Smeriglio Piera, Lee Jieun, Bhutani Nidhi
Dept. of Orthopaedic Surgery Stanford University School of Medicine Stanford CA 94305.
Bioeng Transl Med. 2017 Sep 21;2(3):278-284. doi: 10.1002/btm2.10078. eCollection 2017 Sep.
Bone Marrow-derived mesenchymal stem cells (BM-MSC) are an attractive source for cell-based therapies in cartilage injury owing to their efficient differentiation into chondrocytes and their immune-suppressive abilities. However, their clinical use is hampered by a scarcity of cells leading to compromised efficacy. While expansion of human MSC ex vivo can potentially overcome the scarcity of cells, current methods lead to a rapid loss of the stem cell properties. In this study, we report soluble Collagen VI (cartilage pericellular matrix component) as a potential biologic that can expand the MSC population while maintaining the stem cell phenotype as confirmed by expression of the stem cell markers CD105 and CD90. Short-term treatment with Collagen VI additionally retains the potential of MSC to differentiate into mature chondrocytes in pellet culture. Cartilage pellets generated from MSC treated with Collagen VI or control express comparable amounts of the chondrogenic markers Collagen II, Aggrecan and Sox9, and the extracellular glycosaminoglycans. Our observations confirm that the use of the endogenous and cartilage-specific factor Collagen VI is valuable for a rapid and efficient expansion of MSC for potential use in cartilage regeneration and osteoarthritis.
骨髓间充质干细胞(BM-MSC)因其能高效分化为软骨细胞以及具有免疫抑制能力,成为软骨损伤细胞治疗的一个有吸引力的细胞来源。然而,细胞数量稀少导致疗效受损,限制了它们的临床应用。虽然体外扩增人MSC可能克服细胞稀缺问题,但目前的方法会导致干细胞特性迅速丧失。在本研究中,我们报告了可溶性胶原蛋白VI(软骨细胞周围基质成分)作为一种潜在的生物制剂,它可以扩增MSC群体,同时通过干细胞标志物CD105和CD90的表达证实维持干细胞表型。胶原蛋白VI的短期处理还能在微团培养中保留MSC分化为成熟软骨细胞的潜力。用胶原蛋白VI或对照处理的MSC产生的软骨微团表达相当数量的软骨生成标志物胶原蛋白II、聚集蛋白聚糖和Sox9以及细胞外糖胺聚糖。我们的观察结果证实,使用内源性和软骨特异性因子胶原蛋白VI对于快速有效地扩增MSC以用于软骨再生和骨关节炎具有重要价值。