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Smad signal pathway regulates angiogenesis via endothelial cell in an adipose-derived stromal cell/endothelial cell co-culture, 3D gel model

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Abstract

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.

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Acknowledgments

This work was funded by the National Natural Science Foundation of China (81470721, 31170929), Sichuan Province Youth Science and Technology Innovation Team (2014TD0001).

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    Authors and Affiliations

    1. State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, People’s Republic of China

      Shiyu Lin, Jing Xie, Tao Gong, Sirong Shi, Tao Zhang, Na Fu & Yunfeng Lin

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    1. Shiyu Lin
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    2. Jing Xie
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    3. Tao Gong
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    4. Sirong Shi
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    5. Tao Zhang
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    6. Na Fu
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    7. Yunfeng Lin
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    Correspondence to Yunfeng Lin.

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    Shiyu Lin and Jing Xie contributed equally to this work.

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    Lin, S., Xie, J., Gong, T. et al. Smad signal pathway regulates angiogenesis via endothelial cell in an adipose-derived stromal cell/endothelial cell co-culture, 3D gel model. Mol Cell Biochem 412, 281–288 (2016). https://doi.org/10.1007/s11010-015-2634-5

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    • DOI: https://doi.org/10.1007/s11010-015-2634-5

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