Dikina Anna D, Almeida Henrique V, Cao Meng, Kelly Daniel J, Alsberg Eben
Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, United States.
Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, 152-160 Pearse Street, Dublin 2, Ireland.
ACS Biomater Sci Eng. 2017 Jul 10;3(7):1426-1436. doi: 10.1021/acsbiomaterials.6b00654. Epub 2017 Feb 27.
Osteoarthritis is a leading cause of disability affecting an increasing number of individuals. However, cartilage replacement therapies are inadequate, and better cartilage regeneration products must be developed. In this work, we describe a human mesenchymal stem cell (hMSC)-based approach for fabricating extracellular matrix (ECM) scaffolds from tissue-engineered cartilage sheets and then for inducing chondrogenesis of reseeded hMSCs within the ECM scaffolds. Two types of ECM scaffolds were fabricated: one from high-density hMSC sheets cultured with media-supplemented transforming growth factor beta-1 (TGF-β1; -MS) and the other from high-density hMSC sheets incorporated with TGF-β1-laden gelatin microspheres (+MS), which significantly enhance chondrogenesis within the sheet system. Interestingly, when scaffolds were reseeded with hMSCs, -MS scaffolds lead to significantly more glycosaminoglycan (GAG) accumulation than +MS scaffolds. Importantly, ECM scaffolds could be soak loaded with TGF-β1 to produce cartilage of similar quality as that of constructs cultured with TGF-β1 in the media, thereby removing the need for supplementing the media with the growth factor. Lastly, tissues formed with the scaffolds were larger with more uniform cartilage matrix elaboration compared to scaffold-free groups making this strategy a clinically promising auto- or allogeneic therapy.
骨关节炎是导致残疾的主要原因，影响着越来越多的人。然而，软骨置换疗法并不完善，必须开发出更好的软骨再生产品。在这项研究中，我们描述了一种基于人骨髓间充质干细胞（hMSC）的方法，该方法从组织工程软骨片制造细胞外基质（ECM）支架，然后诱导重新接种在ECM支架内的hMSC发生软骨生成。制造了两种类型的ECM支架：一种来自用添加了转化生长因子β-1（TGF-β1；-MS）的培养基培养的高密度hMSC片，另一种来自掺入载有TGF-β1的明胶微球的高密度hMSC片（+MS），这显著增强了片层系统内的软骨生成。有趣的是，当用hMSC重新接种支架时，-MS支架比+MS支架导致更多的糖胺聚糖（GAG）积累。重要的是，ECM支架可以用TGF-β1浸泡加载，以产生与在培养基中用TGF-β1培养的构建体质量相似的软骨，从而无需在培养基中补充生长因子。最后，与无支架组相比，用支架形成的组织更大，软骨基质的形成更均匀，这使得该策略成为一种具有临床前景的自体或异体疗法。
