Lin Shiyu, Xie Jing, Gong Tao, Shi Sirong, Zhang Tao, Fu Na, Lin Yunfeng
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, People's Republic of China.
Mol Cell Biochem. 2016 Jan;412(1-2):281-8. doi: 10.1007/s11010-015-2634-5. Epub 2015 Dec 22.
Co-implantation of adipose-derived stromal cells (ASCs) and endothelial cells (ECs) can markedly expedite the formation of functional microvascular beds and provides possible methods for cell-based revascularization therapies to treat various diseases. Furthermore, we investigated the role of TGFβ/Smad signaling pathway for angiogenesis in a three-dimensional (3D) collagen gel model established in vitro with co-culture between ASCs and ECs. We found that angiogenesis was attenuated in the co-culture gels after inhibition of ALK5/Smad2/3 with SB431542. Genes coding for VEGF-A, VEGF-B, VE-ca, FGF-1, PDGF, BMP-4, and BMP-7 were significantly reduced in both mono-cultured and co-cultured ECs. Furthermore, the decrease in co-cultured ECs was prominent relative to mono-cultured ECs. Taken together, these findings suggest that in the co-culture between ASCs and ECs, TGFβ/Smad signal pathway regulates angiogenesis via ECs; moreover, the findings that the co-cultured ECs were regulated more significantly than mono-cultured ECs suggest that suppression of Smad signal pathway may regulate the paracrine secretion of ASCs to further modulate angiogenesis of ECs.
脂肪来源的基质细胞（ASC）与内皮细胞（EC）的共植入能够显著加速功能性微血管床的形成，并为基于细胞的血管再生疗法治疗各种疾病提供了可能的方法。此外，我们在体外建立的三维（3D）胶原凝胶模型中，通过ASC与EC的共培养，研究了TGFβ/Smad信号通路在血管生成中的作用。我们发现，用SB431542抑制ALK5/Smad2/3后，共培养凝胶中的血管生成减弱。在单培养和共培养的EC中，编码VEGF-A、VEGF-B、VE-ca、FGF-1、PDGF、BMP-4和BMP-7的基因显著减少。此外，相对于单培养的EC，共培养的EC中的减少更为明显。综上所述，这些发现表明，在ASC与EC的共培养中，TGFβ/Smad信号通路通过EC调节血管生成；此外，共培养的EC比单培养的EC受到更显著调节的发现表明，抑制Smad信号通路可能调节ASC的旁分泌分泌，以进一步调节EC的血管生成。
