Hypoxia-preconditioned adipose-derived stem cells combined with scaffold promote urethral reconstruction by upregulation
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RESEARCH
Open Access
Hypoxia-preconditioned adipose-derived stem cells combined with scaffold promote urethral reconstruction by upregulation of angiogenesis and glycolysis Xiang Wan†, Min-kai Xie†, Huan Xu†, Zi-wei Wei, Hai-jun Yao, Zhong Wang* and Da-chao Zheng*
Abstract Rationale: Tissue engineering is a promising alternative for urethral reconstruction, and adipose-derived stem cells (ADSCs) are widely used as seeding cells. Hypoxia preconditioning can significantly enhance the therapeutic effects of ADSCs. The low oxygen tension of postoperative wound healing is inevitable and may facilitate the nutritional function of ADSCs. This study aimed to investigate if hypoxia-preconditioned ADSCs, compared to normoxiapreconditioned ADSCs, combined with scaffold could better promote urethral reconstruction and exploring the underlying mechanism. Methods: In vitro, paracrine cytokines and secretomes that were secreted by hypoxia- or normoxia-preconditioned ADSCs were added to cultures of human umbilical vein endothelial cells (HUVECs) to measure their functions. In vivo, hypoxia- or normoxia-preconditioned ADSCs were seeded on a porous nanofibrous scaffold for urethral repair on a defect model in rabbits. Results: The in vitro results showed that hypoxia could enhance the secretion of VEGFA by ADSCs, and hypoxiapreconditioned ADSCs could enhance the viability, proliferation, migration, angiogenesis, and glycolysis of HUVECs (p < 0.05). After silencing VEGFA, angiogenesis and glycolysis were significantly inhibited (p < 0.05). The in vivo results showed that compared to normoxia-preconditioned ADSCs, hypoxia-preconditioned ADSCs combined with scaffolds led to a larger urethral lumen diameter, preserved urethral morphology, and enhanced angiogenesis (p < 0.05). Conclusions: Hypoxia preconditioning of ADSCs combined with scaffold could better promote urethral reconstruction by upregulating angiogenesis and glycolysis. Hypoxia-preconditioned ADSCs combined with novel scaffold may provide a promising alternative treatment for urethral reconstruction. Keywords: Hypoxia, Adipose-derived stem cells, Angiogenesis, Glycolysis, Urethral, Tissue engineering
* Correspondence: [email protected]; [email protected] † Xiang Wan, Min-kai Xie and Huan Xu contributed equally to this work. Department of Urology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, No.639, Zhizaoju Road in Huangpu District, Shanghai 200011, China © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not includ
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