or in combination to their hematopoietic counterparts, could exploit current banking processes while laying the foundation for clinical trials exploring placenta-derived cell therapies in regenerative medicine.

Human umbilical-cord-blood mononucleated cells enhance the survival of lethally irradiated mice: dosage and the window of time.

PubMed

Kovalenko, Olga A; Azzam, Edouard I; Ende, Norman

2013-11-01

The purpose of this study was to evaluate the window of time and dose of human umbilical-cord-blood (HUCB) mononucleated cells necessary for successful treatment of radiation injury in mice. Female A/J mice (27-30 weeks old) were exposed to an absorbed dose of 9-10 Gy of (137)Cs γ-rays delivered acutely to the whole body. They were treated either with 1 × 10(8) or 2 × 10(8) HUCB mononucleated cells at 24-52 h after the irradiation. The antibiotic Levaquin was applied 4 h postirradiation. The increased dose of cord-blood cells resulted in enhanced survival. The enhancement of survival in animals that received 2 × 10(8) HUCB mononucleated cells relative to irradiated but untreated animals was highly significant (P < 0.01). Compared with earlier studies, the increased dose of HUCB mononucleated cells, coupled with early use of an antibiotic, extended the window of time for effective treatment of severe radiation injury from 4 to 24-52 h after exposure.

Neonatal oxidative stress depends on oxygen blood pressure in umbilical artery.

PubMed

Proietti, F; De Bernardo, G; Longini, M; Sordino, D; Scaramuzzini, G; Tataranno, M L; Belvisi, E; Bazzini, F; Perrone, S; Buonocore, G

2016-01-01

With advancing gestation, partial pressure of oxygen (pO2) and pH fall significantly. Hypoxia is a main factor inducing free radical generation and thereby oxidative stress (OS). Placental and fetal tissue response when oxygen becomes restricted is complex and partially known. We tested the hypothesis that changes in umbilical artery and vein blood gas concentrations modulate OS occurrence in the newborn. Seventy umbilical artery and vein plasma samples were collected from healthy term newborns immediately after delivery. F2 Isoprostanes (F2-Isop) were measured in all samples as reliable markers of lipid peroxidation. Significantly lower pCO2 and higher pO2 and pH were found in umbilical vein than in artery, as expected. A positive correlation was detected between pH and pO2 only in umbilical artery (p=0.019). F2-Isop levels were no different between artery and vein in cord blood. Significant correlations were found between F2-Isop and pCO2 (p=0.025) as well as between F2-Isop and pH in umbilical vein (p=0.027). F2-Isop correlated with pCO2 (p=0.007) as well as with pO2 values (p=0.005) in umbilical artery blood. Oxidative stress (OS) in newborns depends on oxygen concentrations in umbilical artery. OS biomarkers significantly correlate with pO2 and in umbilical artery but not in umbilical vein. In normoxic conditions fetal-maternal gas exchanges occurring in placenta re-establish normal higher oxygen levels in umbilical vein than artery, with a normal production of free radicals without any deleterious effects.

Dynamic Adhesion of Umbilical Cord Blood Endothelial Progenitor Cells under Laminar Shear Stress

PubMed Central

Angelos, Mathew G.; Brown, Melissa A.; Satterwhite, Lisa L.; Levering, Vrad W.; Shaked, Natan T.; Truskey, George A.

2010-01-01

Late outgrowth endothelial progenitor cells (EPCs) represent a promising cell source for rapid reendothelialization of damaged vasculature after expansion ex vivo and injection into the bloodstream. We characterized the dynamic adhesion of umbilical-cord-blood-derived EPCs (CB-EPCs) to surfaces coated with fibronectin. CB-EPC solution density affected the number of adherent cells and larger cells preferentially adhered at lower cell densities. The number of adherent cells varied with shear stress, with the maximum number of adherent cells and the shear stress at maximum adhesion depending upon fluid viscosity. CB-EPCs underwent limited rolling, transiently tethering for short distances before firm arrest. Immediately before arrest, the instantaneous velocity decreased independent of shear stress. A dimensional analysis indicated that adhesion was a function of the net force on the cells, the ratio of cell diffusion to sliding speed, and molecular diffusivity. Adhesion was not limited by the settling rate and was highly specific to α5β1 integrin. Total internal reflection fluorescence microscopy showed that CB-EPCs produced multiple contacts of α5β1 with the surface and the contact area grew during the first 20 min of attachment. These results demonstrate that CB-EPC adhesion from blood can occur under physiological levels of shear stress. PMID:21112278

Placental and cord blood brain derived neurotrophic factor levels are decreased in nondiabetic macrosomia.

PubMed

Cai, Qian-Ying; Zhang, Heng-Xin; Wang, Chen-Chen; Sun, Hao; Sun, Shu-Qiang; Wang, Yu-Huan; Yan, Hong-Tao; Yang, Xin-Jun

2017-08-01

To measure levels of placental brain derived neurotrophic factor (BDNF) gene expression and umbilical cord blood BDNF in neonates with nondiabetic macrosomia and determine associations between these levels and macrosomia. This case-control study included 58 nondiabetic macrosomic and 59 normal birth weight mother-infant pairs. Data were collected from interviews and our hospital's database. BDNF gene expression was quantified in placental tissues using quantitative real-time polymerase chain reaction (n = 117). Umbilical cord blood BDNF levels were measured by enzyme-linked immunosorbent assay (n = 90). Multivariate logistic regression models were used to evaluate associations between BDNF levels and macrosomia. Placental BDNF gene expression (P = 0.026) and cord blood BDNF (P = 0.008) were lower in neonates with nondiabetic macrosomia than in normal birth weight controls. Cord blood BDNF was significantly lower in vaginally delivered macrosomic neonates than vaginally delivered controls (P = 0.014), but cord BDNF did not differ between vaginal and cesarean section delivery modes in macrosomic neonates. Cord blood BDNF was positively associated with gestational age in control neonates (r = 0.496, P < 0.001), but not in macrosomic neonates. Cord blood BDNF was positively associated with placental BDNF relative expression (r s  = 0.245, P = 0.02) in the total group. Higher cord blood BDNF levels were independently associated with protection against nondiabetic macrosomia (adjusted odds ratio 0.992; 95% confidence interval 0.986-0.998). Both placental BDNF gene expression and cord blood BDNF were downregulated in neonates with nondiabetic macrosomia compared with normal birth weight neonates. Cord BDNF may partly derive from BDNF secreted by the placenta. Higher cord plasma BDNF levels protected against nondiabetic macrosomia.

Mesenchymal stromal cell supported umbilical cord blood ex vivo expansion enhances regulatory T cells and reduces graft versus host disease.

PubMed

Fan, Xiubo; Gay, Florence Pik Hoon; Ong, Shin-Yeu; Ang, Justina May Lynn; Chu, Pat Pak Yan; Bari, Sudipto; Lim, Tony Kiat Hon; Hwang, William Ying Khee

2013-05-01

Double cord blood transplantation (DCBT) may shorten neutrophil and platelet recovery times compared with standard umbilical cord blood transplantation. However, DCBT may be associated with a higher incidence of graft versus host disease (GVHD). In this study, we explored the effect of ex vivo expansion of a single cord blood unit (CBU) in a DCBT setting on GVHD and engraftment. Post-thaw cryopreserved CBUs from cord blood banks, hereinafter termed "banked" CBUs, were co-cultured with confluent bone marrow mesenchymal stromal cells (MSCs) supplemented with a cytokine cocktail comprising 100 ng/mL stem cell factor, 50 ng/mL flt3-ligand, 100 ng/mL thrombopoietin and 20 ng/mL insulin-like growth factor binding protein 2 for 12 days. When DCBT of one unexpanded and one expanded CBU was performed in non-obese diabetic/severe combined immunodeficient-IL2Rgamma(null) (NOD/SCID-IL2γ(-/-), NSG) mice, the expanded CBU significantly boosted in vivo hematopoiesis of the unexpanded CBU. The median survival of NSG mice was significantly improved from 63.4% (range, 60.0-66.7%) for mice receiving only unexpanded units to 86.5% (range, 80.0-92.9%) for mice receiving an expanded unit (P < 0.001). The difference in survival appeared to be due to a lower incidence of GVHD in the mice receiving expanded cells. This effect on GVHD was mediated by a significant increase in regulatory T cells seen in the presence of MSC co-culture. MSC-supported ex vivo expansion of "banked" CBU boosted unexpanded CBU hematopoiesis in vivo, increased regulatory T cell content and decreased the incidence of GVHD. Copyright © 2013. Published by Elsevier Inc.

Outcomes after Umbilical Cord Blood Transplantation for Myelodysplastic Syndromes.

PubMed

Gerds, Aaron T; Woo Ahn, Kwang; Hu, Zhen-Huan; Abdel-Azim, Hisham; Akpek, Gorgun; Aljurf, Mahmoud; Ballen, Karen K; Beitinjaneh, Amer; Bacher, Ulrike; Cahn, Jean-Yves; Chhabra, Saurabh; Cutler, Corey; Daly, Andrew; DeFilipp, Zachariah; Gale, Robert Peter; Gergis, Usama; Grunwald, Michael R; Hale, Gregory A; Hamilton, Betty Ky; Jagasia, Madan; Kamble, Rammurti T; Kindwall-Keller, Tamila; Nishihori, Taiga; Olsson, Richard F; Ramanathan, Muthalagu; Saad, Ayman A; Solh, Melhem; Ustun, Celalettin; Valcárcel, David; Warlick, Erica; Wirk, Baldeep M; Kalaycio, Matt; Alyea, Edwin; Popat, Uday; Sobecks, Ronald; Saber, Wael

2017-06-01

For patients with hematologic malignancies undergoing allogeneic hematopoietic cell transplantation, umbilical cord blood transplantation (UCBT) has become an acceptable alternative donor source in the absence of a matched sibling or unrelated donor. To date, however, there have been few published series dedicated solely to describing the outcomes of adult patients with myelodysplastic syndrome (MDS) who have undergone UCBT. Between 2004 and 2013, 176 adults with MDS underwent UCBT as reported to the Center for International Blood and Marrow Transplant Research. Median age at the time of transplantation was 56 years (range, 18-73 years). The study group included 10% with very low, 23% with low, 19% with intermediate, 19% with high, and 13% with very high-risk Revised International Prognostic Scoring System (IPSS-R) scores. The 100-day probability of grade II-IV acute graft-versus-host disease (GVHD) was 38%, and the 3-year probability of chronic GVHD was 28%. The probabilities of relapse and transplantation-related mortality (TRM) at 3 years were 32% and 40%, respectively, leading to a 3-year disease-free survival (DFS) of 28% and an overall survival (OS) of 31%. In multivariate analysis, increasing IPSS-R score at the time of HCT was associated with inferior TRM (P = .0056), DFS (P = .018), and OS (P = .0082), but not with GVHD or relapse. The presence of pretransplantation comorbidities was associated with TRM (P = .001), DFS (P = .02), and OS (P = .001). Reduced-intensity conditioning was associated with increased risk of relapse (relative risk, 3.95; 95% confidence interval, 1.78-8.75; P < .001), and although a higher proportion of myeloablative UCBTs were performed in patients with high-risk disease, the effect of conditioning regimen intensity was the same regardless of IPSS-R score. For some individuals who lack a matched sibling or unrelated donor, UCBT can result in long-term DFS; however, the success of UCBT in this population

Neural differentiation of novel multipotent progenitor cells from cryopreserved human umbilical cord blood

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Myoung Woo; Moon, Young Joon; Yang, Mal Sook

2007-06-29

Umbilical cord blood (UCB) is a rich source of hematopoietic stem cells, with practical and ethical advantages. To date, the presence of other stem cells in UCB remains to be established. We investigated whether other stem cells are present in cryopreserved UCB. Seeded mononuclear cells formed adherent colonized cells in optimized culture conditions. Over a 4- to 6-week culture period, colonized cells gradually developed into adherent mono-layer cells, which exhibited homogeneous fibroblast-like morphology and immunophenotypes, and were highly proliferative. Isolated cells were designated 'multipotent progenitor cells (MPCs)'. Under appropriate conditions for 2 weeks, MPCs differentiated into neural tissue-specific cell types,more » including neuron, astrocyte, and oligodendrocyte. Differentiated cells presented their respective markers, specifically, NF-L and NSE for neurons, GFAP for astrocytes, and myelin/oligodendrocyte for oligodendrocytes. In this study, we successfully isolated MPCs from cryopreserved UCB, which differentiated into the neural tissue-specific cell types. These findings suggest that cryopreserved human UCB is a useful alternative source of neural progenitor cells, such as MPCs, for experimental and therapeutic applications.« less

Amnioinfusion for potential or suspected umbilical cord compression in labour.

PubMed

Hofmeyr, G Justus; Lawrie, Theresa A

2012-01-18

Amnioinfusion aims to prevent or relieve umbilical cord compression during labour by infusing a solution into the uterine cavity. To assess the effects of amnioinfusion for potential or suspected umbilical cord compression on maternal and perinatal outcome . We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 October 2011). Randomised trials of amnioinfusion compared with no amnioinfusion in women with babies at risk of umbilical cord compression in labour. The original review had one author only (Justus Hofmeyr (GJH)). For this update, two authors (GJH and T Lawrie) assessed 13 additional trial reports for eligibility and quality. We extracted data and checked for accuracy. We have included 19 studies, with all but two studies having fewer than 200 participants. Transcervical amnioinfusion for potential or suspected umbilical cord compression was associated with the following reductions: caesarean section overall (13 trials, 1493 participants; average risk ratio (RR) 0.62, 95% confidence interval (CI) 0.46 to 0.83); fetal heart rate (FHR) decelerations (seven trials, 1006 participants; average RR 0.53, 95% CI 0.38 to 0.74); Apgar score less than seven at five minutes (12 trials, 1804 participants; average RR 0.47, 95% CI 0.30 to 0.72); meconium below the vocal cords (three trials, 674 participants, RR 0.53, 95% CI 0.31 to 0.92); postpartum endometritis (six trials, 767 participants; RR 0.45, 95% CI 0.25 to 0.81) and maternal hospital stay greater than three days (four trials, 1051 participants; average RR 0.45, 95% CI 0.25 to 0.78). Transabdominal amnioinfusion showed similar trends, though numbers studied were small.Mean cord umbilical artery pH was higher in the amnioinfusion group (seven trials, 855 participants; average mean difference 0.03, 95% CI 0.00 to 0.06) and there was a trend toward fewer neonates with a low cord arterial pH (less than 7.2 or as defined by trial authors) in the amnioinfusion group (eight trials, 972

Management of umbilical cord clamping.

PubMed

Webbon, Lucy

2013-02-01

The Royal College of Midwives (RCM) has updated its third stage of labour guidelines (RCM 2012) to be clearly supportive of a delay in umbilical cord clamping, although specific guidance on timing is yet to be announced. It is therefore imperative that both midwives and student midwives understand and are able to integrate delaying into their practice, as well as communicating to women the benefits; only in this way can we give women fully informed choices on this aspect of care. The main benefit of delayed cord clamping is the protection it can provide in reducing childhood anaemia, which is a major issue, especially in poorer countries. A review of the evidence found no risks linked to delayed clamping, and no evidence that it cannot be used in combination with the administration of uterotonic drugs. Delayed cord clamping can be especially beneficial for pre term and compromised babies.

Maternal and umbilical cord blood levels of mercury, lead, cadmium, and essential trace elements in Arctic Canada

DOE Office of Scientific and Technical Information (OSTI.GOV)

Butler Walker, Jody; Houseman, Jan; Seddon, Laura

Maternal and umbilical cord blood levels of mercury (Hg), lead (Pb), cadmium (Cd), and the trace elements copper (Cu), zinc (Zn), and selenium (Se) are reported for Inuit, Dene/Metis, Caucasian, and Other nonaboriginal participants from Arctic Canada. This is the first human tissue monitoring program covering the entire Northwest Territories and Nunavut for multiple contaminants and establishes a baseline upon which future comparisons can be made. Results for chlorinated organic pesticides and PCBs for these participants have been reported elsewhere. Between May 1994 and June 1999, 523 women volunteered to participate by giving their written informed consent, resulting in themore » collection of 386 maternal blood samples, 407 cord samples, and 351 cord:maternal paired samples. Geometric mean (GM) maternal total mercury (THg) concentrations ranged from 0.87{mu}g/L (SD=1.95) in the Caucasian group of participants (n=134) to 3.51{mu}g/L (SD=8.30) in the Inuit group (n=146). The GM of the Inuit group was 2.6-fold higher than that of the Dene/Metis group (1.35{mu}g/L, SD=1.60, n=92) and significantly higher than those of all other groups (P<0.0001). Of Inuit women participants, 3% (n=4) were within Health Canada's level of concern range (20-99{mu}g/L) for methylmercury (MeHg) exposure. Of Inuit and Dene/Metis cord samples, 56% (n=95) and 5% (n=4), respectively, exceeded 5.8{mu}g/L MeHg, the revised US Environmental Protection Agency lower benchmark dose. GM maternal Pb was significantly higher in Dene/Metis (30.9{mu}g/L or 3.1{mu}g/dL; SD=29.1{mu}g/L) and Inuit (31.6{mu}g/L, SD=38.3) participants compared with the Caucasian group (20.6{mu}g/L, SD=17.9) (P<0.0001). Half of all participants were smokers. GM blood Cd in moderate smokers (1-8 cigarettes/day) and in heavy smokers (>8 cigarettes/day) was 7.4-fold higher and 12.5-fold higher, respectively, than in nonsmokers. The high percentage of smokers among Inuit (77%) and Dene/Metis (48%) participants highlights the

Human umbilical cord blood stem cells show PDGF-D–dependent glioma cell tropism in vitro and in vivo

PubMed Central

Gondi, Christopher S.; Veeravalli, Krishna Kumar; Gorantla, Bharathi; Dinh, Dzung H.; Fassett, Dan; Klopfenstein, Jeffrey D.; Gujrati, Meena; Rao, Jasti S.

2010-01-01

Despite advances in clinical therapies and technologies, the prognosis for patients with malignant glioma is poor. Neural stem cells (NSCs) have a chemotactic tropism toward glioma cells. The use of NSCs as carriers of therapeutic agents for gliomas is currently being explored. Here, we demonstrate that cells isolated from the umbilical cord blood show mesenchymal characteristics and can differentiate to adipocytes, osteocytes, and neural cells and show tropism toward cancer cells. We also show that these stem cells derived from the human umbilical cord blood (hUCB) induce apoptosis-like cell death in the glioma cell line SNB19 via Fas-mediated caspase-8 activation. From our glioma tropism studies, we have observed that hUCB cells show tropism toward glioma cells in vitro, in vivo, and ex vivo. We determined that this migration is partially dependent on the expression levels of platelet-derived growth factor (PDGF)-D from glioma cells and have observed that local concentration gradient of PDGF-D is sufficient to cause migration of hUCB cells toward the gradient as seen from our brain slice cultures. In our animal experiment studies, we observed that intracranially implanted SNB19 green fluorescent protein cells induced tropism of the hUCB cells toward themselves. In addition, the ability of these hUCBs to inhibit established intracranial tumors was also observed. We also determined that the migration of stem cells toward glioma cells was partially dependent on PDGF secreted by glioma cells and that the presence of PDGF-receptor (PDGFR) on hUCB is required for migration. Our results demonstrate that hUCB are capable of inducing apoptosis in human glioma cells and also show that glioma tropism and hUCB tropism toward glioma cells are partially dependent on the PDGF/PGGFR system. PMID:20406896

Epstein-Barr Virus-positive T-cell Lymphoproliferative Disease Following Umbilical Cord Blood Transplantation for Acute Myeloid Leukemia.

PubMed

Yui, Shunsuke; Yamaguchi, Hiroki; Imadome, Ken-ichi; Arai, Ayako; Takahashi, Mikiko; Ohashi, Ryuji; Tamai, Hayato; Moriya, Keiichi; Nakayama, Kazutaka; Shimizu, Akira; Inokuchi, Koiti

2016-01-01

We report a case of the extremely rare condition Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disease (LPD) which occurred after umbilical cord blood transplantation. A 25-year-old Japanese man underwent cord blood transplantation from a male human leukocyte antigen 4/6-matched donor due to acute myeloid leukemia with trisomy 8. Bone marrow examination on day 30 showed chimerism with at least 90% donor cells and complete hematological response. Chronic symptoms of graft-versus-host disease appeared only on the skin and were successfully treated with cyclosporine alone. Three years later, however, the patient experienced repeated cold-like symptoms and was hospitalized with liver dysfunction. A high fever developed and was followed by significant edema of the right side of the face. The EBV DNA copy number in whole peripheral blood was 2×10(4)/mL. Liver biopsy showed invasion of EBV-infected CD8-positive T cells. Southern blotting analysis of the whole peripheral blood showed that the T-cell receptor Cβ1 rearrangement was positive. On the basis of these results, EBV-positive T-cell LPD was diagnosed and treated with prednisolone, cyclosporine, and etoposide, followed by cyclophosphamide, doxorubicin, vincristine, and prednisone. However, the patient died of cardiac function failure, pneumonia, and pulmonary hemorrhage, all of unidentified cause. Most cases of EBV-related LPD after hematopoietic stem cell transplantation consist of EBV-positive B-cell LPD, and, to our knowledge, de novo EBV-positive T-cell LPD subsequent to transplantation has not been previously reported.

Endocytosed factor V is trafficked to CD42b+ proplatelet extensions during differentiation of human umbilical cord blood-derived megakaryocytes.

PubMed

Gertz, Jacqueline M; McLean, Kelley C; Bouchard, Beth A

2018-05-15

Plasma- and platelet-derived factor Va are essential for thrombin generation catalyzed by the prothrombinase complex; however, several observations demonstrate that the platelet-derived cofactor, which is formed following megakaryocyte endocytosis and modification of the plasma procofactor, factor V, is more hemostatically relevant. Factor V endocytosis, as a function of megakaryocyte differentiation and proplatelet formation, was assessed by flow cytometry and microscopy in CD34 + hematopoietic progenitor cells isolated from human umbilical cord blood and cultured for 12 days in the presence of cytokines to induce ex vivo differentiation into megakaryocytes. Expression of an early marker of megakaryocyte differentiation, CD41, endocytosis of factor V, and the percentage of CD41 + cells that endocytosed factor V increased from days 6 to 12 of differentiation. In contrast, statistically significant decreases in expression of the stem cell marker, CD34, and in the percentage of CD34 + cells that endocytosed factor V were observed. A statistically significant increase in the expression of CD42b, a late marker of megakaryocyte differentiation, was also observed over time, such that by Day 12, all CD42b + cells endocytosed factor V and expressed CD41. This endocytosed factor V was trafficked to proplatelet extensions and was localized in a punctate pattern in the cytoplasm consistent with its storage in α-granules. In conclusion, loss of CD34 and expression of CD42b define cells capable of factor V endocytosis and trafficking to proplatelet extensions during differentiation of megakaryocytes ex vivo from progenitor cells isolated from umbilical cord blood. © 2018 Wiley Periodicals, Inc.

Motivating Cord Blood Donation with Information and Behavioral Nudges.

PubMed

Grieco, Daniela; Lacetera, Nicola; Macis, Mario; Di Martino, Daniela

2018-01-10

Umbilical cord blood is a source of hematopoietic stem cells essential to treat life-threatening diseases, such as leukemia and lymphoma. However, only a very small percentage of parents donate upon delivery. The decision to donate the cord blood occurs at a very specific time and when parents likely experience emotional, informational, and decisional overloads; these features of cord blood donation make it different from other pro-social activities. In collaboration with an OB-GYN clinic in Milan, Italy, we conducted the first randomized controlled trial that applies tools from behavioral science to foster cord blood donation, and quantified the gains that informational and behavioral "nudges" can achieve. We found that information and "soft" commitments increased donations; approaching expecting parents closer to the delivery date and providing them with multiple reminders, moreover, had the strongest impact. However, a significant portion of women who expressed consent to donate could not do so because of organizational constraints. We conclude that simple, non-invasive behavioral interventions that address information gaps and procrastination, and that increase the salience of the activity can substantially enhance altruistic donations of cord blood, especially when coupled with organizational support.

Exposure to Low Levels of Lead in Utero and Umbilical Cord Blood DNA Methylation in Project Viva: An Epigenome-Wide Association Study.

PubMed

Wu, Shaowei; Hivert, Marie-France; Cardenas, Andres; Zhong, Jia; Rifas-Shiman, Sheryl L; Agha, Golareh; Colicino, Elena; Just, Allan C; Amarasiriwardena, Chitra; Lin, Xihong; Litonjua, Augusto A; DeMeo, Dawn L; Gillman, Matthew W; Wright, Robert O; Oken, Emily; Baccarelli, Andrea A

2017-08-25

Early-life exposure to lead is associated with deficits in neurodevelopment and with hematopoietic system toxicity. DNA methylation may be one of the underlying mechanisms for the adverse effects of prenatal lead on the offspring, but epigenome-wide methylation data for low levels of prenatal lead exposure are lacking. We investigated the association between prenatal maternal lead exposure and epigenome-wide DNA methylation in umbilical cord blood nucleated cells in Project Viva, a prospective U.S.-based prebirth cohort with relatively low levels of lead exposure. Among 268 mother-infant pairs, we measured lead concentrations in red blood cells (RBC) from prenatal maternal blood samples, and using HumanMethylation450 Bead Chips, we measured genome-wide methylation levels at 482,397 CpG loci in umbilical cord blood and retained 394,460 loci after quality control. After adjustment for batch effects, cell types, and covariates, we used robust linear regression models to examine associations of prenatal lead exposure with DNA methylation in cord blood at epigenome-wide significance level [false discovery rate (FDR)<0.05]. The mean [standard deviation (SD)] maternal RBC lead level was 1.22 (0.63) μg/dL. CpG cg10773601 showed an epigenome-wide significant negative association with prenatal lead exposure (-1.4% per doubling increase in lead exposure; p=2.3×10-7) and was annotated to C-Type Lectin Domain Family 11, Member A ( CLEC11A ), which functions as a growth factor for primitive hematopoietic progenitor cells. In sex-specific analyses, we identified more CpGs with FDR<0.05 among female infants (n=38) than among male infants (n=2). One CpG (cg24637308), which showed a strong negative association with prenatal lead exposure among female infants (-4.3% per doubling increase in lead exposure; p=1.1×10-06), was annotated to Dynein Heavy Chain Domain 1 gene ( DNHD1 ) which is highly expressed in human brain. Interestingly, there were strong correlations between blood

The effects of umbilical cord milking in extremely preterm infants: a randomized controlled trial

PubMed Central

March, MI; Hacker, MR; Parson, AW; Modest, AM; de Veciana, M

2014-01-01

OBJECTIVE Delayed cord clamping has been shown to decrease the need for transfusion in preterm neonates, but may delay resuscitation. The aim of this study was to determine whether umbilical cord milking compared with immediate cord clamping in extremely preterm deliveries reduces the need for neonatal red blood cell transfusion. STUDY DESIGN Women admitted to a tertiary care center and expected to deliver between 24 to 28 completed weeks of gestation were randomized to cord milking before clamping or immediate cord clamping. The primary outcome was the risk of neonatal transfusion, reported as risk ratio (RR) and 95% confidence interval (CI). RESULT Of 113 women who were enrolled and randomized, 56 were assigned to cord milking with 36 remaining eligible and completing the study and 57 were assigned to the control group with 39 remaining eligible and completing the study. Albeit not statistically significant, neonates in the cord milking group were less likely to require transfusion compared with those in the control group (RR: 0.86; 95% CI: 0.73 to 1.0). Neonates whose cords were milked had higher hematocrits at birth (P = 0.004) and were less likely to develop an intraventricular hemorrhage (P = 0.0195). CONCLUSION Milking the umbilical cord of a preterm neonate is an easy intervention with the potential to improve perinatal outcomes. Our results suggest that milking of the cord increases the neonate’s initial hematocrit and may lessen the need for transfusion in the neonatal period. The observed reduction in the incidence of intraventricular hemorrhage may have important long-term implications that warrant further study. PMID:23867960

Musculoskeletal tissue engineering with human umbilical cord mesenchymal stromal cells

PubMed Central

Wang, Limin; Ott, Lindsey; Seshareddy, Kiran; Weiss, Mark L; Detamore, Michael S

2011-01-01

Multipotent mesenchymal stromal cells (MSCs) hold tremendous promise for tissue engineering and regenerative medicine, yet with so many sources of MSCs, what are the primary criteria for selecting leading candidates? Ideally, the cells will be multipotent, inexpensive, lack donor site morbidity, donor materials should be readily available in large numbers, immunocompatible, politically benign and expandable in vitro for several passages. Bone marrow MSCs do not meet all of these criteria and neither do embryonic stem cells. However, a promising new cell source is emerging in tissue engineering that appears to meet these criteria: MSCs derived from Wharton’s jelly of umbilical cord MSCs. Exposed to appropriate conditions, umbilical cord MSCs can differentiate in vitro along several cell lineages such as the chondrocyte, osteoblast, adipocyte, myocyte, neuronal, pancreatic or hepatocyte lineages. In animal models, umbilical cord MSCs have demonstrated in vivo differentiation ability and promising immunocompatibility with host organs/tissues, even in xenotransplantation. In this article, we address their cellular characteristics, multipotent differentiation ability and potential for tissue engineering with an emphasis on musculoskeletal tissue engineering. PMID:21175290

Evaluation of three high abundance protein depletion kits for umbilical cord serum proteomics

PubMed Central

2011-01-01

Background High abundance protein depletion is a major challenge in the study of serum/plasma proteomics. Prior to this study, most commercially available kits for depletion of highly abundant proteins had only been tested and evaluated in adult serum/plasma, while the depletion efficiency on umbilical cord serum/plasma had not been clarified. Structural differences between some adult and fetal proteins (such as albumin) make it likely that depletion approaches for adult and umbilical cord serum/plasma will be variable. Therefore, the primary purposes of the present study are to investigate the efficiencies of several commonly-used commercial kits during high abundance protein depletion from umbilical cord serum and to determine which kit yields the most effective and reproducible results for further proteomics research on umbilical cord serum. Results The immunoaffinity based kits (PROTIA-Sigma and 5185-Agilent) displayed higher depletion efficiency than the immobilized dye based kit (PROTBA-Sigma) in umbilical cord serum samples. Both the PROTIA-Sigma and 5185-Agilent kit maintained high depletion efficiency when used three consecutive times. Depletion by the PROTIA-Sigma Kit improved 2DE gel quality by reducing smeared bands produced by the presence of high abundance proteins and increasing the intensity of other protein spots. During image analysis using the identical detection parameters, 411 ± 18 spots were detected in crude serum gels, while 757 ± 43 spots were detected in depleted serum gels. Eight spots unique to depleted serum gels were identified by MALDI- TOF/TOF MS, seven of which were low abundance proteins. Conclusions The immunoaffinity based kits exceeded the immobilized dye based kit in high abundance protein depletion of umbilical cord serum samples and dramatically improved 2DE gel quality for detection of trace biomarkers. PMID:21554704

Outcome of Second Transplantation Using Umbilical Cord Blood for Graft Failure after Allogeneic Hematopoietic Stem Cell Transplantation for Aplastic Anemia.

PubMed

Onishi, Yasushi; Mori, Takehiko; Kako, Shinichi; Koh, Hideo; Uchida, Naoyuki; Kondo, Tadakazu; Kobayashi, Takeshi; Yabe, Hiromasa; Miyamoto, Toshihiro; Kato, Koji; Suzuki, Ritsuro; Nakao, Shinji; Yamazaki, Hirohito

2017-12-01

Graft failure (GF) is the most critical life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT) for aplastic anemia, for which a second transplantation is the only effective treatment. Optimal procedures have not been established for the second transplantation in this setting, however. Here we retrospectively analyzed the outcomes of 22 patients with aplastic anemia, age ≥16 years, who underwent umbilical cord blood transplantation for GF after the first HSCT using the registry database of the Japan Society for Hematopoietic Cell Transplantation. The median age of patients was 36 years (range, 16 to 72 years), and the median time from the first to the second transplant was 77 days (range, 29 to 1061 days). The cumulative incidence of neutrophil engraftment at day 60 post-transplantation was 45.5% (95% confidence interval [CI], 23.6% to 65.0%). With a median follow-up of 50 months, the 4-year overall survival (OS) was 38.5% (95% CI, 18.4% to 58.5%). Mycofenolate mofetil-based graft-versus-host disease prophylaxis demonstrated greater neutrophil recovery than prophylaxis with calcineurin inhibitor alone or methotrexate-based prophylaxis (66.7% versus 37.5%; P = .04). The use of such conditioning regimens as fludarabine + melphalan or cyclophosphamide + low-dose total body irradiation was associated with better engraftment (58.3% versus 30%; P = .05) and better 4-year OS (55.6% versus 20%; P = .05) than other regimens. Although further investigation is needed, umbilical cord blood could be an effective and promising option for stem cell source for urgent second transplantation in patients with aplastic anemia who develop GF after the first HSCT. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Fostering public cord blood banking and research in Canada.

PubMed

Isasi, Rosario; Dalpe, Gratien; Knoppers, Bartha M

2013-12-01

In June 2013, Canadian Blood Services (CBS) established the National Public Cord Blood Bank (NPCBB) accessible to Canadian and international patients and researchers. The NPCBB promotes efforts that contribute to research and improved clinical care by making units not suitable for banking or transplantation available for research. In the context of the NPCBB of the CBS, this article will focus on the practical tools (e.g., consent protocols) developed to optimize umbilical cord blood (UCB) banking and research while enabling ethical provenance of UCB stem cells. The Canadian approach represents an ideal model for comparison as it is a country in which the national public bank (and other regional/provincial public banks) coexists with private companies.

Relationship between the tensile strengths and diameters of human umbilical cords.

PubMed

Fernando, D M G; Gamage, S M K; Ranmohottige, S; Weerakkody, I; Abeyruwan, H; Parakrama, H

2018-05-01

Mothers of alleged infanticides might claim that umbilical cord broke during precipitate delivery causing injuries detected on baby at autopsy. There is paucity of evidence regarding this possibility. The objective of the study was to determine relationship between tensile strength and diameter or weight per unit length of cord. Diameters and weights per unit length of fresh umbilical cords were determined. Tensile strengths were measured by Hounsfield Testing Machine. Relationship between tensile strength versus cord diameter and weight per unit length were analyzed. Of 122 cords, average tensile strength, diameter and weight per centimeter were 50.4 N, 7.73 mm and 6.87 g respectively. The tensile strengths were directly proportional to diameter. There was no association between tensile strength and weight per centimeter. Measurement of the diameter of cord is important during autopsy to predict tensile strength and thereby to presume whether cord could have broken by the weight of the baby. Copyright © 2018 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Placental umbilical cord whole blood transfusion to combat anemia in the background of advanced rheumatoid arthritis and emaciation and its potential role as immunoadjuvant therapy.

PubMed

Bhattacharya, N

2006-01-01

.6 ml SD, median 82.4 ml, mean packed cell volume 48.2 +/- 2.1 SD, mean percent hemoglobin concentration 16.4 g/dl +/- 1.5 g/dl SD) of placental umbilical cord whole blood was transfused (from 1 April 1999 to April 2005) after lower uterine cesarean section (LUCS) from consenting mothers to 28 informed consenting patients with advanced rheumatoid arthritis who had plasma hemoglobin of 8 g/dl or less. After collection, the blood was immediately transfused following the standard adult blood transfusion protocol. Each case was passed through the institutional ethical committee. The patients received two to six units of freshly collected placental umbilical cord blood without encountering any clinical, immunological or non-immunological reactions. Three days after completion of the transfusion of placental umbilical cord blood, the peripheral blood hematopoietic stem cell (CD34) estimation revealed a rise from the pretransfusion base level (.09%), varying from 2.03 to 23%, which returned to base level in most of the cases at the three-month CD34 re-estimation, without provoking any clinical graft vs host reaction in any of the patients.

Cryopreservation of umbilical cord blood with a novel freezing solution that mimics intracellular ionic composition.

PubMed

Nicoud, Ian B; Clarke, Dominic M; Taber, Greta; Stolowski, Kristin M; Roberge, Sarah E; Song, Melissa K; Mathew, Aby J; Reems, Jo-Anna

2012-09-01

Cryopreservation protocols have remained relatively unchanged since the first umbilical cord blood banking program was established. This study evaluated the preservation efficacy of a novel intracellular-like cryopreservation solution (CryoStor, BioLife Solutions, Inc.), the rate of addition of two cryopreservation solutions to cord blood units (CBUs), and reduced final dimethyl sulfoxide (DMSO) concentration of 5%. Split-sample CBUs were cryopreserved with either an in-house 20% DMSO-based cryopreservation solution or CryoStor CS10 at a rate of 1 mL/min (n = 10; i.e., slow addition) or as a bolus injection (n = 6; i.e., fast addition). Infrared images of exothermic effects of the cryopreservation solutions were monitored relative to the rate of addition. Prefreeze and postthaw colony-forming unit assays, total nucleated cells, and CD34+ cell counts were compared. Maximum temperature excursions observed were less than 6°C, regardless of the rate of solution addition. Fast addition resulted in peak excursions approximately twice that of slow addition but the magnitude and duration were minimal and transient. Slow addition of CryoStor CS10 (i.e., final concentration ≤ 5% DMSO) resulted in significantly better postthaw CD34+ cell recoveries; no other metrics were significantly different. Fast addition of CryoStor resulted in similar postthaw metrics compared to slow addition of the in-house solution. Slow and fast addition of cryopreservation solutions result in mean temperature changes of approximately 3.3 to 4.45°C. Postthaw recoveries with CryoStor were equivalent to or slightly better than with the in-house cryopreservation solution. CryoStor also provides several advantages including reduced processing time, formulation consistency, and reduced DMSO in the frozen product (≤ 5%). © 2012 American Association of Blood Banks.

Breakthrough infection of Geotrichum capitatum during empirical caspofungin therapy after umbilical cord blood transplantation.

PubMed

Oya, Shuki; Muta, Tsuyoshi

2018-06-20

We experienced a breakthrough fungal infection caused by Geotrichum capitatum during empirical therapy with caspofungin. A 68-year-old male patient with refractory acute lymphoblastic leukemia had received umbilical cord blood transplantation after two courses of induction therapy. Empirical therapy with caspofungin was initiated 5 days before transplantation. Tacrolimus was continuously infused to prevent graft-versus-host disease. A minidose of methotrexate was intravenously administered on days 1 and 3 post-transplantation, which was changed to prednisolone from day 7 due to severe mucositis. During a recurrence of fever on day 11, blood cultures were found to be positive for a yeast-like organism, which was later confirmed by mass spectrometry to be G. capitatum. The serum levels of beta-D-glucan were elevated to 747 pg/mL. Caspofungin was switched to liposomal amphotericin B; however, radiological findings revealed pulmonary, splenic, and central nervous system involvement. Progressive renal and hepatic dysfunction subsequently developed. The patient died on day 25 post-transplantation secondary to the development of hemophagocytic syndrome and respiratory failure. We emphasize that recurrent febrile episodes, prolonged neutropenia, and underlying gastrointestinal mucosal damage require extreme caution due to the possibility of breakthrough infection caused by new fungal pathogens during empirical therapy with caspofungin.

Transplantation of human cord blood mononuclear cells and umbilical cord-derived mesenchymal stem cells in autism

PubMed Central

2013-01-01

Background Autism is a pervasive neurodevelopmental disorder. At present there are no defined mechanisms of pathogenesis and therapy is mostly limited to behavioral interventions. Stem cell transplantation may offer a unique treatment strategy for autism due to immune and neural dysregulation observed in this disease. This non-randomized, open-label, single center phase I/II trial investigated the safety and efficacy of combined transplantation of human cord blood mononuclear cells (CBMNCs) and umbilical cord-derived mesenchymal stem cells (UCMSCs) in treating children with autism. Methods 37 subjects diagnosed with autism were enrolled into this study and divided into three groups: CBMNC group (14 subjects, received CBMNC transplantation and rehabilitation therapy), Combination group (9 subjects, received both CBMNC and UCMSC transplantation and rehabilitation therapy), and Control group (14 subjects, received only rehabilitation therapy). Transplantations included four stem cell infusions through intravenous and intrathecal injections once a week. Treatment safety was evaluated with laboratory examinations and clinical assessment of adverse effects. The Childhood Autism Rating Scale (CARS), Clinical Global Impression (CGI) scale and Aberrant Behavior Checklist (ABC) were adopted to assess the therapeutic efficacy at baseline (pre-treatment) and following treatment. Results There were no significant safety issues related to the treatment and no observed severe adverse effects. Statistically significant differences were shown on CARS, ABC scores and CGI evaluation in the two treatment groups compared to the control at 24 weeks post-treatment (p < 0.05). Conclusions Transplantation of CBMNCs demonstrated efficacy compared to the control group; however, the combination of CBMNCs and UCMSCs showed larger therapeutic effects than the CBMNC transplantation alone. There were no safety issues noted during infusion and the whole monitoring period. Trial registration

Cryopreservation of umbilical cord blood-derived mesenchymal stem cells without dimethyl sulfoxide.

PubMed

Wang, Hai-Yan; Lun, Zhao-Rong; Lu, Shu-Shen

2011-01-01

Cryopreservation of umbilical cord blood-derived mesenchymal stem cells (UCB-derived MSCs) is crucial step for its clinical applications in cell transplantation therapy. In the cryopreservation of MSCs, dimethyl sulfoxide has been widely used as a cryoprotectant (CPA). However, it has been proved that DMSO has toxic side effects to human body. In this study, DMSO-free CPA solutions which contained ethylene glycol (EG), 1, 2-propylene glycol (PG) and sucrose as basic CPAs, supplemented with polyvinyl alcohol (PVA) as an additive, were developed for the cryopreservation of UCB-derived MSCs. The cryopreservation of UCB-derived MSCs was achieved by vitrification via plunging into liquid nitrogen and by programmed freezing via an optical-DSC system respectively. The viability of thawed UCB-derived MSCs was tested by trypan blue exclusion assay. Results showed that the viability of thawed UCB-derived MSCs was enhanced from 71.2% to 95.4% in the presence of PVA for vitrification, but only < 10% to 45% of viability was found for programmed freezing. These results indicate that PVA exerts a beneficial effect on the cryopreservation of UCB-derived MSCs and suggest the vitrification in combination with the dimethyl sulfoxide free CPA solutions supplemented with PVA would be an efficient protocol for the cryopreservation of UCB-derived MSCs.

A Comparative Study to Evaluate Myogenic Differentiation Potential of Human Chorion versus Umbilical Cord Blood-derived Mesenchymal Stem Cells.

PubMed

Bana, Nikoo; Sanooghi, Davood; Soleimani, Mansoureh; Hayati Roodbari, Nasim; Alavi Moghaddam, Sepideh; Joghataei, Mohammad Taghi; Sayahpour, Forough Azam; Faghihi, Faezeh

2017-08-01

Musculodegenerative diseases threaten the life of many patients in the world. Since drug administration is not efficient in regeneration of damaged tissues, stem cell therapy is considered as a good strategy to restore the lost cells. Since the efficiency of myogenic differentiation potential of human Chorion- derived Mesenchymal Stem Cells (C-MSCs) has not been addressed so far; we set out to evaluate myogenic differentiation property of these cells in comparison with Umbilical Cord Blood- derived Mesenchymal Stem Cells (UCB-MSCs) in the presence of 5-azacytidine. To do that, neonate placenta Umbilical Cord Blood were transferred to the lab. After characterization of the isolated cells using flowcytometry and multilineage differentiation capacity, the obtained Mesenchymal Stem Cells were cultured in DMEM/F12 supplemented with 2% FBS and 10μM of 5-azacytidine to induce myogenic differentiation. Real-time PCR and immunocytochemistry were used to assess the myogenic properties of the cells. Our data showed that C-MSCs and UCB-MSCs were spindle shape in morphology. They were positive for CD90, CD73 and CD44 antigens, and negative for hematopoietic markers. They also differentiated into osteoblast and adipoblast lineages. Real-time PCR results showed that the cells could express MyoD, desmin and α-MHC at the end of the first week (P<0.05). No significant upregulation was detected in the expression of GATA-4 in both groups. Immunocytochemical staining revealed the expression of Desmin, cTnT and α-MHC. Results showed that these cells are potent to differentiate into myoblast- like cells. An upregulation in the expression of some myogenic markers (desmin, α- MHC) was observed in C-MSCs in comparison with UCB-MSCs. Copyright © 2017. Published by Elsevier Ltd.

Developing Educational Resources to Advance Umbilical Cord Blood Banking and Research: A Canadian Perspective.

PubMed

Beak, Carla Pereira; Chargé, Sophie B; Isasi, Rosario; Knoppers, Bartha M

2015-05-01

In 2013 Canadian Blood Services (CBS) launched the National Public Cord Blood Bank (NPCBB), a program to collect, process, test, and store cord blood units donated for use in transplantation. A key component of the creation of the NPCBB is the establishment of a program that enables cord blood not suitable for banking or transplantation to be used for biomedical research purposes. Along with the development of processes and policies to manage the NPCBB and the cord blood research program, CBS-in collaboration with researchers from the Stem Cell Network-have also developed educational tools to provide relevant information for target audiences to aid implementation and operation. We describe here one of these tools, the REB Primer on Research and Cord Blood Donation (the Primer), which highlights key ethical and legal considerations and identifies Canadian documents that are relevant to the use of cord blood in biomedical research. The Primer also introduces the NPCBB and describes the systems CBS is implementing to address ethical issues. The Primer is intended to assist research ethics boards in evaluating the ethical acceptability of research protocols, to facilitate harmonized decision-making by providing a common reference, and to highlight the role of research ethics boards in governance frameworks. With the Primer we hope to illustrate how the development of such educational tools can facilitate the ethical implementation and governance of programs related to stem cell research in Canada and abroad.

What has methylmercury in umbilical cords told us? - Minamata disease.

PubMed

Yorifuji, Takashi; Kashima, Saori; Tsuda, Toshihide; Harada, Masazumi

2009-12-20

Severe methylmercury poisoning occurred in Minamata and neighboring communities in the 1950s and 1960s. The exposed patients manifested neurological signs, and some patients exposed in utero were born with so-called congenital Minamata disease. In a previous report, Nishigaki and Harada evaluated the methylmercury concentrations in the umbilical cords of inhabitants and demonstrated that methylmercury actually passed through the placenta (Nishigaki and Harada, 1975). However, the report involved a limited number of cases (only 35) and did not quantitatively evaluate the regional differences in the transition of methylmercury exposure. Therefore, in the present study, we evaluated the temporal and spatial distributions of methylmercury concentrations in umbilical cords, with an increased number of participants and additional descriptive analyses. Then, we examined whether the methylmercury concentrations corresponded with the history of the Minamata disease incident. A total of 278 umbilical cord specimens collected after birth were obtained from babies born between 1925 and 1980 in four study areas exposed to methylmercury. Then, we conducted descriptive analyses, and drew scatterplots of the methylmercury concentrations of all the participants and separated by the areas. In the Minamata area, where the first patient was identified in 1956, the methylmercury concentration reached a peak around 1955. Subsequently, about 5 years later, the concentrations peaked in other exposed areas with the expected exposure distribution corresponding with acetaldehyde production (the origin of methylmercury). This historical incident several decades ago in Minamata and neighboring communities clearly shows that regional pollution affected the environment in utero. Furthermore, the temporal and spatial distributions of the methylmercury concentrations in the umbilical cords tell us the history of the Minamata disease incident.

Zika virus detected in amniotic fluid and umbilical cord blood in an in vitro fertilization-conceived pregnancy in Venezuela.

PubMed

Benjamin, Isaac; Fernández, Gissel; Figueira, José Valentin; Parpacén, Leticia; Urbina, María Teresa; Medina, Randolfo

2017-06-01

To describe the consequences of Zika virus infection at 10 weeks of gestation in an IVF-conceived pregnancy in Venezuela. A case report. Private assisted reproduction unit. A 36-year-old patient who conceived her first pregnancy through IVF and became infected with Zika virus at 10 weeks' gestation in Venezuela. In vitro fertilization with fresh ET. Clinical, laboratory, and imaging Zika diagnostic methods. Zika virus detection by real-time polymerase chain reaction (PCR) in maternal plasma, PCR in amniotic fluid and umbilical cord blood. Ultrasonography findings of anatomic abnormalities. Zika infection was confirmed at 10 weeks' gestation by real-time PCR; ultrasound results appeared normal. At 19 weeks' gestation, an ultrasound revealed biometry on three SDs below the means for all parameters but with no apparent anatomic abnormality. Zika virus was positive in maternal urine and amniotic fluid by PCR at 19 weeks' gestation. Ultrasound at 21 weeks + 4 days of gestation showed fetal cerebellar hypoplasia with ventricular dysmorphia, particularly marked on the left, consistent with microcephaly and ventriculomegaly. Because of the poor prognosis, pregnancy was interrupted at 24 weeks' gestation, in France. The PCR in umbilical cord blood taken in this procedure was positive for Zika virus. Initial ultrasound findings in pregnancy may not be informative. Only at 21 weeks + 4 days of gestation did an ultrasound reveal fetal microcephaly and ventriculomegaly. Combined clinical, laboratory, and imaging findings provided a complete picture of the severe damage caused by Zika infection. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Association of Cord Blood Magnesium Concentration and Neonatal Resuscitation

PubMed Central

Johnson, Lynn H.; Mapp, Delicia C.; Rouse, Dwight J.; Spong, Catherine Y.; Mercer, Brian M.; Leveno, Kenneth J.; Varner, Michael W.; Iams, Jay D.; Sorokin, Yoram; Ramin, Susan M.; Miodovnik, Menachem; O'Sullivan, Mary J.; Peaceman, Alan M.; Caritis, Steve N.

2014-01-01

Objective Assess the relationship between umbilical cord blood magnesium concentration and level of delivery room resuscitation received by neonates. Study design Secondary analysis of a controlled fetal neuroprotection trial that enrolled women at imminent risk for delivery between 24 and 31 weeks’ gestation and randomly allocated them to receive intravenous magnesium sulfate or placebo. The cohort included 1507 infants for whom total cord blood magnesium concentration and delivery room resuscitation information were available. Multivariable logistic regression was used to estimate the association between cord blood magnesium concentration and highest level of delivery room resuscitation, using the following hierarchy: none, oxygen only, bag-mask ventilation with oxygen, intubation or chest compressions. Results There was no relationship between cord blood magnesium and delivery room resuscitation (odds ratio [OR] 0.92 for each 1.0 mEq/L increase in magnesium; 95% confidence interval [CI]: 0.83-1.03). Maternal general anesthesia was associated with increased neonatal resuscitation (OR 2.51; 95% CI: 1.72-3.68). Each 1-week increase in gestational age at birth was associated with decreased neonatal resuscitation (OR 0.63; 95% CI: 0.60 – 0.66). Conclusion Cord blood magnesium concentration does not correlate with the level of delivery room resuscitation of infants exposed to magnesium sulfate for fetal neuroprotection. PMID:22056282

Simultaneous isolation of vascular endothelial cells and mesenchymal stem cells from the human umbilical cord.

PubMed

Kadam, Sachin S; Tiwari, Shubha; Bhonde, Ramesh R

2009-01-01

The umbilical cord represents the link between mother and fetus during pregnancy. This cord is usually discarded as a biological waste after the child's birth; however, its importance as a "store house" of stem cells has been explored recently. We developed a method of simultaneous isolation of endothelial cells (ECs) from the vein and mesenchymal stem cells from umbilical cord Wharton's jelly of the same cord. The isolation protocol has been simplified, modified, and improvised with respect to choice of enzyme and enzyme mixture, digestion time, cell yield, cell growth, and culture medium. Isolated human umbilical vascular ECs (hUVECs) were positive for von-Willibrand factor, a classical endothelial marker, and could form capillary-like structures when seeded on Matrigel, thus proving their functionality. The isolated human umbilical cord mesenchymal stem cells (hUCMSCs) were found positive for CD44, CD90, CD 73, and CD117 and were found negative for CD33, CD34, CD45, and CD105 surface markers; they were also positive for cytoskeleton markers of smooth muscle actin and vimentin. The hUCMSCs showed multilineage differentiation potential and differentiated into adipogenic, chondrogenic, osteogenic, and neuronal lineages under influence of lineage specific differentiation medium. Thus, isolating endothelial cells as well as mesenchymal cells from the same umbilical cord could lead to complete utilization of the available tissue for the tissue engineering and cell therapy.

High acceptance rate of hybrid allogeneic-autologous umbilical cord blood banking among actual and potential Swiss donors.

PubMed

Wagner, Anna-Margaretha; Krenger, Werner; Suter, Eva; Ben Hassem, Dorra; Surbek, Daniel V

2013-07-01

Two competitive concepts of umbilical cord blood (UCB) banking are currently available: either allogeneic UCB is donated to a public bank or autologous cells are stored in a private bank. Allogeneic-autologous hybrid banking is a new concept that combines these two approaches. However, acceptance of hybrid UCB banking among potential donors is unknown to date. In a prospective survey, we aimed to establish the acceptance of the hybrid banking model among actual and potential UCB donors in Switzerland. The study groups consisted of parents and pregnant women with or without children. As control group, women at reproductive ages were investigated. The majority of participants agreed fundamentally with UCB donation, and overall acceptance of private banking was 47%. If a possibility for hybrid banking were to be made available, 49% would opt for such a public-private model and only 13% would choose private banking alone. Among the proponents of hybrid banking, a majority of participants chose donor cell splitting over the sequential banking mode. Fifty-six percent of responders wished prior notification before the release of their donated UCB to a foreign recipient. This is the first study which compared the acceptance of allogeneic, autologous, and hybrid allogeneic-autologous UCB banking in different target groups. We demonstrated that hybrid cord blood banking is the preferred model of banking among actual and potential UCB donors. With increasing demand for UCB in the future, health care providers should therefore consider offering hybrid banking as a viable storage option. © 2012 American Association of Blood Banks.

Heterogeneity in cord blood DHA concentration: towards an explanation.

PubMed

Muhlhausler, B S; Gibson, R A; Yelland, L N; Makrides, M

2014-10-01

This paper aimed to identify the dietary and non-dietary determinants of docosahexaenoic acid (DHA) levels in umbilical cord blood at delivery. DHA was measured in cord blood plasma phospholipids of 1571 participants from the DOMInO (DHA to Optimize Mother Infant Outcome) randomized controlled trial. Socioeconomic, lifestyle and clinical data relating to the mother and current pregnancy were obtained from all women and their relationships with cord blood DHA assessed. DHA concentrations in the cord plasma phospholipids at delivery covered a 3-4 fold range in both control and DHA groups. The total number of DHA-rich intervention supplement capsules consumed over the course of pregnancy and gestational age at delivery individually explained 21% and 16% respectively of the variation in DHA abundance in the cord blood plasma phospholipids at delivery, but no other clinical or life-style factors explored in this study could account for >2% of the variation. Indeed, more than 65% of the variation remained unaccounted for even when all factors were included in the analysis. These data suggest that factors other than maternal DHA intake have an important role in determining cord blood DHA concentrations at delivery, and may at least partially explain the variation in the response of infants to maternal DHA supplementation reported in published trials. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Interest of lactate micro-dosage in scalp and umbilical cord in cases of abnormal fetal heart rate during labor. Prospective study on 162 patients].

PubMed

Paris, A; Maurice-Tison, S; Coatleven, F; Vandenbossche, F; Dallay, D; Horovitz, J

2012-06-01

To compare the interest of lactate microanalysis with pH measurement (Gold Standard procedure) in cord blood and fetal scalp blood samples for the assessment of abnormal fetal heart rate (FHR) during labour. A prospective observational study conducted from July 1st 2007 till March 31st 2008 on 162 patients with abnormal FHR during labour. Sampling failure for scalp lactate was less than 1 % compared to a failure of 10.5 % for scalp pH (P<0.001). There was a good correlation between pH and lactates in fetal scalp blood samples and in cord blood samples, between lactate in the last fetal scalp sample and in cord blood. When there was umbilical acidosis (pH≤7.15 or lactate≥5mmol/L), Apgar score at 5 minutes was significantly lower than when there was no acidosis (4.66±3.59 versus 8.35±2.73 for pH ; 6.6±3.77 versus 8.45±2.58 for lactate). The specificity of the lactate in the umbilical cord artery (≥5 mmol/laws) was 76.4 % for predicting an Apgar score at 5 minutes less than 7 ; 79.7 % for predicting the need for immediate neonatal care ; 77.3 % for predicting an hospital stay in neonatal unit. These figures were generally worse but close to those found for a threshold value of umbilical artery pH≤7.15. The values of lactate in cord blood and fetal scalp blood samples were comparable to pH values (Gold standard procedure). This method is easy to perform and is an attractive alternative to pH for monitoring fetal asphyxia. It is our opinion that the combination of the two methods is of interest. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

[Activity of agglutinin inhibitor of the kujavian pea (Pisum sativum L.) in mothers' blood and umbilical cord blood considering the course of pregnancy and delivery].

PubMed

Lange-Konior, K

1999-01-01

The aim of the paper was to evaluate the activity of inhibitor of the phytoagglutinin Pisum sativum (IfPs) in sera of mothers' and umbilical blood of their newborns in confrontation with the course of pregnancy and delivery. The investigations involved 152 tests of sera collected from women delivering at Department of Obstetrics and Perinatology in the Institute of Gynecology and Obstetrics PMU in Szczecin in the years 1992-1993, as well as 156 samples of sera stemming from their newborn infants and were taken from the umbilical cord vessels. The method of investigations being used in the paper was the reaction of inhibiting the phytohemagglutination, wherein the inhibiting action of sera in bearing women and of sera in umbilical blood exerted on agglutinating one was assessed in relation to human erythrocytes of the group 0 with Pisum sativum lectin properties. The accepted titer of inhibitor of the agglutinin Pisum sativum (IfPs) was expressed as the highest dilution of serum, at which complete inhibition of phytohemagglutination was still preserved. The performed investigations have disclosed statistically significant differences between the activity of IfPs occurring in sera of the mothers and the inhibiting factor in umbilical blood sera of the newborns (Tab. 1). No effect of the duration of pregnancy and the course of pregnancy on the IfPs activity in sera of mothers was disclosed. The absence of inhibitor of Pisum sativum lectin in umbilical blood sera was essentially frequently recorded in premature termination of pregnancy between 31-37 weeks of its duration as well as in sera of newborns born by cesarean section and newborns with birth mass being equal or lower than 2500 g in comparison to sera of full term newborns born by forces of nature (Tab. 2, 3, 5). The birth status of newborns according to Apgar scale did not have any influence of IfPs activity in their sera, however, IfPs activity in sera of umbilical blood was statistically significantly more

[Diagnosis of primary hyperlipoproteinemia in umbilical cord blood (author's transl)].

PubMed

Parwaresch, M R; Radzun, H J; Mäder, C

1977-10-01

The aim of the present investigation was to assay the frequency of primary dyslipoproteinemia in a random sample of one hundred newborns and to describe the minimal methodical requirements for sound diagnosis. After comparison of different methods total lipids were determined by gravimetry, cholesterol and triglycerides by enzymatic methods, nonesterified fatty acids by direct colorimetry; phospholipids were estimated indirectly. All measurements were applied to umbilical cord sera and to lipoprotein fractions separated by selective precipitation. The diagnosis of hyperlipoproteinemia type IV, which is the most frequent one in adults, is highly afflicted with pitfalls in the postnatal period. A primary hyper-alpha-liproteinemia occured in one case and type II-hyperlipoproteinemia in two cases, one of the parents being involved in each case. For mass screening triglycerides should be assayed in serum and cholesterol in precipitated and resolubilized LDL-fraction, for which the minimal requirements are described.

Human umbilical cord mesenchymal stromal cells in regenerative medicine.

PubMed

Detamore, Michael S

2013-11-25

Cells of the human umbilical cord offer tremendous potential for improving human health. Cells from the Wharton’s jelly (umbilical cord stroma) in particular, referred to as human umbilical cord mesenchymal stromal cells (HUCMSCs), hold several advantages that make them appealing for translational research. In the previous issue of Stem Cell Research & Therapy, Chon and colleagues made an important contribution to the HUCMSC literature not only by presenting HUCMSCs as an emerging cell source for intervertebral disc regeneration in general and the nucleus pulposus in particular, but also by demonstrating that an extracellular matrix-based strategy might be preferred over the use of growth factors. By culturing HUCMSCs under hypoxia in serum-free conditions in the presence of Matrigel with laminin-111, they were able to achieve intense collagen II staining by 21 days without the addition of exogenous growth factors. There is tremendous translational significance here in that such raw materials may alleviate the need for the use of growth factors in some instances, and this may have important ramifications in reducing product cost and streamlining regulatory approval. Chon and colleagues provide a promising example of the potential of HUCMSCs, demonstrating the ability to guide HUCMSC differentiation even in the absence of serum and growth factors and supporting the use of HUCMSCs as a viable alternative in intervertebral disc regeneration.

Exposure to Low Levels of Lead in Utero and Umbilical Cord Blood DNA Methylation in Project Viva: An Epigenome-Wide Association Study

PubMed Central

Hivert, Marie-France; Cardenas, Andres; Zhong, Jia; Rifas-Shiman, Sheryl L.; Agha, Golareh; Colicino, Elena; Just, Allan C.; Amarasiriwardena, Chitra; Lin, Xihong; Litonjua, Augusto A.; DeMeo, Dawn L.; Gillman, Matthew W.; Wright, Robert O.; Oken, Emily

2017-01-01

Background: Early-life exposure to lead is associated with deficits in neurodevelopment and with hematopoietic system toxicity. DNA methylation may be one of the underlying mechanisms for the adverse effects of prenatal lead on the offspring, but epigenome-wide methylation data for low levels of prenatal lead exposure are lacking. Objectives: We investigated the association between prenatal maternal lead exposure and epigenome-wide DNA methylation in umbilical cord blood nucleated cells in Project Viva, a prospective U.S.-based prebirth cohort with relatively low levels of lead exposure. Methods: Among 268 mother–infant pairs, we measured lead concentrations in red blood cells (RBC) from prenatal maternal blood samples, and using HumanMethylation450 Bead Chips, we measured genome-wide methylation levels at 482,397 CpG loci in umbilical cord blood and retained 394,460 loci after quality control. After adjustment for batch effects, cell types, and covariates, we used robust linear regression models to examine associations of prenatal lead exposure with DNA methylation in cord blood at epigenome-wide significance level [false discovery rate (FDR)<0.05]. Results: The mean [standard deviation (SD)] maternal RBC lead level was 1.22 (0.63) μg/dL. CpG cg10773601 showed an epigenome-wide significant negative association with prenatal lead exposure (−1.4% per doubling increase in lead exposure; p=2.3×10−7) and was annotated to C-Type Lectin Domain Family 11, Member A (CLEC11A), which functions as a growth factor for primitive hematopoietic progenitor cells. In sex-specific analyses, we identified more CpGs with FDR<0.05 among female infants (n=38) than among male infants (n=2). One CpG (cg24637308), which showed a strong negative association with prenatal lead exposure among female infants (−4.3% per doubling increase in lead exposure; p=1.1×10−06), was annotated to Dynein Heavy Chain Domain 1 gene (DNHD1) which is highly expressed in human brain. Interestingly

[THE USE AND STORAGE OF STEM CELLS AND CORD BLOOD: FRENCH AND ENGLISH LAW COMPARATIVE APPROACH].

PubMed

Madanamoothoo, Allane

2015-07-01

Becoming parents is one of the greatest wishes of a lot of couples. When their dreams come true, prior to the birth of the child, parents have to face several points: the choice of the name, place of delivery, breast or bottle feeding, etc. Recently, they have to face the issues of cord blood stem cells. Researchers and cord blood banks are also interested in those cells. In many countries a lot of advertising is made around umbilical cord blood stem cells. In France as in England, the use and preservation of cord blood are regulated by the legislators without necessarily having the same approach. The objective of this paper is to present English and French law approaches' on cord blood stem cells.

Reduced intensity haplo plus single cord transplant compared to double cord transplant: improved engraftment and graft-versus-host disease-free, relapse-free survival

PubMed Central

van Besien, Koen; Hari, Parameswaran; Zhang, Mei-Jie; Liu, Hong-Tao; Stock, Wendy; Godley, Lucy; Odenike, Olatoyosi; Larson, Richard; Bishop, Michael; Wickrema, Amittha; Gergis, Usama; Mayer, Sebastian; Shore, Tsiporah; Tsai, Stephanie; Rhodes, Joanna; Cushing, Melissa M.; Korman, Sandra; Artz, Andrew

2016-01-01

Umbilical cord blood stem cell transplants are commonly used in adults lacking HLA-identical donors. Delays in hematopoietic recovery contribute to mortality and morbidity. To hasten recovery, we used co-infusion of progenitor cells from a partially matched related donor and from an umbilical cord blood graft (haplo-cord transplant). Here we compared the outcomes of haplo-cord and double-cord transplants. A total of 97 adults underwent reduced intensity conditioning followed by haplo-cord transplant and 193 patients received reduced intensity conditioning followed by double umbilical cord blood transplantation. Patients in the haplo-cord group were more often from minority groups and had more advanced malignancy. Haplo-cord recipients received fludarabine-melphalan-anti-thymocyte globulin. Double umbilical cord blood recipients received fludarabine-cyclophosphamide and low-dose total body irradiation. In a multivariate analysis, haplo-cord had faster neutrophil (HR=1.42, P=0.007) and platelet (HR=2.54, P<0.0001) recovery, lower risk of grade II–IV acute graft-versus-host disease (HR=0.26, P<0.0001) and chronic graft-versus-host disease (HR=0.06, P<0.0001). Haplo-cord was associated with decreased risk of relapse (HR 0.48, P=0.001). Graft-versus-host disease-free, relapse-free survival was superior with haplo-cord (HR 0.63, P=0.002) but not overall survival (HR=0.97, P=0.85). Haplo-cord transplantation using fludarabine-melphalan-thymoglobulin conditioning hastens hematopoietic recovery with a lower risk of relapse relative to double umbilical cord blood transplantation using the commonly used fludarabine-cyclophosphamide-low-dose total body irradiation conditioning. Graft-versus-host disease-free and relapse-free survival is significantly improved. Haplo-cord is a readily available graft source that improves outcomes and access to transplant for those lacking HLA-matched donors. Trials registered at clinicaltrials.gov identifiers 00943800 and 01810588. PMID

Isolation of mesenchymal stromal/stem cells from cryopreserved umbilical cord blood cells.

PubMed

Fujii, Sumie; Miura, Yasuo; Iwasa, Masaki; Yoshioka, Satoshi; Fujishiro, Aya; Sugino, Noriko; Kaneko, Hitomi; Nakagawa, Yoko; Hirai, Hideyo; Takaori-Kondo, Akifumi; Ichinohe, Tatsuo; Maekawa, Taira

2017-07-05

Umbilical cord blood (UCB) has advantages over other tissues because it can be obtained without an invasive procedure and complex processing. We explored the availability of cryopreserved UCB cells as a source of mesenchymal stromal/stem cells (MSCs). MSCs were successfully isolated from six of 30 UCB units (median volume, 34.0 mL; median nucleated cell number, 4.4×10 8 ) that were processed and cryopreserved using CP-1/human serum albumin. This isolation rate was lower than that (57%) from non-cryopreserved UCB cells. The number of nucleated cells before and after hydroxyethyl starch separation, UCB unit volume, and cell viability after thawing did not significantly differ between UCB units from which MSCs were successfully isolated and those from which they were not. When CryoSure-DEX40 was used as a cryoprotectant, MSCs were isolated from two of ten UCB units. Logistic regression analysis demonstrated that the cryopreservation method was not significantly associated with the success of MSC isolation. The isolated MSCs had a similar morphology and surface marker expression profile as bone marrow-derived MSCs and were able to differentiate into osteogenic, adipogenic, and chondrogenic cells. In summary, MSCs can be isolated from cryopreserved UCB cells. However, the cryopreservation process reduces the isolation rate; therefore, freshly donated UCB cells are preferable for the isolation of MSCs.

Effect of umbilical cord milking in term and near term infants: randomized control trial.

PubMed

Upadhyay, Amit; Gothwal, Sunil; Parihar, Rajeshwari; Garg, Amit; Gupta, Abhilasha; Chawla, Deepak; Gulati, Ish K

2013-02-01

The objective of the study was to investigate the effect of umbilical cord milking as compared with early cord clamping on hematological parameters at 6 weeks of age among term and near term neonates. This was a randomized control trial. Eligible neonates (>35 weeks' gestation) were randomized in intervention and control groups (100 each). Neonates of both groups got early cord clamping (within 30 seconds). The cord of the experimental group was milked after cutting and clamping at 25 cm from the umbilicus, whereas in control group cord was clamped near (2-3 cm) the umbilicus and not milked. Both groups got similar routine care. Unpaired Student t and Fisher exact tests were used for statistical analysis. Baseline characteristics were comparable in the 2 groups. Mean hemoglobin (Hgb) (11.9 [1.5] g/dL and mean serum ferritin 355.9 [182.6] μg/L) were significantly higher in the intervention group as compared with the control group (10.8 [0.9] g/dL and 177.5 [135.8] μg/L), respectively, at 6 weeks of age. The mean Hgb and hematocrit at 12 hours and 48 hours was significantly higher in intervention group (P = .0001). The mean blood pressure at 30 minutes, 12 hours, and 48 hours after birth was significantly higher but within normal range. No significant difference was observed in the heart rate, respiratory rate, polycythemia, serum bilirubin, and need of phototherapy in the 2 groups. Umbilical cord milking is a safe procedure and it improved Hgb and iron status at 6 weeks of life among term and near term neonates. Copyright © 2013 Mosby, Inc. All rights reserved.

Effect of allo- and xenotransplantation of embryonic nervous tissue and umbilical cord blood-derived stem cells on structural and functional state of cerebral cortex of albino rats in posttraumatic period.

PubMed

Ereniev, S I; Semchenko, V V; Sysheva, E V; Bogdashin, I V; Shapovalova, V V; Khizhnyak, A S; Gasanenko, L N

2005-11-01

Comparative study of the structural and functional state of cerebral cortex of adult albino rats after intracerebral allo- and xenotransplantation of embryonic nervous tissue and intravenous injection of umbilical cord blood-derived stem cells at different terms after diffuse-focal cerebral trauma revealed the best cerebroprotective effect on day 7 of posttraumatic period in animals receiving embryonic nervous tissue.

Private Cord Blood Banking: Experiences And Views Of Pediatric Hematopoietic Cell Transplantation Physicians

PubMed Central

Thornley, Ian; Eapen, Mary; Sung, Lillian; Lee, Stephanie J.; Davies, Stella M.; Joffe, Steven

2011-01-01

Objective Private cord blood banks are for-profit companies that facilitate storage of umbilical cord blood for personal or family use. Pediatric hematopoietic cell transplantation (HCT) physicians are currently best situated to use cord blood therapeutically. We sought to describe the experiences and views of these physicians regarding private cord blood banking. Participants and Methods Emailed cross-sectional survey of pediatric HCT physicians in the United States and Canada. 93/152 potentially eligible physicians (93/130 confirmed survey recipients) from 57 centers responded. Questions addressed the number of transplants performed using privately banked cord blood, willingness to use banked autologous cord blood in specific clinical settings, and recommendations to parents regarding private cord blood banking. Results Respondents reported having performed 9 autologous and 41 allogeneic transplants using privately banked cord blood. In 36/40 allogeneic cases for which data were available, the cord blood had been collected because of a known indication in the recipient. Few respondents would choose autologous cord blood over alternative stem cell sources for treatment of acute lymphoblastic leukemia in second remission. In contrast, 55% would choose autologous cord blood to treat high-risk neuroblastoma, or to treat severe aplastic anemia in the absence of an available sibling donor. No respondent would recommend private cord blood banking for a newborn with one healthy sibling when both parents were of Northern European descent; 11% would recommend banking when parents were of different minority ethnicities. Conclusions Few transplants have been performed using cord blood stored in the absence of a known indication in the recipient. Willingness to use banked autologous cord blood varies depending on disease and availability of alternative stem cell sources. Few pediatric HCT physicians endorse private cord blood banking in the absence of an identified recipient

Umbilical cord cell banking-implications for the future

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gunning, Jennifer

2005-09-01

The first successful cord cell transplant to a sibling with Fanconi's anaemia took place 15 years ago. This proven utility of cord blood led to the establishment of cord blood banks both private and public and there are now nearly 100 cord blood banks worldwide. It is estimated that over 200,000 cord blood units (CBU) are held by the private sector and over 160,000 CBU are registered with the largest public cord blood registry. There is a tension between private cord blood banks, which store CBU for autologous or family use, and public banks, which store CBU for unrelated usemore » and the ethics of private cord blood storage has been questioned. But more general ethical questions also arise regarding ownership, consent, confidentiality, costs and quality standards and patenting. In looking at these ethical issues one also needs to look at potential future use of cord blood stem cells. Up until now cord cells have principally been used in the treatment of paediatric blood and immune disorders. Improvements in cell expansion technology will make CBU more appropriate also for treating adults with such disorders. However, it has also been demonstrated that cord blood stem cells have the capacity to differentiate into other types of cells, neuronal, bone, epithelial and muscle which would have a future role to play in cell therapy and regenerative medicine.« less

Institutional Knots: A Comparative Analysis of Cord Blood Policy in Canada and the United States.

PubMed

Denburg, Avram

2016-02-01

Umbilical cord blood is a rich source of blood stem cells, which are of critical clinical importance in the treatment of a variety of malignant and genetic conditions requiring stem cell transplantation. Many countries have established national public cord blood banks; such banks often coexist with a panoply of private options for cord blood banking. Until recently, Canada was the only G8 country without a national cord blood bank. This differs markedly from the United States, which years ago established a national cord blood bank policy and inventory. This article investigates potential reasons for this discrepancy through a comparative analysis of the evolution of programs and policies on national cord blood banking in Canada and the United States. My analysis suggests that cross-national discrepancies in policy on public cord blood banking were determined primarily by institutional factors, principal among them formal governmental structure and the legacy of past policies. Institutional entrepreneurialism in the health sector played a constitutive role in the earlier evolution of national cord blood policy in the United States as compared to Canada. Copyright © 2016 by Duke University Press.

Methylmercury level in umbilical cords from patients with congenital Minamata disease.

PubMed

Harada, M; Akagi, H; Tsuda, T; Kizaki, T; Ohno, H

1999-08-30

A total of 151 umbilical cords during the period from 1950 to 1969 were collected from the residents of the Minamata area (including 25 patients with congenital Minamata disease) for methylmercury (MeHg) analysis. When the MeHg discharge from the Chisso Company's Minamata factory into the Minamata Bay is compared with the incidence of congenital Minamata disease, the abrupt increase of the former in 1952 [Nishimura H. Chem. Today 1998;323:60-66] was found to precede that of the latter by approximately 2 years, thereby indicating that MeHg is the cause of the disaster. This was confirmed by the elevated levels of MeHg in the umbilical cords from residents of the Minamata area [from 0.35 +/- 0.30 (S.D.) ppm in 1952 to 0.96 +/- 0.75 ppm in 1955], the MeHg levels (1.60 +/- 1.00 ppm) in the cords from patients with congenital Minamata disease showing the highest values [P < 0.01 vs. acquired Minamata disease (0.72 +/- 0.65 ppm), mental retardation (0.74 +/- 0.64 ppm), other diseases (0.22 +/- 0.15 ppm), and no symptoms (0.28 +/- 0.20 ppm), respectively]. Thus, in order to fill a gap, which extends over a long period of time, in studies on environmental Hg pollution, umbilical cord samples were considered to be a useful tool.

A comparison of cryopreservation methods: Slow-cooling vs. rapid-cooling based on cell viability, oxidative stress, apoptosis, and CD34+ enumeration of human umbilical cord blood mononucleated cells

PubMed Central

2011-01-01

Background The finding of human umbilical cord blood as one of the most likely sources of hematopoietic stem cells offers a less invasive alternative for the need of hematopoietic stem cell transplantation. Due to the once-in-a-life time chance of collecting it, an optimum cryopreservation method that can preserve the life and function of the cells contained is critically needed. Methods Until now, slow-cooling has been the routine method of cryopreservation; however, rapid-cooling offers a simple, efficient, and harmless method for preserving the life and function of the desired cells. Therefore, this study was conducted to compare the effectiveness of slow- and rapid-cooling to preserve umbilical cord blood of mononucleated cells suspected of containing hematopoietic stem cells. The parameters used in this study were differences in cell viability, malondialdehyde content, and apoptosis level. The identification of hematopoietic stem cells themselves was carried out by enumerating CD34+ in a flow cytometer. Results Our results showed that mononucleated cell viability after rapid-cooling (91.9%) was significantly higher than that after slow-cooling (75.5%), with a p value = 0.003. Interestingly, the malondialdehyde level in the mononucleated cell population after rapid-cooling (56.45 μM) was also significantly higher than that after slow-cooling (33.25 μM), with a p value < 0.001. The apoptosis level in rapid-cooling population (5.18%) was not significantly different from that of the mononucleated cell population that underwent slow-cooling (3.81%), with a p value = 0.138. However, CD34+ enumeration was much higher in the population that underwent slow-cooling (23.32 cell/μl) than in the one that underwent rapid-cooling (2.47 cell/μl), with a p value = 0.001. Conclusions Rapid-cooling is a potential cryopreservation method to be used to preserve the umbilical cord blood of mononucleated cells, although further optimization of the number of CD34+ cells after

Neonatal testicular infarction--possibly due to compression of the umbilical cord?

PubMed

Eifinger, Frank; Ahrens, Ulrike; Wille, Sebastian; Roth, Bernhard; Engelmann, Udo

2010-06-01

Neonatal testicular infarction is a rare occurrence. We report on a newborn infant with bilateral testicular infarction. At birth, the uncut umbilical cord ran taut between the thighs making a complete loop around the genitals, compressing the testes. At the age of 6 hours, because of increasing agitation and the beginnings of scrotal discoloration, the infant was operated on, showing a bilateral testicular infarction potentially induced by strangulation of the twisted umbilical cord. Here, we discuss the clinical findings of neonatal testicular infarction and give advice as to the management of this serious complication with regard to the available published data. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Spontaneous transient rise of CD34 cells in peripheral blood after 72 hours in patients suffering from advanced malignancy with anemia: effect and prognostic implications of treatment with placental umbilical cord whole blood transfusion.

PubMed

Bhattacharya, N

2006-01-01

Cord blood, because of its rich mix of fetal and adult hemoglobin, platelet and WBC counts, and a plasma filled with cytokine and growth factors, as well as its hypoantigenic nature and altered metabolic profile, has all the potential of a real and safe alternative to adult blood during emergencies or any etiology of blood loss. In the present study transfusion-related CD34 levels of the peripheral blood from six randomly selected patients suffering from advanced clinical Stage IV malignancy were analyzed between 16 August 1999 and 16 May 2001. This study attempts to ascertain the fate of hematopoietic stem cells (CD34) after placental umbilical cord whole blood transfusion, as assessed from the peripheral blood CD34 level 72 hours after cord blood transfusion in sex- and HLA-randomized patients. Among the six cases, Case 2 (breast sarcoma) received the lowest amount of card blood (6 units), while Case 6 (breast cancer) received the largest amount (32 units). The youngest patient, suffering from non-Hodgkin's lymphoma (Case 3), was a 16-year-old boy who received eight units of cord blood to combat anemia. Other patients received amounts varying from 7-15 units: Case 4 received 15 units (metachronous lymph node metastatsis), Case 1 received 14 units (breast cancer), and Case 5 received seven units (lung cancer). There was no transfusion-related clinical immunological or nonimmunological reaction. Studies of CD34 levels showed an initial rise followed by a fall in two cases, two cases registered very little effect on the CD34 level, i.e., no change from the baseline, and one case demonstrated a very slow rise from the baseline. However, one case showed a frequent steep rise up to 99% and a sustained high CD34 level. This patient is alive with clinical remission of the disease. It appears from this preliminary study that freshly collected cord blood transfusion may cause a transient transplant impact of transfused cord blood CD34 stem cells on the host without

Three-dimensional HDlive imaging of an umbilical cord cyst.

PubMed

Inubashiri, Eisuke; Nishiyama, Naomi; Tatedo, Sayuri; Minami, Hiina; Saitou, Atushi; Watanabe, Yukio; Sugawara, Masaki

2018-04-01

Umbilical cord cysts (UCC) are a rare congenital malformation. Previous reports have suggested that the second- and third-trimester UCC may be associated with other structural anomalies or chromosomal abnormalities. Therefore, high-quality imaging is clinically important for the antenatal diagnosis of UCC and to conduct a precise anatomical survey of intrauterine abnormalities. There have been few reports of antenatal diagnosis of UCC with the conventional two- and three-dimensional ultrasonography. In this report, we demonstrate the novel visual depiction of UCC in utero with three-dimensional HDlive imaging, which helps substantially with prenatal diagnosis. A case with an abnormal placental mass at 16 weeks and 5 days of gestation was observed in detail using HDlive. HDlive revealed very realistic images of the intrauterine abnormality: the oval lesion was smooth with regular contours and a homogenous wall at the site of cord insertion on the placenta. In addition, we confirmed the absent of umbilical cord, placental, and fetal structural anomalies. Here, we report a case wherein HDlive may have provided clinically valuable information for prenatal diagnosis of UCC and offered a potential advantage relative to the conventional US.

Banking Umbilical Cord Blood (UCB) Stem Cells: Awareness, Attitude and Expectations of Potential Donors from One of the Largest Potential Repository (India).

PubMed

Pandey, Deeksha; Kaur, Simar; Kamath, Asha

2016-01-01

The concept of Umbilical Cord blood (UCB) stem cells is emerging as a non-invasive, efficacious alternative source of hematopoietic stem cells to treat a variety of blood and bone marrow diseases, blood cancers, metabolic disorders and immune deficiencies. Aim of the present study was to determine the level of awareness about banking UCB among pregnant women in India. We also assessed patient perception for banking of UCB and explored the patient expectations of banking UCB in future. This is the first study to assess current attitudes, in a sample population of potential donors from one of the largest potential UCB repository (India). Obtaining this information may help optimize recruitment efforts and improve patient education. Present explorative questionnaire based survey included 254 pregnant women in the final analysis. We established only 26.5% pregnant women in our study population knew what exactly is meant by UCB. A large proportion (55.1%) was undecided on whether they want to bank UCB or not. Women were more aware of the more advertised private cord blood banking compared to public banking. More than half of the pregnant women expected their obstetrician to inform them regarding UCB. One-third of the women in our population had undue expectations from banking of the UCB. Obstetricians should play a more active role in explaining the patients regarding pros and cons of UCB banking.

Improvement of renal function after human umbilical cord mesenchymal stem cell treatment on chronic renal failure and thoracic spinal cord entrapment: a case report.

PubMed

Rahyussalim, Ahmad Jabir; Saleh, Ifran; Kurniawati, Tri; Lutfi, Andi Praja Wira Yudha

2017-11-30

Chronic renal failure is an important clinical problem with significant socioeconomic impact worldwide. Thoracic spinal cord entrapment induced by a metabolic yield deposit in patients with renal failure results in intrusion of nervous tissue and consequently loss of motor and sensory function. Human umbilical cord mesenchymal stem cells are immune naïve and they are able to differentiate into other phenotypes, including the neural lineage. Over the past decade, advances in the field of regenerative medicine allowed development of cell therapies suitable for kidney repair. Mesenchymal stem cell studies in animal models of chronic renal failure have uncovered a unique potential of these cells for improving function and regenerating the damaged kidney. We report a case of a 62-year-old ethnic Indonesian woman previously diagnosed as having thoracic spinal cord entrapment with paraplegic condition and chronic renal failure on hemodialysis. She had diabetes mellitus that affected her kidneys and had chronic renal failure for 2 years, with creatinine level of 11 mg/dl, and no urinating since then. She was treated with human umbilical cord mesenchymal stem cell implantation protocol. This protocol consists of implantation of 16 million human umbilical cord mesenchymal stem cells intrathecally and 16 million human umbilical cord mesenchymal stem cells intravenously. Three weeks after first intrathecal and intravenous implantation she could move her toes and her kidney improved. Her creatinine level decreased to 9 mg/dl. Now after 8 months she can raise her legs and her creatinine level is 2 mg/dl with normal urinating. Human umbilical cord mesenchymal stem cell implantations led to significant improvement for spinal cord entrapment and kidney failure. The major histocompatibility in allogeneic implantation is an important issue to be addressed in the future.

Immortalization of Human Fetal Cells: The Life Span of Umbilical Cord Blood-derived Cells Can Be Prolonged without Manipulating p16INK4a/RB Braking PathwayD⃞

PubMed Central

Terai, Masanori; Uyama, Taro; Sugiki, Tadashi; Li, Xiao-Kang; Umezawa, Akihiro; Kiyono, Tohru

2005-01-01

Human umbilical cord blood-derived mesenchymal stem cells (UCBMSCs) are expected to serve as an excellent alternative to bone marrow-derived human mesenchymal stem cells. However, it is difficult to study them because of their limited life span. To overcome this problem, we attempted to produce a strain of UCBMSCs with a long life span and to investigate whether the strain could maintain phenotypes in vitro. UCBMSCs were infected with retrovirus carrying the human telomerase reverse transcriptase (hTERT) to prolong their life span. The UCBMSCs underwent 30 population doublings (PDs) and stopped dividing at PD 37. The UCBMSCs newly established with hTERT (UCBTERTs) proliferated for >120 PDs. The p16INK4a/RB braking pathway leading to senescence can be inhibited by introduction of Bmi-1, a polycomb-group gene, and human papillomavirus type 16 E7, but the extension of the life span of the UCBMSCs with hTERT did not require inhibition of the p16INK4a/RB pathway. The characteristics of the UCBTERTs remained unchanged during the prolongation of life span. UCBTERTs provide a powerful model for further study of cellular senescence and for future application to cell-based therapy by using umbilical cord blood cells. PMID:15647378

Engineering cord blood to improve engraftment after cord blood transplant

PubMed Central

Dave, Hema; Bollard, Catherine M.; Shpall, Elizabeth J.

2017-01-01

Umbilical cord blood transplant (CBT) has traditionally been associated with slower engraftment of neutrophils, delayed immune reconstitution and consequently higher risk of infections as compared with peripheral blood progenitor cell (PBPC) or bone marrow (BM) transplants. This is primarily due to low numbers of total nucleated cells (TNCs) and the naive nature of CB immune cells. The use of double unit CB transplant (DCBT) increases the total cell dose in the graft, but it still does not produce as rapid engraftment as seen with PBPC or even BM transplants. Herein, we discuss strategies to improve engraftment after CBT. We describe methods of (I) expansion of CB graft ex vivo to increase the total cell dose; and (II) enhancement of BM homing capability of CB progenitor cells; (III) ex vivo expansion of CB derived T cells for improving T cell function against viruses, tumors and protection from graft versus host disease (GVHD). With these novel approaches, engraftment after CBT is now reaching levels comparable to that of other graft types. PMID:28607915

Umbilical Cord Blood pH in Intrapartum Hypoxia.

PubMed

Perveen, Fouzia; Khan, Ayesha; Ali, Tahmina; Rabia, Syeda

2015-09-01

To determine the association of cord arterial blood pH with neonatal outcome in cases of intrapartum fetal hypoxia. Descriptive analytical study. Gynaecology Unit-II, Civil Hospital, Karachi, from September 2011 to November 2012. All singleton cephalic fetuses at term gestation were included in the study. Those with any anomaly, malpresentation, medical disorders, maternal age < 18 years, multiple gestation and ruptured membranes were excluded. Patients with abnormal cardiotocography and/or meconium stained liquor were enrolled as index case and immediate next delivery with no such signs as a control. Demographic characteristics, pH level < or > 7.25, neonatal outcome measures (healthy, NICU admission or neonatal death), color of liquor and mode of delivery recorded on predesigned proforma. Statistical analysis performed by SPSS 16 by using independent-t test or chi-square test and ANOVA test as needed. A total of 204 newborns were evaluated. The mean pH level was found to be significantly different (p=0.007) in two groups. The pH value 7.25 had significant association (p < 0.001) with the neonatal outcome. However, the association of neonatal outcome with severity of acidemia was not found to be significant. Grading of Meconium Stained Liquor (MSL) also did not relate positively with pH levels as 85.7% of grade I, 68.9% of grade II and 59.4% of grade III MSLhad pH > 7.25. Majority (63.6%) cases needed caesarean section as compared to 31.4% controls. There is a significant association of cord arterial blood pH at birth with neonatal outcome at pH < or > 7.25; but below the level of pH 7.25 it is still inconclusive.

Recovery of CD45(-)/Lin(-)/SSEA-4(+) very small embryonic-like stem cells by cord blood bank standard operating procedures.

PubMed

Chang, Yu-Jen; Tien, Kuei-Erh; Wen, Cheng-Hao; Hsieh, Tzu-Bou; Hwang, Shiaw-Min

2014-04-01

Very small embryonic-like (VSEL) stem cells are a rare cell population present in bone marrow, cord blood and other tissues that displays a distinct small cell size and the ability to give rise to cells of the three germ layers. VSEL stem cells were reported to be discarded in the red blood cell fraction by Ficoll-Paque density gradient centrifugation during the processing of bone marrow and cord blood specimens. However, most cord blood banks do not include density gradient centrifugation in their procedures while red blood cells are removed by Hespan sedimentation following the Cord Blood Transplantation Study cord blood bank standard operating procedures (COBLT SOP). To clarify the retention of VSEL stem cells, we investigated the recovery of VSEL stem cells following COBLT SOP guidelines. The recovery of CD45(-)/Lin(-)/SSEA-4(+) VSEL stem cells of umbilical cord blood was examined by flow cytometry before and after COBLT SOP processing, and relative expression of pluripotent genes was analyzed by quantitative polymerase chain reaction. CD45(-)/Lin(-)/SSEA-4(+) VSEL stem cells were mostly recovered in the final products following COBLT SOP guidelines. The expression of pluripotent genes could be maintained at >80% in products after hetastarch (Hespan; B. Braun Medical Inc., Irvine, CA, USA) processing. The rare sub-population of CD45(-)/Lin(-)/SSEA-4(+) VSEL stem cells survived after Hespan sedimentation. This finding suggests that umbilical cord blood units cryopreserved by COBLT SOP in cord blood banks should retain most VSEL stem cells present in the un-processed specimens. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Biomonitoring of Lead, Cadmium, Total Mercury, and Methylmercury Levels in Maternal Blood and in Umbilical Cord Blood at Birth in South Korea

PubMed Central

Kim, Yu-Mi; Chung, Jin-Young; An, Hyun Sook; Park, Sung Yong; Kim, Byoung-Gwon; Bae, Jong Woon; Han, Myoungseok; Cho, Yeon Jean; Hong, Young-Seoub

2015-01-01

With rising concerns of heavy metal exposure in pregnancy and early childhood, this study was conducted to assess the relationship between the lead, cadmium, mercury, and methylmercury blood levels in pregnancy and neonatal period. The study population included 104 mothers and their children pairs who completed both baseline maternal blood sampling at the second trimester and umbilical cord blood sampling at birth. The geometric mean maternal blood levels of lead, cadmium, total mercury, and methylmercury at the second trimester were 1.02 ± 1.39 µg/dL, 0.61 ± 1.51 µg/L, 2.97 ± 1.45 µg/L, and 2.39 ± 1.45 µg/L, respectively, and in the newborns, these levels at birth were 0.71 ± 1.42 µg/dL, 0.01 ± 5.31 µg/L, 4.44 ± 1.49 µg/L, and 3.67 ± 1.51 µg/L, respectively. The mean ratios of lead, cadmium, total mercury, and methylmercury levels in the newborns to those in the mothers were 0.72, 0.04, 1.76, and 1.81, respectively. The levels of most heavy metals in pregnant women and infants were higher in this study than in studies from industrialized western countries. The placenta appears to protect fetuses from cadmium; however, total mercury and methylmercury were able to cross the placenta and accumulate in fetuses. PMID:26516876

Neuronal cell reconstruction with umbilical cord blood cells in the brain hypoxia-ischemia.

PubMed

Ghaffaripour, Hossein Ali; Jalali, Mehdi; Nikravesh, Mohammad Reza; Seghatoleslam, Masoumeh; Sanchooli, Javad

2015-01-01

Brain hypoxia-ischemia is a human neonatal injury that is considered a candidate for stem cell therapy. The possible therapeutic potential of human umbilical cord blood (HUCB) stem cells was evaluated in 14-day-old rats subjected to the right common carotid occlusion, a model of neonatal brain hypoxia-ischemia. Seven days after hypoxia-ischemia, rats received either saline solution or 4 × 105 HUCB cells i.v. Rats in control group did not receive any injection. After two weeks, rats were assessed using two motor tests. Subsequently, rats were scarified for histological and immunohistochemical analyses. Our immunohistochemical findings demonstrated selective migration of the injected HUCB cells to the ischemic area as well as reduction in infarct volume. Seven days after surgery, we found significant recovery in the behavioral performance in the test group (12.7 +/- 0.3) compared to the sham group (10.0 +/-0.05), a trend which continued to day 14 (15.3 ± 0.3 vs. 11.9 ± 0.5, P<0.05). Postural and motor asymmetries at days 7 and 14 in the test group showed a significant decrease in the percentage of right turns in comparison to the sham group (75% and 59% vs. 97% and 96%, P<0.05). The results show the potential of HUCB stem cells in reduction of neurologic deficits associated with neonatal hypoxia-ischemia.

Ex-vivo expanded umbilical cord blood stem cells retain capacity for myocardial regeneration.

PubMed

Schlechta, Bernhard; Wiedemann, Dominik; Kittinger, Clemens; Jandrositz, Anita; Bonaros, Nikolaos E; Huber, Johannes C; Preisegger, Karl-Heinz; Kocher, Alfred A

2010-01-01

Umbilical cord blood (UCB) is a source of human hematopoietic precursor cells (HPCs), a stem cell (SC) type that has been used in several trials for myocardial repair. A certain minimal number of cells is required for measurable regeneration and a major challenge of SC-based regenerative therapy constitutes ex-vivo expansion of the primitive cell compartment. The aim of this study was to investigate the ex-vivo expansion potential of UCB-derived HPCs and the ability of these expanded cells to migrate to the site of damage and improve ventricular function in a rodent model of myocardial infarction (MI). UCB-derived HPCs, defined by coexpression of CD133 and CD34, were expanded using various cytokine combinations. MI was induced by left anterior descending artery ligation in nude rats. Cells were injected intravenously 2 days after infarction. The combination of SC factor, thrombopoietin, flt3-ligand and interleukin-6 was found to be the most effective for inducing proliferation of HPCs. The migratory capacity of expanded HPCs was similar to that of non-expanded HPCs and improvement of ejection fraction was significant in both groups, with a relative increase of >60%. UCB-derived HPCs can be reproducibly expanded ex-vivo and retain their potential to improve cardiac function post-MI. (Circ J 2010; 74: 188 - 194).

Intrauterine growth restriction is associated with structural alterations in human umbilical cord and decreased nitric oxide-induced relaxation of umbilical vein.

PubMed

Peyter, A-C; Delhaes, F; Baud, D; Vial, Y; Diaceri, G; Menétrey, S; Hohlfeld, P; Tolsa, J-F

2014-11-01

Intrauterine growth restriction (IUGR) affects ∼8% of all pregnancies and is associated with major perinatal mortality and morbidity, and with an increased risk to develop cardiovascular diseases in adulthood. Despite identification of several risk factors, the mechanisms implicated in the development of IUGR remain poorly understood. In case of placental insufficiency, reduced delivery of oxygen and/or nutrients to the fetus could be associated with alterations in the umbilical circulation, contributing further to the impairment of maternal-fetal exchanges. We compared the structural and functional properties of umbilical cords from growth-restricted and appropriate for gestational age (AGA) term newborns, with particular attention to the umbilical vein (UV). Human umbilical cords were collected at delivery. Morphological changes were investigated by histomorphometry, and UV's reactivity by pharmacological studies. Growth-restricted newborns displayed significantly lower growth parameters, placental weight and umbilical cord diameter than AGA controls. Total cross-section and smooth muscle areas were significantly smaller in UV of growth-restricted neonates than in controls. Maximal vasoconstriction achieved in isolated UV was lower in growth-restricted boys than in controls, whereas nitric oxide-induced relaxation was significantly reduced in UV of growth-restricted girls compared to controls. IUGR is associated with structural alterations of the UV in both genders, and with a decreased nitric oxide-induced relaxation in UV of newborn girls, whereas boys display impaired vasoconstriction. Further investigations will allow to better understand the regulation of umbilical circulation in growth-restricted neonates, which could contribute to devise potential novel therapeutic strategies to prevent or limit the development of IUGR. Copyright © 2014 Elsevier Ltd. All rights reserved.

Giving to receive? The right to donate in umbilical cord blood banking for stem cell therapies.

PubMed

Machin, Laura L; Brown, Nik; McLeod, Danae

2012-03-01

To explore the views of lay and professional stakeholders about the donation of cord blood to public banks in England and the policies surrounding it. Qualitative in-depth interviews were undertaken between April 2009 and August 2010 with 62 participants based in England who play a key role in cord blood banking and therapy. All interviews were recorded, transcribed in full, and coded and analysed thematically. Participants claimed pregnant women had a right to know of the value of cord blood. This highlighted the flaws of the existing donation infrastructure, which was portrayed as playing a significant role in determining public health. Participants called for a right to donate cord blood to readdress the inequity in healthcare services for pregnant women and transplant recipients. Donors maintained a sense of right over their donation when they discussed cord blood donation as potentially benefiting their family as well as society. In order to keep receiving donated body parts, tissue and blood, there is a need to take into account the way in which donation operates within a prevalent 'rights' discourse. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Regeneration of Full-Thickness Rotator Cuff Tendon Tear After Ultrasound-Guided Injection With Umbilical Cord Blood-Derived Mesenchymal Stem Cells in a Rabbit Model.

PubMed

Park, Gi-Young; Kwon, Dong Rak; Lee, Sang Chul

2015-11-01

Rotator cuff tendon tear is one of the most common causes of chronic shoulder pain and disability. In this study, we investigated the therapeutic effects of ultrasound-guided human umbilical cord blood (UCB)-derived mesenchymal stem cell (MSC) injection to regenerate a full-thickness subscapularis tendon tear in a rabbit model by evaluating the gross morphology and histology of the injected tendon and motion analysis of the rabbit's activity. At 4 weeks after ultrasound-guided UCB-derived MSC injection, 7 of the 10 full-thickness subscapularis tendon tears were only partial-thickness tears, and 3 remained full-thickness tendon tears. The tendon tear size and walking capacity at 4 weeks after UCB-derived MSC injection under ultrasound guidance were significantly improved compared with the same parameters immediately after tendon tear. UCB-derived MSC injection under ultrasound guidance without surgical repair or bioscaffold resulted in the partial healing of full-thickness rotator cuff tendon tears in a rabbit model. Histology revealed that UCB-derived MSCs induced regeneration of rotator cuff tendon tear and that the regenerated tissue was predominantly composed of type I collagens. In this study, ultrasound-guided injection of human UCB-derived MSCs contributed to regeneration of the full-thickness rotator cuff tendon tear without surgical repair. The results demonstrate the effectiveness of local injection of MSCs into the rotator cuff tendon. The results of this study suggest that ultrasound-guided umbilical cord blood-derived mesenchymal stem cell injection may be a useful conservative treatment for full-thickness rotator cuff tendon tear repair. ©AlphaMed Press.

Regeneration of Full-Thickness Rotator Cuff Tendon Tear After Ultrasound-Guided Injection With Umbilical Cord Blood-Derived Mesenchymal Stem Cells in a Rabbit Model

PubMed Central

Park, Gi-Young; Lee, Sang Chul

2015-01-01

Rotator cuff tendon tear is one of the most common causes of chronic shoulder pain and disability. In this study, we investigated the therapeutic effects of ultrasound-guided human umbilical cord blood (UCB)-derived mesenchymal stem cell (MSC) injection to regenerate a full-thickness subscapularis tendon tear in a rabbit model by evaluating the gross morphology and histology of the injected tendon and motion analysis of the rabbit’s activity. At 4 weeks after ultrasound-guided UCB-derived MSC injection, 7 of the 10 full-thickness subscapularis tendon tears were only partial-thickness tears, and 3 remained full-thickness tendon tears. The tendon tear size and walking capacity at 4 weeks after UCB-derived MSC injection under ultrasound guidance were significantly improved compared with the same parameters immediately after tendon tear. UCB-derived MSC injection under ultrasound guidance without surgical repair or bioscaffold resulted in the partial healing of full-thickness rotator cuff tendon tears in a rabbit model. Histology revealed that UCB-derived MSCs induced regeneration of rotator cuff tendon tear and that the regenerated tissue was predominantly composed of type I collagens. In this study, ultrasound-guided injection of human UCB-derived MSCs contributed to regeneration of the full-thickness rotator cuff tendon tear without surgical repair. The results demonstrate the effectiveness of local injection of MSCs into the rotator cuff tendon. Significance The results of this study suggest that ultrasound-guided umbilical cord blood-derived mesenchymal stem cell injection may be a useful conservative treatment for full-thickness rotator cuff tendon tear repair. PMID:26371340

Carlecortemcel-l: an ex vivo expanded umbilical cord blood cell graft for allogeneic transplantation.

PubMed

Petropoulos, Demetrios; Chan, Ka Wah

2009-11-01

Success of umbilical cord blood transplantation (UCBT) is mostly affected by the cell dose infused and its application is limited by the size of the recipient. For most adults and older children it is not possible to find a single UCB unit large enough for reliable engraftment. One strategy to increase the number of progenitor cells available is ex vivo expansion of the unit. The main challenge of ex vivo expansion systems is how not to deplete the self-renewing cell population by driving them into differentiation into committed progenitors. Copper modulates basic cell functions, such as survival, proliferation, and differentiation. Reduction of cellular copper in ex vivo culture conditions enabled preferential proliferation of early progenitors and increased engraftment capabilities. The result of a Phase I study of carlecortemcel-l, a product derived from ex vivo expansion of UCB progenitors in the presence of a copper chelator and early-acting cytokines, and the study design for the current pivotal study are presented. A literature review using PubMed and the investigator's brochure from the manufacturer. Early results suggest that carlecortemcel-l infusion is safe and may be associated with favorable non-relapse mortality rates. A pivotal global study is currently being conducted to evaluate safety and efficacy of this product from centralized manufacturing facilities.

Outcomes of unrelated cord blood transplantation in patients with multiple myeloma: a survey on behalf of Eurocord, the Cord Blood Committee of Cellular Therapy and Immunobiology Working Party, and the Chronic Leukemia Working Party of the EBMT.

PubMed

Paviglianiti, Annalisa; Xavier, Erick; Ruggeri, Annalisa; Ceballos, Patrice; Deconinck, Eric; Cornelissen, Jan J; Nguyen-Quoc, Stephanie; Maillard, Natacha; Sanz, Guillermo; Rohrlich, Pierre-Simon; Garderet, Laurent; Volt, Fernanda; Rocha, Vanderson; Kroeger, Nicolaus; Gluckman, Eliane; Fegueux, Nathalie; Mohty, Mohamad

2016-09-01

Although allogeneic stem cell transplantation is not a standard therapy for multiple myeloma, some patients can benefit from this intense therapy. There are few reports on outcomes after umbilical cord blood transplantation in multiple myeloma, and investigation of this procedure is warranted. We retrospectively analyzed 95 patients, 85 with multiple myeloma and 10 with plasma cell leukemia, receiving single or double umbilical cord blood transplantation from 2001 to 2013. Median follow up was 41 months. The majority of patients received a reduced intensity conditioning. The cumulative incidence of neutrophil engraftment was 97%±3% at 60 days, and that of 100-day acute graft-versus-host disease grade II-IV was 41%±5%. Chronic graft-versus-host disease at two years was 22%±4%. Relapse and non-relapse mortality was 47%±5% and 29%±5% at three years, respectively. Three-year progression-free survival and overall survival were 24%±5% and 40%±5%, respectively. Anti-thymocyte globulin was associated with decreased incidence of acute graft-versus-host disease, higher non-relapse mortality, decreased overall and progression-free survival. Patients with high cytogenetic risk had higher relapse, and worse overall and progression-free survival. In conclusion, umbilical cord blood transplantation is feasible for multiple myeloma patients. Copyright© Ferrata Storti Foundation.

One-Unit versus Two-Unit Cord-Blood Transplantation for Hematologic Cancers

PubMed Central

Wagner, John E.; Eapen, Mary; Carter, Shelly; Wang, Yanli; Schultz, Kirk R.; Wall, Donna A.; Bunin, Nancy; Delaney, Colleen; Haut, Paul; Margolis, David; Peres, Edward; Verneris, Michael R.; Walters, Mark; Horowitz, Mary M.; Kurtzberg, Joanne

2014-01-01

BACKGROUND Umbilical-cord blood has been used as the source of hematopoietic stem cells in an estimated 30,000 transplants. The limited number of hematopoietic cells in a single cord-blood unit prevents its use in recipients with larger body mass and results in delayed hematopoietic recovery and higher mortality. Therefore, we hypothesized that the greater numbers of hematopoietic cells in two units of cord blood would be associated with improved outcomes after transplantation. METHODS Between December 1, 2006, and February 24, 2012, a total of 224 patients 1 to 21 years of age with hematologic cancer were randomly assigned to undergo double-unit (111 patients) or single-unit (113 patients) cord-blood transplantation after a uniform myeloablative conditioning regimen and immunoprophylaxis for graft-versus-host disease (GVHD). The primary end point was 1-year overall survival. RESULTS Treatment groups were matched for age, sex, self-reported race (white vs. nonwhite), performance status, degree of donor–recipient HLA matching, and disease type and status at transplantation. The 1-year overall survival rate was 65% (95% confidence interval [CI], 56 to 74) and 73% (95% CI, 63 to 80) among recipients of double and single cord-blood units, respectively (P = 0.17). Similar outcomes in the two groups were also observed with respect to the rates of disease-free survival, neutrophil recovery, transplantation-related death, relapse, infections, immunologic reconstitution, and grade II–IV acute GVHD. However, improved platelet recovery and lower incidences of grade III and IV acute and extensive chronic GVHD were observed among recipients of a single cord-blood unit. CONCLUSIONS We found that among children and adolescents with hematologic cancer, survival rates were similar after single-unit and double-unit cord-blood transplantation; however, a single-unit cord-blood transplant was associated with better platelet recovery and a lower risk of GVHD. PMID:25354103

[Bifidobacterium DNA upregulates Th1 type response of umbilical cord blood mononuclear cell].

PubMed

Zhao, Hui; Wang, Xiao-chuan; Wang, Jing-yi; Yu, Ye-heng; Wang, Chuan-qing; Yang, Yi

2006-06-01

To study the effect of bifidobacterium genomic DNA on umbilical cord blood mononuclear cell (CBMC), and investigate the immunoregulation of bifidobacterium DNA and explore possible mechanisms by which bifidobacterium acts against allergic reaction. Bifidobacterium genomic DNA (bDNA) and human DNA (hDNA) were extracted with phenol/chloroform/isoamyl alcohol and stored at -20 degrees C for later use. Parts of bDNA were completely digested with DNaseI (d-bDNA) at 37 degrees C. CBMCs were isolated with Ficoll from umbilical cord blood and incubated at 37 degrees C in a 5% CO2 humidified incubator. These cells were divided into four groups, control group: without any stimulant; bDNA group: stimulated with 25 microg/ml bDNA; d-bDNA group: stimulated with 25 microg/ml d-bDNA; hDNA group: stimulated with 25 microg/ml hDNA. The cells were stimulated with different stimulants in vitro, at the end of incubation culture supernatant and cells were collected. IL-12 and IL-10 levels in the culture supernatant were measured by enzyme linked immuno sorbent assay (ELISA); cells secreting IL-4 and IFN-gamma were counted by enzyme linked immunospot (ELISPOT) assay; and total RNA was isolated from the cells to assay T-bet and GATA3 mRNA expression levels by reverse transcription polymerase chain reaction (RT-PCR). Six hours after stimulation there was no significant difference in IL-12 level in supernatant among the four groups; 12 hours after stimulation, IL-12 level in supernatant of bDNA treated group was significantly higher than that of each of the other groups, so were the results obtained at 24 hours and 48 hours after stimulation (P < 0.05). No significant difference could be detected in IL-12 level in supernatant among the other 3 groups. On the other hand, 6 hours after stimulation there was no significant difference in IL-10 level in supernatant among the four groups. But 12 and 24 hours after stimulation IL-10 level in supernatant of bDNA treated group was lower than that

[Repair of spinal cord injury with rats' umbilical cord MSCs].

PubMed

Zhu, Yuhai; Feng, Shiqing; Wang, Xue

2009-12-01

To study the growth characteristics of umbilical cord MSCs (UCMSCs) in vitro and its effect on the nerve regeneration after spinal cord injury (SCI). UCMSCs isolated from pregnant rats umbilical cord were cultured and purified in vitro. Sixty female Wistar rats weighing (300 +/- 10) g were randomized into three groups (n=20 per group). UCMSCs group (group A) in which UCMSCs suspension injection was conducted; DMEM control group (group B) in which 10% DMEM injection was conducted; sham group (group C) in which the animal received laminectomy only. Establish acute SCI model (T10) by Impactor model-II device in group A and group B. The recovery of the lower extremity was observed using BBB locomotor scoring system, neurofilament 200 (NF-200) immunofluorescence staining was performed to detect the neural regeneration, and then the corticospinal tract (CST) was observed using the biotinylated dextran amine (BDA) tracing. Cultured UCMSCs were spindle-shaped fibrocyte-like adherent growth, swirling or parallelly. The USMSCs expressed CD29, but not CD31, CD45, and HLA-DR. The BBB score was higher in group A than group B 4, 5, and 6 weeks after operation, and there was a significant difference between two groups (P < 0.05). The BBB scores at different time points were significantly lower in groups A and B than that in group C (P < 0.05). UCMSCs was proved to survive and assemble around the injured place by frozen section of the cords 6 weeks after injury. NF-200 positive response area in groups A, B, and C was (11,943 +/- 856), (7,986 +/- 627), and (13,117 +/- 945) pixels, respectively, suggesting there was a significant difference between groups A, C and group B (P < 0.05), and no significant difference was evident between group A and group C (P > 0.05). BDA anterograde tracing 10 weeks after operation demonstrated that more regenerated nerve fibers went through injured area in group A, but just quite few nerve fibers in group B went through the injuried cavity. The ratios

Banking Umbilical Cord Blood (UCB) Stem Cells: Awareness, Attitude and Expectations of Potential Donors from One of the Largest Potential Repository (India)

PubMed Central

Pandey, Deeksha

2016-01-01

Background The concept of Umbilical Cord blood (UCB) stem cells is emerging as a non-invasive, efficacious alternative source of hematopoietic stem cells to treat a variety of blood and bone marrow diseases, blood cancers, metabolic disorders and immune deficiencies. Aim of the present study was to determine the level of awareness about banking UCB among pregnant women in India. We also assessed patient perception for banking of UCB and explored the patient expectations of banking UCB in future. This is the first study to assess current attitudes, in a sample population of potential donors from one of the largest potential UCB repository (India). Obtaining this information may help optimize recruitment efforts and improve patient education. Material and Method Present explorative questionnaire based survey included 254 pregnant women in the final analysis. Results We established only 26.5% pregnant women in our study population knew what exactly is meant by UCB. A large proportion (55.1%) was undecided on whether they want to bank UCB or not. Women were more aware of the more advertised private cord blood banking compared to public banking. More than half of the pregnant women expected their obstetrician to inform them regarding UCB. One-third of the women in our population had undue expectations from banking of the UCB. Conclusion Obstetricians should play a more active role in explaining the patients regarding pros and cons of UCB banking. PMID:27228155

Over-expression of Oct4 and Sox2 transcription factors enhances differentiation of human umbilical cord blood cells in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guseva, Daria; Hannover Medical School, Hannover; Rizvanov, Albert A.

2014-09-05

Highlights: • Gene and cell-based therapies comprise innovative aspects of regenerative medicine. • Genetically modified hUCB-MCs enhanced differentiation of cells in a mouse model of ALS. • Stem cells successfully transformed into micro-glial and endothelial lines in spinal cords. • Over-expressing oct4 and sox2 also induced production of neural marker PGP9.5. • Formation of new nerve cells, secreting trophic factors and neo-vascularisation could improve symptoms in ALS. - Abstract: Gene and cell-based therapies comprise innovative aspects of regenerative medicine. Even though stem cells represent a highly potential therapeutic strategy, their wide-spread exploitation is marred by ethical concerns, potential for malignantmore » transformation and a plethora of other technical issues, largely restricting their use to experimental studies. Utilizing genetically modified human umbilical cord blood mono-nuclear cells (hUCB-MCs), this communication reports enhanced differentiation of transplants in a mouse model of amyotrophic lateral sclerosis (ALS). Over-expressing Oct4 and Sox2 induced production of neural marker PGP9.5, as well as transformation of hUCB-MCs into micro-glial and endothelial lines in ALS spinal cords. In addition to producing new nerve cells, providing degenerated areas with trophic factors and neo-vascularisation might prevent and even reverse progressive loss of moto-neurons and skeletal muscle paralysis.« less

Cord blood lead level in an urban inner-city hospital.

PubMed

Chawla, S; Elbakoush, F; Natarajan, G; Dwaihy, M; Berry, A; Ravindranath, Y; Bhambhani, K; Narayan, S B

2016-09-16

Lead levels were measured by inductively coupled plasma mass spectrometry (ICP-MS) in umbilical cord blood samples of 150 neonates in an urban inner-city hospital. The mean (SD) gestation and birth weight of our cohort were 38.8 (1.7) weeks and 3,217 (519) grams. There were 89% African-Americans, 53% males and 79% were born via vaginal delivery. Mean (SD) maternal age was 24.5 (5.8) years. History of drug abuse and smoking was reported in 8.7% and 10.7% respectively, with only 1 mother reporting a history of high lead level in childhood. Prenatal vitamin intake was reported in 99.3%. Cord blood lead level was available in 144 patients, with lead level of <1μg/dL seen in 141 (97.9%) and>1 in 3 (2.1%) patients. No patient had cord blood lead level of >2μg/dL. High lead levels during childhood in high-risk urban population, however, suggest the need for intensive efforts for prevention of environmental exposure to lead in early childhood.

Generation of functional islets from human umbilical cord and placenta derived mesenchymal stem cells.

PubMed

Kadam, Sachin; Govindasamy, Vijayendran; Bhonde, Ramesh

2012-01-01

Bone marrow-derived mesenchymal stem cells (BM-MSCs) have been used for allogeneic application in tissue engineering but have certain drawbacks. Therefore, mesenchymal stem cells (MSCs) derived from other adult tissue sources have been considered as an alternative. The human umbilical cord and placenta are easily available noncontroversial sources of human tissue, which are often discarded as biological waste, and their collection is noninvasive. These sources of MSCs are not subjected to ethical constraints, as in the case of embryonic stem cells. MSCs derived from umbilical cord and placenta are multipotent and have the ability to differentiate into various cell types crossing the lineage boundary towards endodermal lineage. The aim of this chapter is to provide a detailed reproducible cookbook protocol for the isolation, propagation, characterization, and differentiation of MSCs derived from human umbilical cord and placenta with special reference to harnessing their potential towards pancreatic/islet lineage for utilization as a cell therapy product. We show here that mesenchymal stromal cells can be extensively expanded from umbilical cord and placenta of human origin retaining their multilineage differentiation potential in vitro. Our report indicates that postnatal tissues obtained as delivery waste represent a rich source of mesenchymal stromal cells, which can be differentiated into functional islets employing three-stage protocol developed by our group. These islets could be used as novel in vitro model for screening hypoglycemics/insulin secretagogues, thus reducing animal experimentation for this purpose and for the future human islet transplantation programs to treat diabetes.

Critical issues for engineering cord blood stem cells to produce insulin.

PubMed

Denner, Larry; Urban, Randall J

2008-09-01

The objectives of using cord blood stem cells for treating type 1 diabetes are simple in principle yet complex in biological and molecular mechanisms. These are defined by the complexity of the insulin-producing unit of the pancreas, the islet. Islets are composed of various cell types that arise from diverse lineages and communicate by hormones, growth factors and small-molecule mediators. These processes are regulated by integration of signal transduction pathways. While advances have been made to engineer umbilical cord blood stem cells to produce insulin, these studies only illuminate the potential of such cells to fulfil a necessary, but not sufficient, requirement for transplantation. The challenges ahead demand detailed understanding of molecular mechanisms to move from an opportunistic, phenotypic approach to transplantation and amelioration of blood glucose, to an orderly and logical approach to a biologically and medically meaningful solution. The issues include expansion to generate large numbers of cells, self-renewal to regulate the destiny of cord blood stem cells to repopulate the hematopoietic system, and multipotency of stem cells to generate the distinct cell types of an islet.

[The bioethics law revision: comparative analysis of contributions from different public and professional offices. Assisted Reproductive Technology, embryo and stem cells research, umbilical cord blood bank].

PubMed

Merviel, P; Cabry, R; Lourdel, E; Brasseur, F; Devaux, A; Copin, H

2009-09-01

The revision of the bioethics law of 2004 must occur in a five year's time. For this revision, the authorities decided to organize general states of bioethics and requested the production of contributions by the companies, institutions or associations. These texts tackle various subjects, like the Assisted Reproductive Technologies, research on the embryo and the stem cells and the banks of umbilical cord blood. Certain opinions converge, others differ, but all take part in the great debate which will take place at the time of the general conference.

Combined Haploidentical and Umbilical Cord Blood Allogeneic Stem Cell Transplantation for High-Risk Lymphoma and Chronic Lymphoblastic Leukemia.

PubMed

Hsu, Jingmei; Artz, Andrew; Mayer, Sebastian A; Guarner, Danielle; Bishop, Michael R; Reich-Slotky, Ronit; Smith, Sonali M; Greenberg, June; Kline, Justin; Ferrante, Rosanna; Phillips, Adrienne A; Gergis, Usama; Liu, Hongtao; Stock, Wendy; Cushing, Melissa; Shore, Tsiporah B; van Besien, Koen

2018-02-01

Limited studies have reported on outcomes for lymphoid malignancy patients receiving alternative donor allogeneic stem cell transplants. We have previously described combining CD34-selected haploidentical grafts with umbilical cord blood (haplo-cord) to accelerate neutrophil and platelet engraftment. Here, we examine the outcome of patients with lymphoid malignancies undergoing haplo-cord transplantation at the University of Chicago and Weill Cornell Medical College. We analyzed 42 lymphoma and chronic lymphoblastic leukemia (CLL) patients who underwent haplo-cord allogeneic stem cell transplantation. Patients underwent transplant for Hodgkin lymphoma (n = 9, 21%), CLL (n = 5, 12%) and non-Hodgkin lymphomas (n = 28, 67%), including 13 T cell lymphomas. Twenty-four patients (52%) had 3 or more lines of therapies. Six (14%) and 1 (2%) patients had prior autologous and allogeneic stem cell transplant, respectively. At the time of transplant 12 patients (29%) were in complete remission, 18 had chemotherapy-sensitive disease, and 12 patients had chemotherapy-resistant disease. Seven (17%), 11 (26%), and 24 (57%) patients had low, intermediate, and high disease risk index before transplant. Comorbidity index was evenly distributed among 3 groups, with 13 (31%), 14 (33%), and 15 (36%) patients scoring 0, 1 to 2, and ≥3. Median age for the cohort was 49 years (range, 23 to 71). All patients received fludarabine/melphalan/antithymocyte globulin conditioning regimen and post-transplant graft-versus-host disease (GVHD) prophylaxis with tacrolimus and mycophenolate mofetil. The median time to neutrophil engraftment was 11 days (range, 9 to 60) and to platelet engraftment 19.5 days (range, 11 to 88). Cumulative incidence of nonrelapse mortality was 11.6% at 100 days and 19 % at one year. Cumulative incidence of relapse was 9.3% at 100 days and 19% at one year. With a median follow-up of survivors of 42 months, the 3-year rates of GVHD relapse free survival

Effect of testosterone and hypoxia on the expansion of umbilical cord blood CD34+ cells in vitro

PubMed Central

Zhou, Liping; Zhang, Xiaowei; Zhou, Panpan; Li, Xue; Xu, Xuejing; Shi, Qing; Li, Dong; Ju, Xiuli

2017-01-01

Successfully expanding hematopoietic stem cells (HSCs) is advantageous for clinical HSC transplantation. The present study investigated the influence of testosterone on the proliferation, antigen phenotype and expression of hematopoiesis-related genes in umbilical cord blood-derived cluster of differentiation (CD)34+ cells under normoxic or hypoxia conditions. Cord blood (CB) CD34+ cells were separated using magnetic activated cell sorting. A cytokine cocktail and feeder cells were used to stimulate the expansion of CD34+ cells under normoxic (20% O2) and hypoxic (1% O2) conditions for 7 days and testosterone was added accordingly. Cells were identified using flow cytometry and reconstruction capacity was determined using a colony-forming unit (CFU) assay. The effects of oxygen concentration and testosterone on the expression of hematopoietic-related genes, including homeobox (HOX)A9, HOXB2, HOXB4, HOXC4 and BMI-1, were measured using reverse transcription-quantitative polymerase chain reaction. The results indicated that the number of CFUs and total cells in the testosterone group increased under normoxic and hypoxic conditions compared with the corresponding control groups. Furthermore, the presence of testosterone increased the number of CFU-erythroid colonies. In liquid culture, the growth of CD34+ cells was rapid under normoxic conditions compared with under hypoxic conditions, however CD34+ cells were maintained in an undifferentiated state under hypoxic conditions. The addition of testosterone under hypoxia promoted the differentiation of CD34+ cells into CD34+CD38+CD71+ erythroid progenitor cells. Furthermore, it was determined that the expression of hematopoietic-related genes was significantly increased (P<0.05) in the hypoxia testosterone group compared with the other groups. Therefore, the results of the current study indicate that a combination of hypoxia and testosterone may be a promising cultivation condition for HSC/hemopoietic progenitor cell

Effect of testosterone and hypoxia on the expansion of umbilical cord blood CD34+ cells in vitro.

PubMed

Zhou, Liping; Zhang, Xiaowei; Zhou, Panpan; Li, Xue; Xu, Xuejing; Shi, Qing; Li, Dong; Ju, Xiuli

2017-11-01

Successfully expanding hematopoietic stem cells (HSCs) is advantageous for clinical HSC transplantation. The present study investigated the influence of testosterone on the proliferation, antigen phenotype and expression of hematopoiesis-related genes in umbilical cord blood-derived cluster of differentiation (CD)34 + cells under normoxic or hypoxia conditions. Cord blood (CB) CD34 + cells were separated using magnetic activated cell sorting. A cytokine cocktail and feeder cells were used to stimulate the expansion of CD34 + cells under normoxic (20% O 2 ) and hypoxic (1% O 2 ) conditions for 7 days and testosterone was added accordingly. Cells were identified using flow cytometry and reconstruction capacity was determined using a colony-forming unit (CFU) assay. The effects of oxygen concentration and testosterone on the expression of hematopoietic-related genes, including homeobox (HOX)A9, HOXB2, HOXB4, HOXC4 and BMI-1, were measured using reverse transcription-quantitative polymerase chain reaction. The results indicated that the number of CFUs and total cells in the testosterone group increased under normoxic and hypoxic conditions compared with the corresponding control groups. Furthermore, the presence of testosterone increased the number of CFU-erythroid colonies. In liquid culture, the growth of CD34 + cells was rapid under normoxic conditions compared with under hypoxic conditions, however CD34 + cells were maintained in an undifferentiated state under hypoxic conditions. The addition of testosterone under hypoxia promoted the differentiation of CD34 + cells into CD34 + CD38 + CD71 + erythroid progenitor cells. Furthermore, it was determined that the expression of hematopoietic-related genes was significantly increased (P<0.05) in the hypoxia testosterone group compared with the other groups. Therefore, the results of the current study indicate that a combination of hypoxia and testosterone may be a promising cultivation condition for HSC

The effect of umbilical cord cleansing with chlorhexidine on omphalitis and neonatal mortality in community settings in developing countries: a meta-analysis

PubMed Central

2013-01-01

Background There is an increased risk of serious neonatal infection arising through exposure of the umbilical cord to invasive pathogen in home and facility births where hygienic practices are difficult to achieve. The World Health Organization currently recommends ‘dry cord care’ because of insufficient data in favor of or against topical application of an antiseptic. The primary objective of this meta-analysis is to evaluate the effects of application of chlorhexidine (CHX) to the umbilical cord to children born in low income countries on cord infection (omphalitis) and neonatal mortality. Standardized guidelines of Child Health Epidemiology Reference Group (CHERG) were followed to generate estimates of effectiveness of topical chlorhexidine application to umbilical cord for prevention of sepsis specific mortality, for inclusion in the Lives Saved Tool (LiST). Methods Systematic review and meta-analysis. Data sources included Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, PubMed, CINHAL and WHO international clinical trials registry. Only randomized trials were included. Studies of children in hospital settings were excluded. The comparison group received no application to the umbilical cord (dry cord care), no intervention, or a non-CHX intervention. Primary outcomes were omphalitis and all-cause neonatal mortality. Results There were three cluster-randomised community trials (total participants 54,624) conducted in Nepal, Bangladesh and Pakistan that assessed impact of CHX application to the newborn umbilical cord for prevention of cord infection and mortality. Application of any CHX to the umbilical cord of the newborn led to a 23% reduction in all-cause neonatal mortality in the intervention group compared to control [RR 0.77, 95 % CI 0.63, 0.94; random effects model, I2=50 %]. The reduction in omphalitis ranged from 27 % to 56 % compared to control group depending on severity of infection. Based on CHERG rules, effect

Generation of glucose-responsive, insulin-producing cells from human umbilical cord blood-derived mesenchymal stem cells.

PubMed

Prabakar, Kamalaveni R; Domínguez-Bendala, Juan; Molano, R Damaris; Pileggi, Antonello; Villate, Susana; Ricordi, Camillo; Inverardi, Luca

2012-01-01

We sought to assess the potential of human cord blood-derived mesenchymal stem cells (CB-MSCs) to derive insulin-producing, glucose-responsive cells. We show here that differentiation protocols based on stepwise culture conditions initially described for human embryonic stem cells (hESCs) lead to differentiation of cord blood-derived precursors towards a pancreatic endocrine phenotype, as assessed by marker expression and in vitro glucose-regulated insulin secretion. Transplantation of these cells in immune-deficient animals shows human C-peptide production in response to a glucose challenge. These data suggest that human cord blood may be a promising source for regenerative medicine approaches for the treatment of diabetes mellitus.

Umbilical cord blood-derived natural killer cells combined with Bevacizumab for colorectal cancer treatment.

PubMed

Xu, Chen; Liu, Dongning; Chen, Zhixin; Zhuo, Fan; Sun, Huankui; Hu, Jiaping; Li, Taiyuan

2018-06-19

Colorectal cancer (CRC) is among cancers with highest incidence globally and currently ranks fourth as the leading cause of cancer-related deaths worldwide. It remains an urgent need for novel strategies in the management of patients with advanced CRC. Adoptive transfer of allogeneic natural killer (NK) cells represent an attractive option in the treatment of patients with CRC. In this study, we successfully expanded NK cells from umbilical cord blood (UCB) with membrane-bound IL-21, termed eUCB-NK cells. eUCB-NK cells efficiently lysed CRC cell lines in vitro and secreted significantly higher levels of IFN-γ, TNF-α, GM-CSF and CCL3 compared with IL-2 stimulated NK cells. Adoptive transfer of these NK cells significantly inhibited the growth of HT29 xenografts, whereas LoVo tumors were not effectively controlled with eUCB-NK cells. More NK cells inside HT29 tumors, not seen in LoVo tumors, might contribute to the differences in response to eUCB-NK cells. Combination of bevacizumab can increase extravasation of adoptively transferred NK cells into the LoVo tumors and improve the therapeutic activity of eUCB-NK cells. These results justified clinical translation of this UCB-derived NK cell-based therapeutics, either used alone or combined with bevacizumab, as a novel treatment option for patients with CRC.

One-unit versus two-unit cord-blood transplantation for hematologic cancers.

PubMed

Wagner, John E; Eapen, Mary; Carter, Shelly; Wang, Yanli; Schultz, Kirk R; Wall, Donna A; Bunin, Nancy; Delaney, Colleen; Haut, Paul; Margolis, David; Peres, Edward; Verneris, Michael R; Walters, Mark; Horowitz, Mary M; Kurtzberg, Joanne

2014-10-30

Umbilical-cord blood has been used as the source of hematopoietic stem cells in an estimated 30,000 transplants. The limited number of hematopoietic cells in a single cord-blood unit prevents its use in recipients with larger body mass and results in delayed hematopoietic recovery and higher mortality. Therefore, we hypothesized that the greater numbers of hematopoietic cells in two units of cord blood would be associated with improved outcomes after transplantation. Between December 1, 2006, and February 24, 2012, a total of 224 patients 1 to 21 years of age with hematologic cancer were randomly assigned to undergo double-unit (111 patients) or single-unit (113 patients) cord-blood transplantation after a uniform myeloablative conditioning regimen and immunoprophylaxis for graft-versus-host disease (GVHD). The primary end point was 1-year overall survival. Treatment groups were matched for age, sex, self-reported race (white vs. nonwhite), performance status, degree of donor-recipient HLA matching, and disease type and status at transplantation. The 1-year overall survival rate was 65% (95% confidence interval [CI], 56 to 74) and 73% (95% CI, 63 to 80) among recipients of double and single cord-blood units, respectively (P=0.17). Similar outcomes in the two groups were also observed with respect to the rates of disease-free survival, neutrophil recovery, transplantation-related death, relapse, infections, immunologic reconstitution, and grade II-IV acute GVHD. However, improved platelet recovery and lower incidences of grade III and IV acute and extensive chronic GVHD were observed among recipients of a single cord-blood unit. We found that among children and adolescents with hematologic cancer, survival rates were similar after single-unit and double-unit cord-blood transplantation; however, a single-unit cord-blood transplant was associated with better platelet recovery and a lower risk of GVHD. (Funded by the National Heart, Lung, and Blood Institute and the

Evaluating a switch from meconium to umbilical cord tissue for newborn drug testing: A retrospective study at an academic medical center.

PubMed

Palmer, Kendra L; Wood, Kelly E; Krasowski, Matthew D

2017-04-01

The objective of this study was to compare detection rates of newborn drug exposure at an academic medical center transitioning from meconium to umbilical cord tissue toxicology testing. We performed an Institutional Review Board-approved retrospective chart review on all newborns (n=2072) for whom newborn drug testing was ordered at our academic medical center between June 2012 and August 2015 (in August 2013, umbilical cord tissue became the preferred specimen). Meconium toxicology testing was positive for at least one compound in 221 cases (21.3% of 1037 total specimens), with non-medical drug use identified in 85 cases (8.2%). Umbilical cord tissue toxicology testing was positive for at least one compound in 302 cases (29.2%), with non-medical drug use identified in 107 cases (10.3%). Of the cases involving non-medical drug use, the most common compounds detected were tetrahydrocannabinol and amphetamines. Non-medical drug use did not differ significantly between meconium and umbilical cord tissue, either as a total or for classes of drugs such as amphetamines, cannabinoids, and opiates. Maternal non-medical use of tramadol (not tested for in meconium) was identified in 5 cases (0.4%). There were significant differences in rate of detection of iatrogenic medications. Specifically, morphine, lorazepam, phenobarbital, and codeine were more commonly detected in meconium, while oxycodone was more commonly detected in umbilical cord tissue. Umbilical cord tissue toxicology testing yielded a similar detection rate compared to meconium testing. The use of umbilical cord tissue avoids detection of medications given to the neonate prior to meconium collection. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Determinants of brain-derived neurotrophic factor (BDNF) in umbilical cord and maternal serum.

PubMed

Flöck, A; Weber, S K; Ferrari, N; Fietz, C; Graf, C; Fimmers, R; Gembruch, U; Merz, W M

2016-01-01

Brain-derived neurotrophic factor (BDNF) plays a fundamental role in brain development; additionally, it is involved in various aspects of cerebral function, including neurodegenerative and psychiatric diseases. Involvement of BDNF in parturition has not been investigated. The aim of our study was to analyze determinants of umbilical cord BDNF (UC-BDNF) concentrations of healthy, term newborns and their respective mothers. This cross-sectional prospective study was performed at a tertiary referral center. Maternal venous blood samples were taken on admission to labor ward; newborn venous blood samples were drawn from the umbilical cord (UC), before delivery of the placenta. Analysis was performed with a commercially available immunoassay. Univariate analyses and stepwise multivariate regression models were applied. 120 patients were recruited. UC-BDNF levels were lower than maternal serum concentrations (median 641 ng/mL, IQR 506 vs. median 780 ng/mL, IQR 602). Correlation between UC- and maternal BDNF was low (R=0.251, p=0.01). In univariate analysis, mode of delivery (MoD), gestational age (GA), body mass index at delivery, and gestational diabetes were determinants of UC-BDNF (MoD and smoking for maternal BDNF, respectively). Stepwise multivariate regression analysis revealed a model with MoD and GA as determinants for UC-BDNF (MoD for maternal BDNF). MoD and GA at delivery are determinants of circulating BDNF in the mother and newborn. We hypothesize that BDNF, like other neuroendocrine factors, is involved in the neuroendocrine cascade of delivery. Timing and mode of delivery may exert BDNF-induced effects on the cerebral function of newborns and their mothers. Copyright © 2015 Elsevier Ltd. All rights reserved.

Acceptability of Bedside Resuscitation With Intact Umbilical Cord to Clinicians and Patients' Families in the United States.

PubMed

Katheria, Anup C; Sorkhi, Samuel R; Hassen, Kasim; Faksh, Arij; Ghorishi, Zahra; Poeltler, Debra

2018-01-01

While delayed umbilical cord clamping in preterm infants has shown to improve long-term neurological outcomes, infants who are thought to need resuscitation do not receive delayed cord clamping even though they may benefit the most. A mobile resuscitation platform allows infants to be resuscitated at the mother's bedside with the cord intact. The newborn is supplied with placental blood during the resuscitation in view of the mother. The objective of the study is to assess the usability and acceptability of mobile resuscitation platform, LifeStart trolley, among the infants' parents and perinatal providers. A resuscitation platform was present during every delivery that required advanced neonatal providers for high-risk deliveries. Perinatal providers and parents of the infants were given a questionnaire shortly after the delivery. 60 neonatal subjects were placed on the trolley. The majority of deliveries were high risk for meconium-stained amniotic fluid (43%), and non-reassuring fetal heart rate (45%). About 50% of neonatal providers felt that there were some concerns regarding access to the baby. No parents were uncomfortable with the bedside neonatal interventions, and most parents perceived that communication was improved because of the proximity to the care team. Bedside resuscitation with umbilical cord intact through the use of a mobile resuscitation trolley is feasible, safe, and effective, but about half of the perinatal providers expressed concerns. Logistical issues such as improved space management and/or delivery setup should be considered in centers planning to perform neonatal resuscitation with an intact cord.

Exosomes derived from human umbilical cord blood mesenchymal stem cells stimulates rejuvenation of human skin.

PubMed

Kim, Yoon-Jin; Yoo, Sae Mi; Park, Hwan Hee; Lim, Hye Jin; Kim, Yu-Lee; Lee, Seunghee; Seo, Kwang-Won; Kang, Kyung-Sun

2017-11-18

Human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) play an important role in cutaneous wound healing, and recent studies suggested that MSC-derived exosomes activate several signaling pathways, which are conducive in wound healing and cell growth. In this study, we investigated the roles of exosomes that are derived from USC-CM (USC-CM Exos) in cutaneous collagen synthesis and permeation. We found that USC-CM has various growth factors associated with skin rejuvenation. Our in vitro results showed that USC-CM Exos integrate in Human Dermal Fibroblasts (HDFs) and consequently promote cell migration and collagen synthesis of HDFs. Moreover, we evaluated skin permeation of USC-CM Exos by using human skin tissues. Results showed that Exo-Green labeled USC-CM Exos approached the outermost layer of the epidermis after 3 h and gradually approached the epidermis after 18 h. Moreover, increased expressions of Collagen I and Elastin were found after 3 days of treatment on human skin. The results showed that USC-CM Exos is absorbed into human skin, it promotes Collagen I and Elastin synthesis in the skin, which are essential to skin rejuvenation and shows the potential of USC-CM integration with the cosmetics or therapeutics. Copyright © 2017 Elsevier Inc. All rights reserved.

Copeptin concentration in cord blood in infants with early-onset sepsis, chorioamnionitis and perinatal asphyxia.

PubMed

Schlapbach, Luregn J; Frey, Stefanie; Bigler, Susanna; Manh-Nhi, Chiem; Aebi, Christoph; Nelle, Mathias; Nuoffer, Jean-Marc

2011-05-19

Vasopressin is one of the most important physiological stress and shock hormones. Copeptin, a stable vasopressin precursor, is a promising sepsis marker in adults. In contrast, its involvement in neonatal diseases remains unknown. The aim of this study was to establish copeptin concentrations in neonates of different stress states such as sepsis, chorioamnionitis and asphyxia. Copeptin cord blood concentration was determined using the BRAHMS kryptor assay. Neonates with early-onset sepsis (EOS, n = 30), chorioamnionitis (n = 33) and asphyxia (n = 25) were compared to a control group of preterm and term (n = 155) neonates. Median copeptin concentration in cord blood was 36 pmol/l ranging from undetectable to 5498 pmol/l (IQR 7 - 419). Copeptin cord blood concentrations were non-normally distributed and increased with gestational age (p < 0.0001). Neonates born after vaginal compared to cesarean delivery had elevated copeptin levels (p < 0.0001). Copeptin correlated strongly with umbilical artery pH (Spearman's Rho -0.50, p < 0.0001), umbilical artery base excess (Rho -0.67, p < 0.0001) and with lactate at NICU admission (Rho 0.54, p < 0.0001). No difference was found when comparing copeptin cord blood concentrations between neonates with EOS and controls (multivariate p = 0.30). The highest copeptin concentrations were found in neonates with asphyxia (median 993 pmol/l). Receiver-operating-characteristic curve analysis showed that copeptin cord blood concentrations were strongly associated with asphyxia: the area under the curve resulted at 0.91 (95%-CI 0.87-0.96, p < 0.0001). A cut-off of 400 pmol/l had a sensitivity of 92% and a specifity of 82% for asphyxia as defined in this study. Copeptin concentrations were strongly related to factors associated with perinatal stress such as birth acidosis, asphyxia and vaginal delivery. In contrast, copeptin appears to be unsuitable for the diagnosis of EOS.

Copeptin concentration in cord blood in infants with early-onset sepsis, chorioamnionitis and perinatal asphyxia

PubMed Central

2011-01-01

Background Vasopressin is one of the most important physiological stress and shock hormones. Copeptin, a stable vasopressin precursor, is a promising sepsis marker in adults. In contrast, its involvement in neonatal diseases remains unknown. The aim of this study was to establish copeptin concentrations in neonates of different stress states such as sepsis, chorioamnionitis and asphyxia. Methods Copeptin cord blood concentration was determined using the BRAHMS kryptor assay. Neonates with early-onset sepsis (EOS, n = 30), chorioamnionitis (n = 33) and asphyxia (n = 25) were compared to a control group of preterm and term (n = 155) neonates. Results Median copeptin concentration in cord blood was 36 pmol/l ranging from undetectable to 5498 pmol/l (IQR 7 - 419). Copeptin cord blood concentrations were non-normally distributed and increased with gestational age (p < 0.0001). Neonates born after vaginal compared to cesarean delivery had elevated copeptin levels (p < 0.0001). Copeptin correlated strongly with umbilical artery pH (Spearman's Rho -0.50, p < 0.0001), umbilical artery base excess (Rho -0.67, p < 0.0001) and with lactate at NICU admission (Rho 0.54, p < 0.0001). No difference was found when comparing copeptin cord blood concentrations between neonates with EOS and controls (multivariate p = 0.30). The highest copeptin concentrations were found in neonates with asphyxia (median 993 pmol/l). Receiver-operating-characteristic curve analysis showed that copeptin cord blood concentrations were strongly associated with asphyxia: the area under the curve resulted at 0.91 (95%-CI 0.87-0.96, p < 0.0001). A cut-off of 400 pmol/l had a sensitivity of 92% and a specifity of 82% for asphyxia as defined in this study. Conclusions Copeptin concentrations were strongly related to factors associated with perinatal stress such as birth acidosis, asphyxia and vaginal delivery. In contrast, copeptin appears to be unsuitable for the diagnosis of EOS. PMID:21595972

Human umbilical cord plasma proteins revitalize hippocampal function in aged mice

PubMed Central

Castellano, Joseph M.; Mosher, Kira I.; Abbey, Rachelle J.; McBride, Alisha A.; James, Michelle L.; Berdnik, Daniela; Shen, Jadon C.; Zou, Bende; Xie, Xinmin S.; Tingle, Martha; Hinkson, Izumi V.; Angst, Martin S.; Wyss-Coray, Tony

2017-01-01

Ageing drives changes in neuronal and cognitive function, the decline of which is a major feature of many neurological disorders. The hippocampus, a brain region subserving roles of spatial and episodic memory and learning, is sensitive to the detrimental effects of ageing at morphological and molecular levels. With advancing age, synapses in various hippocampal subfields exhibit impaired long-term potentiation1, an electrophysiological correlate of learning and memory. At the molecular level, immediate early genes are among the synaptic plasticity genes that are both induced by long-term potentiation2, 3, 4 and downregulated in the aged brain5, 6, 7, 8. In addition to revitalizing other aged tissues9, 10, 11, 12, 13, exposure to factors in young blood counteracts age-related changes in these central nervous system parameters14, 15, 16, although the identities of specific cognition-promoting factors or whether such activity exists in human plasma remains unknown17. We hypothesized that plasma of an early developmental stage, namely umbilical cord plasma, provides a reservoir of such plasticity-promoting proteins. Here we show that human cord plasma treatment revitalizes the hippocampus and improves cognitive function in aged mice. Tissue inhibitor of metalloproteinases 2 (TIMP2), a blood-borne factor enriched in human cord plasma, young mouse plasma, and young mouse hippocampi, appears in the brain after systemic administration and increases synaptic plasticity and hippocampal-dependent cognition in aged mice. Depletion experiments in aged mice revealed TIMP2 to be necessary for the cognitive benefits conferred by cord plasma. We find that systemic pools of TIMP2 are necessary for spatial memory in young mice, while treatment of brain slices with TIMP2 antibody prevents long-term potentiation, arguing for previously unknown roles for TIMP2 in normal hippocampal function. Our findings reveal that human cord plasma contains plasticity-enhancing proteins of high

Human cord blood applications in cell therapy: looking back and look ahead.

PubMed

Zhou, Hongyan; Chang, Stephen; Rao, Mahendra

2012-08-01

Human umbilical cord blood (UCB) has been used as a reliable source of stem cells for blood-borne diseases and disorders. Recent advances in cell reprogramming technology to produce induced pluripotent stem (iPS) cells, which can be differentiated to multiple adult cell types, has further expanded the potential of cord blood cell therapy for treatment of non-blood-borne diseases. However, in order to harness this breakthrough technology and to provide clinical-grade cells for the patient, standardization of iPS production and differentiation, and good manufacturing practice (GMP) need to be employed. UCB is an ethical source of stem cells and has been used to treat diseases including leukemia, cancer and blood disorders. The development of iPS cell technology could potentially greatly increase the application of cord blood cells as a treatment for a broader range of diseases, UCB-iPS banks could, therefore, be a valuable complementary source of clinical-grade cells for cell therapy. The current applicability of GMP to UCB and UCB-iPS cell-based cell therapy will be discussed. Although cord blood stem cell therapies have been practiced for decades, UCB-iPS cell therapies are a new innovation currently in development. Successful clinical applications of such novel cell therapies will depend on the production of GMP-compliant cells and the establishment of cell banks.

Umbilical Cord Blood Platelet Lysate as Serum Substitute in Expansion of Human Mesenchymal Stem Cells.

PubMed

Shirzad, Negin; Bordbar, Sima; Goodarzi, Alireza; Mohammad, Monire; Khosravani, Pardis; Sayahpour, Froughazam; Baghaban Eslaminejad, Mohamadreza; Ebrahimi, Marzieh

2017-10-01

The diverse clinical applications for human mesenchymal stem cells (hMSCs) in cellular therapy and regenerative medicine warrant increased focus on developing adequate culture supplements devoid of animal-derived products. In the present study, we have investigated the feasibility of umbilical cord blood-platelet lysate (UCB-PL) as a standard substitute for fetal bovine serum (FBS) and human peripheral blood-PL (PB-PL). In this experimental study, platelet concentrates (PC) from UCB and human PB donors were frozen, melted, and sterilized to obtain PL. Quality control included platelet cell counts, sterility testing (viral and microbial), total protein concentrations, growth factor levels, and PL stability. The effects of UCB-PL and PB-PL on hMSCs proliferation and differentiation into osteocytes, chondrocytes, and adipocytes were studied and the results compared with FBS. UCB-PL contained high levels of protein content, platelet-derived growth factor- AB (PDGF-AB), and transforming growth factor (TGF) compared to PB-PL. All growth factors were stable for at least nine months post-storage at -70˚C. hMSCs proliferation enhanced following treatment with UCB-PL. With all three supplements, hMSCs could differentiate into all three lineages. PB-PL and UCB-PL both were potent in hMSCs proliferation. However, PB promoted osteoblastic differentiation and UCB-PL induced chondrogenic differentiation. Because of availability, ease of use and feasible standardization of UCB-PL, we have suggested that UCB-PL be used as an alternative to FBS and PB-PL for the cultivation and expansion of hMSCs in cellular therapy. Copyright© by Royan Institute. All rights reserved.

Human umbilical cord derived matrix: A scaffold suitable for tissue engineering application.

PubMed

Dan, Pan; Velot, Émilie; Mesure, Benjamin; Groshenry, Guillaume; Bacharouche, Jalal; Decot, Véronique; Menu, Patrick

2017-01-01

Human tissue derived natural extracellular matrix (ECM) has great potential in tissue engineering. We sought to isolate extracellular matrix derived from human umbilical cord and test its potential in tissue engineering. An enzymatic method was applied to isolate and solubilized complete human umbilical cord derived matrix (hUCM). The obtained solution was analyzed for growth factors, collagen and residual DNA contents, then used to coat 2D and 3D surfaces for cell culture application. The hUCM was successfully isolated with trypsin digestion to acquire a solution containing various growth factors and collagen but no residual DNA. This hUCM solution can form a coating on 2D and 3D substrates suitable cell culture. We developed a new matrix derived from human source that can be further used in tissue engineering.

Extreme umbilical cord lengths, cord knot and entanglement: Risk factors and risk of adverse outcomes, a population-based study

PubMed Central

Kessler, Jörg

2018-01-01

Objectives To determine risk factors for short and long umbilical cord, entanglement and knot. Explore their associated risks of adverse maternal and perinatal outcome, including risk of recurrence in a subsequent pregnancy. To provide population based gestational age and sex and parity specific reference ranges for cord length. Design Population based registry study. Setting Medical Birth Registry of Norway 1999–2013. Population All singleton births (gestational age>22weeks<45 weeks) (n = 856 300). Methods Descriptive statistics and odds ratios of risk factors for extreme cord length and adverse outcomes based on logistic regression adjusted for confounders. Main outcome measures Short or long cord (<10th or >90th percentile), cord knot and entanglement, adverse pregnancy outcomes including perinatal and intrauterine death. Results Increasing parity, maternal height and body mass index, and diabetes were associated with increased risk of a long cord. Large placental and birth weight, and fetal male sex were factors for a long cord, which again was associated with a doubled risk of intrauterine and perinatal death, and increased risk of adverse neonatal outcome. Anomalous cord insertion, female sex, and a small placenta were associated with a short cord, which was associated with increased risk of fetal malformations, placental complications, caesarean delivery, non-cephalic presentation, perinatal and intrauterine death. At term, cord knot was associated with a quadrupled risk of perinatal death. The combination of a cord knot and entanglement had a more than additive effect to the association to perinatal death. There was a more than doubled risk of recurrence of a long or short cord, knot and entanglement in a subsequent pregnancy of the same woman. Conclusion Cord length is influenced both by maternal and fetal factors, and there is increased risk of recurrence. Extreme cord length, entanglement and cord knot are associated with increased risk of adverse

Assessment of Neuroprotective Properties of Melissa officinalis in Combination With Human Umbilical Cord Blood Stem Cells After Spinal Cord Injury

PubMed Central

Hosseini, Seyed Ruhollah; Joghataei, Mohammad Taghi; Hooshmandi, Mehdi; Sadraie, Seyed Homayoon; Yaghoobi, Kayvan; Mohammadi, Alireza

2016-01-01

Introduction The pathophysiology of spinal cord injury (SCI) has a classically bad prognosis. It has been demonstrated that human umbilical cord blood stem cells (hUCBSCs) and Melissa officinalis (MO) are useful for the prevention of neurological disease. Methods Thirty-six adult male rats were randomly divided into intact, sham, control (SCI), MO, hUCBSC, and MO-hUCBSC groups. Intraperitoneal injection of MO (150 mg/kg) was commenced 24 hr post-SCI and continued once a day for 14 days. Intraspinal grafting of hUCBSCs was commenced immediately in the next day. The motor and sensory functions of all animals were evaluated once a week after the commencement of SCI. Electromyography (EMG) was performed in the last day in order to measure the recruitment index. Immunohistochemistry, reverse transcription-polymerase chain reaction, and transmission electron microscopy evaluations were performed to determine the level of astrogliosis and myelination. Results The results revealed that motor function (MO-hUCBSC: 15 ± 0.3, SCI: 8.2 ± 0.37, p < .001), sensory function (MO-hUCBSC: 3.57 ± 0.19, SCI: 6.38 ± 0.23, p < .001), and EMG recruitment index (MO-hUCBSC: 3.71 ± 0.18, SCI: 1.6 ± 0.1, p < .001) were significantly improved in the MO-hUCBSC group compared with SCI group. Mean cavity area (MO-hUCBSC: 0.03 ± 0.03, SCI: 0.07 ± 0.004, p < .001) was reduced and loss of lower motor neurons (MO-hUCBSC: 7.6 ± 0.43, SCI: 3 ± 0.12, p < .001) and astrogliosis density (MO-hUCBSC: 3.1 ± 0.15, SCI: 6.25 ± 1.42, p < 0.001) in the ventral horn of spinal cord were prevented in MO-hUCBSC group compared with SCI group. Conclusion The results revealed that the combination of MO and hUCBSCs in comparison with the control group has neuroprotective effects in SCI. PMID:27815336

Bioadhesive control of plasma proteins and blood cells from umbilical cord blood onto the interface grafted with zwitterionic polymer brushes.

PubMed

Chang, Yu; Chang, Yung; Higuchi, Akon; Shih, Yu-Ju; Li, Pei-Tsz; Chen, Wen-Yih; Tsai, Eing-Mei; Hsiue, Ging-Ho

2012-03-06

In this work, bioadhesive behavior of plasma proteins and blood cells from umbilical cord blood (UCB) onto zwitterionic poly(sulfobetaine methacrylate) (polySBMA) polymer brushes was studied. The surface coverage of polySBMA brushes on a hydrophobic polystyrene (PS) well plate with surface grafting weights ranging from 0.02 mg/cm(2) to 0.69 mg/cm(2) can be effectively controlled using the ozone pretreatment and thermal-induced radical graft-polymerization. The chemical composition, grafting structure, surface hydrophilicity, and hydration capability of prepared polySBMA brushes were determined to illustrate the correlations between grafting properties and blood compatibility of zwitterionic-grafted surfaces in contact with human UCB. The protein adsorption of fibrinogen in single-protein solutions and at complex medium of 100% UCB plasma onto different polySBMA brushes with different grafting coverage was measured by enzyme-linked immunosorbent assay (ELISA) with monoclonal antibodies. The grafting density of the zwitterionic brushes greatly affects the PS surface, thus controlling the adsorption of fibrinogen, the adhesion of platelets, and the preservation of hematopoietic stem and progenitor cells (HSPCs) in UCB. The results showed that PS surfaces grafted with polySBMA brushes possess controllable hydration properties through the binding of water molecules, regulating the bioadhesive and bioinert characteristics of plasma proteins and blood platelets in UCB. Interestingly, it was found that the polySBMA brushes with an optimized grafting weight of approximately 0.1 mg/cm(2) at physiologic temperatures show significant hydrated chain flexibility and balanced hydrophilicity to provide the best preservation capacity for HSPCs stored in 100% UCB solution for 2 weeks. This work suggests that, through controlling grafting structures, the hemocompatible nature of grafted zwitterionic polymer brushes makes them well suited to the molecular design of regulated

Awareness and acceptance of public cord blood banking among practicing obstetricians in the United States.

PubMed

Walker, Tim; Steckler, Del; Spellman, Stephen; Haven, Darlene; Welte, Kathy; Boo, Michael

2012-04-01

This study measured: 1) levels of awareness and understanding among practicing obstetricians regarding umbilical cord blood (UCB) donation and the use of UCB in transplant therapy, 2) motivations for obstetricians to support donation and collection for donation to a public cord blood bank (CBB), and 3) current practices for discussing this option with their patients. Obstetricians practicing in major metropolitan areas in the United States were randomly surveyed in 2009. Of 2041 surveys mailed, 295 were returned, 139 from obstetricians with privileges at hospitals affiliated with a public CBB (affiliated) and 156 from obstetricians without such privileges (nonaffiliated). Cross-tabulation analyses were conducted to compare responses between these two groups. Both affiliated and nonaffiliated obstetricians report being somewhat or very familiar with the use of cord blood in transplant therapy (88% vs. 82%, respectively; p = NS), but some misperceptions concerning clinical application exist. Eighty percent of affiliated obstetricians feel confident discussing cord blood options with their patients; however, 49% indicated that they have insufficient knowledge of cord blood donation to effectively answer patients' questions about donation. Obstetricians are generally familiar with the utility of donated cord blood in transplantation, but could benefit from additional information regarding how cord blood is used in transplantation. Further, obstetricians play an important role in encouraging women to donate their baby's cord blood to a public CBB, are willing to do so, and indicate a desire for more information so they can effectively educate their patients. © 2011 American Association of Blood Banks.

Determination of amphetamine and methamphetamine in umbilical cord using liquid chromatography-tandem mass spectrometry

PubMed Central

Jones, Joseph; Rios, Rosemarie; Jones, Mary; Lewis, Douglas; Plate, Charles

2009-01-01

The use of meconium as a drug-screening matrix for newborns has been the gold standard of care for the past two decades. A recent study using matched pairs of meconium and umbilical cord demonstrated a high degree of agreement. The use of liquid chromatography-tandem mass spectrometry as a means to confirm amphetamines presumptive positive umbilical cord specimens for amphetamine and methamphetamine is described here for the first time. The limit of detection for both compounds was 0.2 ng/g. The limit of quantitation for both compounds was 0.6 ng/g. The assay was linear for both compounds up to 100 ng/g. PMID:19783234

Evaluation of hyaluronan from different sources: Streptococcus zooepidemicus, rooster comb, bovine vitreous, and human umbilical cord.

PubMed

Shiedlin, Aviva; Bigelow, Russell; Christopher, William; Arbabi, Saman; Yang, Laura; Maier, Ronald V; Wainwright, Norman; Childs, Alice; Miller, Robert J

2004-01-01

Sodium hyaluronate (HA) is widely distributed in extracellular matrixes and can play a role in orchestrating cell function. Consequently, many investigators have looked at the effect of exogenous HA on cell behavior in vitro. HA can be isolated from several sources (e.g., bacterial, rooster comb, umbilical cord) and therefore can possess diverse impurities. This current study compares the measured impurities and the differences in biological activity between HA preparations from these sources. It was demonstrated that nucleic acid and protein content was highest in human umbilical cord and bovine vitreous HA and was low in bacterial and rooster comb HA. Macrophages exposed to human umbilical cord HA produced significantly higher amounts of TNF-alpha relative to control or bacterial-derived HA. These results indicate that the source of HA should be considered due to differences in the amounts and types of contaminants that could lead to widely different behaviors in vitro and in vivo.

[Measurement of umbilical activin A level in preterm infants].

PubMed

Zhong, Ying; Li, Juan; Wei, Ke-Lun

2011-10-01

To evaluate the clinical significance of umbilical activin A in preterm infants. Forty-one preterm infants (gestation 28 to 36 weeks) were enrolled. Fetal membranes, umbilical cords and blood samples from umbilical vein were obtained. Umbilical activin A level was measured using ELISA. The histological examinations of fetal membranes and umbilical cords were performed. The umbilical level of activin A averaged 2069 pg/mL in the 41 preterm infants. The umbilical activin A level in the 5 infants with intrauterine infection was higher than in those without intrauterine infection (2510 pg/mL vs 1975 pg/mL; P<0.01). Umbilical activin A level at cutoff of 2490 pg/mL showed a sensitivity of 80.0% and a specificity of 90.6% as a marker of intrauterine infection. There were no significant differences in the umbilical activin A level between the infants with and without respiratory distress syndrome. Umbilical activin A level was positively correlated with the duration of postnatal oxygen therapy (r=0.326, P<0.05). Umbilical activin A may serve a marker of intrauterine infection in preterm infants. The umbilical activin A level is correlated with the duration of postnatal oxygen therapy.

Proteomic evaluation of human umbilical cord tissue exposed to polybrominated diphenyl ethers in an e-waste recycling area.

PubMed

Li, Minghui; Huo, Xia; Pan, Yukui; Cai, Haoxing; Dai, Yifeng; Xu, Xijin

2018-02-01

Parental exposure to polybrominated diphenyl ethers (PBDEs) is associated with adverse birth outcomes. This study aims to examine differentially-expressed protein profiles in umbilical cord tissue, derived from mothers exposed to PBDEs, and investigate candidate biomarkers to reveal the underlying molecular mechanisms. Umbilical cord samples were obtained from women residing in an electronic waste (e-waste) recycling area (Guiyu) and reference area (Haojiang) in China. The concentration of PBDEs in umbilical cord tissue was determined by gas chromatography and mass spectrometry (GC/MS). Isobaric tagging for relative and absolute quantification (iTRAQ)-based proteomic technology was conducted to analyze differentially-expressed protein profiles. The total PBDE concentration was approximately five-fold higher in umbilical cords from Guiyu than from Haojiang (median 71.92ng/g vs. 15.52ng/g lipid, P<0.01). Neonatal head circumference, body-mass index (BMI) and Apgar1 score were lower in Guiyu and negatively correlated with PBDE concentration (P<0.01). Proteomic analysis showed 697 proteins were differentially expressed in the e-waste-exposed group compared with the reference group. The differentially-expressed proteins were principally involved in antioxidant defense, apoptosis, cell structure and metabolism. Among them, catalase and glutathione S-transferase omega-1, were down-regulated, and cytochrome c was found to be up-regulated, changes which were further verified by enzyme-linked immunosorbent assays. These results suggest that an antioxidant imbalance and cell apoptosis in the umbilical cord following PBDE exposure is associated with neonatal birth outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Maternal body-mass index and cord blood circulating endothelial colony-forming cells.

PubMed

Moreno-Luna, Rafael; Muñoz-Hernandez, Rocio; Lin, Ruei-Zeng; Miranda, Maria L; Vallejo-Vaz, Antonio J; Stiefel, Pablo; Praena-Fernández, Juan M; Bernal-Bermejo, Jose; Jimenez-Jimenez, Luis M; Villar, Jose; Melero-Martin, Juan M

2014-03-01

Endothelial colony-forming cells (ECFCs) are a subset of circulating endothelial progenitor cells that are particularly abundant in umbilical cord blood. We sought to determine whether ECFC abundance in cord blood is associated with maternal body-mass index (BMI) in nonpathologic pregnancies. We measured the level of ECFCs in the cord blood of neonates (n = 27) born from non-obese healthy mothers with nonpathologic pregnancies and examined whether ECFC abundance correlated with maternal BMI. We also examined the effect of maternal BMI on ECFC phenotype and function using angiogenic and vasculogenic assays. We observed variation in ECFC abundance among subjects and found a positive correlation between prepregnancy maternal BMI and ECFC content (r = 0.51, P = .007), which was independent of other obstetric factors. Despite this variation, ECFC phenotype and functionality were deemed normal and highly similar between subjects with maternal BMI <25 kg/m(2) and BMI between 25-30 kg/m(2), including the ability to form vascular networks in vivo. This study underlines the need to consider maternal BMI as a potential confounding factor for cord blood levels of ECFCs in future comparative studies between healthy and pathologic pregnancies. Copyright © 2014 Mosby, Inc. All rights reserved.

The Cord Blood Apgar: a novel scoring system to optimize selection of banked cord blood grafts for transplantation

PubMed Central

Page, Kristin M.; Zhang, Lijun; Mendizabal, Adam; Wease, Stephen; Carter, Shelly; Shoulars, Kevin; Gentry, Tracy; Balber, Andrew E.; Kurtzberg, Joanne

2012-01-01

BACKGROUND Engraftment failure and delays, likely due to diminished cord blood unit (CBU) potency, remain major barriers to the overall success of unrelated umbilical cord blood transplantation (UCBT). To address this problem, we developed and retrospectively validated a novel scoring system, the Cord Blood Apgar (CBA), which is predictive of engraftment after UCBT. STUDY DESIGN AND METHODS In a single-center retrospective study, utilizing a database of 435 consecutive single cord myeloablative UCBTs performed between January 1, 2000, to December 31, 2008, precryopreservation and postthaw graft variables (total nucleated cell, CD34+, colony-forming units, mononuclear cell content, and volume) were initially correlated with neutrophil engraftment. Subsequently, based on the magnitude of hazard ratios (HRs) in univariate analysis, a weighted scoring system to predict CBU potency was developed using a randomly selected training data set and internally validated on the remaining data set. RESULTS The CBA assigns transplanted CBUs three scores: a precryopreservation score (PCS), a postthaw score (PTS), and a composite score (CS), which incorporates the PCS and PTS values. CBA-PCS scores, which could be used for initial unit selection, were predictive of neutrophil (CBA-PCS ≥ 7.75 vs. <7.75, HR 3.5; p < 0.0001) engraftment. Likewise, CBA-PTS and CS scores were strongly predictive of Day 42 neutrophil engraftment (CBA-PTS ≥ 9.5 vs. <9.5, HR 3.16, p < 0.0001; CBA-CS ≥ 17.75 vs. <17.75, HR 4.01, p < 0.0001). CONCLUSION The CBA is strongly predictive of engraftment after UCBT and shows promise for optimizing screening of CBU donors for transplantation. In the future, a segment could be assayed for the PTS score providing data to apply the CS for final CBU selection. PMID:21810098

The Royan Public Umbilical Cord Blood Bank: Does It Cover All Ethnic Groups in Iran Based on HLA Diversity?

PubMed

Ebrahimkhani, Saeideh; Farjadian, Shirin; Ebrahimi, Marzieh

2014-04-01

Umbilical cord blood (UCB) stem cells allow the transplantation of partially human leukocyte antigen (HLA)-matched grafts and are a valuable resource for the treatment of hematologic malignancies and heritable hematologic, immunologic and metabolic diseases, especially when a compatible bone marrow donor is unavailable. The aim of this study was to determine how many ethnic groups in Iran are covered by the available UCB units based on HLA diversity. From 2009 until mid-2013, 4,981 (30.3%) of the 16,437 UCB samples collected met the storage criteria and were cryopreserved at a public cord blood bank (CBB) in Tehran, Iran. HLA-A, -B and -DRB1 were typed in 1,793 samples. The mean volume of the cryopreserved samples was 81.25 ± 20.3 ml. The range of total nucleated cells per unit was 51 × 10(7)-107 × 10(7). The most common HLA alleles were HLA-A*2 (17%) and HLA-A*24 (15.6%), HLA-B*35 (16.8%) and HLA-B*51 (13.9%), and HLA-DRB1*11 (20%) and HLA-DRB1*15 (14%). The predominant haplotypes were HLA-A*24-B*35-DRB1*11 (2%), HLA-A*02-B*50-DR*07 (1.8%), and HLA-A*02-B*51-DRB1*11 (1.5%). Based on the HLA-DRB1 profiles, the UCB units available at the Royan public UCB bank are a potentially adequate resource for hematopoietic stem cell transplantation for Iranian recipients belonging to particular ethnic groups. Regular educational programs to improve the public knowledge of UCB for transplantation can enhance the public CBB stocks for all Iranian ethnic groups in the future.

Umbilical cord blood androgen levels and ASD-related phenotypes at 12 and 36 months in an enriched risk cohort study.

PubMed

Park, Bo Y; Lee, Brian K; Burstyn, Igor; Tabb, Loni P; Keelan, Jeff A; Whitehouse, Andrew J O; Croen, Lisa A; Fallin, Margaret D; Hertz-Picciotto, Irva; Montgomery, Owen; Newschaffer, Craig J

2017-01-01

Autism spectrum disorder (ASD) affects more than 1% of children in the USA. The male-to-female prevalence ratio of roughly 4:1 in ASD is a well-recognized but poorly understood phenomenon. An explicit focus on potential etiologic pathways consistent with this sex difference, such as those involving prenatal androgen exposure, may help elucidate causes of ASD. Furthermore, the multi-threshold liability model suggests that the genetic mechanisms in females with ASD may be distinct and may modulate ASD risk in families with female ASD in the pedigree. We examined umbilical cord blood from 137 children in the Early Autism Risk Longitudinal Investigation (EARLI) cohort. EARLI is an ASD-enriched risk cohort with all children having an older sibling already diagnosed with ASD. Fetal testosterone (T), androstenedione (A4), and dehyroepiandrosterone (DHEA) levels were measured in cord blood using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Robust linear regression models were used to determine associations between cord blood androgen levels and 12-month Autism Observation Scales for Infants (AOSI) scores and 36-month Social Responsiveness Scale (SRS) scores adjusting for potential confounders. Increasing androgens were not associated with increasing 12-month AOSI score or 36-month total SRS score in either boys or girls. However, the association between T and autistic traits among subjects with a female older affected sibling was greater at 12 months (test of interaction, P  = 0.008) and deficits in reciprocal social behavior at 36 months were also greater (test of interaction, P  = 0.006) than in subjects whose older affected sibling was male. While increased prenatal testosterone levels were not associated with autistic traits at 12 or 36 months, our findings of a positive association in infants whose older ASD-affected siblings were female suggests an androgen-related mechanism that may be dependent on, or related to, genetic liability factors

Correlation of ultrasound estimated placental volume and umbilical cord blood volume in term pregnancy.

PubMed

Pannopnut, Papinwit; Kitporntheranunt, Maethaphan; Paritakul, Panwara; Kongsomboon, Kittipong

2015-01-01

To investigate the correlation between ultrasound measured placental volume and collected umbilical cord blood (UCB) volume in term pregnancy. An observational cross-sectional study of term singleton pregnant women in the labor ward at Maha Chakri Sirindhorn Medical Center was conducted. Placental thickness, height, and width were measured using two-dimensional (2D) ultrasound and calculated for placental volume using the volumetric mathematic model. After the delivery of the baby, UCB was collected and measured for its volume immediately. Then, birth weight, placental weight, and the actual placental volume were analyzed. The Pearson's correlation was used to determine the correlation between each two variables. A total of 35 pregnant women were eligible for the study. The mean and standard deviation of estimated placental volume and actual placental volume were 534±180 mL and 575±118 mL, respectively. The median UCB volume was 140 mL (range 98-220 mL). The UCB volume did not have a statistically significant correlation with the estimated placental volume (correlation coefficient 0.15; p=0.37). However, the UCB volume was significantly correlated with the actual placental volume (correlation coefficient 0.62; p<0.001) and birth weight (correlation coefficient 0.38; p=0.02). The estimated placental volume by 2D ultrasound was not significantly correlated with the UCB volume. Further studies to establish the correlation between the UCB volume and the estimated placental volume using other types of placental imaging may be needed.

Induction of vascular endothelial phenotype and cellular proliferation from human cord blood stem cells cultured in simulated microgravity

NASA Astrophysics Data System (ADS)

Chiu, Brian; Z-M Wan, Jim; Abley, Doris; Akabutu, John

2005-05-01

Recent studies have demonstrated that stem cells derived from adult hematopoietic tissues are capable of trans-differentiation into non-hematopoietic cells, and that the culture in microgravity ( μg) may modulate the proliferation and differentiation. We investigated the application of μg to human umbilical cord blood stem cells (CBSC) in the induction of vascular endothelial phenotype expression and cellular proliferation. CD34+ mononuclear cells were isolated from waste human umbilical cord blood samples and cultured in simulated μg for 14 days. The cells were seeded in rotary wall vessels (RWV) with or without microcarrier beads (MCB) and vascular endothelial growth factor was added during culture. Controls consisted of culture in 1 G. The cell cultures in RWV were examined by inverted microscopy. Cell counts, endothelial cell and leukocyte markers performed by flow-cytometry and FACS scan were assayed at days 1, 4, 7 and at the termination of the experiments. Culture in RWV revealed significantly increased cellular proliferation with three-dimensional (3D) tissue-like aggregates. At day 4, CD34+ cells cultured in RWV bioreactor without MCB developed vascular tubular assemblies and exhibited endothelial phenotypic markers. These data suggest that CD34+ human umbilical cord blood progenitors are capable of trans-differentiation into vascular endothelial cell phenotype and assemble into 3D tissue structures. Culture of CBSC in simulated μg may be potentially beneficial in the fields of stem cell biology and somatic cell therapy.

Use of cord blood derived T-cells in cancer immunotherapy: milestones achieved and future perspectives.

PubMed

Lo Presti, Vania; Nierkens, Stefan; Boelens, Jaap Jan; van Til, Niek P

2018-03-01

Hematopoietic cell transplantation is a potentially lifesaving procedure for patients with hematological malignancies who are refractory to conventional chemotherapy and/or irradiation treatment. Umbilical cord blood (CB) transplantation, as a hematopoietic stem and progenitor cell (HSPC) source, has several advantages over bone marrow transplantation with respect to matching and prompt availability for transplantation. Additionally, CB has some inherent features, such as rapid expansion of T cells, lower prevalence of graft-versus-host disease and higher graft versus tumor efficacy that make this HSPC cell source more favorable over other HSPC sources. Areas covered: This review summarizes the current CB and CB derived T cell applications aiming to better disease control for hematological malignancies and discusses future directions to more effective therapies. Expert commentary: CB transplantation could be used as a platform to extract cord blood derived T cells for ex vivo expansion and/or gene modification to improve cellular immunotherapies. In addition, combining cord blood gene-engineered T cell products with vaccination strategies, such as cord blood derived dendritic cell based vaccines, may provide synergistic immunotherapies with enhanced anti-tumor effects.

The injury of fine particulate matter from cooking oil fumes on umbilical cord blood vessels in vitro.

PubMed

Hou, Lijuan; Zhang, Jian; Zhang, Chao; Xu, Yachun; Zhu, Xiaoxia; Yao, Cijiang; Liu, Ying; Li, Tao; Cao, Jiyu

2017-01-01

Cooking oil fumes (COFs) derived PM 2.5 is the major source of indoor air pollution in Asia. For this, a pregnant rat model within different doses of cooking oil fumes (COFs) derived PM 2.5 was established in pregnancy in our research. Our previous studies have showed that exposure to COFs-derived PM 2.5 was related to adverse pregnancy outcomes. However, the mechanisms of signaling pathways remain unknown. Therefore, this study aimed to investigate the underlying mechanisms induced by COFs-derived PM2.5 injury on umbilical cord blood vessels (UCs) in vitro. Exposure to COFs-derived PM 2.5 resulted in changing the expression of eNOS, ET-1, ETRA, and ETRB. In additions, western blot analysis indicated that the HIF-1α/iNOS/NO signaling pathway and VEGF/VEGFR1/iNOS signaling pathway were involved in UCs injury triggered by COFs-derived PM 2.5 . In conclusion, our data suggested that exposure to COFs-derived PM 2.5 resulted in increasing of oxidative stress and inflammation, as well as dysfunction of UCs. Copyright © 2016 Elsevier B.V. All rights reserved.

Neonatal, placental, and umbilical cord blood parameters in pregnant women residing in areas with intensive pesticide application.

PubMed

Quintana, María Martha; Vera, Berta; Magnarelli, Gladis; Guiñazú, Natalia; Rovedatti, María Gabriela

2017-09-01

In rural populations, the proximity to areas with intensive pesticide application represents a risk factor of xenobiotic exposure. Here, we investigated whether newborns born to mothers residing in an area with intensive pesticide application show alterations in placental and neonatal morphometric standards, umbilical cord blood (UCB) biochemical parameters, and/or biomarkers related to oxidative stress and oxidative damage. Samples were collected from 151 healthy pregnant women residing in a rural area (rural group; RG) during the pesticide spraying (SS) and nonspraying (NSS) seasons, as well as from women from an urban population (control group; CG), and grouped according to the delivery type (vaginal or cesarean). In the vaginal delivery group, the placental weight and placental index were higher in the RG groups than in the CG (p = 0.01), whereas in the cesarean delivery group, newborn weight was lower in the RG-SS group than in the CG. In the RG-SS group, UCB erythrocyte osmotic fragility and the DNA damage index (DI) were higher, and superoxide dismutase (SOD) activity was lower than in the RG-NSS group. Acetylcholinesterase and SOD activities were found to be inversely correlated with the DI.

Chaotic time series prediction for prenatal exposure to polychlorinated biphenyls in umbilical cord blood using the least squares SEATR model

NASA Astrophysics Data System (ADS)

Xu, Xijin; Tang, Qian; Xia, Haiyue; Zhang, Yuling; Li, Weiqiu; Huo, Xia

2016-04-01

Chaotic time series prediction based on nonlinear systems showed a superior performance in prediction field. We studied prenatal exposure to polychlorinated biphenyls (PCBs) by chaotic time series prediction using the least squares self-exciting threshold autoregressive (SEATR) model in umbilical cord blood in an electronic waste (e-waste) contaminated area. The specific prediction steps basing on the proposal methods for prenatal PCB exposure were put forward, and the proposed scheme’s validity was further verified by numerical simulation experiments. Experiment results show: 1) seven kinds of PCB congeners negatively correlate with five different indices for birth status: newborn weight, height, gestational age, Apgar score and anogenital distance; 2) prenatal PCB exposed group at greater risks compared to the reference group; 3) PCBs increasingly accumulated with time in newborns; and 4) the possibility of newborns suffering from related diseases in the future was greater. The desirable numerical simulation experiments results demonstrated the feasibility of applying mathematical model in the environmental toxicology field.

Chaotic time series prediction for prenatal exposure to polychlorinated biphenyls in umbilical cord blood using the least squares SEATR model

PubMed Central

Xu, Xijin; Tang, Qian; Xia, Haiyue; Zhang, Yuling; Li, Weiqiu; Huo, Xia

2016-01-01

Chaotic time series prediction based on nonlinear systems showed a superior performance in prediction field. We studied prenatal exposure to polychlorinated biphenyls (PCBs) by chaotic time series prediction using the least squares self-exciting threshold autoregressive (SEATR) model in umbilical cord blood in an electronic waste (e-waste) contaminated area. The specific prediction steps basing on the proposal methods for prenatal PCB exposure were put forward, and the proposed scheme’s validity was further verified by numerical simulation experiments. Experiment results show: 1) seven kinds of PCB congeners negatively correlate with five different indices for birth status: newborn weight, height, gestational age, Apgar score and anogenital distance; 2) prenatal PCB exposed group at greater risks compared to the reference group; 3) PCBs increasingly accumulated with time in newborns; and 4) the possibility of newborns suffering from related diseases in the future was greater. The desirable numerical simulation experiments results demonstrated the feasibility of applying mathematical model in the environmental toxicology field. PMID:27118260

Comparison of stored umbilical cord blood and adult donor blood: transfusion feasibility.

PubMed

Tokan, Rola Sahyoun; Arsan, Saadet; Erdeve, Omer; Solaz, Nuri; Avcı, Aslıhan; Ulkar, Serenay Elgün; Gülyapar, Elif; Ustünyurt, Zeynep; Bıyıklı, Zeynep; Kemahlı, Sabri

2012-09-01

This study aimed to compare the storage properties of red blood cell (RBC) concentrates of umbilical cordblood (UCB) and adult donor blood (ADB), and to evaluate the feasibility of UCB-RBC concentrate as an autologoussource for blood transfusion in very low birth weight (VLBW) preterm neonates. In all, 30 newborn (10 preterm, 20 full term) UCB and 31 ADB units were collected.RBC concentrates were stored and compared with regard to pH, potassium (K(+)), 2,3-biphosphoglycerate (2-3-BPG),adenosine tri-phosphate (ATP), plasma Hb, and bacterial contamination on d 1, 21, and 35 of storage. The K(+) level increased with time and differed significantly between storage d 1 and 21, and between storaged 1 and 35 in both the UCB and ADB units. Initial and d 21 K(+) levels were higher in the UCB units than in the ADBunits. The 2,3-BPG level did not differ significantly between the UCB-PRC and ADB-PRC samples. After 35 d of storageboth UCB-PRC and ADB-PRC samples exhibited significant differences from the initial free Hb, intracellular ATP, andpH values. Significant differences in intracellular ATP and pH were also observed between the UCB-PRC and ADB-PRCsamples. The volume of harvested and prepared UCB-PRC can be used for some of the blood transfusions requiredduring the neonatal period and thus may decrease the number of allogeneic transfusions, especially in preterm newborns.The hematological and biochemical changes that occurred in UCB during storage were comparable with those observedin ADB, and do not pose a risk to the immature metabolism of neonates. UCB-RPC prepared and stored under standardconditions can be a safe alternative RBC source for transfusions in VLBW newborns.

Noninvasive fetal electrocardiography following intermittent umbilical cord occlusion in the preterm ovine fetus.

PubMed

Cleal, J K; Thomas, M; Hanson, M A; Paterson-Brown, S; Gardiner, H M; Green, L R

2010-03-01

To investigate whether a noninvasive fetal electrocardiography (fECG) system can identify cardiovascular responses to fetal hypoxaemia and validate the results using standard invasive fECG monitoring techniques. Prospective cohort study. Biological research facilities at The University of Southampton. Late gestation ovine fetuses; n = 5. Five fetal lambs underwent implantation of vascular catheters, umbilical cord occluder and invasive ECG chest electrodes under general anaesthesia (3% halothane/O(2)) at 119 days of gestation (term approximately 147 days of gestation). After 5 days of recovery blood pressure, blood gases, glucose and pH were monitored. At 124 and 125 days of gestation following a 10-minute baseline period a 90-second cord occlusion was applied. Noninvasive fetal ECG was recorded from maternal transabdominal electrodes using advanced signal-processing techniques, concurrently with invasive fECG recordings. Comparison of T:QRS ratios of the ECG waveform from noninvasive and invasive fECG monitoring systems. Our fECG monitoring system is able to demonstrate changes in waveforms during periods of hypoxaemia similar to those obtained invasively, which could indicate fetal distress. These findings may indicate a future use for noninvasive electrocardiography during human fetal monitoring both before and during labour in term and preterm pregnancies.

Effects of Cryopreservation Duration on the Outcome of Single-Unit Cord Blood Transplantation.

PubMed

Jaing, Tang-Her; Chen, Shih-Hsiang; Wen, Yu-Chuan; Chang, Tsung-Yen; Yang, Ya-Chun; Tsay, Pei-Kwei

2018-01-01

Cryopreservation is widely used in umbilical cord blood (UCB) banking, yet its impact on progenitor cell function remains largely unaddressed. It is unknown whether long-term cryopreservation affects UCB transplantation outcomes. Herein, we evaluated the impact of UCB age on clinical outcomes and investigated the effect of cryopreservation duration of UCB on hematopoietic potency in 91 patients receiving single cord blood transplantations. UCB cryopreservation duration was 0.7 to 13.4 y. The most common indication of transplant was thalassemia (48%). There was no significant association between cryopreservation duration and neutrophil engraftment probability ( P = 0.475). Cryopreservation duration did not affect the post-thaw viability and subsequent neutrophil engraftment rate. Therefore, UCB units can undergo cryopreservation for at least 8 y with no impact on clinical outcomes.

Use of cost-effectiveness analysis to determine inventory size for a national cord blood bank.

PubMed

Howard, David H; Meltzer, David; Kollman, Craig; Maiers, Martin; Logan, Brent; Gragert, Loren; Setterholm, Michelle; Horowitz, Mary M

2008-01-01

Transplantation with stem cells from stored umbilical cord blood units is an alternative to living unrelated bone marrow transplantation. The larger the inventory of stored cord units, the greater the likelihood that transplant candidates will match to a unit, but storing units is costly. The authors present the results of a study, commissioned by the Institute of Medicine, as part of a report on the establishment of a national cord blood bank, examining the optimal inventory level. They emphasize the unique challenges of undertaking cost-effectiveness analysis in this field and the contribution of the analysis to policy. The authors estimate the likelihood that transplant candidates will match to a living unrelated marrow donor or a cord blood unit as a function of cord blood inventory and then calculate the life-years gained for each transplant type by match level using historical data. They develop a model of the cord blood inventory level to estimate total costs as a function of the number of stored units. The cost per life-year gained associated with increasing inventory from 50,000 to 100,000 units is $44,000 to $86,000 and from 100,000 to 150,000 units is $64,000 to $153,000, depending on the assumption about the degree to which survival rates for cord transplants vary by match quality. Expanding the cord blood inventory above current levels is cost-effective by conventional standards. The analysis helped shape the Institute of Medicine's report, but it is difficult to determine the extent to which the analysis influenced subsequent congressional legislation.

Cord blood leptin and gains in body weight and fat mass during infancy.

PubMed

Chaoimh, Carol Ní; Murray, Deirdre M; Kenny, Louise C; Irvine, Alan D; Hourihane, Jonathan O'B; Kiely, Mairead

2016-11-01

Low early-life leptin concentrations may promote faster weight gain in infancy. We aimed to examine the associations between cord blood leptin concentrations and changes in weight and body composition during infancy. Serum leptin was measured at 15 weeks gestation, in umbilical cord blood collected at delivery and at 2 years in 334 children from the Cork Baseline Birth Cohort Study. Body composition was measured at 2 days and 2 months using air displacement plethysmography. Conditional change in weight standard deviation scores over a number of age intervals in the first 2 years and conditional change in fat mass index (FMI) and fat-free mass index (FFMI) (kg/(length)m(2)) between birth and 2 months were calculated and associations with cord blood leptin were examined using linear regression. At birth, cord blood leptin was positively correlated with FMI (r = 0.48, P < 0.001) and showed a weaker correlation with FFMI (r = 0.12, P = 0.05). After adjustment for confounders, higher cord blood leptin (per ng/mL) was associated with slower conditional weight gain between birth and 2 months (β (95% CI): -0.024 (-0.035, -0.013), P < 0.001) but not over subsequent age intervals. Cord blood leptin was also inversely associated with conditional change in FMI (-0.021 (-0.034, -0.007, P = 0.003) but not FFMI between birth and 2 months. These are the first data to show that associations between higher cord blood leptin and slower weight gain during infancy are driven by lower increases in adiposity, at least in early infancy. © 2016 European Society of Endocrinology.

Risk factors of CMV infection in patients after umbilical cord blood transplantation: a multicenter study in China

PubMed Central

Tong, Juan; Liu, Huilan; Geng, Liangquan; Zheng, Changcheng; Tang, Baolin; Song, Kaidi; Yao, Wen; Liu, Xin

2013-01-01

Objective This retrospective study examined risk factors for cytomegalovirus (CMV) infection after umbilical cord blood transplantation (UCBT) and the impact of CMV infection on patient survival. Methods In all 176 patients, plasma CMV DNA was negative prior to the transplantation, and examined twice a week for 100 d, and then once weekly for additional 300 d. Preemptive antiviral therapy (ganciclovir or foscarnet) was started in patients with >1,000/mL copies of CMV DNA but no full-blown CMV disease, and was discontinued upon two consecutive negative reports of blood CMV DNA test. The survival and risk factors for CMV infection or disease were examined using logistic regression. Results CMV infection developed in 71% (125/176) of the patients, with a median onset of 32 d. Four patients (2.3%) developed CMV disease. Neither the 5-year overall survival (OS) nor event-free survival (EFS) differed significantly in infected patients vs. those with no infection (59.4% vs. 64.8%, P=0.194; 53.4% vs. 59.1%, P=0.226). A stepwise multivariate analysis indicated an association of CMV infection with age, high-dose glucocorticoids, the number of transplanted CD34+ cells, and the number of platelet transfusion, but not with gender, the conditioning regimen, and the day of neutrophil recovery and chronic graft-versus-host disease (cGVHD). Conclusions CMV infection is very common after UCBT, but does not seem to affect long-term survival with preemptive antiviral treatment. PMID:24385697

Analysis of perfluorinated chemicals in umbilical cord blood by ultra-high performance liquid chromatography/tandem mass spectrometry.

PubMed

Lien, Guang-Wen; Wen, Ting-Wen; Hsieh, Wu-Shiun; Wu, Kuen-Yuh; Chen, Chia-Yang; Chen, Pau-Chung

2011-03-15

Perfluorinated compounds (PFCs) can cross the placental barrier and enter fetal circulation. This study aimed at developing a fast and sensitive ultra-high performance liquid chromatography/tandem mass spectrometry method for the determination of twelve perfluorinated compounds in cord blood. Samples were processed with protein precipitation using formic acid and methanol, mixed with stable isotope labeled standard, followed by sonication and centrifugation, and were analyzed using a Waters ACQUITY UPLC coupled with a Waters Quattro Premier XE triple-quadrupole mass spectrometer. The instrument was operated in selected reaction monitoring (SRM) with negative electrospray ionization. Using BEH C(18) column (2.1 mm×50 mm, 1.7 μm) with 10-mM N-methylmorpholine/methanol gradient elution provided a fast chromatographic separation (5.5 min) and sharp peaks. Intra- and inter-day calibration bias was less than 7% and intra- and inter-day calibration of relative standard deviations were within 0.02-8.22% for all the analytes and concentrations. The recoveries of PFCs spiked into bovine serum ranged from 85 to 104% with relative standard deviations from 0.02 to 6.37%. The limits of quantitation (LOQs), defined as a signal-to-noise ratio of ten, ranged from 0.15 to 3.1 ng/mL for the twelve PFCs. Perfluorooctanoic acid (PFOA), perfluorooctyl sulfonate (PFOS), perfluoroundecanoic acid (PFUA) and perfluorononanoic acid (PFNA) were detected in up to 68% of umbilical cord plasma (n=444) in Taiwan Birth Panel Study and the health effect of these chemicals on children developmental deserves further investigation. Copyright © 2011 Elsevier B.V. All rights reserved.

Comparison of umbilical cord ghrelin concentrations in full-term pregnant women with or without gestational diabetes.

PubMed

Karakulak, Murat; Saygili, Uğur; Temur, Muzaffer; Yilmaz, Özgür; Özün Özbay, Pelin; Calan, Mehmet; Coşar, Hese

2017-05-01

Ghrelin is a potent orexigenic peptide hormone secreted from the gastrointestinal tract that plays a crucial role in the regulation of lipids and glucose metabolism. Ghrelin also has links with fetal development and growth. Gestational diabetes mellitus (GDM) causes fetal macrosomia, but there is no available evidence of a relationship between ghrelin levels and birth weight in women with GDM. The purpose of this study is to investigate whether umbilical cord ghrelin concentrations are altered in full-term pregnant women with GDM compared to women without GDM and whether birth weight is correlated with ghrelin levels. Sixty pregnant women with GDM and 64 healthy pregnant women without GDM were included in this cross-sectional study. Blood samples were drawn from the umbilical vein following birth. Ghrelin concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Umbilical vein ghrelin levels were decreased in women with GDM (879.6 ± 256.1 vs. 972.2 ± 233.6 pg/ml in women without GDM, p=0.033), whereas birth weights were higher for babies in the GDM than in the non-GDM group (3448 ± 410 vs. 3308 ± 365 gr, respectively, p=0.046). Umbilical ghrelin levels were inversely correlated with birth weight (r=-0.765, p<0.001). Multiple regression analysis revealed that birth weight was independently and negatively associated with umbilical ghrelin levels (β= -2.077, 95% CI=-2.652 to -1.492, p=0.002). Umbilical ghrelin levels were lower in GDM women. Birth weight was inversely associated with umbilical ghrelin levels. This association may be explained by a negative feedback mechanism between ghrelin and birth weight.

DECREASED LEVEL OF CORD BLOOD CIRCULATING ENDOTHELIAL COLONY-FORMING CELLS IN PREECLAMPSIA

PubMed Central

Muñoz-Hernandez, Rocio; Miranda, Maria L.; Stiefel, Pablo; Lin, Ruei-Zeng; Praena-Fernández, Juan M.; Dominguez-Simeon, Maria J.; Villar, Jose; Moreno-Luna, Rafael; Melero-Martin, Juan M.

2014-01-01

Preeclampsia is a pregnancy-related disorder associated with increased cardiovascular risk for the offspring. Endothelial colony-forming cells (ECFCs) are a subset of circulating endothelial progenitor cells that participate in the formation of vasculature during development. However, the effect of preeclampsia on fetal levels of ECFCs is largely unknown. In this study, we sought to determine whether cord blood ECFC abundance and function are altered in preeclampsia. We conducted a prospective cohort study that included women with normal (n=35) and preeclamptic (n=15) pregnancies. We measured ECFC levels in the umbilical cord blood of neonates and characterized ECFC phenotype, cloning-forming ability, proliferation and migration towards VEGF-A and FGF-2, in vitro formation of capillary-like structures, and in vivo vasculogenic ability in immunodeficient mice. We found that the level of cord blood ECFCs was statistically lower in preeclampsia than in control pregnancies (P = .04), a reduction that was independent of other obstetric factors. In addition, cord blood ECFCs from preeclamptic pregnancies required more time to emerge in culture than control ECFCs. However, once derived in culture, ECFC function was deemed normal and highly similar between preeclampsia and control, including the ability to form vascular networks in vivo. This study demonstrates that preeclampsia affects ECFC abundance in neonates. A reduced level of ECFCs during preeclamptic pregnancies may contribute to an increased risk of developing future cardiovascular events. PMID:24752434

Conditioned Media from Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Inhibits Melanogenesis by Promoting Proteasomal Degradation of MITF.

PubMed

Kim, Eun Sung; Jeon, Hong Bae; Lim, Hoon; Shin, Ji Hyun; Park, So Jung; Jo, Yoon Kyung; Oh, Wonil; Yang, Yoon Sun; Cho, Dong-Hyung; Kim, Ju-Yeon

2015-01-01

Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) secrete various beneficial molecules, which have anti-apoptotic activity and cell proliferation. However, the effect of hUCB-MSCs in melanogenesis is largely unclear. In this study, we show that conditioned media (CM) derived from hUCB-MSCs inhibit melanogenesis by regulating microphthalmia-associated transcription factor (MITF) expression via the ERK signalling pathway. Treatment of hUCB-MSC-CM strongly inhibited the alpha-melanocyte stimulating hormone-induced hyperpigmentation in melanoma cells as well as melanocytes. Treatment of hUCB-MSC-CM induced ERK1/2 activation in melanocytes. In addition, inhibition of ERK1/2 suppressed the anti-pigmentation activity of the hUCB-MSC-CM in melanocytes and in vitro artificial skin models. We also found that the expression of MITF was appreciably diminished while expression of phosphorylated MITF, which leads to its proteasomal degradation, was increased in cells treated with hUCB-MSC-CM. These results suggested that hUCB-MSC-CM significantly suppresses melanin synthesis via MITF degradation by the ERK pathway activation.

Awareness of cord blood collection and the impact on banking.

PubMed

Bhandari, Rusha; Lindley, Amy; Bhatla, Deepika; Babic, Aleksandar; Mueckl, Kathy; Rao, Rakesh; Brooks, Paula; Geiler, Vicki; Gross, Gilad; Al-Hosni, Mohamad; Shenoy, Shalini

2017-07-01

Umbilical cord blood (UCB) is an important source of hematopoietic stem cells for transplantation especially in minority populations with limited chances of finding a histocompatible volunteer donor in the registry. UCB has the advantages of early availability, successful outcomes despite some histocompatibility mismatch, and low incidence of chronic graft-versus-host disease. Public cord blood banks that disseminate UCB products for transplant depend on voluntary donation at participating hospitals and obstetrical providers for collection. Using survey questionnaires, we evaluated attitudes toward UCB donation, the frequency of donation, and provider opinions on UCB collection in the greater St. Louis metropolitan area that caters to minority ethnicities in significant numbers. Our data suggest that nervousness and lack of information regarding the donation and utility of the product were ubiquitous reasons for not donating. Additionally, irrespective of age or level of education, women relied on healthcare providers for information regarding UCB donation. Providers reported primarily time constraints to discussing UCB donation at prenatal visits (54%). Of the interviewees, 62% donated UCB. Fallout due to refusal or preferring private banking was miniscule. These results suggest that dedicated personnel focused on disseminating information, obtaining consent, and collecting the UCB product at major hospitals can enrich cord blood banks especially with minority cords. Sustained and focused efforts could improve upon a relatively high wastage rate and ensure a robust supply of UCB products at local public banks. © 2017 Wiley Periodicals, Inc.

A Novel Method for Isolation of Pluripotent Stem Cells from Human Umbilical Cord Blood.

PubMed

Monti, Manuela; Imberti, Barbara; Bianchi, Niccolò; Pezzotta, Anna; Morigi, Marina; Del Fante, Claudia; Redi, Carlo Alberto; Perotti, Cesare

2017-09-01

Very small embryonic-like cells (VSELs) are a population of very rare pluripotent stem cells isolated in adult murine bone marrow and many other tissues and organs, including umbilical cord blood (UCB). VSEL existence is still not universally accepted by the scientific community, so for this purpose, we sought to investigate whether presumptive VSELs (pVSELs) could be isolated from human UCB with an improved protocol based on the isolation of enriched progenitor cells by depletion of nonprogenitor cells with magnetic separation. Progenitor cells, likely including VSELs, cultured with retinoic acid were able to form dense colonies and cystic embryoid bodies and to differentiate toward the ecto-meso-endoderm lineages as shown by the positivity to specific markers. VSEL differentiative potential toward mesodermal lineage was further demonstrated in vitro upon exposure to an established inductive protocol, which induced the acquisition of renal progenitor cell phenotype. VSEL-derived renal progenitors showed regenerative potential in a cisplatin model of acute kidney injury by restoring renal function and tubular structure through induction of proliferation of endogenous renal cells. The data presented here foster the great debate that surrounds VSELs and, more in general, the existence of cells endowed with pluripotent features in adult tissues. In fact, the possibility to find and isolate subpopulations of cells that fully fit all the criteria utilized to define pluripotency remains, nowadays, almost unproven. Thus, efforts to better characterize the phenotype of these intriguing cells are crucial to understand their possible applications for regenerative and precision medicine purposes.

UV-activated 7-dehydrocholesterol-coated titanium implants promote differentiation of human umbilical cord mesenchymal stem cells into osteoblasts.

PubMed

Satué, María; Ramis, Joana M; Monjo, Marta

2016-01-01

Vitamin D metabolites are essential for bone regeneration and mineral homeostasis. The vitamin D precursor 7-dehydrocholesterol can be used after UV irradiation to locally produce active vitamin D by osteoblastic cells. Furthermore, UV-irradiated 7-dehydrocholesterol is a biocompatible coating for titanium implants with positive effects on osteoblast differentiation. In this study, we examined the impact of titanium implants surfaces coated with UV-irradiated 7-dehydrocholesterol on the osteogenic differentiation of human umbilical cord mesenchymal stem cells. First, the synthesis of cholecalciferol (D3) was achieved through the incubation of the UV-activated 7-dehydrocholesterol coating for 48 h at 23℃. Further, we investigated in vitro the biocompatibility of this coating in human umbilical cord mesenchymal stem cells and its potential to enhance their differentiation towards the osteogenic lineage. Human umbilical cord mesenchymal stem cells cultured onto UV-irradiated 7-dehydrocholesterol-coated titanium implants surfaces, combined with osteogenic supplements, upregulated the gene expression of several osteogenic markers and showed higher alkaline phosphatase activity and calcein blue staining, suggesting increased mineralization. Thus, our results show that the use of UV irradiation on 7-dehydrocholesterol -treated titanium implants surfaces generates a bioactive coating that promotes the osteogenic differentiation of human umbilical cord mesenchymal stem cells, with regenerative potential for improving osseointegration in titanium-based bone anchored implants. © The Author(s) 2015.

Prenatal dioxin exposure estimated from dioxins in breast milk and sex hormone levels in umbilical cord blood in Vietnamese newborn infants.

PubMed

Boda, Hitomi; Nghi, Tran Ngoc; Nishijo, Muneko; Thao, Pham Ngoc; Tai, Pham The; Van Luong, Hoang; Anh, Tran Hai; Morikawa, Yuko; Nishino, Yoshikazu; Nishijo, Hisao

2018-02-15

Dioxin concentrations remain elevated in the environment and humans residing near the former US Air Force base in Bien Hoa city, South Vietnam. We recruited 210 mother-infant pairs for whom breast milk dioxin levels were reported in our previous study. Cord blood samples were collected from 162 mother-infant pairs. We selected 16 cord blood samples with a volume over 20mL and fat content of ≥0.03g. Toxic equivalent levels of polychlorinated dibenzodioxins and polychlorinated dibenzofurans (TEQ-PCDD/Fs) and concentrations of 17 congeners, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD), in cord blood were measured and compared with levels in breast milk (Study 1). Levels of 2,3,7,8-TCDD and TEQ-PCDD/Fs in cord blood samples were highly and significantly correlated with those in breast milk samples in the same pairs. This suggests dioxins in breast milk reflect prenatal dioxin exposure. Estradiol (E2) and testosterone (TS) were measured in cord blood serum from 162 samples. Associations between dioxins in breast milk and cord blood sex hormones were analyzed by infant sex, after adjusting for confounding factors (Study 2). Increased levels of TEQ-PCDD/Fs in breast milk were associated with decreased cord blood TS in girls. In boys, a significant reduction of cord blood TS was observed in those exposed to 2,3,7,8-TCDD at high levels (≥5.5pg/g lipid). There was no significant association between E2 and dioxins in breast milk in either sex. These results suggest increased prenatal dioxin exposure is associated with decreased cord TS, but in boys, only high level of 2,3,7,8-TCDD influence cord blood TS. Copyright © 2017. Published by Elsevier B.V.

Cryopreserved, Xeno-Free Human Umbilical Cord Mesenchymal Stromal Cells Reduce Lung Injury Severity and Bacterial Burden in Rodent Escherichia coli-Induced Acute Respiratory Distress Syndrome.

PubMed

Curley, Gerard F; Jerkic, Mirjana; Dixon, Steve; Hogan, Grace; Masterson, Claire; O'Toole, Daniel; Devaney, James; Laffey, John G

2017-02-01

Although mesenchymal stem/stromal cells represent a promising therapeutic strategy for acute respiratory distress syndrome, clinical translation faces challenges, including scarcity of bone marrow donors, and reliance on bovine serum during mesenchymal stem/stromal cell proliferation. We wished to compare mesenchymal stem/stromal cells from human umbilical cord, grown in xeno-free conditions, with mesenchymal stem/stromal cells from human bone marrow, in a rat model of Escherichia coli pneumonia. In addition, we wished to determine the potential for umbilical cord-mesenchymal stem/stromal cells to reduce E. coli-induced oxidant injury. Randomized animal study. University research laboratory. Male Sprague-Dawley rats. Acute respiratory distress syndrome was induced in rats by intratracheal instillation of E. coli (1.5-2 × 10 CFU/kg). "Series 1" compared the effects of freshly thawed cryopreserved umbilical cord-mesenchymal stem/stromal cells with bone marrow-mesenchymal stem/stromal cells on physiologic indices of lung injury, cellular infiltration, and E. coli colony counts in bronchoalveolar lavage. "Series 2" examined the effects of cryopreserved umbilical cord-mesenchymal stem/stromal cells on survival, as well as measures of injury, inflammation and oxidant stress, including production of reactive oxidative species, reactive oxidative species scavenging by superoxide dismutase-1 and superoxide dismutase-2. In "Series 1," animals subjected to E. coli pneumonia who received umbilical cord-mesenchymal stem/stromal cells had improvements in oxygenation, respiratory static compliance, and wet-to-dry ratios comparable to bone marrow-mesenchymal stem/stromal cell treatment. E. coli colony-forming units in bronchoalveolar lavage were reduced in both cell therapy groups, despite a reduction in bronchoalveolar lavage neutrophils. In series 2, umbilical cord-mesenchymal stem/stromal cells enhanced animal survival and decreased alveolar protein and proinflammatory

Cord blood banking - bio-objects on the borderlands between community and immunity.

PubMed

Brown, Nik; Williams, Rosalind

2015-01-01

Umbilical cord blood (UCB) has become the focus of intense efforts to collect, screen and bank haematopoietic stem cells (HSCs) in hundreds of repositories around the world. UCB banking has developed through a broad spectrum of overlapping banking practices, sectors and institutional forms. Superficially at least, these sectors have been widely distinguished in bioethical and policy literature between notions of the 'public' and the 'private', the commons and the market respectively. Our purpose in this paper is to reflect more critically on these distinctions and to articulate the complex practical and hybrid nature of cord blood as a 'bio-object' that straddles binary conceptions of the blood economies. The paper draws upon Roberto Esposito's reflections on biopolitics and his attempt to transcend the dualistic polarisations of immunity and community, or the private and the public. We suggest that his thoughts on immunitary hospitality resonate with many of the actual features and realpolitik of a necessarily internationalised and globally distributed UCB 'immunitary regime'.

Neuroprotective Effects of Transplanted Mesenchymal Stromal Cells-derived Human Umbilical Cord Blood Neural Progenitor Cells in EAE.

PubMed

Rafieemehr, Hassan; Kheyrandish, Maryam; Soleimani, Masoud

2015-12-01

Multiple Sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system. The aim of this study was to investigate the neuroprotective effects of transplanted human umbilical cord blood mesenchymal stromal cells (UCB-MSC) derived neural progenitor cell (MDNPC) in EAE, an experimental model of MS. To initiate neuronal differentiation of UCB-MSCs, the pre-induction medium was removed and replaced with induction media containing retinoic acid, b FGF, h EGF, NGF, IBMX and ascorbic acid for one week. The expression of neural genes was examined in comparison to control group by real-time PCR assay. Then, experimental autoimmune encephalitis (EAE) was induced using myelin oligodendrocyte glycoprotein (MOG, 35-55 peptides) in 24 C57BL/6 mice. After induction, the mice were divided in four groups (n=6) as follows: healthy, PBS, UCB-MSCs and MDNPC, respectively. At the end of the study, disease status in all the groups was analyzed using hematoxylin-eosin (H&E) staining of brain sections. We found that UCB-MSCs exhibit neuronal differentiation potential in vitro and transplanted MDNPC lowered clinical score and reduced CNS leukocyte infiltration compared to untreated mice. Our results showed that MDNPC from UCB may be a proper candidate for regenerative therapy in MS and other neurodegenerative diseases.

Effects of Intravenous Administration of Human Umbilical Cord Blood Stem Cells in 3-Acetylpyridine-Lesioned Rats

PubMed Central

Calatrava-Ferreras, Lucía; Gonzalo-Gobernado, Rafael; Herranz, Antonio S.; Reimers, Diana; Montero Vega, Teresa; Jiménez-Escrig, Adriano; Richart López, Luis Alberto; Bazán, Eulalia

2012-01-01

Cerebellar ataxias include a heterogeneous group of infrequent diseases characterized by lack of motor coordination caused by disturbances in the cerebellum and its associated circuits. Current therapies are based on the use of drugs that correct some of the molecular processes involved in their pathogenesis. Although these treatments yielded promising results, there is not yet an effective therapy for these diseases. Cell replacement strategies using human umbilical cord blood mononuclear cells (HuUCBMCs) have emerged as a promising approach for restoration of function in neurodegenerative diseases. The aim of this work was to investigate the potential therapeutic activity of HuUCBMCs in the 3-acetylpyridine (3-AP) rat model of cerebellar ataxia. Intravenous administered HuUCBMCs reached the cerebellum and brain stem of 3-AP ataxic rats. Grafted cells reduced 3-AP-induced neuronal loss promoted the activation of microglia in the brain stem, and prevented the overexpression of GFAP elicited by 3-AP in the cerebellum. In addition, HuUCBMCs upregulated the expression of proteins that are critical for cell survival, such as phospho-Akt and Bcl-2, in the cerebellum and brain stem of 3-AP ataxic rats. As all these effects were accompanied by a temporal but significant improvement in motor coordination, HuUCBMCs grafts can be considered as an effective cell replacement therapy for cerebellar disorders. PMID:23150735

Potency of umbilical cord blood- and Wharton's jelly-derived mesenchymal stem cells for scarless wound healing.

PubMed

Doi, Hanako; Kitajima, Yuriko; Luo, Lan; Yan, Chan; Tateishi, Seiko; Ono, Yusuke; Urata, Yoshishige; Goto, Shinji; Mori, Ryoichi; Masuzaki, Hideaki; Shimokawa, Isao; Hirano, Akiyoshi; Li, Tao-Sheng

2016-01-05

Postnatally, scars occur as a consequence of cutaneous wound healing. Scarless wound healing is highly desired for patients who have undergone surgery or trauma, especially to exposed areas. Based on the properties of mesenchymal stem cells (MSCs) for tissue repair and immunomodulation, we investigated the potential of MSCs for scarless wound healing. MSCs were expanded from umbilical cord blood (UCB-MSCs) and Wharton's jelly (WJ-MSCs) from healthy donors who underwent elective full-term pregnancy caesarean sections. UCB-MSCs expressed lower levels of the pre-inflammatory cytokines IL1A and IL1B, but higher levels of the extracellular matrix (ECM)-degradation enzymes MMP1 and PLAU compared with WJ-MSCs, suggesting that UCB-MSCs were more likely to favor scarless wound healing. However, we failed to find significant benefits for stem cell therapy in improving wound healing and reducing collagen deposition following the direct injection of 1.0 × 10(5) UCB-MSCs and WJ-MSCs into 5 mm full-thickness skin defect sites in nude mice. Interestingly, the implantation of UCB-MSCs tended to increase the expression of MMP2 and PLAU, two proteases involved in degradation of the extracellular matrix in the wound tissues. Based on our data, UCB-MSCs are more likely to be a favorable potential stem cell source for scarless wound healing, although a better experimental model is required for confirmation.

In vitro differentiation of human umbilical cord blood-derived mesenchymal stem cells into hepatocyte-like cells.

PubMed

Hong, Seung Hyun; Gang, Eun Ji; Jeong, Ju Ah; Ahn, Chiyoung; Hwang, Soo Han; Yang, Il Ho; Park, Hwon Kyum; Han, Hoon; Kim, Hoeon

2005-05-20

In addition to long-term self-renewal capability, human mesenchymal stem cells (MSCs) possess versatile differentiation potential ranging from mesenchyme-related multipotency to neuroectodermal and endodermal competency. Of particular concern is hepatogenic potential that can be used for liver-directed stem cell therapy and transplantation. In this study, we have investigated whether human umbilical cord blood (UCB)-derived MSCs are also able to differentiate into hepatocyte-like cells. MSCs isolated from UCB were cultured under the pro-hepatogenic condition similar to that for bone marrow (BM)-derived MSCs. Expression of a variety of hepatic lineage markers was analyzed by flow cytometry, RT-PCR, Western blot, and immunofluorescence. The functionality of differentiated cells was assessed by their ability to incorporate DiI-acetylated low-density lipoprotein (DiI-Ac-LDL). As the cells were morphologically transformed into hepatocyte-like cells, they expressed Thy-1, c-Kit, and Flt-3 at the cell surface, as well as albumin, alpha-fetoprotein, and cytokeratin-18 and 19 in the interior. Moreover, about a half of the cells were found to acquire the capability to transport DiI-Ac-LDL. Based on these observations, and taking into account immense advantages of UCB over other stem cell sources, we conclude that UCB-derived MSCs retain hepatogenic potential suitable for cell therapy and transplantation against intractable liver diseases.

Neonatal nucleated red blood cell counts in small-for-gestational age fetuses with abnormal umbilical artery Doppler studies.

PubMed

Bernstein, P S; Minior, V K; Divon, M Y

1997-11-01

The presence of elevated nucleated red blood cell counts in neonatal blood has been associated with fetal hypoxia. We sought to determine whether small-for-gestational-age fetuses with abnormal umbilical artery Doppler velocity waveforms have elevated nucleated red blood cell counts. Hospital charts of neonates with the discharge diagnosis of small for gestational age (birth weight < 10th percentile) who were delivered between October 1988 and June 1995 were reviewed for antepartum testing, delivery conditions, and neonatal outcome. We studied fetuses who had an umbilical artery systolic/diastolic ratio within 3 days of delivery and a complete blood cell count on the first day of life. Multiple gestations, anomalous fetuses, and infants of diabetic mothers were excluded. Statistical analysis included the Student t test, chi 2 analysis, analysis of variance, and simple and stepwise regression. Fifty-two infants met the inclusion criteria. Those with absent or reversed end-diastolic velocity (n = 19) had significantly greater nucleated red blood cell counts than did those with end-diastolic velocity present (n = 33) (nucleated red blood cells/100 nucleated cells +/- SD: 135.5 +/- 138 vs 17.4 +/- 23.7, p < 0.0001). These infants exhibited significantly longer time intervals for clearance of nucleated red blood cells from their circulation (p < 0.0001). They also had lower birth weights (p < 0.05), lower initial platelet count (p = 0.0006), lower arterial cord blood pH (p < 0.05), higher cord blood base deficit (p < 0.05), and an increased likelihood of cesarean section for "fetal distress" (p < 0.05). Multivariate analysis demonstrated that absent or reversed end-diastolic velocity (p < 0.0001) and low birth weight (p < 0.0001) contributed to the elevation of the nucleated red blood cell count, whereas gestational age at delivery was not a significant contributor. We observed significantly greater nucleated red blood cell counts and lower platelet counts in small

Low immunogenicity of allogeneic human umbilical cord blood-derived mesenchymal stem cells in vitro and in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Miyoung; Jeong, Sang Young; Ha, Jueun

2014-04-18

Highlights: • hUCB-MSCs maintained low immunogenicity even after immune challenge in vitro. • Humanized NSG mice were established using human UCB CD34+ cells. • Repeated intravenous hUCB-MSC injection into mice did not lead to immune responses and adverse events. • Allogeneic hUCB-MSCs maintained low immunogenicity in vitro and in vivo. - Abstract: Evaluation of the immunogenicity of human mesenchymal stem cells (MSCs) in an allogeneic setting during therapy has been hampered by lack of suitable models due to technical and ethical limitations. Here, we show that allogeneic human umbilical cord blood derived-MSCs (hUCB-MSCs) maintained low immunogenicity even after immune challengemore » in vitro. To confirm these properties in vivo, a humanized mouse model was established by injecting isolated hUCB-derived CD34+ cells intravenously into immunocompromised NOD/SCID IL2γnull (NSG) mice. After repeated intravenous injection of human peripheral blood mononuclear cells (hPBMCs) or MRC5 cells into these mice, immunological alterations including T cell proliferation and increased IFN-γ, TNF-α, and human IgG levels, were observed. In contrast, hUCB-MSC injection did not elicit these responses. While lymphocyte infiltration in the lung and small intestine and reduced survival rates were observed after hPBMC or MRC5 transplantation, no adverse events were observed following hUCB-MSC introduction. In conclusion, our data suggest that allogeneic hUCB-MSCs have low immunogenicity in vitro and in vivo, and are therefore “immunologically safe” for use in allogeneic clinical applications.« less

Donating umbilical cord blood to a public bank or storing it in a private bank: knowledge and preference of blood donors and of pregnant women.

PubMed

Screnci, Maria; Murgi, Emilia; Pirrè, Guglielma; Valente, Elisabetta; Gesuiti, Paola; Corona, Francesca; Girelli, Gabriella

2012-07-01

Umbilical cord blood (UCB) is a source of stem cells for allogeneic haematopoietic transplantation in paediatric and adult patients with haematological malignancies and other indications. Voluntary donation is the basis for the success of unrelated UCB transplantation programmes. In the last few years a growing number of private banks offer their services to expectant parents, to store UCB for future use. The debate concerning UCB donation and private preservation has been ongoing for several years. The aims of this single centre study were to explore knowledge about UCB stem cells and attitudes towards voluntary UCB donation or private UCB preservation among both blood donors and pregnant women. This study was conducted at the "Sapienza" University of Rome. Two types of anonymous questionnaires were prepared: one type was administered to 1,000 blood donors while the other type was distributed to 300 pregnant women. Most blood donors as well as the majority of pregnant women had some general knowledge about UCB (89% and 93%, respectively) and were aware of the possibility of donating it (82% and 95%). However, the level of knowledge regarding current therapeutic use resulted generally low, only 91 (10%) among informed blood donors and 69 (31%) among informed pregnant women gave a correct answer. The survey revealed a preference for voluntary donation both among blood donors (76%) and among pregnant woman (55%). Indeed, a minority of blood donors (6.5%) and of pregnant women (9%) would opt to store UCB for private use. The study raises the following considerations: (i) the large support for UCB donation expressed by blood donors and by pregnant women suggests that UCB preservation does not represent an obstacle to the expansion of UCB donation and to development of unrelated transplantation programmes; (ii) information about UCB donation and preservation should be carefully given by professionals and institutions.

Gestational intake of methyl donors and global LINE-1 DNA methylation in maternal and cord blood

PubMed Central

Baccarelli, Andrea; Kleinman, Ken P; Burris, Heather H; Litonjua, Augusto A; Rifas-Shiman, Sheryl L; Tarantini, Letizia; Gillman, Matthew W

2012-01-01

Maternal diet affects offspring DNA methylation in animal models, but evidence from humans is limited. We investigated the extent to which gestational intake of methyl donor nutrients affects global DNA methylation in maternal and umbilical cord blood. Among mother-infant pairs in Project Viva, a folate-replete US population, we estimated maternal intakes of vitamin B12, betaine, choline, folate, cadmium, zinc and iron periconceptionally and during the second trimester. We examined associations of these nutrients with DNA methylation, measured as %5-methyl cytosines (%5mC) in Long Interspersed Nuclear Element-1 (LINE-1), in first trimester (n = 830) and second trimester (n = 671) maternal blood and in cord blood at delivery (n = 516). Cord blood methylation was higher for male than female infants {mean [standard deviation (SD)] 84.8 [0.6] vs. 84.4 [0.7]%}. In the multivariable-adjusted model, maternal intake of methyl donor nutrients periconceptionally and during the second trimester of pregnancy was not positively associated with first trimester, second trimester or cord blood LINE-1 methylation. Periconceptional betaine intake was inversely associated with cord blood methylation [regression coefficient = −0.08% (95% confidence interval (CI): −0.14, −0.01)] but this association was attenuated after adjustment for dietary cadmium, which itself was directly associated with first trimester methylation and inversely associated with cord blood methylation. We also found an inverse association between periconceptional choline [−0.10%, 95% CI: −0.17, −0.03 for each SD (∼63 mg/day)] and cord blood methylation in males only. In this folate-replete population, we did not find positive associations between intake of methyl donor nutrients during pregnancy and DNA methylation overall, but among males, higher early pregnancy intakes of choline were associated with lower cord blood methylation. PMID:22430801

Polychlorinated biphenyls in umbilical cord serum of newborns from Rio Grande do Sul state, Brazil.

PubMed

Mohr, Susana; Sifuentes dos Santos, Joice; Schwanz, Thiago Guilherme; Wagner, Roger; Mozzaquatro, Joseane Oliveira; Lorenzoni, Alessandra Scherer; Costabeber, Ijoni Hilda

2015-12-07

Polychlorinated biphenyls (PCBs) are food-chain contaminants that have been shown to contaminate foods worldwide. The newborn are exposed to these organochlorine compounds across the placenta and through breastfeeding. They are proven to be carcinogenic and may contribute to congenital malformation etiology. This study examined levels of five PCB congeners (28, 52, 138, 153 and 180) in umbilical cord serum samples from 148 newborns from Rio Grande do Sul state, Brazil. Serum concentrations of PCBs were analyzed by gas chromatography with electron capture detection and mass spectrometry. Levels of ∑PCBs ranged from 0.35 to 55.17 ng/ml in umbilical cord serum positive samples, and PCB 138 was the most prevalent congener. Only 7.4% of samples presented no PCB congener. Some PCB congener cord serum levels were related to the locale of the mothers' residence, smoking and drinking habits, fruit consumption, and congenital malformation. Copyright © 2015 Elsevier B.V. All rights reserved.