Fensky Florian, Reichert Johannes C, Traube Andrea, Rackwitz Lars, Siebenlist Sebastian, Nöth Ulrich
Biomed Tech (Berl). 2014 Oct;59(5):375-83. doi: 10.1515/bmt-2013-0076.
Hyaline cartilage displays a limited regenerative potential. Consequently, therapeutic approaches have been developed to treat focal cartilage lesions. Larger-sized lesions are commonly treated by osteochondral grafting/mosaicplasty, autologous chondrocyte implantation (ACI) or matrix-induced chondrocyte implantation (MACI). As an alternative cell source to chondrocytes, multipotent mesenchymal stem cells (MSCs) are regarded a promising option. We therefore investigated the feasibility of pre-differentiating human MSCs incorporated in hydrogels clinically applied for MACI (CaReS®). MSC-laden hydrogels were cast and cultured over 10 days in a defined chondrogenic differentiation medium supplemented with TGF-β1. This was followed by an 11-day culture in TGF-β1 free media. After 21 days, considerable contraction of the hydrogels was observed. Histochemistry showed cells of a chondrocyte-like morphology embedded in a proteoglycan-rich extracellular matrix. Real-time polymerase chain reaction (RT-PCR) analysis showed the expression of chondrogenic marker genes, such as collagen type II and aggrecan. In summary, we demonstrate that chondrogenic differentiation of human mesenchymal stem cells embedded in collagen type I hydrogels can be induced under the influence of TGF-β1 over a period of 10 days.
透明软骨的再生潜力有限。因此，人们已开发出多种治疗方法来治疗局灶性软骨损伤。较大面积的损伤通常采用骨软骨移植/镶嵌成形术、自体软骨细胞植入（ACI）或基质诱导软骨细胞植入（MACI）进行治疗。作为软骨细胞的替代细胞来源，多能间充质干细胞（MSCs）被认为是一种有前景的选择。因此，我们研究了预分化临床应用于MACI（CaReS®）的水凝胶中所含人MSCs的可行性。将负载MSCs的水凝胶浇铸成型，并在添加了转化生长因子-β1（TGF-β1）的特定软骨分化培养基中培养10天。随后在不含TGF-β1的培养基中培养11天。21天后，观察到水凝胶有明显收缩。组织化学显示，细胞呈软骨细胞样形态，嵌入富含蛋白聚糖的细胞外基质中。实时聚合酶链反应（RT-PCR）分析显示了软骨生成标记基因的表达，如II型胶原蛋白和聚集蛋白聚糖。总之，我们证明，在TGF-β1的影响下，I型胶原水凝胶中所含人骨髓间充质干细胞可在10天内被诱导发生软骨分化。
