Pinheiro-Machado Erika, Koster Claudia, Smink Alexandra
Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Biosci Rep. 2025 Apr 23;45(5):325-42. doi: 10.1042/BSR20241389.
The secretome of adipose-derived stromal cells (ASC) presents a promising avenue for cell-free therapies due to their rich mixture of bioactive molecules. Different culture conditions can modulate the composition of this mixture, but how this affects the functional properties of the secretome remains to be investigated. This study investigated the in vitro effects of normoxia, cytokines, high glucose, hypoxia, and hypoxia + high glucose-derived ASC secretomes on angiogenesis (tube formation assay), collagen deposition (Picrosirius-Red staining), and immunomodulation (One-way Mixed Lymphocyte Reaction in combination with an antibody-mediated cell-dependent cytotoxicity assay). The data showed that normoxia and hypoxia-derived secretomes consistently exhibited potent proangiogenic effects in both human and rat models. These secretomes also demonstrated positive influences on collagen deposition and immunomodulation. Interestingly, the human ASC hypoxia + high glucose-derived secretome emerged as a stimulator of collagen deposition and modulator of the immune system. Conversely, cytokines and high glucose-derived secretomes have shown less strong effects in almost all functional parameters. In conclusion, our findings indicate that modulating culturing conditions results in secretomes with different functional properties and emphasizes the multifaceted role of ASC secretomes in regenerative processes.
脂肪来源的间充质干细胞（ASC）的分泌组因其富含生物活性分子混合物，为无细胞治疗提供了一条有前景的途径。不同的培养条件可以调节这种混合物的组成，但这如何影响分泌组的功能特性仍有待研究。本研究调查了常氧、细胞因子、高糖、缺氧以及缺氧+高糖条件下ASC分泌组对血管生成（管形成试验）、胶原蛋白沉积（天狼星红染色）和免疫调节（单向混合淋巴细胞反应结合抗体介导的细胞依赖性细胞毒性试验）的体外影响。数据显示，常氧和缺氧条件下的分泌组在人和大鼠模型中均始终表现出强大的促血管生成作用。这些分泌组对胶原蛋白沉积和免疫调节也显示出积极影响。有趣的是，人ASC缺氧+高糖条件下的分泌组成为胶原蛋白沉积的刺激剂和免疫系统的调节剂。相反，细胞因子和高糖条件下的分泌组在几乎所有功能参数上的作用较弱。总之，我们的研究结果表明，调节培养条件会导致具有不同功能特性的分泌组，并强调了ASC分泌组在再生过程中的多方面作用。
