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Efficient Expansion and Delayed Senescence of Human Umbilical Cord Mesenchymal Stem Cells by Microcarrier-Bioreactor System

ABSTRACT: Human umbilical cord mesenchymal stem cells (hUC-MSCs) are widely used in cell therapy due to their powerful immunomodulatory and tissue regenerative capabilities. In order to meet the number and quality of cells for clinical applications, we developed a hUC-MSCs culture process based on homemade microcarriers and stirred bioreactors. In this study, the biological properties of hUC-MSCs amplified by planar culture and microcarrier bioreactor systems are systematically compared. It was found that microcarrier-expanded hUC-MSCs had a relatively lower degree of aging, relatively stronger proliferation capacity, and fewer cells stayed in the cell cycle retardation period. At the same time, RNA-seq was used to compare the differences in gene expression between the two cultures, and the pathways and genes related to cell aging were identified. Comparing the transcription levels of these aging-related gene sets can also confirm that cells cultured by microcarrier reactors are more youthful. Results show that our reactor culture method greatly improved the cell proliferation efficiency, while maintaining the basic properties and younger state of stem cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE233634 | GEO | 2023/09/13

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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Efficient Expansion and Delayed Senescence of Human Umbilical Cord Mesenchymal Stem Cells by Microcarrier-Bioreactor System

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