Umbilical Cord Blood Stem Cells Research Articles

Effect of fetal distress on viability and yield of umbilical cord blood stem cells–a prospective comparative study

IntroductionDifferent factors affect the quality and viability of cord blood stem cells, and therefore the efficacy of umbilical cord stem cell transplantation. Fetal distress is one factor affecting the quantity of CD34+ cells in cord blood. This study was designed to compare the viability and yield of the umbilical cord blood stem cells of women who have undergone emergency lower segment caesarean section for fetal distress or for other causes. Materials and methodsThis cross-sectional analytical study was performed at a tertiary care hospital facility with a total sample size of 68: 34 participants had undergone emergency C-section for fetal distress, and 34 had undergone emergency C-section for other causes. Umbilical cord blood was collected ex-utero in a 350 mL bag with citrate-phosphate-dextrose solution with adenine. Three milliliter of blood were transferred to an ethylenediaminetetraacetic acid (EDTA) tube for cell counts and flow cytometry testing for CD34+. The chi-square test was used to compare the total mononuclear cell, CD34+, and viability between the groups. ResultsThe CD34+ count [mean 4.9 versus 1.1 (× 106 cells/unit)] and total nucleated cell count [mean 14.2 versus 7.5 (× 108/unit)] were significantly higher in cord blood units collected from women who delivered by C-section for fetal distress (p-value <0.05). However, the volume of umbilical cord stem cells and viability of stem cells did not vary significantly based on the presence or absence of fetal distress (p-value >0.05). ConclusionThe current study shows that umbilical cord blood collected during fetal distress has a significantly higher content of stem cells and total nucleated cells than the non-fetal distress group

The Ethical Challenges of Umbilical Cord Blood Stem Cell Banking: A Qualitative Study

Background: Umbilical cord blood serves as a potent source of hematopoietic stem cells, utilized in treating specific diseases and preserved in blood banks. Objectives: This study aims to explore the ethical issues associated with these repositories. Methods: This qualitative research involved conducting 14 interviews with experts and the families of recipients or donors of umbilical cord blood. Participants were selected purposefully from May to November 2021. Results: The investigation identified five principal ethical challenges: presentation of information, interpersonal relationships among involved parties, respect for human dignity, adherence to rules and regulations, and the handling of tissue samples. These challenges encompassed various categories and subcategories, including informed consent, communication and advertising of information, financial considerations, conflicts of interest, professional interactions, ownership rights concerning the child and parents, privacy and confidentiality issues, compliance with regulations and guidelines, and the clinical and research uses of the tissue samples. Conclusions: The study unveiled significant ethical concerns in the domain of umbilical cord blood stem cell banking. Addressing these ethical dilemmas necessitates the involvement of health policymakers and medical ethics experts, along with a comprehensive understanding of these banks' multifaceted nature by the community.

The Evaluation of Mass/DNA Copy Number of Mitochondria in Umbilical Cord Blood-derived Hematopoietic Stem Cells Cocultured with MSCs

The Evaluation of Mass/DNA Copy Number of Mitochondria in Umbilical Cord Blood-derived Hematopoietic Stem Cells Cocultured with MSCs

Therapeutic effect and study of human umbilical cord blood mononuclear cells in patients with ischaemic bowel disease

Ischaemic bowel disease (ICBD) is a group of intestinal ischaemia syndromes caused by various aetiologies of reduced intestinal blood flow or vascular occlusion. ICBD can present as abdominal pain, bloody stool, and diarrhoea. This disease often occurs in middle-aged and elderly individuals with cardiovascular and cerebrovascular diseases. The incidence of ischaemic bowel disease has been increasing for decades, and it is difficult to diagnose, resulting in rapid disease progression and a high mortality rate. Therefore, fully understanding this disease, improving the diagnosis rate of this disease, and finding appropriate treatment methods are urgently needed to improve the condition and prognosis of patients. Umbilical cord blood stem cells are accessible, have weak immunogenicity, and have various biological functions, such as angiogenesis, inflammation and immune regulation. Many studies have confirmed that cord blood stem cells can relieve ischaemia, and these cells have attracted tremendous amounts of attention in regenerative medicine in recent years. In this paper, we discuss the clinical characteristics of ICBD, analyse the characteristics of human umbilical cord blood mononuclear cells (HUCB-MNCs), and use its to treat ischaemic bowel disease. Additionally, we compare the clinical manifestations and related indicators before and after treatment to evaluate the efficacy and safety of these methods.

Implantation of hUCB-MSCs generates greater hyaline-type cartilage than microdrilling combined with high tibial osteotomy.

To compare the outcomes of treating large cartilage defects in knee osteoarthritis using human allogeneic umbilical cord blood-derived mesenchymal stem cell (hUCB-MSC) implantation or arthroscopic microdrilling as a supplementary cartilage regenerative procedure combined with high tibial osteotomy (HTO). This 1-year prospective comparative study included 25 patients with large, near full-thickness cartilage defects (International Cartilage Repair Society grade ≥ IIIB) in the medial femoral condyles and varus malalignment. Defects were treated with hUCB-MSC implantation or arthroscopic microdrilling combined with HTO. The primary outcomes were pain visual analogue scale and International Knee Documentation Committee subjective scores at 12, 24and 48 weeks. Secondary outcomes included arthroscopic, histologicaland magnetic resonance imaging assessments at 1 year. Fifteen and 10 patients were treated via hUCB-MSC implantation and microdrilling, respectively. Baseline demographics, limb alignmentand clinical outcomes did not significantly differ between the groups. Cartilage defects and total restored areas were significantly larger in the hUCB-MSC group (7.2 ± 1.9 vs. 5.2 ± 2.1 cm2, p = 0.023; 4.5 ± 1.4 vs. 3.0 ± 1.6 cm2, p = 0.035). The proportion of moderate-to-strong positive type II collagen staining was significantly higher in the hUCB-MSC group compared to that in the microdrilled group (93.3% vs. 60%, respectively). Rigidity upon probing resembled that of normal cartilage tissue more in the hUCB-MSC group (86.7% vs. 50.0%, p = 0.075). Histological findings revealed a higher proportion of hyaline cartilage in the group with implanted hUCB-MSC (p = 0.041). hUCB-MSC implantation showed comparable clinical outcomes to those of microdrilling as supplementary cartilage procedures combined with HTO in the short term, despite the significantly larger cartilage defect in the hUCB-MSC group. The repaired cartilage after hUCB-MSC implantation showed greater hyaline-type cartilage with rigidity than that after microdrilling. Level II, Prospective Comparative Cohort Study.

Prognostic Factors for Clinical Outcome and Cartilage Regeneration after Implantation of Allogeneic Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Large-Sized Cartilage Defects with Osteoarthritis.

To analyze the prognostic factors for clinical outcomes and cartilage regeneration after the implantation of allogeneic human umbilical cord blood mesenchymal stem cell (hUCB-MSC) for treating large-sized cartilage defects with osteoarthritis. This study is a case-series with multiple subgroup analyses that divides the included patients into multiple subgroups based on various factors. Overall, 47 patients who underwent hUCB-MSC implantation were included. The patient-reported outcomes, magnetic resonance imaging (MRI), and second-look arthroscopy were used to assess the outcomes. Combined realignment surgery significantly correlated with clinical outcomes, particularly pain. No other factors significantly influenced the clinical outcomes in short-term period. Subgroups with large defect sizes or meniscal insufficiency showed significantly poor MRI and arthroscopy outcomes (MRI, P = 0.001, P = 0.001; arthroscopy, P = 0.032, P = 0.042). The logistic regression showed that patients with a 1 cm2 larger defect size were 1.91 times less likely to achieve favorable MRI outcomes (P = 0.017; odds ratio [OR], 1.91). Cut-off value to predict the poor outcome was >5.7 cm2 (area under the curve, 0.756). A cartilage defect size >5.7 cm2 was the major poor prognostic factor for cartilage regeneration on MRI (P = 0.010; OR, 17.46). If the postoperative alignment shifted by 1° opposite to the cartilage defect, it was 1.4 times more likely to achieve favorable MRI outcomes (P = 0.028; OR, 1.4). Combining realignment surgery showed a better prognosis for pain improvement. Cartilage defect size, meniscal function, and postoperative alignment are significant prognostic factors for cartilage regeneration. A cartilage defect size >5.7 cm2 was significantly related to poor cartilage regeneration.

Haploidentical donor peripheral blood stem cell transplantation using third-party cord blood compared with matched unrelated donor transplantation for patients with hematologic malignancies

Objectives: To assess the efficacy of cord blood-assisted haploid peripheral blood stem cell transplantation (haplo-cord-PBSCT) versus unrelated donor peripheral blood stem cell transplantation (UD-PBSCT) in the treatment of malignant hematological diseases. Methods: A retrospective analysis was performed on one hundred and four patients with malignant hematological diseases who underwent haplo-cord-PBSCT and fifty-two patients who underwent UD-PBSCT at Xiangya Hospital of Central South University between January 2016 and December 2021. Results: ①The median implantation time for neutrophils in the haplo-cord-PBSCT and UD-PBSCT groups was 13 (9-22) days and 13 (10-24) days, respectively (P=0.834), whereas the median implantation time for platelets was 15 (7-103) days and 14 (8-38) days, respectively (P=0.816). The cumulative implantation rate of neutrophils at 30 days after transplantation in the haplo-cord-PBSCT group and the UD-PBSCT group was 100% (P=0.314), and the cumulative platelet implantation rate at 100 days after transplantation was 95.2% (95% CI 88.3% - 98.1% ) and 100% (P=0.927), respectively. 30 days after transplantation, both groups of patients achieved complete donor chimerism, and no umbilical cord blood stem cells were implanted. ②The cumulative incidence rates of grade Ⅱ-Ⅳ acute GVHD within 100 days after transplantation in the haplo-cord-PBSCT group and the UD-PBSCT group were 29.1% (95% CI 20.1% -38.1% ) and 28.8% (95% CI 17.2% -41.6% (P=0.965), respectively. The cumulative incidence rates of grade Ⅲ/Ⅳ acute GVHD were 7.8% (95% CI 3.6% -14.0% ) and 9.6% (95% CI 3.5% -19.5% ) (P=0.725). The cumulative incidence rates of 2-year chronic GVHD in the haplo-cord-PBSCT group and the UD-PBSCT group were 45.3% (95% CI 36.1% -56.1% ) and 35.1% (95% CI 21.6% -44.1% ), respectively (P=0.237). The cumulative incidence rates of severe chronic GVHD at 2 years after transplantation were 13.6% (95% CI 7.6% -21.3% ) and 12.9% (95% CI 5.1% -24.3% ), respectively (P=0.840). ③The 2-year CIR after transplantation in the haplo-cord-PBSCT group and UD-PBSCT group were 12.8% (95% CI 7.0% -20.5% ) and 10.0% (95% CI 3.6% -20.2% ), respectively (P=0.341), and the NRM were 14.7% (95% CI 8.4% -22.6% ) and 16.2% (95% CI 7.4% -28.0% ), respectively (P=0.681). ④The 2-year OS rates in the haplo-cord-PBSCT and UD-PBSCT groups after transplantation were 82.2% (95% CI 74.8% -90.3% ) and 75.5% (95% CI 64.2% -88.7% ), respectively (P=0.276). The 2-year DFS rates were 69.9% (95% CI 61.2% -79.8% ) and 73.8% (95% CI 62.4% -87.3% ), respectively (P=0.551). The 2-year rates of GVHD-free/recurrence-free survival (GRFS) were 55.3% (95% CI 44.8% -64.8% ) and 64.7% (95% CI 52.8% -79.3% ), respectively (P=0.284) . Conclusion: The findings of this study indicate that haplo-cord-PBSCT and UD-PBSCT have comparable efficacy and safety in the treatment of malignant hematological diseases and can be used as an alternative treatment options.

Allogeneic umbilical cord blood-derived mesenchymal stem cell implantation versus microdrilling combined with high tibial osteotomy for cartilage regeneration

This study compared cartilage regeneration outcomes in knee osteoarthritis (OA) using allogeneic human umbilical cord blood-derived mesenchymal stem cell (hUCB-MSC) implantation and microdrilling with high tibial osteotomy (HTO). Fifty-four patients (60 knees) were included: 24 (27 knees) in the hUCB-MSC group and 30 (33 knees) in the microdrilling group. Both groups showed significant improvements in pain and functional scores at 6, 12, and 24 months compared to baseline. At 24 months, the hUCB-MSC group had significantly improved scores. Arthroscopic assessment at 12 months revealed better cartilage healing in the hUCB-MSC group. In subgroup analysis according to the defect site, hUCB-MSC implantation showed superior cartilage healing for anterior lesions. In conclusion, both treatments demonstrated effectiveness for medial OA. However, hUCB-MSC implantation had better patient-reported outcomes and cartilage regeneration than microdrilling. The study suggests promising approaches for cartilage restoration in large knee defects due to OA.

Modeling of solar UV-induced photodamage on the hair follicles in human skin organoids

Solar ultraviolet (sUV) exposure is known to cause skin damage. However, the pathological mechanisms of sUV on hair follicles have not been extensively explored. Here, we established a model of sUV-exposed skin and its appendages using human induced pluripotent stem cell-derived skin organoids with planar morphology containing hair follicles. Our model closely recapitulated several symptoms of photodamage, including skin barrier disruption, extracellular matrix degradation, and inflammatory response. Specifically, sUV induced structural damage and catagenic transition in hair follicles. As a potential therapeutic agent for hair follicles, we applied exosomes isolated from human umbilical cord blood-derived mesenchymal stem cells to sUV-exposed organoids. As a result, exosomes effectively alleviated inflammatory responses by inhibiting NF-κB activation, thereby suppressing structural damage and promoting hair follicle regeneration. Ultimately, our model provided a valuable platform to mimic skin diseases, particularly those involving hair follicles, and to evaluate the efficacy and underlying mechanisms of potential therapeutics.

Allogeneic NK cells induce monocyte-to-dendritic cell conversion, control tumor growth, and trigger a pro-inflammatory shift in patient-derived cultures of primary and metastatic colorectal cancer

IntroductionNatural killer (NK) cells are innate lymphocytes with a key role in the defense against tumors. Recently, allogeneic NK cell-based therapies have gained interest because of their ability to directly...

Umbilical Cord Blood Stem Cells As Third-Party Adjuvant Infusion in Human Leukocyte Antigen Antibody-Positive Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Introduction: The presence of human leukocyte antigen (HLA) antibodies, even if not donor-specific antibodies (DSA), is an important risk factor for graft failure (GF) or poor graft function (PGF) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, there is no ideal strategy for eradicating or descending HLA antibodies in this population. In the present study, we investigated the efficacy and safety of unrelated umbilical cord blood stem cells (CBCs) as a third-party adjuvant infusion in patients with HLA antibodies undergoing allo-HSCT. Methods:Patients undergoing allo-HSCT from July 2017 to June 2021 were enrolled in this study and HLA antibodies were routinely tested before transplantation. Patients were divided into three groups: Group A (patients with positive/weak positive HLA antibodies and with CBCs infusion), Group B (patients with HLA antibodies positive/weak positive without CBCs infusion), and Group C (patients without HLA antibody nor CBCs infusion). Single unrelated CBCs (HLA4/6 or more compatible ) were infused four hours before donor stem cells. The clinical characteristics of the patients and the paired donors were collected. The occurrence of granulocyte and platelet engraftment time, graft-versus-host disease (GVHD), cytomegalovirus (CMV), Epstein-Barr virus (EBV) reactivation, one-year and two-year relapse-free survival (RFS), transplantation-related mortality (TRM), and overall survival (OS) for all three groups of patients were also analyzed in this study. Results:A total of 90 patients were included in this study (17 in group A, 36 in group B, and 37 in group C). The baseline clinical characteristics of the patients were presented in Table 1. No obvious adverse effects were observed in the process of CBCs infusion. All the patients achieved 100% donor chimerism without CBCs engraftment. There were no significant differences in granulocyte and platelet engraftment time between the three groups. Two patients in Group A and C, and 3 patients in Group B developed PGF, respectively. There were no significant differences in the incidence and grades of acute or chronic GVHD among the three groups ( Figure A, B). In the first 3 months after allo-HSCT, the incidence of EBV reactivation was higher in patients in Group B than that in Group A and C, respectively ( Figure C). There were no significant differences in the CMV reactivation between the three groups in the first 3 months after transplantation ( Figure D). Patients in Group A and B both had lower 1-year RFS and higher 1-year TRM, compared with Group C, respectively ( Figure E, F). However, there were no significant statistical differences in 2-year RFS and TRM between the three groups. Although patients in Group A had longer 2-year OS than that in Group B, there were no significant differences between the two groups: Group A vs Group B (76.5% vs 55.6%, P = 0.194), Group B vs Group C (55.6% vs 85.5%, P &amp;lt; 0.05)( Figure G). A multifactorial Cox regression risk model was established to explore the risk factors affecting OS and suggested that patients' pre-transplantation status (with active malignant disease or minimal residual disease positive) and HLA antibodies pre-transplant were the most independent risk factors for OS (HR = 4.380, 95% CI = 1.544-12.427, P&amp;lt;0.05; HR = 0.196, 95% CI = 0.065-0.587, P&amp;lt;0.05). Conclusions: Patients with positive/weak positive HLA antibodies receiving CBCs as a third-party adjunctive infusion were safe, and there was a benefit in the incidence of EBV reactivation compared to such a population without CBCs infusion. The patients with negative HLA antibodies had higher 1-year RFS and lower 1-year TRM than those with positive/weakly positive HLA antibodies regardless CBCs infusion. Due to the small number of included cases, we will expand the sample number to further validate our results in the future.

Developing a Multichannel Bioreactor with a Collagen Scaffold, ECM, and Cryoprecipitate to Significantly Produce Platelets from Umbilical Cord Blood Stem Cells

Background: Platelets play a key role in the treatment of thrombocytopenia. Nowadays, platelets (PLTs) are only obtained through blood donation. However, due to the limitations in their preparation and storage, they are produced in laboratories, especially through bioreactors that convert megakaryocytes from stem cells into large-scale injectable PLTs.&#x0D; Materials and Methods: In this study, the CD34 cells isolated from cord blood were differentiated into megakaryocytes. A 6-chamber bioreactor with a two-layer collagen scaffold, several ECM factors, and human cryoprecipitate were used to simulate the structure of the bone marrow. After the addition of megakaryocytes to the scaffold, PLTs were produced due to the flow pressure and the interaction between the scaffold structure and the ECM factors.&#x0D; Results: CD41 + cells were expanded 100 times as much as CD34 + cord blood stem cells. The mean PLT release from one megakaryocyte in the pure collagen scaffold was 17.42 PLTs. Once fibrin, fibronectin, hyaluronic acid, and cryoprecipitates were added to collagen, the mean PLT release was 21.4, 22.4, 23.9, and 27.37, respectively. With the simultaneous addition of three factors to collagen (CFFH) and then four factors (CFFHC), the number of PLTs reached 30.52 and then 34.&#x0D; Conclusion: Functional PLTs can be produced on a large scale with a multi-chamber bioreactor using a combination of ECM and cryoprecipitate with collagen scaffolding.

Human umbilical cord blood-derived mesenchymal stem cells therapy for cerebral infarction in animal model: A meta-analysis

Aim: Cerebral infarction (CI) is a serious cerebrovascular infarction disease. In recent years, the use of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) has received attention as a new alternative for treating CI in animal model. This systematic review evaluated the efficacy and safety of hUCB-MSCs, using as a treatment in improving functional recovery of CI in animal model. Methods: Electronic databases through July 5, 2023 were searched to identify relevant studies that controlled hUCB-MSCs treatment studies focusing on CI in animal model. We independently selected and assessed the relevant studies. Results: 27 studies that fulfilled the inclusion criteria were included. Compared with control group, significant beneficial effects were observed in hUCB-MSCs group regarding the neurological deficit scores (mean difference [MD]: −1.57, 95% confidential interval [CI]: −2.06, −1.08, P&lt;0.00001), infarct size (MD: −2.82, 95% CI: −4.14, −1.49, P&lt;0.0001).

A Study to Assess the Effectiveness of Structured Teaching Proframme on Knowledge regarding Umbilical Cord Blood Stem Cell Therapy among III Year B.SC. Nursing students in selected Nursing College at Rajkot

A study to assess the effectiveness of structured teaching programme on knowledge regarding umbilical cord blood stem cell therapy among III year B.Sc. Nursing students in selected nursing college, at Rajkot. The objectives of the study was (a) To Assess the existing knowledge regarding umbilical cord blood stem cell therapy among III-year B.Sc. Nursing Students in selected Nursing College at Rajkot. (b) To Assess the effectiveness of Structured teaching programmed (STP) on knowledge regarding umbilical cord blood stem cell therapy among III-year B.Sc. Nursing Students in selected Nursing College at Rajkot. (c) To find out Association between their selected Demographic variables and their pre-test level of knowledge regarding umbilical cord blood stem cell therapy. The research design adopted was One Group Pre-test and Post-test design. The study had been conducted in selected college at Rajkot. Non probability sampling technique had been adopted to select the desired samples. The sample size was 40. As a part of intervention, a STP on knowledge regarding umbilical cord blood stem cell therapy was provided to students for 30 minutes and the data was collected by structured interview with set of questionnaires that is administered to assess the level of knowledge regarding umbilical cord blood stem cell therapy among III year B.Sc. Nursing students in selected nursing college, at Rajkot. The data were analyzed by using both descriptive and inferential statistical method paired “t” test was used to evaluating the effectiveness of STP on knowledge regarding umbilical cord blood stem cell therapy. The obtained value 20.693, which shows highly significant at the level of p&lt;0.001. There is significant association between demographic variables such as gender, types of family with pretest level of knowledge on umbilical cord blood stem cell therapy. The study concluded that the STP was effectiveness in improving of knowledge regarding umbilical cord blood stem cell therapy.

A Study to Assess the Effectiveness of Structured Teaching Proframme on Knowledge regarding Umbilical Cord Blood Stem Cell Therapy among III Year B.SC. Nursing students in selected Nursing College at Rajkot

A study to assess the effectiveness of structured teaching programme on knowledge regarding umbilical cord blood stem cell therapy among III year B.Sc. Nursing students in selected nursing college, at Rajkot. The objectives of the study was (a) To Assess the existing knowledge regarding umbilical cord blood stem cell therapy among III-year B.Sc. Nursing Students in selected Nursing College at Rajkot. (b) To Assess the effectiveness of Structured teaching programmed (STP) on knowledge regarding umbilical cord blood stem cell therapy among III-year B.Sc. Nursing Students in selected Nursing College at Rajkot. (c) To find out Association between their selected Demographic variables and their pre-test level of knowledge regarding umbilical cord blood stem cell therapy. The research design adopted was One Group Pre-test and Post-test design. The study had been conducted in selected college at Rajkot. Non probability sampling technique had been adopted to select the desired samples. The sample size was 40. As a part of intervention, a STP on knowledge regarding umbilical cord blood stem cell therapy was provided to students for 30 minutes and the data was collected by structured interview with set of questionnaires that is administered to assess the level of knowledge regarding umbilical cord blood stem cell therapy among III year B.Sc. Nursing students in selected nursing college, at Rajkot. The data were analyzed by using both descriptive and inferential statistical method paired “t” test was used to evaluating the effectiveness of STP on knowledge regarding umbilical cord blood stem cell therapy. The obtained value 20.693, which shows highly significant at the level of p&lt;0.001. There is significant association between demographic variables such as gender, types of family with pretest level of knowledge on umbilical cord blood stem cell therapy. The study concluded that the STP was effectiveness in improving of knowledge regarding umbilical cord blood stem cell therapy.

Tacrolimus Improves Therapeutic Efficacy of Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Diabetic Retinopathy by Suppressing DRP1-Mediated Mitochondrial Fission.

Diabetic retinopathy (DR) is a leading cause of blindness in diabetic patients. Umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) are emerging as a promising new drug for degenerative disease associated with diabetes. Recent studies have shown that high glucose-increased excessive calcium levels are a major risk factor for mitochondrial reactive oxygen species (mtROS) accumulation and apoptosis. This study aimed to investigate the role of high glucose-induced NFATC1 signaling in mitochondrial oxidative stress-stimulated apoptosis and the effect of tacrolimus on the therapeutic efficacy of subconjunctival transplantation of UCB-MSCs in a DR rat model. High glucose increased mtROS and cleaved caspase-9 expression in UCB-MSCs. High glucose conditions increased O-GlcNAcylated protein expression and nuclear translocation of NFATC1. Tacrolimus pretreatment recovered high glucose-induced mtROS levels and apoptosis. In the DR rat model, subconjunctival transplantation of tacrolimus-pretreated MSCs improved retinal vessel formation, retinal function, and uveitis. In high glucose conditions, tacrolimus pretreatment reduced protein and mRNA expression levels of DRP1 and inhibited mitochondrial fission. In conclusion, we demonstrated that high glucose-induced O-GlcNAcylation activates NFATC1 signaling, which is important for DRP1-mediated mitochondrial fission and mitochondrial apoptosis. Finally, we proposed NFATC1 suppression by tacrolimus as a promising therapeutic strategy to improve the therapeutic efficacy of UCB-MSC transplantation for DR treatment.

Abstract 4 Excellent Event-Free-Survival and Immunoglobulin Independence for Patients with Severe Combined Immunodeficiency Transplanted with Umbilical Cord Blood Stem Cells

Abstract Introduction An HLA matched related donor (MRD) is the preferred donor source for performing a hematopoietic stem cell transplant (HSCT) in patients with severe combined immunodeficiency (SCID) (Heimall 2017). However, many patients lack an MRD and thus an alternative donor, must be used. In these situations, an umbilical cord blood (UCB) represents a promising stem cell source (Gragert 2014, Martinez 2022). Objectives The primary outcome of interest was one-year event free survival (EFS) and the secondary outcome was time to immunoglobulin therapy independence based on donor source. Methods All patients diagnosed with SCID who underwent HSCT at Texas Children’s Hospital from 2003 to 2021 were included. EFS was defined as survival 365 days post-transplant without additional transplant, stem cell “top-off”, or donor lymphocyte infusion. The date of last immunoglobulin infusion was recorded to track time to immunoglobulin therapy independence. Results A total of 67 patients were included in the cohort. One-year EFS was 74.25% for all patients using the Kaplan-Meier method. When stratified by donor/stem cell source, EFS was 88.94% for UCB, 72.92% for MRD, 60.00% for URD, and 41.67% for haplo. There was statistical significance in EFS between URD UCB and the haploidentical group (p = 0.0006). The median time to IVIG independence was 8.6 months for all patients, 7.3 months for UCB, 23.4 months for URD, 26.6 months for haplo, and 32.5 months for MRD. When stratified by donor/stem cell source, cumulative incidence analysis showed UCB patients achieved Immunoglobulin independence earlier when compared to all other groups (UCB vs haplo p = 0.0335, UCB vs MRD p = 0.0012, UCB vs URD p = 0.0488). Discussion This single-center cohort of 67 patients demonstrates excellent survival for SCID patients undergoing HSCT, confirming prior studies (Pai 2014, Heimall 2017). EFS was highest in patients treated with an UCBT. In our analysis of immune reconstitution, we found that SCID patients transplanted with UCB, had a significantly shorter time to IVIG independence compared to other stem cell donors/sources. Given the high survival of UCB patients and this robust immune reconstitution, UCB may represent the best alternative stem cell source for SCID patients without a MRD option.

Fresh Umbilical Cord Blood-A Source of Multipotent Stem Cells, Collection, Banking, Cryopreservation, and Ethical Concerns.

Umbilical cord blood (UCB) is a rich source of hematopoietic cells that can be used to replace bone marrow components. Many blood disorders and systemic illnesses are increasingly being treated with stem cells as regenerative medical therapy. Presently, collected blood has been stored in either public or private banks for allogenic or autologous transplantation. Using a specific keyword, we used the English language to search for relevant articles in SCOPUS and PubMed databases over time frame. According to our review, Asian countries are increasingly using UCB preservation for future use as regenerative medicine, and existing studies indicate that this trend will continue. This recent literature review explains the methodology of UCB collection, banking, and cryopreservation for future clinical use. Between 2010 and 2022, 10,054 UCB stem cell samples were effectively cryopreserved. Furthermore, we have discussed using Mesenchymal Stem Cells (MSCs) as transplant medicine, and its clinical applications. It is essential for healthcare personnel, particularly those working in labor rooms, to comprehend the protocols for collecting, transporting, and storing UCB. This review aims to provide a glimpse of the details about the UCB collection and banking processes, its benefits, and the use of UCB-derived stem cells in clinical practice, as well as the ethical concerns associated with UCB, all of which are important for healthcare professionals, particularly those working in maternity wards; namely, the obstetrician, neonatologist, and anyone involved in perinatal care. This article also highlights the practical and ethical concerns associated with private UCB banks, and the existence of public banks. UCB may continue to grow to assist healthcare teams worldwide in treating various metabolic, hematological, and immunodeficiency disorders.

HHV-6B infection after umbilical cord blood stem cell transplantation with pruritus as the first symptom.

HHV-6B infection after umbilical cord blood stem cell transplantation with pruritus as the first symptom.

Human umbilical cord blood-derived mesenchymal stem cells restored hematopoiesis by improving radiation induced bone marrow niche remodeling in rats

BackgroundFunctional hematopoiesis is governed by the bone marrow (BM) niche, which is compromised by radiotherapy, leading to radiation induced BM failure. The aim of this study was to demonstrate the radiation induced pathological remodeling of the niche and the efficacy of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in restoring hematopoiesis via improvement of the niche. MethodsThirty male Wistar rats were equally assigned to three groups: control (CON), irradiated (IR), and IR+hUCB‐MSCs. Biochemical, histopathological and immunohistochemical analyses were performed to detect collagen type III and IV, Aquaporin 1+ sinusoidal endothelial cells and immature hematopoietic cells, CD11c+ dendritic cells, Iba1+ macrophages, CD9+ megakaryocytes, Sca-1+, cKit+, CD133 and N-cadherin+ hematopoietic stem and progenitor cells, CD20+, Gr1+ mature hematopoietic cells, in addition to ki67+ proliferation, Bcl-2+ anti-apoptotic, caspase-3+ apoptotic, TNF-α+ inflammatory cells. Histoplanimetry data were statistically analyzed using the one-way analysis of variance followed by the post hoc Duncan’s test. Moreover, Pearson’s correlation was used to assess the correlation between various parameters. ResultsIn comparison to the IR group, the IR+hUCB-MSCs group showed restored cell populations and extracellular collagen components of the BM niche with significant increase in hematopoietic stem, progenitor, mature and proliferating cells, and a considerable decrease in apoptotic and inflammatory cells. Furthermore, highly significant correlations between BM niche and blood biochemical, histopathological, and immunohistochemical parameters were observed. ConclusionhUCB-MSCs restored functional hematopoiesis through amelioration of the BM niche components via reduction of oxidative stress, DNA damage, inflammation, and apoptosis with upregulation of cellular proliferation.