Locally applied vascular endothelial growth factor A increases the osteogenic healing capacity of human adipose-derived stem cells by promoting osteogenic and endothelial differentiation.
Locally applied vascular endothelial growth factor A increases the osteogenic healing capacity of human adipose-derived stem cells by promoting osteogenic and endothelial differentiation.
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DOI：
10.1002/stem.581
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发表时间：
2011-02
期刊：
影响因子：
5.2
通讯作者：
Quarto, Natalina
中科院分区：
文献类型：
--
作者：
Behr, Bjoern;Tang, Chad;Germann, Guenter;Longaker, Michael T.;Quarto, Natalina
人脂肪来源的干细胞（hASC）以其在应用于骨缺损时促进骨愈合的能力而闻名。对于骨组织再生，需要足够的血管生成和骨生成。血管内皮生长因子A（VEGFA）具有促进共同祖细胞向两种谱系分化的潜力。为了验证这一假设，在体外测试了VEGFA在成骨分化期间对hASC的影响。此外，将hASC接种在用VEGFA局部处理的鼠临界大小的颅骨缺损中。碱性磷酸酶活性、茜素红染色和QRT-PCR分析表明，VEGFA可促进体外成骨分化。此外，局部应用VEGFA的hASC显着改善愈合的关键尺寸的颅骨缺损在体内。这种修复伴随着血管生成的显著增强。旁分泌和在较小程度上，VEGFA处理的hASCs的细胞自主效应都是血管生成的原因。这些数据通过利用CD 31-/CD 45-小鼠ASCsGFP+细胞得到证实。总之，我们证明了VEGFA在体外和体内增加了hASCS的成骨分化，这伴随着血管生成的增强。此外，我们发现在骨再生过程中，VEGFA治疗后hASCs血管生成的增加归因于旁分泌和细胞自主效应。因此，局部应用的VEGFA可能被证明是一种有价值的生长因子，可以介导多能hASC在骨再生的背景下的骨生成和血管生成。
Human adipose derived stem cells (hASCs) are known for their capability to promote bone healing when applied to bone defects. For bone tissue regeneration, both sufficient angiogenesis and osteogenesis is desirable. Vascular endothelial growth factor A (VEGFA) has the potential to promote differentiation of common progenitor cells to both lineages. To test this hypothesis, the effects of VEGFA on hASCs during osteogenic differentiation were tested in vitro. In addition, hASCs were seeded in murine critical-sized calvarial defects locally treated with VEGFA. Our results suggest that VEGFA improves osteogenic differentiation in vitro as indicated by alkaline phosphatase activity, alizarin red staining, and QRT-PCR analysis. Moreover, local application of VEGFA to hASCs significantly improved healing of critical sized calvarial defects in vivo. This repair was accompanied by a striking enhancement of angiogenesis. Both paracrine and, to a lesser degree, cell-autonomous effects of VEGFA treated hASCs were accountable for angiogenesis. These data were confirmed by utilization of CD31-/CD45- mouse ASCsGFP+ cells. In summary, we demonstrated that VEGFA increased osteogenic differentiation of hASCS in vitro and in vivo, which was accompanied by an enhancement of angiogenesis. Additionally, we showed that during bone regeneration, the increase in angiogenesis of hASCs upon treatment with VEGFA was attributable to both paracrine and cell-autonomous effects. Thus, locally applied VEGFA might prove to be a valuable growth factor that can mediate both osteogenesis and angiogenesis of multipotent hASCs in the context of bone regeneration.
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