Umbilical Cord Blood Units Research Articles

Higher survival following transplantation with a mismatched unrelated donor with posttransplant cyclophosphamide-based graft-versus-host disease prophylaxis than with double unit umbilical cord blood in patients with acute myeloid leukemia in first complete remission: A study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

The best donor option for acute myeloid leukemia (AML) patients lacking an HLA-matched donor has remained intensively debated. We herein report the results of a large retrospective registry study comparing hematopoietic cell transplantation (HCT) outcomes between double-unit umbilical cord blood transplantation (dCBT, n = 209) versus 9/10 HLA-matched unrelated donor (UD) with posttransplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis (UD 9/10, n = 270) in patients with AML in first complete remission (CR1). Inclusion criteria consisted of adult patient, AML in CR1 at transplantation, either peripheral blood stem cells (PBSC) from UD 9/10 with PTCy as GVHD prophylaxis or dCBT without PTCy, transplantation between 2013 and 2021, and no in vivo T-cell depletion. The 180-day cumulative incidence of grade II-IV acute GVHD was 29% in UD 9/10 versus 44% in dCBT recipients (p = .001). After adjustment for covariates, dCBT recipients had a higher non-relapse mortality (HR = 2.35, 95% CI: 1.23-4.48; p = .01), comparable relapse incidence (HR = 1.12, 95% CI: 0.67-1.86; p = .66), lower leukemia-free survival (HR = 1.5, 95% CI: 1.01-2.23; p = .047), and lower overall survival (HR = 1.66, 95% CI: 1.08-2.55; p = .02) compared with patients receiving UD 9/10 HCT. In summary, our results suggest that transplantation outcomes are better with UD 9/10 with PTCy-based GVHD prophylaxis than with dCBT for AML patients in CR1. These data might support the use of UD 9/10 with PTCy-based GVHD prophylaxis over dCBT in AML patients lacking an HLA-matched donor.

Bacterial species in cord blood and their significance in the context of clinical use

Approximately 90 % of infants born before 28 full weeks(extremely-preterm-infants) receive erythrocyte transfusions in early life. Umbilical cord blood(UCB) has been investigated as an alternative source for erythrocyte transfusions to preterm neonates. This retrospective study aimed to compile/evaluate spectrum of bacteria groups/species intermittently detected in processed UCB at National-Swedish-Cord blood bank, (NS-CBB) during the years 2008–2020.Consecutive data from the years 2008–2020 were investigated. UCB from healthy newborns born after 37 full weeks of gestation was collected following clamping of cord (1 min) through cannulation of umbilical vein(vaginal-and C-section-deliveries). In total, 5194 cord blood units (UCBUs) that met NS-CBB-guidelines for total nucleated-cell-content(TNC) were manufactured from 8875 collections. Of 5194 UCBUs,77,6 % were from vaginal-and 22,4 % from C-section deliveries.Samples(10 mL) were collected from surplus eryhtrocyte fraction post-processing(n = 5194), transferred into BACT/ALERT® aerobic/anaerobic culture flasks and monitored 10 days using BACT/ALERT®−3D-Microbial-Detection-Systems. Positive samples were subcultured and typed for bacterial groups and/or species.Out of 5194 processed sampled UCB units,186 (3,6 %) were discarded due to positive sterility tests, 92 % were detected in samples from vaginal-deliveries and 8 % from C-section-deliveries. In all,16 different groups of bacteria and 27 species were identified. Common bacterial/groups and species were anaerobe gram-negative rods(n = 28),coagulase-negative-staphylococci(n = 21),gram-positive rods(n = 21),anaerobe-gram-positive cocci(n = 20) and viridans-streptococci(n = 13). Extracted from these results,in positive samples(n = 13) from C-section deliveries, bacteria were found:viridans-streptococci(n = 7),Aerococcus-urinae(n = 1), Staphylococcus lugdunensis(n = 1),other coagulase-negative staphylococci(n = 1) or a mix of aerobic/anaerobic bacteria(n = 3).Our results are in alignment with previously published contamination rates in processed UCBUs. Still, results point towards importance of strict microbial monitoring when manufacturing UCBUs to achieve patient-safe- products for stem-cell transplantation/transfusion.

Characterization of cord blood immune and stem cells from Vietnamese infants

Cord blood has emerged as a valuable and versatile resource, holding within its grasp a myriad of immune and stem cell types with immense therapeutic potential. Moreover, immune profiling in cord blood, a burgeoning field of research, offers profound insight into the early immune development of newborns, paving the way for understanding immune health, disease susceptibility, and therapeutic interventions. Therefore, in this research, we aimed to characterize the diverse immune and stem cell types present in the cord blood of Vietnamese infants. In this study, a total of 59 cord blood samples were examined for immune cell populations. Cell populations were identified using flow cytometry based on the expression of specific markers on the cell surface. The results showed that the CD3+/CD4+ population accounted for the greatest proportion of lymphocytes (46.71 ± 8.99%), followed by the CD3+/CD8+ population (22.58 ± 6.73%). The mature B-cell population (CD3-/CD19+) accounted for 9.52 ± 3.28%, while CD3+/CD19+ cells accounted for an average of 8.59 ± 5.77%. Moreover, the NK population (CD3-/CD56+ cells) accounted for 6.44 ± 4.9%, T lymphocytes carrying both CD4 and CD8 markers (CD3+/CD4+/CD8+) accounted for 0.63 ± 0.41%, and NKT cells (CD3+/CD56+) accounted for only 0.30 ± 0.53%. Moreover, the number of hematopoietic stem cells (HSCs) tends to increase in umbilical cord blood units with a high volume and number of TNCs and MNCs. In contrast, the number of HSCs was negatively correlated with the ratio of B lymphocytes. The TCD4 ratio was positively correlated with the number of HSCs but negatively correlated with the NK ratio (p = 0.01). The study initially characterized the diversity of some stem and immune cell types present in the umbilical cord blood of Vietnamese infants. These findings laid the groundwork for developing novel immune profiles and expanding the potential applications of umbilical cord blood in cellular therapy.

Evaluation of factors affecting total nucleated cells in umbilical cord blood collected for the Calabria Cord Blood Bank.

Total nucleated cell (TNC) count is the most important biological feature to consider in assessing the quality of umbilical cord blood (UCB) for hematopoietic stem cell (HSC) transplantation. Certain obstetric factors have been reported to increase TNC count in UCB units collected for transplantation. The aim of our study was to analyze how various maternal, neonatal and obstetric factors affected TNC count in the UCBs we collected for our cord blood bank in southern Italy. We performed a retrospective analysis of 634 medical records of UCBs collected by Calabria Cord Blood Bank (CCBB), Reggio Calabria, Italy, between January 1, 2010, and December 31, 2016. We analyzed various maternal, neonatal and obstetric variables factors and related this factor with the characteristic of TNC. We found that the average number of TNCs was significantly greater in vaginal delivery than in caesarean delivery. We also found that TNCs were higher in the 40th week of pregnancy and when Apgar 1' scores were ≤9. The effect of a newborn's gender was less evident on TNC count. Knowledge of factors predictive of a higher TNC count would help cord blood banks more efficiently identify donors likely to yield high-quality UCBs for transplantation.

Perspectives for the Use of Umbilical Cord Blood in Transplantation and Beyond: Initiatives for an Advanced and Sustainable Public Banking Program in Greece.

The umbilical cord blood (UCB) donated in public UCB banks is a source of hematopoietic stem cells (HSC) alternative to bone marrow for allogeneic HSC transplantation (HSCT). However, the high rejection rate of the donated units due to the strict acceptance criteria and the wide application of the haploidentical HSCT have resulted in significant limitation of the use of UCB and difficulties in the economic sustainability of the public UCB banks. There is an ongoing effort within the UCB community to optimize the use of UCB in the field of HSCT and a parallel interest in exploring the use of UCB for applications beyond HSCT i.e., in the fields of cell therapy, regenerative medicine and specialized transfusion medicine. In this report, we describe the mode of operation of the three public UCB banks in Greece as an example of an orchestrated effort to develop a viable UCB banking system by (a) prioritizing the enrichment of the national inventory by high-quality UCB units from populations with rare human leukocyte antigens (HLA), and (b) deploying novel sustainable applications of UCB beyond HSCT, through national and international collaborations. The Greek paradigm of the public UCB network may become an example for countries, particularly with high HLA heterogeneity, with public UCB banks facing sustainability difficulties and adds value to the international efforts aiming to sustainably expand the public UCB banking system.

Mismatched Unrelated Donor Transplantation with Ptcy-Based Gvhd Prophylaxis Is Associated with Better Survival Than Double Unit Umbilical Cord Blood Transplantation in Patients with AML in First CR: A Study from the ALWP of the EBMT

Background: The best donor option for acute myeloid leukemia (AML) patients lacking an HLA-matched donor has remained unknown. The recently reported BNT CTN 1101 trial observed higher non-relapse mortality (NRM) and lower overall survival (OS) in patients randomized to double-unit unrelated umbilical cord blood transplantation (dCBT) in comparison to those randomized to HLA-haploidentical bone marrow transplantation with post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis 1. In addition, recent registry studies observed at least as good transplantation outcomes in AML patients given grafts from 9/10 HLA-matched unrelated donor (UD 9/10) with PTCy-based GVHD prophylaxis as those given grafts from HLA-haploidentical donors 2,3. These observations prompted us to perform a retrospective registry study comparing hematopoietic cell transplantation (HCT) outcomes between UD 9/10 and dCBT. Methods: Inclusion criteria consisted of adult patient, AML in CR1 at transplantation, either peripheral blood stem cells (PBSC) from UD 9/10 with PTCy as GVHD prophylaxis or dCBT, transplantation between 2013 and 2021, and no in vivo T-cell depletion. Results: A total of 208 dCBT patients and 270 UD 9/10 allo-HCT were included. The 180-day cumulative incidence of grade II-IV acute GVHD was 29% in UD 9/10 versus 44% in dCBT recipients (P=0.001). The 2-year cumulative incidences of relapse and of NRM were 23.5% and 12.5%, respectively, in UD 9/10 recipients versus 27% (P=0.39) and 18% (P=0.07), respectively in dCBT recipients. Two-year OS and LFS were 70% and 64%, respectively, in UD 9/10 recipients versus 60% (P=0.016) and 55% (P=0.028), respectively in dCBT recipients. In multivariate analyses, in comparison with UD 9/10 recipients, dCBT patients had a higher non-relapse mortality (HR=2.35, 95% CI: 1.23-4.48; P=0.01), comparable relapse incidence (HR=1.12, 95% CI: 0.67-1.86; P=0.66), lower leukemia-free survival (HR=1.5, 95% CI: 1.01-2.23; P=0.047), and lower overall survival (HR=1.66, 95% CI: 1.08-2.55; P=0.02). Conclusions: In summary, our results suggest that transplantation outcomes are better with UD 9/10 with PTCy-based GVHD prophylaxis than with dCBT for AML patients in CR1. These data might support the use of UD 9/10 with PTCy-based GVHD prophylaxis in AML patients lacking an HLA-matched donor. References Fuchs, E. J. et al. Double unrelated umbilical cord blood vs HLA-haploidentical bone marrow transplantation: the BMT CTN 1101 trial. Blood 137, 420-428 (2021).Baron, F. et al. Comparison of HLA-mismatched unrelated donor transplantation with post-transplant cyclophosphamide versus HLA-haploidentical transplantation in patients with active acute myeloid leukemia. Bone Marrow Transplant. 57, 1657-1663 (2022).Battipaglia, G. et al. Post-transplant cyclophosphamide in one-antigen mismatched unrelated donor transplantation versus haploidentical transplantation in acute myeloid leukemia: a study from the Acute Leukemia Working Party of the EBMT. Bone Marrow Transplant. 57, 562-571 (2022).

Mesenchymal Stromal Cells from Perinatal Tissues as an Alternative for Ex Vivo Expansion of Hematopoietic Progenitor and Stem Cells from Umbilical Cord Blood.

Umbilical cord blood (UCB) serves as a source of hematopoietic stem and progenitor cells (HSPCs) utilized in the regeneration of hematopoietic and immune systems, forming a crucial part of the treatment for various benign and malignant hematological diseases. UCB has been utilized as an alternative HSPC source to bone marrow (BM). Although the use of UCB has extended transplantation access to many individuals, it still encounters significant challenges in selecting a histocompatible UCB unit with an adequate cell dose for a substantial proportion of adults with malignant hematological diseases. Consequently, recent research has focused on developing ex vivo expansion strategies for UCB HSPCs. Our results demonstrate that co-cultures with the investigated mesenchymal stromal cells (MSCs) enable a 10- to 15-fold increase in the cellular dose of UCB HSPCs while partially regulating the proliferation capacity when compared to HSPCs expanded with early acting cytokines. Furthermore, the secretory profile of UCB-derived MSCs closely resembles that of BM-derived MSCs. Moreover, both co-cultures exhibit alterations in cytokine secretion, which could potentially impact HSPC proliferation during the expansion process. This study underscores the fact that UCB-derived MSCs possess a remarkably similar supportive capacity to BM-derived MSCs, implying their potential use as feeder layers in the ex vivo expansion process of HSPCs.

The effect of caffeine intake and passive smoking on umbilical cord blood unit's quality parameters.

Today cord blood (CB) is a valuable source of hematopoietic stem cells to treat many hematological disorders. One of the limitations of CB utilization is the reduced number of nucleated cells including stem cells. Therefore, CB banks around the world have developed strategies in an attempt to improve donor selection and the quality of the CB inventory. This study aimed to determine the impact of passive smoking and caffeine consumption on CB quality. CBs were obtained from mothers who gave birth at King Abdulaziz Medical City. All mothers gave their informed consent. Personal interviews about the mother's demographics, smoking status and exposure, and caffeine consumption executed, followed by a chart review to analyze maternal and neonatal factors. Laboratory testing was performed on all collected CB units. Using descriptive statistics, maternal and newborn factors were analyzed. T-test or Mann-Whitney U Test, as appropriate, for continuous variables analysis to study the effect of second hand smoking and coffee consumption for the primary outcome. Our study demonstrated a reduction in CB MNC, including lymphocytes, in caffeine consumers among pregnant donors, as well as a reduction in cell potency activities, including total CFU and BFU-E. The effect of passive cigarette smoking on the same cohort was insignificant. Outcome of this study will help in optimizing the quality and quantity of stem cell harvesting from CB to get the maximum benefit and such knowledge will raise the awareness among pregnant women.

Haploidentical Cord Blood Transplantation with 8 mg/kg Antithymocyte Globulin as Graft-versus-Host Disease Prophylaxis Compared to Haploidentical Transplantation with 10 mg/kg Antithymocyte Globulin in the Treatment of Acute Leukemia

Clinical outcomes of the transplantation strategy combined with a haploidentical stem cell graft and an unrelated umbilical cord blood unit (haplo-cord HSCT) with low-dose antithymocyte globulin (ATG) as graft-versus-host disease (GVHD) prophylaxis for the treatment of acute leukemia remains unclear. This study aimed to explore the clinical outcomes of haplo-cord HSCT in acute leukemia patients with the GVHD prevention strategy of 8 mg/kg ATG compared with haploidentical transplantation with 10 mg/kg ATG. A total of 130 patients with acute leukemia who underwent allogeneic HSCT between January 2016 and December 2020 were included in this study, including 70 patients who received haploidentical stem cell grafts and unrelated umbilical cord blood units (haplo-cord HSCT) with 8 mg/kg ATG (haplo-cord-ATG8 group) and haploidentical HSCT with 10 mg/kg ATG (haplo-ATG10 group) in 60 patients. Clinical data were collected and analyzed retrospectively. Patients in the haplo-cord-ATG8 group were significantly older compared with the haplo-ATG10 group (P=.000). Haplo-cord HSCT with reduced ATG to 8 mg/kg results in more rapid neutrophil recovery (P=.036). No between-group differences were observed in platelet recovery or the incidences of Epstein-Barr virus viremia, bloodstream infection, or hemorrhagic cystitis. The rate of grade II-IV acute GVHD by day 100 post-transplantation was higher in the haplo-ATG10 group (27.16% versus 11.48%; P=.033), as was the rate of chronic GVHD at 1 year (14.60% versus 3.36%; P=.048). The rate of cytomegalovirus reaction was higher in the haplo-ATG10 group (48.31% versus 26.30%; P=.022). With a median follow-up of 27.4 months for the haplo-cord-ATG8 group and 27.5 months for the haplo-ATG10 group, overall survival (OS) at 2 years was 79.4% versus 62.8% (P=.005), event-free survival (EFS) was 76.3% versus 55.9% (P=.001), the cumulative incidence of relapse was 10.11% versus 25.97% (P=.164), and nonrelapse mortality (NRM) was 14.33% versus 24.43% (P=.0040). Multivariate analysis identified Center for International Blood and Marrow Transplant Research Disease Risk Index was the sole significant predictor of relapse, NRM, OS, and EFS. Haplo-cord HSCT supported by cord blood with 8 mg/kg ATG as GVHD prophylaxis results in better outcomes compared with haplo-HSCT with 10 mg/kg ATG.

Umbilical Cord Blood Processing Techniques and Their Comparative Advantages: A Review

Background: Umbilical Cord Blood (UCB) has steadily gained prominence in haematopoietic stem cell transplantation (HSCT). Despite UCB advantages, the main disadvantage of UCB in haematopoietic stem cell transplantation (HSCT) is its limited cell dose. Initially, UCB used to be processed and then made to undergo cryopreservation as whole cord blood banking leading to the problem of storing sufficiently large number of cryoprotected UCB units which requires vast amounts of costly storage space in liquid nitrogen. The sole purpose of processing is to concentrates the stem cells and reduce the volume for storage. Different UCB processing methods have been developed. 
 Aim: This review is aimed at bringing together the literature on the different processing methods and highlighting the underlying principles of each method, the relative efficiency and advantages of the methods.
 Methodology: The work involved mainly the critical review of all available academic, professional and industry documents on cord blood processing. The relevant information was obtained from textbooks, academic journals, conference proceedings, the internet among others. The major UCB processing methods include Plasma Depletion, Density Gradient Centrifugation (DGC), Hetastarch, PrepaCyte-CB and Sepax. A study of the potential impact of Hetastarch and PrepaCyte processing methods on transplantation outcomes revealed no difference that was significant was observed between patients receiving cells after the processing regimens were compared.
 Results: A comparison of the engraftment time of PrepaCyte-CB with five other processing methods revealed a quicker engraftment time for PrepaCyte-CB processed cord blood units compared to other processing methods. PrepaCyte-CB also recovers significantly more viable stem cells than AutoXpress (AXP) and hydroxyethyl starch (HES) processing methods. Other workers demonstrated that Sepax depletion produces higher recovery of cells that are nucleated. The effect initial volume of cord blood had on the recovery of nucleated cells for the different method of processing were also compared. Recovery when using Sepax is reduced as the unit size processed increases. Hetastarch, which is a density gradient, and plasma depletion separation is also affected in like manner, however, processing done using PrepaCyte-CB was not affected by the initial volume of the collected unit. The advantage of Sepax is that it is fully automated and this allows for mass processing of samples, suitable for bigger cord blood banks. For erythrocyte removal, density gradient separation is a better method that is effective. PrepaCyte-CB is the second most efficient method for removing RBC. The result of Total Nucleated Cells (TNC) and Mono Nucleated Cells (MNC) recovery rate of Hespan and Sepax against AXP processing methods shows that both Hespan and Sepax reproducibly recover greater than 95% of the cord blood stem cells in a typical collection and result in a reduced final volume for final storage.
 Conclusion: The five most popular processing techniques are Plasma Depletion, Density Gradient, Hetastarch, PrepaCyte-CB and Automated Centrifugal Machine (Sepax). Most methods involve centrifugation, sedimentation and/or filtration for reducing the red cell content, plasma volume, or both. The different UCB processing methods each has its advantages and disadvantages.

Hospitalization and Healthcare Resource Utilization of Omidubicel-Onlv versus Umbilical Cord Blood Transplantation for Hematologic Malignancies: Secondary Analysis from a Pivotal Phase 3 Clinical Trial

A phase 3 trial (ClincialTrials.gov identifier NCT02730299) of omidubicel-onlv, a nicotinamide-modified allogeneic hematopoietic progenitor cell therapy manufactured from a single umbilical cord blood (UCB) unit, showed faster hematopoietic recovery, reduced rate of infections, and shorter hospital stay compared with patients randomized to standard UCB. This prospective secondary analysis of the phase 3 trial characterized resource utilization in the first 100 days post-transplantation with omidubicel-onlv compared with UCB. This analysis examined resource utilization, including hospital length of stay, hospital care setting, visits by provider type, rate of transfusions, and readmissions, among the 108 treated patients (omidubicel-onlv, n = 52; UCB, n = 56) from day 0 to day 100 post-transplantation. Demographics were generally balanced between the 2 arms, except a higher proportion of females (52% versus 37%) and older median age (40 years versus 36 years) were noted in the omidubicel-onlv arm. Compared with patients receiving UCB transplantation, patients receiving omidubicel-onlv had a shorter average total hospital length of stay (mean, 41.2 days versus 50.8 days; P = .027) in the first 100 days post-transplantation and more days alive and out of the hospital (mean, 55.8 days versus 43.7 days; P = .023). Fewer patients died in the omidubicel-onlv arm compared with the UCB arm (12% vs 16%) before day 100 post-transplantation. During primary hospitalization (ie, time from transplantation to discharge), fewer patients receiving omidubicel-onlv required intensive care unit (ICU) admission (10% versus 23%) and spent fewer days in the ICU (mean, .4 day versus 4.7 days; P = .028) and transplant unit (mean, 25.3 days versus 32.9 days; P = .022) compared with those receiving UCB. Patients receiving omidubicel-onlv required fewer outpatient consultant and nonconsultant visits and fewer platelet or other transfusions within 100 days from transplantation. Our findings suggest that faster hematopoietic recovery in omidubicel-onlv patients is associated with significantly shorter hospital stay and reduced healthcare resource use compared with UCB.

Single laboratory evaluation of umbilical cord blood units processing methodologies for banking.

To compare the efficiency of 3 different processing methods (Sepax, AutoXpress [AXP], and manual processing with hydroxyethyl starch [HES] sedimentation) used at Stemlab during a 10-year period. Historical data were compiled and the analytical results obtained for the 3 different methods were compared. The manual processing (HES) method yielded the highest level of total nucleated cell recovery after processing, and the AXP system yielded the highest CD34+ cell number. The red blood cell reduction was also significantly higher with the HES method. Also, HES showed comparable results to Toticyte technology for umbilical cord blood (UCB) processing. These results show that the HES method is as effective as automated technologies for UCB volume reduction; hence, it is a suitable methodology for private and public UCB banks. The HES method also proved to be superior to Toticyte technology for medical applications, with higher recovery yields of total nucleated cells after thawing and equivalent CD34+ cell recovery and functionality.

Nomenclature for factors of the HLA system, update January, February, and March 2023.

Nomenclature for factors of the HLA system, update January, February, and March 2023.

Using umbilical cord blood as a source of paediatric packed red blood cells: Processing and quality control.

Umbilical cord blood (UCB) has been used as a source of red blood cells (RBCs) for neonatal/paediatric transfusion purposes. This study adopted two different procedures to obtain umbilical RBC (U-RBC) to compare its quality control parameters to those of fractionated adult RBC (A-RBC), for paediatric purposes. UCB units (24) were filtered and processed based on two different methods, namely, conventional/manual (P1;n12) and automatic (P2;n12). They were compared to five fractionated A-RBCs. U-RBC and A-RBC were stored for 14 days and had their haematological, biochemical, haemolytic and microbiological parameters analysed at D1, D7 and D14. Cytokines and growth factors (GFs) in residual U-RBC plasma were measured. Mean volume of processed U-RBC units was 45 mL for P1 and 39 mL for P2; the mean haematocrit level reached 57% for P1 and 59% for P2. A-RBC recorded a mean volume of 44 mL. Haematologic and biochemical parameters analysed in U-RBC and A-RBC presented similar behaviours during storage time, except for parameter values, which differed between them. Pro-inflammatory and immunomodulatory cytokines, as well as GFs, were higher in U-RBC residual plasma than in that A-RBC. UCB can be processed into RBC based on either manual or automated protocols. U-RBC units met the referenced quality parameters defined for A-RBC. Some features, mainly the biochemical ones, should be further investigated to help improve quality parameters, with emphasis on differences found in, and particularities of, this material and on recipients of this new transfusion practice.

Expanding the Abu Dhabi Bone Marrow Transplant Program (AD-BMT<sup>®</sup>) Scope with the Collection and Cryopreservation of Cord Blood Stem Cells

<i>Introduction:</i> The umbilical cord blood (UCB) is the blood from the placenta's blood vessels and the portion of the umbilical cord that remains attached to the newborn after the delivery when the cord is clamped and cut. UCB is rich in hematopoietic stem cells (HSC) and other stem cells (SC). Between 1974 and 1988, scientific knowledge and UCB application possibilities for human therapy opened a new significative era in cell therapy, using UCB HSC as an alternative source of SC for bone marrow transplant and the cure of patients with malignant hematological diseases. <i>Objective:</i> The possibility of having a UCB bank (UCB-B) in Abu Dhabi encouraged us to make this analysis. <i>Method:</i> A literature review from Google Scholar, PubMed, SciELO, Scopus, and other sources, about the increasing application of UCB-SC and storage in UCB-B was done to update about all the possibilities for translational medicine. <i>Results:</i> We prepared a UCB overview, including the pioneering use of UCB-SC for HSC transplantation, their biological composition, characteristics, and the UC-associated tissues like Wharton-Jelly and the human term placenta, UCB advantages, and disadvantages in HSC transplantation, the number of clinical trials applying UCB donation samples, and promising possibilities for regenerative medicine. The existence of different types of UCB-Bs, and the development of new specific cellular manipulation techniques. The UCB-B regulatory framework and some ethical issues were also included in the review. <i>Conclusions:</i> After 30 years of UCB-B, more than 100 public UCB-Bs worldwide, with millions of UCB units donated altruistically, more than 800,000 clinical-grade products are now available: a great source of transplantable SC and other cellular material for the development of new therapies. Even though the UCB as a source of HSC for transplantation has been recently statistical ranked in third place, after HSC apheresis collected and bone marrow aspirates, until now, more than 50,000 UCB HSC allogeneic transplants (HSC-Allo-T) have been performed worldwide in both children and adults to treat many different diseases, including hematologic, metabolic, immunologic, neoplastic, and neurologic disorders. A significant effort has been focused on enhancing engraftment to reduce the risk of infection and cost. <i>Recommendations:</i> To that end, we must understand in detail the molecular mechanisms controlling SC self-renewal that may lead to the development of ex-vivo systems for HSCs expansion, characterize the mechanisms regulating the homing of HSC and determine the relative place of UCB HSC-Allo-T, as compared to other sources.

Immune Reconstitution Profiling Suggests Antiviral Protection after Transplantation with Omidubicel: A Phase 3 Substudy

Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative treatment for hematological malignancies and non-malignant disorders. Rapid immune reconstitution (IR) following allogeneic HCT has been shown to be associated with improved clinical outcomes and lower infection rates. A global phase 3 trial (NCT02730299) of omidubicel, an advanced cell therapy manufactured from an appropriately human leukocyte antigen-matched single umbilical cord blood (UCB) unit, showed faster hematopoietic recovery, reduced rates of infection, and shorter hospitalizations in patients randomized to omidubicel compared with those randomized to standard UCB. This optional, prospective substudy of the phase 3 trial characterized the IR kinetics following HCT with omidubicel compared with UCB in a systematic and detailed manner. In this substudy, 37 patients from 14 global sites were included (omidubicel: n=17, UCB: n=20). Peripheral blood samples were collected over 10 predefined time points from 7 to 365 days post-HCT. Flow cytometry immunophenotyping, T cell receptor excision circle quantification, and T cell receptor sequencing were employed to evaluate the longitudinal IR kinetics post-transplant and their association with clinical outcomes. Patient characteristics in the two comparator cohorts were overall statistically similar, except for age and total body irradiation (TBI) based conditioning regimens. The median age (range) for patients who received omidubicel or UCB was 30 (13-62) years and 43 (19-55) years, respectively. The percentages of patients receiving TBI based conditioning regimens were 47% and 70% for omidubicel and UCB recipients, respectively. Graft characteristics differed in their cellular composition. Omidubicel recipients received a 33-fold higher median dose of CD34+ stem cells, while receiving one third of the median CD3+ lymphocyte dose infused to UCB transplanted patients. Compared with UCB, omidubicel recipients exhibited faster IR of all measured lymphoid and myelomonocytic subpopulations, predominantly in the first 14 days post-transplant. This effect involved circulating natural killer (NK) cells, helper T cells, monocytes, and dendritic cells, with superior long-term B cell recovery from Day 28. One-week post-HCT, omidubicel recipients exhibited 4.1 and 7.7 -fold increases in the median helper T and NK cell counts respectively, compared to their UCB transplanted counterparts. By three weeks post-HCT, omidubicel transplanted patients were 3-fold more likely to achieve clinically relevant helper T and NK cell counts of 100 cells/ µL or above. Similar to UCB, omidubicel yielded a balanced cellular subpopulation composition and diverse T cell receptor repertoire in the short to long term. Omidubicel's CD34+ cell content correlated with faster IR by Day 7 post-HCT, which in turn coincided with earlier hematopoietic recovery. Lastly, early NK and helper T cell reconstitution correlated with a decreased rate of post-HCT viral infections, suggesting a plausible explanation for this phenomenon among omidubicel recipients in the phase 3 study. Our findings suggest that omidubicel efficiently promotes IR across multiple immune cells, including CD4+ T cells, B cells, NK cells, and dendritic cell subtypes as early as 7 days post-transplant, potentially endowing recipients of omidubicel with early protective immunity.

Characterization of 40 novel HLA class I and class II alleles identified in umbilical cord blood units.

Forty novel HLA class I and class II alleles were identified in umbilical cord blood (UCB) samples and categorized based on various types of mutations: non-synonymous, synonymous, frameshift, and premature termination codon. This study described 14 novel HLA-A alleles, 9 novel HLA-B alleles, 4 novel HLA-C alleles, 3 novel HLA-DRB1 alleles and 10 novel HLA-DQB1 alleles. Comparing the new allele sequence with the most homologous sequence, 60% of the novel alleles exhibited non-synonymous substitution, 32.5% observed with synonymous substitution, 5% displayed premature stop codon, and 2.5% presented with frameshift mutation. The majority of the new alleles contained a single nucleotide variation when compared with the most similar sequence.

CD44, CD90 and CD96 expression in immune thrombocytopenia purpura (ITP) patients

ABSTRACT Studying the expression of hematopoietic stem cell markers from different sources might be useful in understanding stem cell biology in different niche conditions. The study aimed to assess the difference in cell surface markers (CD44, CD90, CD96) on hematopoietic stem cells in three different niche conditions; umbilical cord blood (UCB), normal bone marrow (NBM) and bone marrow samples from idiopathic (immune) thrombocytopenic purpura (IBM). This study was conducted on 300 cases divided into three study groups; 100 umbilical cord blood units collected from mothers undergoing cesarian section in gynecology and obstetrics department, 100 bone marrow samples from idiopathic (immune) thrombocytopenic purpura patients collected from university children hospital and 100 normal bone marrow samples with no evidence of disease in bone marrow tissue. CD44 was significantly elevated in UCB and NBM groups compared to IBM group (<0.001). There was also a significant elevation of CD90 and CD96 in IBM group compared to NBM group and UCB (<0.001). CD90 and CD96 play a role in the pathogenesis of ITP disorder and could be applied as a targeted therapy to improve the outcome of this disease.

Safety and Efficacy of Allogeneic Umbilical Cord Blood Therapy for Global Development Delay and Intellectual Disability.

Most pediatric patients with global developmental delay (GDD) or intellectual disability (ID) have disrupted development. Since allogeneic umbilical cord blood (UCB) may exert neurotrophic effects, a prospective clinical trial was conducted to assess the efficacy and safety of UCB therapy for GDD and ID. A total of 13 children (ages 23-149 months) with GDD and ID were enrolled and followed up for 12 months. Under criteria of histocompatibility and cell number, allogeneic UCB units were selected and infused once intravenously, and adverse events were monitored. The Bayley Scale of Infant Development-II (BSID-II) was used as primary outcome measurement tool, and evaluations for various functional abilities were also implemented. Safety assessment did not reveal significant adverse effects. Functional improvements in mental and motor developments along with daily living activities and languages were observed at 12 months postintervention compared with the baseline abilities (P < 0.05). Furthermore, mental developmental quotient derived from BSID-II mental scale revealed significantly facilitated improvement during the first 3 months (P < 0.05). In the survey conducted 80.7 ± 13.0 months after UCB infusion to assess satisfaction and long-term safety, no long-term adverse effects were reported, and 70% of the guardians reported satisfaction with the UCB infusion. Long-term changes in two patients who were regularly followed up beyond the study completion were noticeable. One case observed for 4 years showed dramatic improvement until 12 months after UCB therapy, whereas she showed insignificant improvement beyond 12 months after the therapy. Another case showed alleviation of autism with findings of anti-inflammatory response in his peripheral blood after UCB infusion. This clinical study provides support for further applications of UCB as a therapeutic avenue for children with GDD or ID owing to its safety and partial efficacy. Due to patient heterogeneity, further studies focusing on specific clinical manifestations and etiologies are required. Registered at www.clinicaltrials.gov (NCT01769716).

Umbilical Cord Blood Transplantation: Connecting Its Origin to Its Future.

Transplantation of umbilical cord blood (UCB) is an attractive alternative source of hematopoietic stem cells (HSCs). The unique properties of cord blood and its distinct immune tolerance and engraftment kinetics compared to bone marrow (BM) and peripheral blood progenitor cells, permit a wider disparity in human leukocyte antigen levels between a cord blood donor and recipient after an unrelated umbilical cord blood transplant (UCBT). In addition, it is readily available and has a lowered risk of graft-versus-host disease (GvHD), with similar long-term clinical outcomes, compared to BM transplants. However, the relatively low number of cells administered by UCB units, as well as the associated delayed engraftment and immune reconstitution, pose limitations to the wide application of UCBT. Research into several aspects of UCBT has been evaluated, including the ex vivo expansion of cord blood HSCs and the process of fucosylation to enhance engraftment. Additionally, UCB has also been used in the treatment of several neurodegenerative and cardiovascular disorders with varying degrees of success. In this article, we will discuss the biology, clinical indications, and benefits of UCBT in pediatric and adult populations. We will also discuss future directions for the use of cord blood.