Project description:Despite its therapeutic potential and unique immunological properties, the immune composition of umbilical cord blood lacks consistent and comprehensive characterizations. Human umbilical cord blood (UCB) is often discarded after delivery and is difficult to obtain for research purposes. Furthermore, most research on UCB is focused on properties of CD34+ hematopoietic stem cells for transplantation. The Binns Program for Cord Blood Research at Stanford University has the unique advantage of regular collection and isolation of mononuclear cells (MNC) from UCB donors. This study provides a robust characterization of the immune subset compositions of the CD34-negative MNC fraction of UCB (n=50). The study also compares the UCB data to adult peripheral blood (PB) mononuclear cells to identify differences in immune maturity. Using flow cytometry and single-cell RNA sequencing (scRNA-seq), we analyzed UCB and adult PB MNC samples to characterize the cell surface protein and transcriptomic profiles of different immune subsets. Our study findings bring a higher-definition understanding of the unique immunological properties of umbilical cord blood. Study findings reveal a distinct immune profile in UCB, such as a higher average percentage of CD19 B Lymphocytes, CD4 T Cells, CD4 Naive T Cells, CD4 Recent Thymic Emigrants, CD8 Naive T Cells, CD8 Recent Thymic Emigrants, and CD19 Naive B Cells compared to adult PB. Additionally, there were fewer CD19 Memory B Cells in UCB compared to PB. The scRNA-Seq showed concordance in the proportion of immune cell types but captured more differentiated subtypes of cells. Additionally, scRNA-Seq showed unique clustering patterns in UCB, which reflect cell types that converge in adulthood as the immune system matures. These analyses yield the intriguing possibility that the immune heterogeneity of individuals at birth gives way to more stereotyped immune subsets as the immune system is exposed to the external environment and undergoes maturation. Overall, our findings provide a robust characterization of MNC UCB immune subsets and insights into how immune function develops from birth to adulthood.
Project description:Comparison of the CD34+CD38- versus CD34+CD38+ fractions of human umbilical cord blood and comparison of the slow-dividing fraction versus the fast dividing fraction of the CD34+/CD38- population.
Project description:Umbilical cord blood banking is critical for the success of umbilical cord blood transplants. Here we analyzed transcriptomic differences between 27-year cryopreserved umbilical cord blood hematopoietic stem cells (HSCs) and multipotent progenitor cells (MPPs) and those derived from fresh cord blood. We also leveraged differences in engraftment capacity to examine the transcriptomes of HSCs/HPCs defined by engraftment capacity, demonstrating the feasibility of this approach for identifying potency markers to aid in the selection of cord blood units for transplantation and revealing novel potential regulators of cord blood HSC/HPC engraftment.
Project description:Neonatal health is dependent on early risk stratification, diagnosis, and timely management of many potentially devastating conditions. Preterm infants are at increased risk of prematurity-related complications, including: early-onset sepsis, chronic lung disease, intraventricular hemorrhage, necrotizing enterocolitis, and neurodevelopmental impairment.Many of these conditions are poorly predicted in real-time by clinical data, including currently available diagnostic testing. Thus, biomarkers have been sought to aid early and targeted treatment and prognosis for these conditions. Umbilical cord blood may represent a novel source of molecular signatures that provides a window into the state of the fetus at birth. Umbilical cord blood inflammatory markers have been studied as diagnostic indicators of early-onset sepsis. Specific cord blood cytokines have been studied as predictors or correlates of retinopathy of prematurity, atopic disease, infantile hemangioma, placental histopathology, and more. However, few of these cord blood biomarkers have been translated into diagnostic tools in clinical practice. Longitudinal profiling of postnatal proteomic changes has provided insights into the development of the immune system over the first weeks to months of life. While proteomic profiling of cord blood has demonstrated immunologic differences between preterm and term infants, prior research has lacked inclusion of preterm infants across the continuum of gestational age and consideration of key perinatal characteristics such as the route of delivery, preeclampsia, intraamniotic infection, and neonatal sepsis that are likely to affect protein expression. In this study, we have comprehensively characterized the cord blood proteome from infants born between 25 to 42 weeks using MS to provide a benchmark of normative cord blood proteomic profile and examine proteome differences across the developmental range of gestational ages.
Project description:screening of signature deterimes the individual variations in the therapeutic efficacy of human umbilical cord blood-derived mesenchymal stem cells There is paucity of information whether human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) from separate donors might have different effects on improving myocardial repair after myocardial infarction (MI).
Project description:There were no studies about gene expression of umbilical cord tissue before. We performed this study to identify the gene expression of umbilical cord tissue.
Project description:This study will determine the safety and applicability of experimental forms of umbilical cord blood (UCB) transplantation for patients with high risk hematologic malignancies who might benefit from a hematopoietic stem cell transplant (HSCT) but who do not have a standard donor option (no available HLA-matched related donor (MRD), HLA-matched unrelated donor (MUD)), or single UCB unit with adequate cell number and HLA-match).
Project description:We used microarray technology to establish the differential RNA expression profiles in umbilical cord blood exosomes from preeclampsia patients compared with normal controls.