Stem Cell Facility, DBT-Centre of Excellence for Stem Cell Research), All India Institute of Medical Sciences, 1stFloor, ORBO Complex, Ansari Nagar, New Delhi, India.
Cell Tissue Res. 2022 Jun;388(3):535-548. doi: 10.1007/s00441-022-03615-y. Epub 2022 Mar 22.
Mesenchymal stromal cells (MSCs) are emerging as an ideal candidate for regenerative medicine. It is known that the culture conditions impact the cellular properties of MSCs and their therapeutic behavior. Moreover, maintenance of MSCs in low oxygen tension for a short duration has shown to be beneficial for MSCs as it is similar to that of their physiological niche. However, the precise mechanism through which hypoxia pre-conditioning affects MSCs is not clear yet. Thus, in this study, we have investigated the effect of hypoxia exposure (1% O) on tissue-specific MSCs over a period of time under serum-free culture conditions and evaluated the changes in expression of immuno-modulatory molecules and exosome biogenesis and secretion markers. It was observed that all MSCs responded differentially towards hypoxia exposure as indicated by the expression of HIF-1α. Moreover, this short-term exposure did not induce any changes in MSCs cellular morphology, proliferation rate, and surface marker profiling. In addition, we observed an enhancement in the expression of immunomodulatory factors (HLA-G, PGE-2, and IDO) after hypoxia exposure of 12 to 24 h in all tissue-specific MSCs. Interestingly, we have also observed the upregulation in exosome secretion that was further corelated to the upregulation of expression of exosome biogenesis and secretion markers (ALIX, TSG101, RAB27a, RAB27b). Though there was a differential response of MSCs where WJ-MSCs and BM-MSCs showed upregulation of these markers at 6-12 h of hypoxia pre-conditioning, while AD-MSCs showed similar changes beyond 24 h of hypoxia exposure.
间充质基质细胞（MSCs）作为再生医学的理想候选者而备受关注。已知培养条件会影响 MSCs 的细胞特性及其治疗行为。此外，将 MSCs 维持在低氧张力下短暂时间已被证明对 MSCs 有益，因为这类似于其生理龛位的情况。然而，低氧预处理影响 MSCs 的精确机制尚不清楚。因此，在这项研究中，我们研究了在无血清培养条件下，短时间（1% O）暴露于低氧环境对组织特异性 MSCs 的影响，并评估了免疫调节分子和外泌体生物发生和分泌标志物表达的变化。结果表明，所有 MSCs 对低氧暴露的反应不同，这表明 HIF-1α的表达。此外，这种短期暴露不会引起 MSCs 细胞形态、增殖率和表面标志物分析的任何变化。此外，我们观察到，在所有组织特异性 MSCs 中，低氧暴露 12 至 24 小时后，免疫调节因子（HLA-G、PGE-2 和 IDO）的表达增强。有趣的是，我们还观察到外泌体分泌的上调，这与外泌体生物发生和分泌标志物（ALIX、TSG101、RAB27a、RAB27b）的上调进一步相关。尽管 MSCs 的反应存在差异，其中 WJ-MSCs 和 BM-MSCs 在低氧预处理 6-12 小时时显示出这些标志物的上调，而 AD-MSCs 在低氧暴露超过 24 小时时显示出相似的变化。
