Cord Blood Research Articles

Sterility of cord blood units: Evaluation of the collection, preparation and conservation process with a view to establishing a bank of stem cells from cord blood at the Biological Resources Center of the Institut Pasteur de Côte d’Ivoire (2024)

Introduction: Cord blood stem cells are used as an alternative to bone marrow and peripheral blood cell transplantation. For this purpose, cord blood banks have been established worldwide for the collection and cryopreservation of cord blood units. These banks must implement rigorous protocols to ensure the microbiological safety of grafts. The aim of this study is to evaluate the process of selecting mothers and collecting and processing these samples developed for this purpose. Methodology: Pregnant women were enrolled in the study on the basis of selection criteria. Maternal blood and cord blood samples were collected by the in utero method. Serological analyses of maternal blood for the detection of vertically transmitted infections and microbiological examinations of cord blood units were carried out. Results: 31 women out of 46 (68.4%) were enrolled. All had negative serology for the targeted pathogens. Similarly, microbiology revealed no microbial contamination of the cord blood units. Conclusion: This work demonstrates that the procedures for selecting mothers and processing implementations are effective in ensuring the microbiological safety of cord blood units and could be suggested in the context of banking cord blood stem cells at the Institut Pasteur de Côte d’Ivoire.

Protein Kinase C Isozyme Immaturity/Deficiency in Cord Blood Monocytes and Neutrophils

Reduced/deficient expression of Protein Kinase C (PKC)ζ in Cord blood (CB) T cells is associated with allergy development in children and a propensity to maintain an immature T-helper (Th)2 cytokine profile. In addition, other PKC isozymes are also low in CBTCs. Since previous studies have reported that cord blood/neonatal monocyte and neutrophil functions are significantly lower than cells from adults, it was of interest to see if the CBTC PKC levels were reflected in CB monocytes and neutrophils. Compared to adult blood, CB expresses low levels of PKCα, β2, ε, θ, μ, ζ and λ/ι in monocytes and PKCα, β2, η, θ, μ, ζ and λ/ι in neutrophils. The T-cell PKCζ levels were positively correlated with levels in CB monocytes but not in neutrophils. However, neither the monocytes nor the neutrophil PKCζ were associated with T-cell development towards a Th1 or Th2 cytokine propensity, based on the production of interferon-gamma and interleukin-4 in response to phytohemagglutinin and phorbol myristate acetate. The results demonstrate that some newborn babies display a deficiency in PKC isozymes in monocytes and neutrophils, as reported for T cells. However, unlike T cells, the PKCζ levels of the phagocytes did not correlate with regulation of development towards a Th1 or Th2 cytokine phenotype.

Safety and feasibility of umbilical cord blood transplantation in children with neuronal ceroid lipofuscinosis: a retrospective study.

Ceroid lipofuscinosis neuronal (CLN) encompasses rare inherited neurodegenerative disorders that present in childhood with clinical features including epilepsy, psychomotor delay, progressive vision loss, and premature death. Published experience utilizing umbilical cord blood transplant (UCBT) for these disorders is limited. This retrospective analysis includes patients with CLN (2, 3, and 5) who underwent UCBT from 2012 to 2020. All subjects (n = 8) received standard-of-care myeloablative conditioning. Four also enrolled in clinical trial NCT02254863 and received intrathecal DUOC-01 cells posttransplant. Median age at UCBT was 5.9 years. All subjects achieved neutrophil engraftment with >95% donor chimerism at a median of 28.5 days. Sinusoidal obstructive syndrome was not observed. Severe acute graft-versus-host disease occurred in 12.5%. Other complications included autoimmune hemolytic anemia (25%) and viral reactivation/infection (62.5%). No transplant-related mortality was observed. Two CLN2 patients died, 1 from progressive disease and 1 from unknown cause at days +362 and +937, respectively. With median follow-up of 8 years, overall survival at 100 days and 24 months was 100% and 88%, respectively. Three of 4 CLN3 subjects stabilized Hamburg motor and language scores. While UCBT appears safe and feasible in these patients, given the variable expression and natural history, extended follow-up and further studies are needed to elucidate the potential impact of UCBT on clinical outcomes.

Effect of mesenchymal stem cell derived from umbilical cord blood on rabbit intrauterine adhesion model

Objective: To investigate the repair effect of human umbilical cord blood mesenchymal stem cells (hUCB-MSC) on endometrium of intrauterine adhesion (IUA) by establishing animal model. Methods: Eighteen healthy female New Zealand white rabbits were divided into a control group, an IUA group and an hUCB-MSC transplantation group according to random number table method. The control group underwent laparotomy only. The IUA group underwent IUA modeling surgery using curettage and lipopolysaccharide (LPS) cotton placed in uterine cavity for double injury. The hUCB-MSC transplantation group received the same IUA modeling surgery followed by multipoint injection of hUCB-MSC suspension (2×106 cells/ml, 500 μl) into the bilateral uterine myometrium one week after surgery. Four weeks after the IUA modeling surgery, the rabbits were euthanized and samples were collected. Hematoxylin and eosin (HE) staining and Masson staining were used to assess the number of endometrial glands and the fibrosis rate. RNA sequencing was performed on the endometrium of the IUA group and hUCB-MSC transplantation group.The mRNA and protein expression of the fibrosis markers [transforming growth factor β1 (TGF-β1) and tissue inhibitors of metalloproteinase 1 (TIMP1)] and RNA sequencing-related parameters were detected by quantitative real-time PCR (qRT-PCR) and Western blot. Results: Compared with the control group, the number of glands in IUA group decreased (26.33±1.53 vs 4.33±1.53, P<0.001), and the fibrosis rate increased (18.01%±2.21% vs 69.55%±2.42%, P<0.001), indicating successful modeling. HE and Masson staining revealed that the number of glands in the hUCB-MSC transplantation group was increased compared with that in IUA group (17.33±2.52 vs 4.33±1.53, P<0.001), and the fibrosis rate decreased (69.55%±2.42% vs 41.55%±1.99%,P=0.001). Western blot analyses of fibrosis-related proteins (TGF-β1 and TIMP1) showed elevated levels of TGF-β1 (0.91±0.05) and TIMP1 (0.99±0.01) proteins in the IUA group compared to control group (0.61±0.04, 0.68±0.07) (P=0.001, 0.015). The hUCB-MSC transplantation group exhibited reduced expression of TGF-β1 (0.69±0.04) and TIMP1 (0.62±0.08) proteins compared to the IUA group (P=0.005, 0.014). Western Blot results related to the PI3K/AKT signaling pathway [phosphorylated phosphatidylinositol 3-kinase (p-PI3K), phosphorylated protein kinase B (p-AKT)] showed that the expression of p-PI3K(1.05±0.05) and p-AKT(1.17±0.06) in the IUA group increased compared to the control group (0.78±0.03, 0.85±0.05) (P=0.002, 0.002). The expression of p-PI3K (0.74±0.02) and p-AKT (0.93±0.04) proteins in the hUCB-MSC transplantation group decreased compared to the IUA group (P=0.003, 0.005). Conclusion: hUCB-MSC can repair the damaged endometrium in rabbit intrauterine adhesion model by increasing the number of endometrial glands and improving its level of fibrosis.

The inflammatory and oxidative phenotype of gestational diabetes is epigenetically transmitted to the offspring: role of methyltransferase MLL1-induced H3K4me3.

Hyperglycaemia during gestational diabetes (GD) predisposes women and their offspring to later cardiometabolic disease. The hyperglycaemia-mediated epigenetic changes remain to be elucidated. Methyltransferase MLL1-induced trimethylation of histone 3 at lysine 4 (H3K4me3) activates inflammatory and oxidative phenotype. This epigenetic mark in GD women and its transmission to the offspring were investigated. Peripheral blood mononuclear cells (PBMC) were collected from GD and control (C) women and also from adolescents born to women of both groups. Endothelial human umbilical vein endothelial cells (HUVEC) and cord blood mononuclear cells (CBMC) were from umbilical cords. The NF-κBp65 and NOX4 expressions were investigated by reverse transcription quantitative polymerase chain reaction and immunofluorescence (IF). MLL1 and H3K4me3 were investigated by immunoblotting and IF. H3K4me3 on NF-κBp65 and NOX4 promoters was studied by chromatin immunoprecipitation. Superoxide anion generation was measured by electron spin resonance spectroscopy. Plasma cytokines were measured by enzyme-linked immunosorbent assay. To investigate the role of MLL1, HUVEC were exposed to inhibitor MM102 or siRNA transfection. PBMC, CBMC, and HUVEC showed an increase of NF-κBp65, IL-6, ICAM-1, MCP-1, and VCAM-1 mRNAs. These findings were associated with H3K4me3 enrichment in the promoter of NF-κBp65. Elevated H3K4me3 and cytokine levels were observed in GD adolescents. MLL1 drives H3K4me3 not only on NF-kB p65, but also on NOX4 promoter. Inhibition of MLL1 blunted NF-κBp65 and NOX4 by modulating inflammatory and oxidative phenotype. Such proof-of-concept study shows persistence of MLL1-dependent H3K4me3 in offspring born to GD women, suggesting an epigenetic-driven transmission of maternal phenotype. These findings may pave the way for pharmacological reprogramming of adverse histone modifications to mitigate abnormal phenotypes underlying early ASCVD.

Comparison of cord blood alarin levels of full-term infants according to birth weight.

To compare the cord blood alarin levels of infants in different birth weight groups with those of infantsborn to mothers diagnosed with gestational diabetes mellitus (GDM) who were not subgrouped according to birth weight. This prospective study was conducted between September 2023 and January 2024. Healthy term babies whose families agreed to participate in the study were divided into four groups according to their birth weight (small for gestational age (SGA), appropriate for gestational age (AGA) and large for gestational age (LGA)) and whether their mothers had GDM. There was a significant difference between the cord blood alarin levels of the AGA and SGA groups (p=0.014). There was also a significant difference between the cord blood alarin levels of the AGA and GDM groups (p=0.012). However, the cord blood alarin levels of the LGA group (whose mothers did not have GDM) were similar to those of the AGA group (p=0.394). We found evidence that alarin levels in umbilical cord blood are associated with low birth weight and GDM.

Umbilical Cord Blood-Derived Products in Autoimmune Systemic Syndromes with Severe Dryness: A Pilot Study

Background and Objectives: Human umbilical cord blood serum (HUCBS) stands out as a potent adjunct to conventional therapies for ocular surface disorders (OSDs) caused by, among many, autoimmune systemic syndromes. By expediting ocular surface regeneration and fostering epithelial integrity, HUCBS not only enhances subjective patient experiences but also improves objective clinical indicators. This makes it particularly useful in patients with corneal ulcers through ocular surface regeneration and anti-inflammatory activity. This study aims to explore the efficacy of HUCBS in patients who had previously received other treatments unsuccessfully. Materials and Methods: This study was a prospective, non-comparative, interventional case series study involving 49 patients (30 females and 19 males) aged 15–82 years with severe OSDs who were unresponsive to standard treatments. The study was conducted at the San Marco Hospital, Catania, Italy. Patients were categorized into four groups based on the etiology of their severe OSDs: Group I consisted of twenty four patients with filamentary keratitis and corneal ulcers associated with rheumatologic diseases such as Sjogren’s syndrome and systemic sclerosis; Group II comprised thirteen patients with graft-versus-host disease; Group III consisted of nine patients with corneal neurotrophic ulcers; and Group IV included three patients with Steven–Johnson syndrome. The outcomes were evaluated before and after treatment using the following assessments: OSDI (Ocular Surface Disease Index) and SANDE (Symptom Assessment in Dry Eye) questionnaires, VAS (Visual Analog Scale), Slit Lamp Examination, Esthesiometry, Lissamine Green Staining, NIBUT (Non-Invasive Break-Up Time), BUT (Break-Up Time), Fluorescein Staining with Photography and Oxford Classification, The Schirmer Test, Best-Corrected Visual Acuity (BCVA), and Meibography. Results: We observed a significant improvement in the outcomes from the SANDE, VAS, and OSDI questionnaires, The Schirmer Test, BUT, BCVA, and Oxford Classification, after treatment with UCBS. Clinical variables, such as corneal inflammation, conjunctivalization, corneal neovascularization, and pain, were also considered individually. Nevertheless, pain and inflammation reduced markedly over time until complete healing was achieved in all cases. Conclusions: Our pilot study highlights the substantial efficacy of HUCBS in patients with systemic autoimmune diseases who have shown inadequate responses to prior treatments for dry eye. This underscores the need for further comprehensive investigations in this field.

Heavy Metals in Umbilical Cord Blood: Effects on Epigenetics and Child Development

Heavy metals like arsenic, mercury, cadmium, and lead are harmful pollutants that can change how our genes are regulated without altering the DNA sequence, specifically through a process called DNA methylation (DNAm) at 5-methylcytosine, an epigenetic mark that we will focus on in this review. These changes in DNAm are most sensitive during pregnancy, a critical time for development when these modifications can affect how traits are expressed. Historically, most research on these environmental effects has focused on adults, but now there is more emphasis on studying the impacts during early development and childhood. The placenta acts as a protective barrier between the mother and the baby, and by examining it, scientists can identify changes in key genes that might affect long-term health. This review looks at how exposure to heavy metals during pregnancy can cause changes in the gene regulation by DNAm in newborns, as seen in their umbilical cord blood. These changes reflect the baby’s genetic state during pregnancy and can be influenced by the mother’s environment and genetics, as well as the baby’s own genetics.

Knowledge, Attitudes, and Practices of Pregnant Women and Hospital Staff Regarding Umbilical Cord Blood Banking: Systematic Review and Meta-Analysis

Background/Objectives: The aim of this study is to assess the knowledge, attitudes, and practices of pregnant women and hospital staff regarding umbilical cord blood (UCB) donation and storage to understand its limitations in clinical practice. Methods: MEDLINE, Scopus, LILACS, EMBASE, Scielo.br, and PROSPERO were searched from inception to 30 November 2023 with no geographic or language restrictions. The study eligibility criteria included cross-sectional studies that interviewed pregnant women and/or hospital staff about their knowledge, attitudes, and practices regarding private or public storage. A random-effects restricted maximum-likelihood model with Freeman–Tukey Double arcsine transformation meta-analysis was carried out to calculate the pooled estimates. MOOSE guidelines were followed. STATA 14.1 was used for statistical analysis. The Newcastle–Ottawa Scale and ROBINS-I tool were used for quality and risk of bias assessments. Results: In total, 19 studies providing data for 19,904 pregnant women and 1245 hospital staff members were included. Pooled pregnant women awareness was 61% ((95% CI 0.60 to 0.62), I2 = 0%, τ2 = 0.00, Q = 11.0 (p = 0.950)), and 61% for hospital staff (95% CI 0.58 to 0.64), I2 = 0%, τ2 = 0.00, Q = 4.00 (p = 0.310)). In total, 57% ((95% CI 0.56 to 0.58), I2 = 0, τ2 = 0.00, Q = 4.00 (p = 0.320)) of pregnant women had a positive attitude about UCB, while 34% ((95% CI 0.32 to 0.36), I2 = 0%, τ2 = 0.00, Q = 4.00 (p = 0.310)) were in favor of donating UCB for research and 65% ((95% CI 0.63 to 0.66), I2 = 0%, τ2 = 0.00, Q = 4.0 (p = 0.350)) were planning UCB storage. A significant (p &lt; 0.001) preference for public relative to private banking (51% ([95% CI 0.49 to 0.54], I2 = 0%, τ2 = 0.00, Q = 4.0 (p = 0.310)) vs. 12% ([95% CI 0.10 to 0.13], I2 = 0%, τ2 = 0.00, Q = 4.0 (p = 0.300))) was noted for pregnant women. The same was retrievable for professionals (84% ([95% CI 0.79 to 0.88], I2 = 0%, τ2 = 0.00, Q = 2.0 (p = 0.110)) vs. 6% ([95% CI 0.03 to 0.09], I2 = 0%, τ2 = 0.00, Q = 1.0 (p = 0.070); p &lt; 0.001)). Conclusions: Despite these efforts, lack of knowledge and positive attitudes about UCB banking remain, emphasizing the need for increasing educational programs on the subject.

Impact of fetal umbilical cord blood CD34+ cells on breast cancer cell lines: a mechanism of fetal microchimerism?

Introduction Fetal microchimerism could be involved in the regulation of breast cancer oncogenesis. CD34+ cells could be of a particular interest as up to 12% of the CD34+ population in maternal blood are of fetal origin. The aim of this research was to analyze the impact of umbilical cord blood (UCB) CD34+ on MCF-7 and MDA-MB-231 breast cancer cell lines, in order to uncover novel biological mechanisms and suggest novel treatment options for breast cancer. Methods UCB CD34+ cells were obtained from healthy women at full-term delivery. Direct cultures were grown with MCF-7 and MDA-MB-231 cells. Proliferation, migration, invasion, and transcriptomic analysis of breast cancer cells were compared between cultures exposed and non-exposed to UCB CD34+ cells. Interactions between UCB CD34+ and breast cancer cells were analyzed under fluorescent microscopy. Functional analyses were generated with QIAGEN's Ingenuity Pathway Analysis (IPA) and Gene Set Enrichment Analysis (GSEA). Results Direct contact between UCB CD34+ and breast cancer cell lines induced a reduction in the proliferative capacities of MCF-7 and MDA-MB-231 and diminished the migration abilities of MDA-MB-231 cells. In 3D co-culture, UCB CD34+ cells were attracted by tumor spheroids and incorporated into tumor cells. These cell-to-cell interactions were responsible for transcriptome modifications coherent with observed functional modifications. Among the cytokines secreted by UCB CD34+, IFN was identified as a potential upstream regulator responsible for the molecular modifications observed in transcriptomic analysis of MCF-7 breast cancer cells exposed to UCB CD34+ cells, as was IL-17A in MDA-MB-231 cells. Conclusion Direct cell-to-cell contact induced functional modifications in breast cancer cells. Interactions between UCB CD34+ and breast cancer cells could induce cell fusion and signal transmission via cytokines. Further analysis of direct cell-to-cell interactions should be performed at a molecular level to further understand the potential role of fetal CD34+ cells in breast cancer.

Predictive Value of Cord Blood Bilirubin for Hyperbilirubinemia in Term Neonates with ABO Incompatibility

Introduction: Jaundice affects 60% of full-term and 80% of preterm neonates. Feto-maternal ABO incompatibilities occur in 20-25% of pregnancies, but severe haemolytic disease develops in only 10%. ABO-incompatible babies have doubled the risk of jaundice requiring treatment and a 5-10 times increased risk of exchange transfusions. Objective: Aim of this study was to determine if cord blood bilirubin (CBB) can predict hyperbilirubinemia in term babies with ABO setup prior to discharge that would help to decrease readmission and subsequently complications due to jaundice. Methods: A hospital-based prospective observational study was conducted at Patan Hospital. Cord blood group and bilirubin levels were collected from newborns of O positive mothers. Babies with A positive and B positive blood groups had their CBB levels measured and were followed daily for 72 hours. Serum bilirubin was tested based on clinical judgment to detect hyperbilirubinemia and treated per NICE guidelines. Data were analysed using SPSS v21.0, Mann-Whitney test, ANOVA, and ROC analysis. Results: Among 66 cases, significant hyperbilirubinemia was seen in 7 neonates (10.6%). It was more common in B positive babies (12.2%) compared to A positive (8%). Mean CBB was 3.45 ± 0.57 in those developing significant hyperbilirubinemia. A CBB of 2.95 mg/dL had the highest sensitivity (86%), specificity (94%), and negative predictive value (98%) for predicting hyperbilirubinemia in ABO setup babies. Conclusion: Term babies with ABO incompatibility and CBB&lt;2.95 mg /dL are unlikely to need further evaluation, while those with cord bilirubin level ≥2.95 mg/dL should have frequent early follow-ups.

Timing of Maternal Stress Differentially Affects Immune and Stress Phenotypes in Progeny

Maternal stress during gestation may affect the development and responsiveness of the hypothalamic–pituitary–adrenal axis (HPA) and immune system in the progeny. Stressor type, duration and gestational stage at which the stressor occurs may all influence the short and long-term effects on the future progeny. The present study advances the characterization of the timing of gestational stress on the stress responsiveness and immune and behavioral phenotypes of the progeny. First, parity sows were hand-fed hydrocortisone acetate (stressed) or placebo (controls) during mid or late gestation. Colostrum and cord blood were collected. Blood samples were obtained from a subset of piglets (n = 36) born to these sows during lactation, pre- and post-weaning, and during an ACTH challenge. Stress and immune measures were assessed. Piglets born to sows stressed during mid-gestation had reduced measures of humoral immunity, including immunoglobulins and interleukin-4. Conversely, piglets born to late-stressed sows exhibited a delayed or dampened stress response to weaning and an ACTH challenge. They also had a skewed pro-inflammatory phenotype, as evidenced by increased interleukin-17 and tumor necrosis factor-α. Overall, these data suggest that the stage of gestation at which gestational stress occurs has differential effects on the HPA axis and immune development of the progeny, resulting in differential stress responsiveness and immune and behavioral phenotypes.

ANKS6 Variants Underlie Polycystic Kidneys in Prenatal and Neonatal Cases

Background: Nephronophthisis (NPHP) is an autosomal recessive genetic disorder that can cause early-onset kidney failure. ANKS6 plays an important role in early kidney development and encodes a protein that interacts with other proteins within the primary cilium. ANKS6 mutations are known to cause nephronophthisis 16 (NPHP-16). Little is known regarding fetal ultrasound imaging and the antenatal diagnosis of fetuses with ANKS6-associated kidney disease. Here, we report the detection of ANKS6 variants in consanguineous families with polycystic kidney antenatally and in the early stages of life. Methods: Three unrelated Saudi Arabian patients (two prenatal patients and one neonate) were investigated. These cases were referred to the hospital due to the presence of echogenic kidneys on antenatal scanning. After clinical and phenotypic evaluation, whole-exome sequencing (WES) was performed on the cord and peripheral blood to identify the molecular genetic causes associated with the echogenic kidney phenotypes. Results: Two homozygous sequence variants were detected in ANKS6. The homozygous missense novel variant ANKS6: c.1159A&gt;C was detected in Families 1 and 2. In the third family, the known homozygous loss-of-function variant ANKS6: c.907+2T&gt;A was detected. Conclusions: We identified homozygous ANKS6 variants in three families presenting with antenatal polycystic kidney disease. The findings provide an expanded clinical presentation of ANKS6 and emphasize the utility of WES in the diagnosis of echogenic kidneys in prenatal settings.

Correction to: Abstract 11: Multicomponent Cord Blood Bank Program, Beyond Transplantation.

Correction to: Abstract 11: Multicomponent Cord Blood Bank Program, Beyond Transplantation.

Development of a quantitative prediction algorithm for human cord blood-derived CD34+ hematopoietic stem-progenitor cells using parametric and non-parametric machine learning models

The transplantation of CD34+ hematopoietic stem-progenitor cells (HSPCs) derived from cord blood serves as the standard treatment for selected hematological, oncological, metabolic, and immunodeficiency disorders, of which the dose is pivotal to the clinical outcome. Based on numerous maternal and neonatal parameters, we evaluated the predictive power of mathematical pipelines to the proportion of CD34+ cells in the final cryopreserved cord blood product adopting both parametric and non-parametric algorithms. Twenty-four predictor variables associated with the cord blood processing of 802 processed cord blood units randomly sampled in 2020–2022 were retrieved and analyzed. Prediction models were developed by adopting the parametric (multivariate linear regression) and non-parametric (random forest and back propagation neural network) statistical models to investigate the data patterns for determining the single outcome (i.e., the proportion of CD34+ cells). The multivariate linear regression model produced the lowest root-mean-square deviation (0.0982). However, the model created by the back propagation neural network produced the highest median absolute deviation (0.0689) and predictive power (56.99%) in comparison to the random forest and multivariate linear regression. The predictive model depending on a combination of continuous and discrete maternal with neonatal parameters associated with cord blood processing can predict the CD34+ dose in the final product for clinical utilization. The back propagation neural network algorithm produces a model with the highest predictive power which can be widely applied to assisting cell banks for optimal cord blood unit selection to ensure the highest chance of transplantation success.

Effects of guanidine acetic acid supplementation from gestation to lactation on reproductive performance, colostrum quality, blood biochemistry, and intestinal microflora diversity of sows.

This experiment aimed to study the effects of guanidine acetic acid (GAA) on reproductive performance, lactation performance and blood biochemical indices of sows, as well as the performance of offspring piglets. A total of 20 sows (Landrace × Yorkshire, parity 4) were used. Half of the sows in each parity were fed a control diet (CG; basic diet, n = 10) or GAA diet (basic diet +1 g/kg GAA, n = 10) from the 85th day of gestation until weaning. The study results are presented as follows: Supplementation of GAA from late gestation to lactation did not adversely affect sow feed intake, backfat thickness, or blood routine indexes (p > 0.05). GAA supplementation showed a tendency to increase the number of healthy piglets and their birth activity (p = 0.06; p = 0.08), while significantly increasing the IUGR score of piglets (p < 0.05). GAA supplementation significantly increased colostrum protein content (p < 0.05) and tended to increase daily milk yield in sows (p = 0.07). GAA supplementation increased the level of immunoglobulin A in sow colostrum (p < 0.05) and showed a tendency to increase proline content (p = 0.10). GAA supplementation significantly decreased triglyceride content in sow cord blood (p < 0.05), with no significant effects observed on HDL-C, LDL-C, TC, and GLU (p > 0.05). GAA supplementation significantly increased eNOS levels in sow cord blood (p < 0.05), while showing no significant effects on IL-6 and IL-10 (p > 0.05). GAA supplementation did not significantly affect the α diversity of sow intestinal flora (ACE, Shannon, Chao1, Simpson, observed_otus, pielou_e, and good_cover), but PCoA analysis revealed differences in intestinal flora structure between groups. Additionally, GAA decreased the relative abundance of Sarciha and unidentified_ruminococcaceae and increased the relative abundance of Lactobacillus, Parabacteroides, and Pedobacter in the gut. GAA boosts nitric oxide synthase in sows' umbilical cord blood, enhancing placental blood vessel development. This improves piglet health and vitality, increases beneficial gut bacteria (Lactobacillus, Parabacteroides, Pedobacter), and raises colostrum protein levels and lactation volume, leading to better piglet growth and performance.

Association Between Prenatal Exposure to Organochlorine Pesticides and Telomere Length in Neonatal Cord Blood

Objectives: Environmental exposure may affect the telomere length (TL) of newborns, which is considered as an early biomarker indicating susceptibility for later life diseases. However, the effects of prenatal organochlorine pesticide (OCP) exposure on newborn TL remain unclear. This study aimed to investigate the association between prenatal exposure levels of OCPs during pregnancy and TL in neonatal cord blood. Methods: A total of 168 mother–infant pairs from a birth cohort in Wuhan, China, were included this study. The concentrations of hexachlorocyclohexanes (HCHs, including β-HCH, α-HCH, and γ-HCH), p,p’-dichlorodiphenyltrichloroethane (p,p’-DDT) and its metabolites (p,p’-dichlorodiphenyldichloroethane, p,p’-DDD; p,p’-dichlorodiphenyldichloroethylene, p,p’-DDE) were measured in cord blood. The associations between the OCPs and the TL in newborns were analyzed by a generalized linear regression model. Stratified analyses by newborn sex, maternal gestational weight gain, and pregnancy body mass index (BMI) were performed to evaluate if the associations were modified by these factors. Results: The detection rates of various OCPs ranged from 50.9% to 100.0%. The median concentration of p,p’-DDE was the highest (33.90 ng/g lipid), followed by β-HCH (8.67 ng/g lipid), and the median concentrations of the other OCPs were between 0.12 and 0.33 ng/g lipid. Among the all newborns, a two-fold increase in the γ-HCH concentration in the cord blood was significantly associated with a 0.024 (95% CI: −0.041, −0.007) decrease in the TL. After stratification by newborn sex, the inverse association between γ-HCH and the TL was only statistically significant in boys, but not in girls (P for interaction &lt;0.05). In addition, after stratification by pre-pregnancy BMI, β-HCH and p,p’-DDT concentrations were significantly associated with a decreased TL in the overweight pre-pregnancy BMI group [−0.111 (95% CI: −0.203, −0.018) and −0.036 (95% CI: −0.049, −0.023), respectively]. Conclusions: Prenatal exposure to OCPs during pregnancy was associated with a decreased neonatal telomere length, which may be affected by the newborn sex and pre-pregnancy BMI. These findings may provide new insights into the mechanisms underlying OCP-induced adverse health effects.

Preserving Stem Cells for Potential Use in Future Reparative Medicine

With its enormous potential for regenerative medicine and therapeutic applications, stem cell preservation represents a major breakthrough in biomedical science. Stem cells are gathered, processed, and stored under carefully monitored circumstances in order to preserve their viability for potential use in the future. Because they may differentiate into a variety of cell types, stem cells—especially those derived from sources like umbilical cord blood—are essential for both therapeutic and research uses. An essential function of cord blood banking is to offer a plentiful supply of immune system cells that may be stored for potential future therapeutic applications. Immunological deficits, osteoarthritis, Parkinson's disease, and heart failure are just a few of the conditions for which stem cell treatments have shown promise. Notwithstanding the promise, there remain obstacles such immunological rejection and the need for more research to fully comprehend the development and functionality of stem cells. It is essential for the general public to be informed about stem cell treatments and cord blood banking in order for expectant parents to make well-informed decisions. Future advancements in the subject depend heavily on resolving ethical issues and enhancing the effectiveness of stem cell-based therapies. To fully realise the promise of stem cell preservation in conventional medicine, more research, creativity, and international cooperation are required.

Hemoglobin-oxygen affinity changes in neonatal blood transfusions: RBC selection insights.

Despite preterm newborns often requiring blood transfusions, we have an incomplete understanding of the impact of adult packed red blood cell (pRBC) transfusions on fetal red blood cell (RBC) oxygen affinity. We investigated the influence of adult pRBC on oxygen binding in fetal RBCs obtained from the umbilical cord of preterm newborns. This included exploring the influence of the biological age of adult pRBCs on the oxygen affinity of fetal blood. Cord blood samples from preterm infants were titrated with young (Y-RBC) and old (O-RBC) adult pRBCs using an in vitro transfusion model. Parameters, including oxygen affinity (p50), hemoglobin variants, and red blood cell indices, were measured. The titration of cord blood with adult pRBCs (n = 19) resulted in a concentration-dependent decrease in p50, indicating an increased oxygen affinity. Hemoglobin variant analysis revealed a shift in composition, with a decrease in fetal hemoglobin (HbF) and an increase in adult hemoglobin (HbA) following titration. The impact of biological age was evident, as O-RBCs had a more pronounced effect on p50 values compared to Y-RBCs. Understanding the physiologic implications of transfusing preterm infants with adult pRBCs is important for optimizing transfusion practices in newborns. In an in vitro model, titrating adult pRBC into fetal blood significantly affects oxygen binding Oxygen affinity of fetal blood is significantly increased after titration of adult pRBC. Compared to older RBC subpopulations of adult pRBC, oxygen-binding properties of younger RBC subpopulations of adult pRBC more closely approximate the oxygen affinity of fetal blood. This work highlights the importance of investigating the influence of adult pRBC transfusion on fetal RBC oxygen binding. This may have implications for morbidities in the newborn period related to oxygen physiology.

Promotion of nerve regeneration and motor function recovery in SCI rats using LOCAS-iPSCs-NSCs

BackgroundSpinal cord injury (SCI) is a severe traumatic spinal condition with a poor prognosis. In this study, a scaffold called linearly ordered collagen aggregates (LOCAS) was created and loaded with induced pluripotent stem cells (iPSCs)-derived neural stem cells (NSCs) from human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) to treat SCI in a rat model.MethodsThe rats underwent a complete transection SCI resulting in a 3-mm break at either the T9 or T10 level of the spinal cord.ResultsScanning electron microscope analysis revealed a uniform pore structure on the coronal plane of the scaffold. The LOCAS had a porosity of 88.52% and a water absorption of 1161.67%. Its compressive modulus and stress were measured at 4.1 MPa and 205 kPa, respectively, with a degradation time of 10 weeks. After 12 weeks, rats in the LOCAS-iPSCs-NSCs group exhibited significantly higher BBB scores (8.6) compared to the LOCAS-iPSCs-NSCs group (5.6) and the Model group (4.2). The CatWalk analysis showed improved motion trajectory, regularity index (RI), and swing speed in the LOCAS-iPSCs-NSCs group compared to the other groups. Motor evoked potentials latency was lower and amplitude was higher in the LOCAS-iPSCs-NSCs group, indicating better neural function recovery. Histological analysis demonstrated enhanced neuronal differentiation of NSCs and nerve fiber regeneration promoted by LOCAS-iPSCs-NSCs, leading to improved motor function recovery in rats. The LOCAS scaffold facilitated ordered neurofilament extension and guided nerve regeneration.ConclusionsThe combination of LOCAS and iPSCs-NSCs demonstrated a positive therapeutic impact on motor function recovery and tissue repair in rats with SCI. This development offers a more resilient bionic microenvironment and presents novel possibilities for clinical SCI repair.