Hypoxia-cultured human adipose-derived mesenchymal stem cells are non-oncogenic and have enhanced viability, motility, and tropism to brain cancer.
Hypoxia-cultured human adipose-derived mesenchymal stem cells are non-oncogenic and have enhanced viability, motility, and tropism to brain cancer.
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DOI：
10.1038/cddis.2014.521
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发表时间：
2014-12-11
影响因子：
9
通讯作者：
Quiñones-Hinojosa A
中科院分区：
文献类型：
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作者：
Feng Y;Zhu M;Dangelmajer S;Lee YM;Wijesekera O;Castellanos CX;Denduluri A;Chaichana KL;Li Q;Zhang H;Levchenko A;Guerrero-Cazares H;Quiñones-Hinojosa A
成人脂肪来源的间充质干细胞(HAMSCs)是一种多能细胞，数量丰富，易于收集，并且绕过了困扰胚胎干细胞的伦理问题。它们的实用性和可获得性导致了临床研究的快速发展，以探索其基于自体和异体细胞的再生潜力、组织保存能力、抗炎特性和抗癌特性等。HAMSCs通常在含21%氧气的环境条件下培养。然而，从生理上讲，hAMSCs存在于氧分压低得多的环境中。此外，在标准条件下培养的hAMSCs表现出有限的增殖和迁移能力，以及有限的生存能力。本研究调查低氧培养条件对术中原代来源的hAMSCs的影响。在低氧条件下培养的hAMSCs(hAMSCs-H)仍然具有多潜能，能够分化为成骨、成软骨和成脂细胞系。此外，hAMSCs-H生长更快，细胞死亡更少。此外，hAMSCs-H比常氧培养的hAMSCs具有更大的运动性，在体内外对来源于患者脑肿瘤起始细胞的胶质母细胞瘤(GBM)表现出更强的归巢能力。重要的是，hAMSCs-H在体外不会转化为肿瘤相关的成纤维细胞，在体内也不会致瘤。相反，hAMSCs-H在体外和体内都促进了脑癌细胞的分化。这些发现提示了一种替代的培养技术，可以增强hAMSCs的功能，这可能是它们用于治疗包括中风、心肌梗死、肌萎缩侧索硬化症和GBM在内的各种病理疾病所必需的。
Adult human adipose-derived mesenchymal stem cells (hAMSCs) are multipotent cells, which are abundant, easily collected, and bypass the ethical concerns that plague embryonic stem cells. Their utility and accessibility have led to the rapid development of clinical investigations to explore their autologous and allogeneic cellular-based regenerative potential, tissue preservation capabilities, anti-inflammatory properties, and anticancer properties, among others. hAMSCs are typically cultured under ambient conditions with 21% oxygen. However, physiologically, hAMSCs exist in an environment of much lower oxygen tension. Furthermore, hAMSCs cultured in standard conditions have shown limited proliferative and migratory capabilities, as well as limited viability. This study investigated the effects hypoxic culture conditions have on primary intraoperatively derived hAMSCs. hAMSCs cultured under hypoxia (hAMSCs-H) remained multipotent, capable of differentiation into osteogenic, chondrogenic, and adipogenic lineages. In addition, hAMSCs-H grew faster and exhibited less cell death. Furthermore, hAMSCs-H had greater motility than normoxia-cultured hAMSCs and exhibited greater homing ability to glioblastoma (GBM) derived from brain tumor-initiating cells from our patients in vitro and in vivo. Importantly, hAMSCs-H did not transform into tumor-associated fibroblasts in vitro and were not tumorigenic in vivo. Rather, hAMSCs-H promoted the differentiation of brain cancer cells in vitro and in vivo. These findings suggest an alternative culturing technique that can enhance the function of hAMSCs, which may be necessary for their use in the treatment of various pathologies including stroke, myocardial infarction, amyotrophic lateral sclerosis, and GBM.