Encapsulated Mesenchymal Stromal Cell Microbeads Promote Endogenous Regeneration of Osteoarthritic Cartilage Ex Vivo.
Encapsulated Mesenchymal Stromal Cell Microbeads Promote Endogenous Regeneration of Osteoarthritic Cartilage Ex Vivo.
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DOI：
10.1002/adhm.202002118
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发表时间：
2021-04
影响因子：
10
通讯作者：
Bhutani, Nidhi
中科院分区：
文献类型：
--
作者：
Sahu, Neety;Agarwal, Pranay;Grandi, Fiorella;Bruschi, Michela;Goodman, Stuart;Amanatullah, Derek;Bhutani, Nidhi
间充质基质细胞(MSCs)的抗炎分泌体对骨关节炎(OA)的治疗是有利的，骨关节炎是一种以低度炎症为特征的疾病。然而，MSC分泌组对患者来源的骨性关节炎组织的确切作用尚不清楚。为了研究这些效应，将藻酸盐包裹的间充质干细胞与患者来源的骨性关节炎软骨共培养8天。经藏红花O染色证实，与单独培养的对照骨性关节炎外植体相比，加入MSC微球培养的骨性关节炎软骨组织中蛋白多糖的分布明显改善。与MSC微球共培养第8天，OA外植体中总糖胺聚糖(SGAG)的含量显著增加，释放到培养液中的SGAG不受MSC微球的影响，提示OA外植体中SGAG的合成是从头开始的。与MSC微球共培养后，骨性关节炎外植体中DNA含量增加，Ki67+细胞数增加，提示有增殖现象。多重细胞因子分析表明，在OA外植体中，分泌的细胞因子IL-10、HGF和sFas增加，TIMP1水平增加，凋亡细胞百分比减少。综上所述，数据表明，海藻酸盐分泌的旁分泌因子包裹了MSCs微珠，以响应骨关节炎软骨，创造了一个合成代谢、增殖和抗凋亡的微环境，诱导临床相关的患者来源的骨关节炎软骨的内源性再生。
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.
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成年人类骨髓衍生，培养，合并，同种异体间质基质细胞（STEMPEUCEL®）的功效和安全性：膝关节骨关节炎中的临床前和临床试验。
影响因子：
4.9
作者：
Gupta PK;Chullikana A;Rengasamy M;Shetty N;Pandey V;Agarwal V;Wagh SY;Vellotare PK;Damodaran D;Viswanathan P;Thej C;Balasubramanian S;Majumdar AS
通讯作者：
Majumdar AS
影响因子：
--
作者：
Gonzalez, Manuel A.;Gonzalez-Rey, Elena;Delgado, Mario
通讯作者：
Delgado, Mario
影响因子：
4.3
作者：
Liu, Yubao;Lin, Lupan;Lin, Fuqing
通讯作者：
Lin, Fuqing
DOI：
10.1073/pnas.1819415116
发表时间：
2019-07-30
影响因子：
11.1
作者：
Mao, Angelo S.;Ozkale, Berna;Mooney, David J.
通讯作者：
Mooney, David J.
源自过表达 miR-92a-3p 的人间充质干细胞的外泌体通过靶向 WNT5A 增强软骨形成并抑制软骨降解。
影响因子：
7.5
作者：
Mao G;Zhang Z;Hu S;Zhang Z;Chang Z;Huang Z;Liao W;Kang Y
通讯作者：
Kang Y