He Yucang, Zhang Zikai, Li Zihao, Lin Ming, Ding Siqi, Wu Hanwen, Yang Fangfang, Cai Zhongming, Li Tian, Wang Jingping, Ke Chen, Pan Shengsheng, Li Liqun
Department of Plastic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
Biotechnol J. 2023 Oct;18(10):e2300021. doi: 10.1002/biot.202300021. Epub 2023 Jun 27.
Adipose-derived stem cells (ADSCs) have important applications in basic research, especially in fat transplantation. Some studies have found that three-dimensional (3D) spheroids formed by mesenchymal stem cells have enhanced therapeutic potential. However, the fundamental basics of this effect are still being discussed. ADSCs were harvested from subcutaneous adipose tissues and 3D spheroids were formed by the automatic aggregation of ADSCs in a non-adhesive 6-well plate. Oxygen glucose deprivation (OGD) was used to simulate the transplantation microenvironment. We found that 3D culture of ADSCs triggered cell autophagy. After inhibiting autophagy by Chloroquine, the rates of apoptosis were increased. When the 3D ADSC-spheroids were re-planked, the number of senescent ADSCs decreased, and the proliferation ability was promoted. In addition, there were more cytokines secreted by 3D ADSC-spheroids including VEGF, IGF-1, and TGF-β. After adding the conditioned medium with human umbilical vein endothelial cells (HUVECs), 3D ADSC-spheroids were more likely to promote migration, and tube formation, stimulating the formation of new blood vessels. Fat grafting experiments in nude mice also showed that 3D ADSC-spheroids enhanced survival and neovascularization of fat grafts. These results suggested that 3D spheroids culturing of ADSCs can increase the therapeutic potential in fat transplantation.
脂肪来源干细胞（ADSCs）在基础研究中具有重要应用，尤其是在脂肪移植方面。一些研究发现，间充质干细胞形成的三维（3D）球体具有增强的治疗潜力。然而，这种效应的基本原理仍在讨论中。从皮下脂肪组织中获取ADSCs，并通过ADSCs在非黏附性6孔板中自动聚集形成3D球体。采用氧糖剥夺（OGD）来模拟移植微环境。我们发现ADSCs的3D培养触发了细胞自噬。用氯喹抑制自噬后，细胞凋亡率增加。当将3D ADSC球体重新接种时，衰老ADSCs的数量减少，增殖能力得到促进。此外，3D ADSC球体分泌更多的细胞因子，包括血管内皮生长因子（VEGF）、胰岛素样生长因子-1（IGF-1）和转化生长因子-β（TGF-β）。加入含人脐静脉内皮细胞（HUVECs）的条件培养基后，3D ADSC球体更易促进迁移和血管生成，刺激新血管形成。裸鼠脂肪移植实验也表明，3D ADSC球体可提高脂肪移植的存活率和新生血管形成。这些结果表明，ADSCs的3D球体培养可增加脂肪移植中的治疗潜力。
