Cell Sheet Tissue Engineering Center (CSTEC), Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, 30 South 2000 East, Salt Lake City, UT 84112, USA.
Department of Biomedical Engineering, University of Utah, 36 S Wasatch Dr, Salt Lake City, UT 84112, USA.
Cells. 2021 Mar 13;10(3):643. doi: 10.3390/cells10030643.
Articular cartilage defects represent an inciting factor for future osteoarthritis (OA) and degenerative joint disease progression. Despite multiple clinically available therapies that succeed in providing short term pain reduction and restoration of limited mobility, current treatments do not reliably regenerate native hyaline cartilage or halt cartilage degeneration at these defect sites. Novel therapeutics aimed at addressing limitations of current clinical cartilage regeneration therapies increasingly focus on allogeneic cells, specifically mesenchymal stem cells (MSCs), as potent, banked, and available cell sources that express chondrogenic lineage commitment capabilities. Innovative tissue engineering approaches employing allogeneic MSCs aim to develop three-dimensional (3D), chondrogenically differentiated constructs for direct and immediate replacement of hyaline cartilage, improve local site tissue integration, and optimize treatment outcomes. Among emerging tissue engineering technologies, advancements in cell sheet tissue engineering offer promising capabilities for achieving both in vitro hyaline-like differentiation and effective transplantation, based on controlled 3D cellular interactions and retained cellular adhesion molecules. This review focuses on 3D MSC-based tissue engineering approaches for fabricating "ready-to-use" hyaline-like cartilage constructs for future rapid in vivo regenerative cartilage therapies. We highlight current approaches and future directions regarding development of MSC-derived cartilage therapies, emphasizing cell sheet tissue engineering, with specific focus on regulating 3D cellular interactions for controlled chondrogenic differentiation and post-differentiation transplantation capabilities.
关节软骨缺损是未来骨关节炎（OA）和退行性关节疾病进展的一个激发因素。尽管有多种临床可用的治疗方法成功地提供了短期疼痛缓解和有限活动度的恢复，但目前的治疗方法并不能可靠地再生天然透明软骨，也不能阻止这些缺损部位的软骨退化。旨在解决当前临床软骨再生治疗局限性的新型治疗方法越来越关注同种异体细胞，特别是间充质干细胞（MSCs），作为具有成软骨谱系承诺能力的强大、储存和可用的细胞来源。采用同种异体 MSC 的创新组织工程方法旨在开发三维（3D）、具有软骨分化特性的构建体，用于透明软骨的直接和即时替代，改善局部组织整合，并优化治疗效果。在新兴的组织工程技术中，基于细胞片层组织工程的进步为体外透明软骨样分化和有效移植提供了有前途的能力，这基于受控的 3D 细胞相互作用和保留的细胞粘附分子。本综述重点介绍了基于 MSC 的组织工程方法，用于制造用于未来快速体内再生软骨治疗的“即用型”透明软骨样构建体。我们强调了当前关于 MSC 衍生的软骨治疗的开发方法和未来方向，强调了细胞片层组织工程，特别关注调节 3D 细胞相互作用以实现受控的软骨分化和分化后移植能力。
