Umbilical Cord Blood Cells Research Articles

Allogenic umbilical cord blood-derived mesenchymal stromal cell implantation was superior to bone marrow aspirate concentrate augmentation for cartilage regeneration despite similar clinical outcomes.

The aim of this study was to compare clinical and second-look arthroscopic outcomes between bone marrow aspirate concentrate (BMAC) augmentation and human umbilical cord blood-derived mesenchymal stromal cell (hUCB-MSC) implantation in high tibial osteotomy (HTO) for medial compartmental knee osteoarthritis and identify the relationship between articular cartilage regeneration and HTO outcomes. A total of 176 patients who underwent HTO combined with a BMAC or hUCB-MSC procedure for medial compartment osteoarthritis (Kellgren-Lawrence grade 3) between June 2014 and September 2018 with a minimum follow-up of 2years were reviewed. After HTO, multiple holes were drilled at cartilage defect sites of the medial femoral condyle (MFC), and then prepared BMAC or hUCB-MSCs in combination with scaffolds were implanted in the MFC lesions. After propensity score matching based on sex, age, body mass index, and lesion size, 55 patients in each of the BMAC and hUCB-MSC groups were successfully matched. Second-look arthroscopic findings were assessed according to the International Cartilage Repair Society (ICRS) Cartilage Repair Assessment (CRA) grading system and Koshino staging system. Clinical outcomes were evaluated using the International Knee Documentation Committee (IKDC), Knee Injury and Osteoarthritis Outcome Score (KOOS), Short-Form 36 (SF-36), and Tegner activity scores. At a mean follow-up of 33months, clinical outcomes including IKDC, KOOS, SF-36, and Tegner activity scores were significantly improved in both groups (p < 0.001); however, there were no differences between the two groups. Second-look arthroscopy showed better healing of regenerated cartilage in the hUCB-MSC group (Grade I [4 cases, 9.1%]; Grade II [30 cases, 68.2%]; Grade III [11 cases, 22.7%]) than in the BMAC group (Grade I [1 case, 2.7%]; Grade II [20 cases, 54.1%]; Grade III [11 cases, 29.7%]; Grade IV [5 cases, 13.5%]) according to the ICRS CRA grading system (p = 0.040). There was no significant intergroup difference in terms of defect coverage based on the Koshino staging system (p = 0.057). Moreover, ICRS CRA grades at second-look arthroscopy were significantly correlated with clinical outcomes (r = -0.337; p = 0.002). There were no significant differences in the clinical outcomes between the two groups. Both treatments provided similar, reliable outcomes in terms of pain relief, functional scores, and quality of life at a mean follow-up of 33months. However, hUCB-MSC implantation was more effective than BMAC augmentation for articular cartilage regeneration.

Influence of maternal and infant factors on CD34+ hematopoietic stem/progenitor cells in umbilical cord blood

OBJECTIVE To study the association of different maternal and infant factors with the number of total nucleated cells and CD34+ hematopoietic stem/progenitor cells in umbilical cord blood, and to provide a reference for reasonable selection of umbilical cord blood in the cord blood bank. METHODS A prospective study was performed for the umbilical cord blood samples of 130 neonates who were born in Dalian Women and Children's Medical Center from June 2019 to January 2020, with a male/female ratio of 1:1. Related perinatal information was collected, including maternal age and blood type, presence or absence of gestational diabetes or gestational hypertension, pregnancy method, mode of delivery, singleton pregnancy/twin pregnancy, body weight and sex of neonates, Apgar score after birth, and the conditions of placenta, amniotic fluid, and umbilical cord. RESULTS The neonates were grouped according to maternal blood type, gestational diabetes, gestational hypertension, pregnancy method, mode of delivery, singleton pregnancy/ twin pregnancy, sex of neonates, Apgar score after birth, placental morphology, meconium staining of amniotic fluid, and umbilical cord around the neck. The comparison between groups showed no significant differences in the numbers of total nucleated cells and CD34+ cells in umbilical cord blood (P > 0.05). Maternal age and neonatal body weight were not correlated with the number of total nucleated cells in umbilical cord blood (P > 0.05), and neonatal body weight was not correlated with the number of CD34+ cells (P > 0.05), while maternal age was positively correlated with the number of CD34+ cells (P < 0.05). CONCLUSIONS The number of CD34+ cells in umbilical cord blood increases with the increase in maternal age, and therefore, umbilical cord blood in the cord blood bank may be selected based on maternal age.

Allogeneic umbilical cord blood cell therapy for children with autism: safety and efficacy of the method

To evaluate effectiveness and safety of umbilical cord blood cells (UCBC) in children with ASD. The study comprised 13 boys and 2 girls, mean age 7.0±0.5 years (test group), and 9 boys and 1 girl, mean age 6.0±1.3 years (control group) diagnosed with autism or autistic syndrome. UCBC were infused intravenously in a single dose of 250±20 million cells, four times at 14±3-day intervals. Dynamics of cognitive functions were assessed with WISC subscales, questionnaire Skvortsov Developmental Profile Survey and brainstem auditory evoked potentials (BAEPs) conducted before therapy and six months after the first injection. The dynamic of autistic symptoms was explored with CASD and ATEC questionnaires, fulfilled at the start of the study, 3 and 6 months later (test group) or at the start of the study, and 6 months later (control group). UCBC was well tolerated and caused no appreciable adverse effects. Observation revealed improvement in cognitive functioning and alleviation of autistic symptoms in patients of the test group six months after the first UCBC injection. Positive dynamics were more noticeable in the test group than in the control group receiving standard therapy. The use of UCBC is safe and might be effective in the complex therapy of autism.

Cell-based treatment for perinatal hypoxic-ischemic encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) is a major cause of acute neonatal brain injury and can lead to disabling long-term neurological complications. Treatment for HIE is limited to supportive care and hypothermia within 6 h injury which is reserved for full-term infants. Preclinical studies suggest the potential for cell-based therapies as effective treatments for HIE. Some clinical trials using umbilical cord blood cells, placenta-derived stem cells, mesenchymal stem cells (MSCs), and others have yielded promising results though more studies are needed to optimize protocols and multi-center trials are needed to prove safety and efficacy. To date, the therapeutic effects of most cell-based therapies are hypothesized to stem from the bystander effect of donor cells. Transplantation of stem cells attenuate the aberrant inflammation cascade following HIE and provide a more ideal environment for endogenous neurogenesis and repair. Recently, a subset of MSCs, the multilineage-differentiating stress-enduring (Muse) cells have shown to treat HIE and other models of neurologic diseases by replacing dead or ischemic cells and have reached clinical trials. In this review, we examine the different cell sources used in clinical trials and evaluate the underlying mechanism behind their therapeutic effects. Three databases–PubMed, Web of Science, and ClinicalTrials.gov–were used to review preclinical and clinical experimental treatments for HIE.

Feasibility of Umbilical Cord Blood Collection in Neonates at Risk of Brain Damage—A Step Toward Autologous Cell Therapy for a High-risk Population

Evidence for umbilical cord blood (UCB) cell therapies as a potential intervention for neurological diseases is emerging. To date, most existing trials worked with allogenic cells, as the collection of autologous UCB from high-risk patients is challenging. In obstetric emergencies the collection cannot be planned. In preterm infants, late cord clamping and anatomic conditions may reduce the availability. The aim of the present study was to assess the feasibility of UCB collection in neonates at increased risk of brain damage. Infants from four high-risk groups were included: newborns with perinatal hypoxemia, gestational age (GA) ≤30 + 0 weeks and/or birthweight <1,500 g, intrauterine growth restriction (IUGR), or monochorionic twins with twin-to-twin transfusion syndrome (TTTS). Feasibility of collection, quantity and quality of obtained UCB [total nucleated cell count (TNC), volume, sterility, and cell viability], and neonatal outcome were assessed. UCB collection was successful in 141 of 177 enrolled patients (hypoxemia n = 10; GA ≤30 + 0 weeks n = 54; IUGR n = 71; TTTS n = 6). Twenty-six cases were missed. The amount of missed cases per month declined over the time. Volume of collected UCB ranged widely (median: 24.5 ml, range: 5.0–102 ml) and contained a median of 0.77 × 108 TNC (range: 0.01–13.0 × 108). TNC and UCB volume correlated significantly with GA. A total of 10.7% (19/177) of included neonates developed brain lesions. To conclude, collection of UCB in neonates at high risk of brain damage is feasible with a multidisciplinary approach and intensive training. High prevalence of brain damage makes UCB collection worthwhile. Collected autologous UCB from mature neonates harbors a sufficient cell count for potential therapy. However, quality and quantity of obtained UCB are critical for potential therapy in preterm infants. Therefore, for extremely preterm infants alternative cell sources such as UCB tissue should be investigated for autologous treatment options because of the low yield of UCB.

Umbilical Cord Tissue as a Source of Young Cells for the Derivation of Induced Pluripotent Stem Cells Using Non-Integrating Episomal Vectors and Feeder-Free Conditions.

The clinical application of induced pluripotent stem cells (iPSC) needs to balance the use of an autologous source that would be a perfect match for the patient against any safety or efficacy issues that might arise with using cells from an older patient or donor. Drs. Takahashi and Yamanaka and the Office of Cellular and Tissue-based Products (PMDA), Japan, have had concerns over the existence of accumulated DNA mutations in the cells of older donors and the possibility of long-term negative effects. To mitigate the risk, they have chosen to partner with the Umbilical Cord (UC) banks in Japan to source allogeneic-matched donor cells. Production of iPSCs from UC blood cells (UCB) has been successful; however, reprogramming blood cells requires cell enrichment with columns or flow cytometry and specialized growth media. These requirements add to the cost of production and increase the manipulation of the cells, which complicates the regulatory approval process. Alternatively, umbilical cord tissue mesenchymal stromal cells (CT-MSCs) have the same advantage as UCB cells of being a source of young donor cells. Crucially, CT-MSCs are easier and less expensive to harvest and grow compared to UCB cells. Here, we demonstrate that CT-MSCs can be easily isolated without expensive enzymatic treatment or columns and reprogramed well using episomal vectors, which allow for the removal of the reprogramming factors after a few passages. Together the data indicates that CT-MSCs are a viable source of donor cells for the production of clinical-grade, patient matched iPSCs.

Modulators of histone demethylase JMJD1C selectively target leukemic stem cells.

Leukemic stem cells (LSCs) comprise a very rare cell population that results in the development of acute myeloid leukemia. The selective targeting of drivers in LSCs with small molecule inhibitors holds promise for treatment of acute myeloid leukemia. Recently, we reported the identification of inhibitors of the histone lysine demethylase JMJD1C that preferentially kill MLL rearranged acute leukemia cells. Here, we report the identification of jumonji domain modulator #7 (JDM-7). Surface plasmon resonance analysis showed that JDM-7 binds to JMJD1C and its family homolog JMJD1B. JDM-7 did not significantly suppress cell proliferation in liquid cell culture at higher doses, although it led to a significant decrease in semi-solid colony formation experiments at lower concentrations. Moreover, low doses of JDM-7 did not suppress the proliferation of erythroid progenitor cells. We identified that JDM-7 downregulates the LSC self-renewal gene HOXA9 in leukemia cells. We further found that the structure of JDM-7 is similar to that of tadalafil, a drug approved by the US Food and Drug Administration. Molecular docking and surface plasmon resonance analysis showed that tadalafil binds to JMJD1C. Moreover, similar to JDM-7, tadalafil suppressed colony formation of leukemia cells in semi-solid cell culture at a concentration that did not affect primary umbilical cord blood cells. In summary, we have identified JDM-7 and tadalafil as potential JMJD1C modulators that selectively inhibit the growth of LSCs.

On the current status and prospects for the development of clinically significant cell technologies: do not interfere!

The material contains a conversation between doctors-developers, administrators and clinicians on the introduction of banking of umbilical cord blood and umbilical cord cells into healthcare practice. The data on clinical studies conducted in the world to assess the safety and effectiveness of the use of umbilical cord blood cells are presented.

Validation of the single-platform ISHAGE protocol for enumeration of CD34+ hematopoietic stem cells in umbilical cord blood in a Brazilian center

BackgroundThis study aims to validate the single-platform method for enumeration of CD34+ cells, by comparing the performance of two different commercial kits, as well as to evaluate the efficiency of the AccuriTM C6 cytometer in providing direct counts of absolute cell numbers. MethodWe evaluated 20 samples from umbilical cord blood (UCB), comparing the two different methodologies for enumeration of CD34+ cells: single and dual-platform. For the assessment of the single-platform, Procount and SCE kits were used, both of which use fluorescent beads as a counting reference to obtain absolute CD34+ cells numbers. Moreover, after the acquisition of samples in flow cytometer AccuriTM C6, following the protocol established for each kit, the number of CD34+ cells was recalculated, considering the cell count provided by the AccuriTM C6. Main ResultsIn our analysis, the results showed a strong correlation between the number of CD34+ cells/μL (r2=0.77) when comparing the SCE kit and the current dual-platform method. On the other hand, the comparison between Procount kit and dual-platform results showed a moderate correlation for the number of CD34+/μL cells (r2=0.64). ConclusionOur results showed that the AccuriTM C6 flow cytometer can be used safely, applying both the dual and single platform analysis strategy. Considering the ISHAGE protocol-based single-platform approach, as the most appropriate methodology for CD34+ cells enumeration, our results demonstrated that the SCE kit has great potential for national standardization of UCB samples analysis methodology.

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 haematopoietic 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), 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.

Potentiation of cord blood cell therapy with erythropoietin for children with CP: a 2\u2009\xd7\u20092 factorial randomized placebo-controlled trial

BackgroundConcomitant administration of allogeneic umbilical cord blood (UCB) infusion and erythropoietin (EPO) showed therapeutic efficacy in children with cerebral palsy (CP). However, no clinical studies have investigated the effects of UCB and EPO combination therapy using a 2 × 2 four-arm factorial blinded design with four arms. This randomized placebo-controlled trial aimed to identify the synergistic and individual efficacies of UCB cell and EPO for the treatment of CP.MethodsChildren diagnosed with CP were randomly segregated into four groups: (A) UCB+EPO, (B) UCB+placebo EPO, (C) placebo UCB+EPO, and (D) placebo UCB+placebo EPO. Based on the UCB unit selection criteria of matching for ≥ 4/6 of human leukocyte antigen (HLA)-A, -B, and DRB1 and total nucleated cell (TNC) number of ≥ 3 × 107/kg, allogeneic UCB was intravenously infused and 500 IU/kg human recombinant EPO was administered six times. Functional measurements, brain imaging studies, and electroencephalography were performed from baseline until 12 months post-treatment. Furthermore, adverse events were closely monitored.ResultsEighty-eight of 92 children enrolled (3.05 ± 1.22 years) completed the study. Change in gross motor performance measure (GMPM) was greater in group A than in group D at 1 month (△2.30 vs. △0.71, P = 0.025) and 12 months (△6.85 vs. △2.34, P = 0.018) post-treatment. GMPM change ratios were calculated to adjust motor function at the baseline. Group A showed a larger improvement in the GMPM change ratio at 1 month and 12 months post-treatment than group D. At 12 months post-treatment, the GMPM change ratios were in the order of groups A, B, C, and D. These results indicate synergistic effect of UCB and EPO combination better than each single therapy. In diffusion tensor imaging, the change ratio of fractional anisotropy at spinothalamic radiation was higher in group A than group D in subgroup of age ≥ 3 years. Additionally, higher TNC and more HLA-matched UCB units led to better gross motor outcomes in group A. Adverse events remained unchanged upon UCB or EPO administration.ConclusionsThese results indicate that the efficacy of allogeneic UCB cell could be potentiated by EPO for neurological recovery in children with CP without harmful effects.Trial registrationClinicalTrials.gov, NCT01991145, registered 25 November 2013.

T cell Tolerance in Early Life.

T cell-mediated immune tolerance is a state of unresponsiveness of T cells towards specific self or non-self antigens. This is particularly essential during prenatal/neonatal period when T cells are exposed to dramatically changing environment and required to avoid rejection of maternal antigens, limit autoimmune responses, tolerate inert environmental and food antigens and antigens from non-harmful commensal microorganisms, promote maturation of mucosal barrier function, yet mount an appropriate response to pathogenic microorganisms. The cell-intrinsic and cell extrinsic mechanisms promote the generation of prenatal/neonatal T cells with distinct features to meet the complex and dynamic need of tolerance during this period. Reduced exposure or impaired tolerance in early life may have significant impact on allergic or autoimmune diseases in adult life. The uniqueness of conventional and regulatory T cells in human umbilical cord blood (UCB) may also provide certain advantages in UCB transplantation for hematological disorders.

Umbilical cord blood cells for the treatment of preterm white matter injury: Potential effects and treatment options.

Preterm birth is a global public health problem. A large number of preterm infants survive with preterm white matter injury (PWMI), which leads to neurological deficits, and has multifaceted etiology, clinical course, monitoring, and outcomes. The principal upstream insults leading to PWMI initiation are hypoxia-ischemia and infection and/or inflammation and the key target cells are late oligodendrocyte precursor cells. Current PWMI treatments are mainly supportive, and thus have little effect in terms of protecting the immature brain or repairing injury to improve long-term outcomes. Umbilical cord blood (UCB) cells comprise abundant immunomodulatory and stem cells, which have the potential to reduce brain injury, mainly due to anti-inflammatory and immunomodulatory mechanisms, and also through their release of neurotrophic or growth factors to promote endogenous neurogenesis. In this review, we briefly summarize PWMI pathogenesis and pathophysiology, and the specific properties of different cell types in UCB. We further explore the potential mechanism by which UCB can be used to treat PWMI, and discuss the advantages of and potential issues related to UCB cell therapy. Finally, we suggest potential future studies of UCB cell therapy in preterm infants.

Control of Fetal Hemoglobin Levels By NFI Transcription Factors

Sickle cell disease and some forms of b-thalassemia are disorders, which can be improved by therapies that elevate HbF, the fetal form of hemoglobin. It is currently thought that in adult type erythroid cells, silencing of the fetal type b-globin-like genes HBG1 and HBG2 is accomplished predominantly by two major transcription factors: BCL11A and ZBTB7A. However, it is unknown whether there are additional transcription factors that contribute to the repression of the HBG1/2 genes. Here, using a DNA-binding domain focused CRISPR-Cas9 screening approach, we identified NFIA as a novel regulator of HbF expression. NFIA belongs to the NFI transcription factor family, which is composed of NFIA, NFIB, NFIC and NFIX. NFIA and NFIX are the predominantly expressed forms in human erythroid cells, and their expression is higher in adult erythroblast cells when compared to fetal erythroid cells. CRISPR-Cas9 mediated disruption of NFIA in an immortalized human umbilical cord blood-derived erythroid progenitor cell line 2 (HUDEP2) or CD34+ hematopoietic stem and progenitor cell-derived primary erythroblast cells led to a modest reactivation of HBG1/2 mRNA expression, whereas disruption of NFIX had little effect. However, combined NFIA and NFIX disruption produced a substantial increase in HBG1/2 expression, suggesting that these factors function in a partially redundant manner. ChIP-seq and RNA-seq studies showed that NFIA and NFIX have comparable chromatin binding and activity profiles in human erythroid cells. ChIP-seq failed to detect NFI protein occupancy at or near the HBG1/2 genes. However, given the known difficulty in detecting repressor molecules by ChIP at the silent HBG1/2 genes [Martyn et al., Nature Genetics 2018; Liu et al., Cell 2018], we tested a direct involvement of NFI proteins by disrupting putative NFI binding sites near the HBG1/2 genes. Perturbation of one such NFI motif residing upstream of the transcription start site in the HBG1/2 promoters both in HUDEP2 and primary human erythroid cells markedly increased HBG1/2 mRNA levels, comparable to those achieved by combined disruption of NFIA and NFIX. Mutation of another putative NFI motif within intron1 in the HBG1/2 gene also significantly raised HbF levels. While these results implicate NFI proteins in the direct silencing of the HBG1/2 genes, the identity of the bound factors at the NFI motifs remains to be established. Studies are currently ongoing that use alternative approaches such as Cleavage Under Target &amp; Release Using Nuclease (CUT &amp; RUN) to map the chromatin occupancy of NFI factors at the HBG1/2 genomic region. We will also discuss results from ongoing studies of NFI factors in NBSGW mice models. In sum, we uncovered NFI transcription factors as a novel HbF regulator suggesting that the silencing of HbF involves a transcription factor network that is more complex than previously appreciated. Disclosures Weiss: Rubius Inc.: Consultancy, Current equity holder in private company; Cellarity Inc.: Consultancy, Current equity holder in private company; Novartis: Consultancy, Current equity holder in private company; Esperion Therapeutics: Consultancy, Current equity holder in private company; Beam Therapeuticcs: Consultancy, Current equity holder in private company. Blobel:Pfizer: Research Funding; Fulcrum Therapeutics: Consultancy.

Telomere length in newborns is associated with exposure to low levels of air pollution during pregnancy

Telomere length (TL) is a biomarker of biological aging that may be affected by prenatal exposure to air pollution. The aim of this study was to assess the association between prenatal exposure to air pollution and TL in maternal blood cells (leukocytes), placenta and umbilical cord blood cells, sampled immediately after birth in 296 Danish mother-child pairs from a birth cohort. Exposure data was obtained using the high-resolution and spatial–temporal air pollution modeling system DEHM-UBM-AirGIS for PM2.5, PM10, SO2, NH4+, black carbon (BC), organic carbon (OC), CO, O3, NO2, and NOx at residential and occupational addresses of the participating women for the full duration of the pregnancy. The association between prenatal exposure to air pollutants and TL was investigated using distributed lag models. There were significant and positive associations between TL in umbilical cord blood cells and prenatal exposure to BC, OC, NO2, NOx, CO, and O3 during the second trimester. TL in umbilical cord blood was significantly and inversely associated with prenatal exposure to PM2.5, BC, OC, SO2, NH4+, CO and NO2 during the third trimester. There were similar inverse associations between TL from umbilical cord blood cells and air pollution exposure at the residential and occupational addresses. There were weaker or no associations between air pollution exposure and TL in placenta tissue and maternal blood cells. In conclusion, both the second and third trimesters of pregnancy are shown to be sensitive windows of exposure to air pollution affecting fetal TL.

Ambient fine particulate matter and ozone exposures during pregnancy and DNA methylation in umbilical cord blood in the Healthy Start cohort study

Background: Prenatal exposure to air pollution has been associated with low birth weight and adverse childhood health outcomes. Long-term effects of prenatal environmental exposures may be mediated through changes to DNA methylation that, in turn, affect gene regulation and subsequent child phenotype.Methods: In a prospective cohort study of ethnically diverse mother-infant pairs in Colorado, USA, we estimated associations between prenatal exposure to ambient fine particulate matter (PM2.5) and ozone (O3) in each trimester of pregnancy and across the full pregnancy, and DNA methylation of umbilical cord blood cells collected at delivery (2010-2014). Analyses were restricted to 429 eligible women who reported no sustained smoking during pregnancy. Umbilical cord blood DNA methylation was evaluated using the Illumina Infinium 450K array. Linear regression models estimated associations between average air pollution in each period, and methylation (M-value) at each of 436,374 CpG sites remaining after filtering.Results: Median full-pregnancy average PM2.5 concentration was 7.5 ug/m3. After covariate adjustment including technical batches and estimated cell proportions, methylation at 1 CpG was associated with 2nd trimester PM2.5, 39 CpGs were associated with 3rd trimester PM2.5 and 13 CpGs were associated with full-pregnancy average PM2.5 at a false discovery rate &lt;0.05. Genes annotated to these differentially methylated positions included LEP, which produces an adipokine with prominent roles in energy homeostasis, appetite and satiety, and SLC12A5, involved in insulin secretion. Other annotated genes were implicated in immune system regulation and inflammation, neuronal function and neurodevelopment, and cancer. Methylation was not associated with O3 during any period of pregnancy.Conclusions: Prenatal exposure to particulate air pollution was associated with differential methylation of umbilical cord blood DNA among mother-infant pairs in a low exposure setting. Future research should investigate whether epigenetic changes may mediate previously observed effects of air pollution on childhood adverse health outcomes including obesity.

Umbilical Cord Blood and iPSC-Derived Natural Killer Cells Demonstrate Key Differences in Cytotoxic Activity and KIR Profiles.

Natural killer (NK) cells derived or isolated from different sources have been gaining in importance for cancer therapies. In this study, we evaluate and compare key characteristics between NK cells derived or isolated from umbilical cord blood, umbilical cord blood hematopoietic stem/progenitor cells, peripheral blood, and induced pluripotent stem cells (iPSCs). Specifically, we find CD56+ NK cells isolated and expanded directly from umbilical cord blood (UCB56) and NK cells derived from CD34+ hematopoietic stem/progenitors in umbilical cord blood (UCB34) differ in their expression of markers associated with differentiation including CD16, CD2, and killer Ig-like receptors (KIRs). UCB56-NK cells also displayed a more potent cytotoxicity compared to UCB34-NK cells. NK cells derived from iPSCs (iPSC-NK cells) were found to have variable KIR expression, with certain iPSC-NK cell populations expressing high levels of KIRs and others not expressing KIRs. Notably, KIR expression on UCB56 and iPSC-NK cells had limited effect on cytotoxic activity when stimulated by tumor target cells that express high levels of cognate HLA class I, suggesting that in vitro differentiation and expansion may override the KIR-HLA class I mediated inhibition when used across HLA barriers. Together our results give a better understanding of the cell surface receptor, transcriptional, and functional differences between NK cells present in umbilical cord blood and hematopoietic progenitor-derived NK cells which may prove important in selecting the most active NK cell populations for treatment of cancer or other therapies.

Clinical Trials of Stem Cell Therapy for Cerebral Ischemic Stroke

Despite recent developments in innovative treatment strategies, stroke remains one of the leading causes of death and disability worldwide. Stem cell therapy is currently attracting much attention due to its potential for exerting significant therapeutic effects on stroke patients. Various types of cells, including bone marrow mononuclear cells, bone marrow/adipose-derived stem/stromal cells, umbilical cord blood cells, neural stem cells, and olfactory ensheathing cells have enhanced neurological outcomes in animal stroke models. These stem cells have also been tested via clinical trials involving stroke patients. In this article, the authors review potential molecular mechanisms underlying neural recovery associated with stem cell treatment, as well as recent advances in stem cell therapy, with particular reference to clinical trials and future prospects for such therapy in treating stroke.

Impact of Intrauterine Growth Restriction Diseases on The Umbilical Cord Blood CD34+ Cell Counts

Introduction: Different diseases in obstetrics and gynecology can affect the number of CD34+ cells in the umbilical cord blood. Objectives: This study aimed to evaluate the effect of Gestational Diabetes Mellitus (GDM), Gestational Hypertension (GHT) and Morbidly Adherent Placenta (MAP) on the content of CD34+ cells of umbilical cord blood and to compare the effectiveness of Sysmex XN20 analyzer to the flow cytometry method, which is the gold standard in CD34+ cells. Materials abd Methods: The umbilical cord blood (15 ml) was collected after the birth of the newborns. Peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll-Paque Plus. The cells were stained with Procount ™ Progenitor Cell Count Kit with PE Labeled monoclonal anti-CD34+ antibody then analyzed with Flow Cytometry or Sysmex XN20 without staining, to identify CD34+ cells named as hematopoietic progenitor cells (HPC), respectively. Results: Flow cytometric evaluation revealed a significantly elevated (p&lt;0.05) number of cord blood CD34+ cells in GDM and GHT groups compared with healthy controls. MAP patients had comparable CD34+ cells compared with healthy controls. A significant increase in lymphocyte counts was also observed in GDM and GHT groups compared with healthy controls. Sysmex analysis however only revealed an increase in lymphocyte numbers in GHT but picked no differences across groups in HPC. Correlation between Sysmex and flow cytometry results was weak in control, GHT, GDM and MAP groups r: 0570/p&lt;0.01, r: 0.5727/p: 0.0708, r:0.2149/p: 0.4779, r: 0.111/p: 0.779, respectively. Conclusions: CD34+ cells were significantly higher in the GHT and GDM groups compared with healthy control cord blood. The correlations between Flow cytometry and Sysmex were not strong.

Cord Blood Connect: The International Congress for Cord Blood and Perinatal Tissue Research 2020.

The proceedings contain 15 papers The topics discussed include: targeting neuroinflammation with human umbilical cord tissue-derived mesenchymal stromal cells;multiple doses of umbilical cord blood cells improve long-term perinatal brain injury;COVID-19 and its impact on collection and processing of cord blood units at the Cleveland Cord Blood Center;hydrocortisone-treated DUOC-01, a cord blood-derived cell therapy product, ameliorates experimental autoimmune encephalomyelitis;measuring microglial suppression with multiple assays;impact of donor age on outcomes in hematopoietic stem cell transplantation;single UM171-expanded cord blood transplants support robust T-cell reconstitution with low rates of severe infections;autologous umbilical cord blood-derived cell administration in extreme preterm infants: CORD-SAFE study;and umbilical cord blood infusion reactions