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脂肪组织和骨髓来源的干细胞在类似缺血的微环境中反应相似。

Adipose tissue and bone marrow-derived stem cells react similarly in an ischaemia-like microenvironment.

机构信息

Department of Integrative Medical Biology, Section of Anatomy, Umeå University, Sweden.

出版信息

J Tissue Eng Regen Med. 2012 Jun;6(6):473-85. doi: 10.1002/term.452. Epub 2011 Jul 13.

Abstract

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.

摘要

脂肪组织和骨髓间充质干细胞(MSCs)因其内在的神经营养潜力,被证明是治疗神经损伤的自体细胞治疗有前途的细胞来源。然而,移植细胞的大量死亡限制了它们的全部益处。本研究探讨了缺血(通过叠氮化钠和 2-脱氧葡萄糖代谢诱导)和血清来源的有丝分裂原对 MSCs 体外活力和功能特征的影响。与单独阻断糖酵解和氧化磷酸化相比,MSCs 更容易受到联合而非单独阻断糖酵解和氧化磷酸化的影响。细胞凋亡和自噬参与了缺血诱导的细胞死亡。单独的化学缺血和单独的血清耗竭诱导了相似数量的细胞死亡,细胞内 ATP 维持有显著差异。联合缺血和血清剥夺对细胞死亡有相加作用。细胞外基质(ECM)分子层粘连蛋白和纤连蛋白的表达在缺血条件下减弱,且与血清水平无关;然而,BDNF 和 NGF 水平相对保持不变。在缺血条件下观察到 VEGF 的强烈上调,而在血清剥夺条件下则观察到血管生成素-1 的较弱上调。重要的是,这项研究表明,脂肪组织和骨髓组织来源的 MSCs 在缺血样和有丝分裂原缺乏的微环境中,在活力、细胞能量学、细胞死亡机制和各种促生长分子的表达水平方面,表现出相似的反应。此外,研究结果表明,与有丝分裂原耗尽相比,缺血对 MSCs 移植后存活能力的影响更大。

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