Hypoxia preconditioned human adipose derived mesenchymal stem cells enhance angiogenic potential via secretion of increased VEGF and bFGF
Hypoxia preconditioned human adipose derived mesenchymal stem cells enhance angiogenic potential via secretion of increased VEGF and bFGF
复制标题
缺氧预处理的人脂肪间充质干细胞通过分泌增加的 VEGF 和 bFGF 增强血管生成潜力
DOI：
10.1002/cbin.10097
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发表时间：
2013-06-01
影响因子：
3.9
通讯作者：
Lu, Feng
中科院分区：
文献类型：
--
作者：
Liu, Linqi;Gao, Jianhua;Lu, Feng
间充质干细胞(MSCs)是一种成人多能细胞，存在于骨髓、脂肪组织和其他成人组织中。骨髓间充质干细胞可促进体内损伤组织的再生，但其机制尚不清楚。通常情况下，间充质干细胞在环境或常氧条件下(21%O2)培养。然而，MSCs的生理生态位的氧分压要低得多。当被用作修复组织损伤的治疗工具时，在标准条件下培养的MSCs必须适应从培养的21%O2到缺血组织中的1%O2。我们检测了低氧预适应(1%O2)对人脂肪间充质干细胞(AD-MSCs)的影响，以发现最能增强其组织再生能力的条件。与常氧预适应相比，AD-MSCs对缺氧的反应呈阳性反应，即使在恶劣的微环境条件下(如低血清介质)，细胞凋亡率也减少，血管生成因子、血管内皮生长因子和碱性成纤维细胞生长因子的表达增加。人脐静脉内皮细胞在低氧预适应AD-MSCs的培养液中具有较高的活力和较低的凋亡率，并在Matrigel上显著增加毛细血管样结构。提示低氧预适应的AD-MSCs可促进组织再生。
Mesenchymal stem cells (MSCs) are adult multipotent cells found in bone marrow, adipose tissue, and other adult tissues. MSCs improve regeneration of injured tissues in vivo, but the mechanisms remain unclear. Typically, MSCs are cultured under ambient or normoxic conditions (21% O2). However, the physiological niches of MSCs have much lower oxygen tension. When used as a therapeutic tool to repair tissue injuries, MSCs cultured in standard conditions must adapt from 21% O2 in culture to <1% O2 in ischemic tissue. We have examined the effects of hypoxia preconditioning (1% O2) in human adipose derived mesenchymal stem cells (AD‐MSCs) to discover the conditions that best enhance their tissue regenerative potential. We demonstrate that AD‐MSCs respond positively to hypoxia compared with normoxia preconditioning, show decreased apoptosis even in severe microenvironmental conditions (such as a low‐serum medium), and an increased expression of the angiogenic factors, vascular endothelial growth factor and basic fibroblast growth factor. Human umbilical vein endothelial cells have higher vitality and lower apoptosis when cultured in medium taken from hypoxia‐preconditioned AD‐MSCs, as well as significantly increased capillary‐like structures with this medium on Matrigel. The data suggest that hypoxia preconditioned AD‐MSCs can improve tissue regeneration.