Adipose tissue and bone marrow‐derived stem cells react similarly in an ischaemia‐like microenvironment
Adipose tissue and bone marrow‐derived stem cells react similarly in an ischaemia‐like microenvironment
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DOI：
10.1002/term.452
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发表时间：
2012-06
影响因子：
3.3
通讯作者：
K. Tse;P. Kingham;L. Novikov;M. Wiberg
中科院分区：
文献类型：
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作者：
K. Tse;P. Kingham;L. Novikov;M. Wiberg
来自脂肪组织和骨髓的间充质干细胞（MSCs）是神经损伤的自体细胞治疗的有希望的细胞来源，如其内在的神经营养潜能所证明的。然而，移植细胞的广泛死亡限制了它们的全部益处。本研究探讨了缺血（由叠氮化钠和2-脱氧葡萄糖代谢诱导）和血清源性有丝分裂原对体外MSC活力和功能特征的影响。间充质干细胞更容易合并，而不是单独，糖酵解和氧化磷酸化的封锁。细胞凋亡和自噬参与缺血诱导的细胞死亡。单独化学性缺血和单独血清戒断诱导相似量的细胞死亡，具有显著不同的细胞内ATP维持。联合缺血和血清剥夺对细胞死亡有累加效应。细胞外基质（ECM）分子层粘连蛋白和纤连蛋白的表达减弱缺血和独立的血清水平，然而，BDNF和NGF水平保持相对恒定。在缺血条件下观察到VEGF和血管生成素-1的强烈上调，但在血清戒断条件下未观察到。重要的是，这项研究证明了在缺血样和缺乏有丝分裂原的微环境中，脂肪和骨髓组织来源的MSC在活力、细胞能量学、细胞死亡机制和各种生长促进分子的表达水平方面的相似反应。此外，结果表明，缺血对MSC存活移植的能力的影响大于有丝分裂原的撤回。版权所有© 2011约翰威利父子有限公司.
Mesenchymal stem cells (MSCs) from adipose tissue and bone marrow are promising cell sources for autologous cell therapy of nerve injuries, as demonstrated by their intrinsic neurotrophic potential. However, extensive death of transplanted cells limits their full benefits. This study investigated the effects of ischaemia (metabolically induced by sodium azide and 2‐deoxyglucose) and serum‐derived mitogens on the viability and functional profile of MSCs in vitro. MSCs were more susceptible to combined, rather than individual, blockade of glycolysis and oxidative phosphorylation. Apoptosis and autophagy were involved in ischaemia‐induced cell death. Chemical ischaemia alone and serum withdrawal alone induced a similar amount of cell death, with significantly different intracellular ATP maintenance. Combined ischaemia and serum deprivation had additive effects on cell death. Expression of the extracellular matrix (ECM) molecules laminin and fibronectin was attenuated under ischaemia and independent of serum level; however, BDNF and NGF levels remained relatively constant. Strong upregulation of VEGF and to a lesser extent angiopoietin‐1 was observed under ischaemia but not in serum withdrawal conditions. Importantly, this study demonstrated similar reactions of MSCs derived from adipose and bone marrow tissue, in ischaemia‐like and mitogen‐deprived microenvironments in terms of viability, cellular energetics, cell death mechanisms and expression levels of various growth‐promoting molecules. Also, the results suggest that ischaemia has a larger impact on the ability of MSCs to survive transplantation than withdrawal of mitogens. Copyright © 2011 John Wiley & Sons, Ltd.