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Isolation and comparative analysis of mesenchymal stem cells from human umbilical cord

ABSTRACT: A non-controversial and non-invasive source of adult stem cells (ASCs), particularly hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) is human umbilical cord blood. HSCs derived from cord blood have been used for treating leukemia and other blood disorders for the last 30 years. While the presence of MSCs in cord blood is limited, umbilical cord has been found to be promising source of MSCs. However, the cord is an anatomically complex organ and potential isolation of MSCs from its various parts has not been fully explored. In this study we dissected the cord into cord placenta junction (CPJ), cord tissue (CT), and Wharton’s jelly (WJ) and isolated stem cells. These cells exhibited fibroid morphology, expressed MSC-specific markers including CD90, CD73, CD105, CD44, and CD29 and differentiated into chondrogenic, osteogenic, myogenic and neurogenic lineages. In addition, they all expressed pluripotency genes, OCT4, Nanog, Sox2 and KLF4 but expression of these markers was highest in CPJ followed by WJ and CT. CPJ-MSCs also had higher rate of proliferation compared to WJ- and CT-MSCs. Proliferation of WJ- and CT-MSCs was markedly decreased upon passaging with concomitant decrease in expression of MSC and pluripotency markers. Based on their greater self-renewal potential, CPJ-MSCs could be superior to WJ- and CT-MSCs for the applications in therapeutic and regenerative medicine.

ORGANISM(S): Homo sapiens

PROVIDER: GSE72597 | GEO | 2016/06/08

SECONDARY ACCESSION(S): PRJNA294434

REPOSITORIES: GEO

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Project description:BACKGROUND: Perioperative neurocognitive disorder (PND) is a key complication affecting older individuals after anesthesia and surgery. Failure to translate multiple pharmacological therapies for PND from preclinical studies to clinical settings has necessitated the exploration of novel therapeutic strategies. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) treatment has emerged as a promising therapeutic strategy for treating neurodegenerative diseases and has the potential to translate basic science into clinical practice. In this study, we investigated the effects and underlying mechanism of hUC-MSCs on PND in aged mice.METHODS: hUC-MSCs were isolated from an infant umbilical cord and identified using flow cytometry and differentiation assays. We established PND model by undergoing aseptic laparotomy under isoflurane anesthesia maintaining spontaneous ventilation in 18-month-old male C57BL/6 mice. hUC-MSCs were slowly injected into mice by coccygeal vein before anesthesia. Cognitive function, neuroinflammation, neuroplasticity, endogenous neurogenesis and brain-derived neurotrophic factor (BDNF) were assessed. To determine the mechanisms underlying by which hUC-MSCs mediate their neuroprotective effects in PND, K252a, an antagonist of BDNF receptor, was administered intraperitoneally before surgery. Hippocampal BDNF/TrkB/CREB signaling pathway and metabolomic signatures were evaluated.RESULTS: hUC-MSC treatment ameliorated the learning and memory impairment in aged mice with PND. The downstream effects were the suppression of neuroinflammatory responses and restoration of neurogenesis and neuroplasticity dysregulation. Interestingly, the level of mature BDNF, but not that of proBDNF, was increased in the hippocampus after hUC-MSC treatment. Further analysis revealed that the improved cognitive recovery and the restoration of neurogenesis and neuroplasticity dysregulation elicited by exposure to hUC-MSCs were, at least partially, mediated by the activation of the BDNF/TrkB/CREB signaling pathway. Untargeted metabolomic further identified lipid metabolism dysfunction as potential downstream of the BDNF/TrkB/CREB signaling pathway in hUC-MSC-mediated neuroprotection for PND.CONCLUSIONS: Our study highlights the beneficial effects of hUC-MSC treatment on PND and provides a justification to consider the potential use of hUC-MSCs in the perioperative period.

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Isolation and comparative analysis of mesenchymal stem cells from human umbilical cord

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