Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Neurological Disease Institute, Gladstone Institutes, University of California, San Francisco, CA, 94107, USA.
Adv Healthc Mater. 2021 Apr;10(8):e2002118. doi: 10.1002/adhm.202002118. Epub 2021 Jan 12.
The anti-inflammatory secretome of mesenchymal stromal cells (MSCs) is lucrative for the treatment of osteoarthritis (OA), a disease characterized by low-grade inflammation. However, the precise effects of the MSC secretome on patient-derived OA tissue is lacking. To investigate these effects, alginate encapsulated MSCs are co-cultured with patient-derived OA cartilage explants for 8 days. Proteoglycan distribution in OA cartilage explants examined by Safranin O staining is markedly improved when cultured with MSC microbeads as compared to control OA explants cultured alone. Total sulfated glycosaminoglycan (sGAG) content in OA explants is significantly increased upon co-culture with MSC microbeads on day 8. The sGAG released into the culture media is unchanged by the presence of MSC microbeads, suggesting de novo sGAG synthesis in OA explants. Co-culture with MSC microbeads increased the DNA content and Ki67 cells in OA explants, indicating proliferation. An increase in secreted cytokines IL-10, HGF, and sFAS assessed by multiplex cytokine assay, increased TIMP1 levels, and reduction in percent apoptotic cells in OA explants is noted. Together, data demonstrates that paracrine factors secreted by alginate encapsulated MSCs microbeads in response to OA cartilage, create an anabolic, proliferative, and anti-apoptotic microenvironment inducing endogenous regeneration in clinically relevant, patient-derived OA cartilage.
间充质基质细胞（MSCs）的抗炎分泌组对于治疗骨关节炎（OA）是有利的，OA 是一种以低度炎症为特征的疾病。然而，MSCs 分泌组对患者来源的 OA 组织的确切作用尚不清楚。为了研究这些作用，用藻酸盐包被的 MSC 与患者来源的 OA 软骨外植体共培养 8 天。与单独培养的对照 OA 外植体相比，用 MSC 微球共培养后，OA 软骨外植体中的蛋白聚糖分布通过番红 O 染色得到明显改善。在第 8 天与 MSC 微球共培养时，OA 外植体中的总硫酸化糖胺聚糖（sGAG）含量显著增加。OA 外植体释放到培养介质中的 sGAG 不受 MSC 微球的影响，这表明 OA 外植体中存在新的 sGAG 合成。与 MSC 微球共培养增加了 OA 外植体中的 DNA 含量和 Ki67 细胞，表明增殖。通过多重细胞因子分析评估的分泌细胞因子 IL-10、HGF 和 sFAS 的增加、TIMP1 水平的增加以及 OA 外植体中凋亡细胞比例的降低。总的来说，数据表明，藻酸盐包被的 MSC 微球对 OA 软骨的反应分泌的旁分泌因子，在临床上相关的、患者来源的 OA 软骨中产生合成代谢、增殖和抗凋亡的微环境，诱导内源性再生。
