Department of Plastic Surgery, Hand Surgery-Burn Center, University Hospital RWTH Aachen, Aachen, Germany.
Department of Plastic Surgery and Hand Surgery, University Hospital Zurich, Zurich, Switzerland.
J Tissue Eng Regen Med. 2021 Jan;15(1):88-98. doi: 10.1002/term.3152. Epub 2020 Nov 23.
Adipose stem cells (ASCs) possess the capacity to proliferate, to differentiate into various cells types, and they are able to secrete growth factors. These characteristics are supposed to contribute to their potential for regenerative medicine approaches. In order to advance the therapeutic effects of ASCs, different modulatory procedures have been examined. In this context, the endocannabinoid system (ECS) represents an interesting possibility, since the increased availability of cannabinoids and the underlying molecular pathways of the ECS are of relevance for the development of new regenerative strategies. The effects of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) were investigated on ASC metabolic activity, quantified by PrestoBlue conversion, and cell numbers, evaluated by crystal violet staining. enzyme-linked immunosorbent assay (ELISA) measures were performed to determine cytokine release, and differentiation was assessed by specific labeling techniques. AEA increased the metabolic activity, while 2-AG decreased it in a concentration dependent manner. AEA significantly enhanced OilRed O staining after adipogenic differentiation by over 100%, and both compounds significantly increased cresolphthalein staining after osteogenic differentiation. By contrast, they did not affect sphere diameter or safranin O staining after chondrogenic differentiation. Both substances significantly increased the release of insulin-like growth factor-1 and hepatocyte growth factor, while only AEA enhanced transforming growth factor-β secretion. The results demonstrated that stimulating the ECS exerted significant effects on the biology of ASCs. Exposure to endocannabinoids modulated viability, induced release of regenerative growth factors, and promoted adipogenic and osteogenic differentiation. Our findings could be of specific relevance in ASC based therapies for regenerative medicine.
脂肪干细胞 (ASCs) 具有增殖、分化为多种细胞类型的能力，并且能够分泌生长因子。这些特性被认为有助于它们在再生医学方法中的应用潜力。为了提高 ASCs 的治疗效果，已经研究了不同的调节程序。在这种情况下，内源性大麻素系统 (ECS) 代表了一种有趣的可能性，因为大麻素的可用性增加以及 ECS 的潜在分子途径与新的再生策略的发展有关。内源性大麻素大麻素 (AEA) 和 2-花生四烯酸甘油 (2-AG) 的作用通过 PrestoBlue 转化来研究 ASCs 的代谢活性，通过结晶紫染色来评估细胞数量。通过酶联免疫吸附测定 (ELISA) 测量来确定细胞因子的释放，并通过特定的标记技术评估分化。AEA 以浓度依赖的方式增加代谢活性，而 2-AG 则降低代谢活性。AEA 在成脂分化后通过超过 100%显著增强油红 O 染色，两种化合物在成骨分化后均显著增加 cresolphthalein 染色。相比之下，它们不会影响软骨分化后的球体直径或 safranin O 染色。两种物质均显著增加胰岛素样生长因子-1 和肝细胞生长因子的释放，而只有 AEA 增强转化生长因子-β的分泌。结果表明，刺激 ECS 对 ASCs 的生物学产生了显著影响。暴露于内源性大麻素调节细胞活力，诱导再生生长因子的释放，并促进成脂和成骨分化。我们的研究结果可能在基于 ASC 的再生医学治疗中具有特定的相关性。
