Almahasneh Fatimah, Abu-El-Rub Ejlal, Khasawneh Ramada R, Almazari Rawan
Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid 21163, Jordan.
World J Stem Cells. 2024 Apr 26;16(4):434-443. doi: 10.4252/wjsc.v16.i4.434.
Mesenchymal stem cells (MSCs) have been extensively studied for therapeutic potential, due to their regenerative and immunomodulatory properties. Serial passage and stress factors may affect the biological characteristics of MSCs, but the details of these effects have not been recognized yet.
To investigate the effects of stress factors (high glucose and severe hypoxia) on the biological characteristics of MSCs at different passages, in order to optimize the therapeutic applications of MSCs.
In this study, we investigated the impact of two stress conditions; severe hypoxia and high glucose on human adipose-tissue derived MSCs (hAD-MSCs) at passages 6 (P6), P8, and P10. Proliferation, senescence and apoptosis were evaluated measuring WST-1, senescence-associated beta-galactosidase, and annexin V, respectively.
Cells at P6 showed decreased proliferation and increased apoptosis under conditions of high glucose and hypoxia compared to control, while the extent of senescence did not change significantly under stress conditions. At P8 hAD-MSCs cultured in stress conditions had a significant decrease in proliferation and apoptosis and a significant increase in senescence compared to counterpart cells at P6. Cells cultured in high glucose at P10 had lower proliferation and higher senescence than their counterparts in the previous passage, while no change in apoptosis was observed. On the other hand, MSCs cultured under hypoxia showed decreased senescence, increased apoptosis and no significant change in proliferation when compared to the same conditions at P8.
These results indicate that stress factors had distinct effects on the biological processes of MSCs at different passages, and suggest that senescence may be a protective mechanism for MSCs to survive under stress conditions at higher passage numbers.
间充质干细胞（MSCs）因其再生和免疫调节特性而被广泛研究其治疗潜力。连续传代和应激因素可能会影响MSCs的生物学特性，但这些影响的细节尚未明确。
研究应激因素（高糖和严重缺氧）对不同传代MSCs生物学特性的影响，以优化MSCs的治疗应用。
在本研究中，我们研究了两种应激条件；严重缺氧和高糖对第6代（P6）、P8和P10代人脂肪组织来源的MSCs（hAD-MSCs）的影响。分别通过检测WST-1、衰老相关β-半乳糖苷酶和膜联蛋白V来评估增殖、衰老和凋亡情况。
与对照组相比，P6代细胞在高糖和缺氧条件下增殖减少，凋亡增加，而在应激条件下衰老程度无明显变化。与P6代对应细胞相比，应激条件下培养的P8代hAD-MSCs增殖和凋亡显著降低，衰老显著增加。P10代在高糖条件下培养的细胞比上一代对应细胞增殖更低，衰老更高，而凋亡无变化。另一方面，与P8代相同条件相比，缺氧条件下培养的MSCs衰老减少，凋亡增加，增殖无显著变化。
这些结果表明应激因素对不同传代MSCs的生物学过程有不同影响，并表明衰老可能是MSCs在较高传代数的应激条件下存活的一种保护机制。
