Differentiation-dependent secretion of proangiogenic factors by mesenchymal stem cells.
Differentiation-dependent secretion of proangiogenic factors by mesenchymal stem cells.
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DOI：
10.1371/journal.pone.0035579
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Leach JK
中科院分区：
文献类型：
--
作者：
Hoch AI;Binder BY;Genetos DC;Leach JK
间充质干细胞(MSCs)具有增殖潜能、分化为成骨细胞的能力以及分泌刺激血管生成和新生血管的营养因子，是一种很有前途的细胞基骨修复细胞群。为了促进骨愈合，自体或同种异体骨髓间充质干细胞在不同程度上向成骨细胞方向分化后被移植到骨缺损中。然而，成骨分化阶段对血管生成因子分泌的影响尚不清楚。我们假设间充质干细胞的前血管生成潜能取决于其成骨分化的阶段。培养7天后，观察到地塞米松(OM+)对MSCs的成骨分化作用最强。相反，在生长培养液(GM)中培养的MSCs中，VEGF蛋白的分泌和血管生成基因的上调最多。在每种培养条件下使用MSCs的条件培养液，GM条件培养液最大限度地促进内皮细胞的增殖，促进内皮细胞的趋化迁移和小管形成。在条件培养液中加入中和的VEGF165/121抗体可抑制ECFC的增殖和趋化迁移。种植在微载体珠上的ECFC与先前在GM中培养的MSCs在纤维蛋白凝胶中共培养，与先前在OM+中培养的MSCs相比，显示出更好的发芽能力。这些结果证实，在成骨谱系下诱导的MSCs具有降低的促血管生成能力，从而为将MSCs用于骨修复提供了重要的研究结果。
Mesenchymal stem cells (MSCs) are a promising cell population for cell-based bone repair due to their proliferative potential, ability to differentiate into bone-forming osteoblasts, and their secretion of potent trophic factors that stimulate angiogenesis and neovascularization. To promote bone healing, autogenous or allogeneic MSCs are transplanted into bone defects after differentiation to varying degrees down the osteogenic lineage. However, the contribution of the stage of osteogenic differentiation upon angiogenic factor secretion is unclear. We hypothesized that the proangiogenic potential of MSCs was dependent upon their stage of osteogenic differentiation. After 7 days of culture, we observed the greatest osteogenic differentiation of MSCs when cells were cultured with dexamethasone (OM+). Conversely, VEGF protein secretion and upregulation of angiogenic genes were greatest in MSCs cultured in growth media (GM). Using conditioned media from MSCs in each culture condition, GM-conditioned media maximized proliferation and enhanced chemotactic migration and tubule formation of endothelial colony forming cells (ECFCs). The addition of a neutralizing VEGF165/121 antibody to conditioned media attenuated ECFC proliferation and chemotactic migration. ECFCs seeded on microcarrier beads and co-cultured with MSCs previously cultured in GM in a fibrin gel exhibited superior sprouting compared to MSCs previously cultured in OM+. These results confirm that MSCs induced farther down the osteogenic lineage possess reduced proangiogenic potential, thereby providing important findings for consideration when using MSCs for bone repair.
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