Laboratory of Musculoskeletal Biology and Regenerative Medicine, Department of Orthopedics and Rehabilitation, University of Wisconsin-Madison, Madison, WI 53705, USA.
Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA.
Sci Adv. 2021 May 19;7(21). doi: 10.1126/sciadv.abf0907. Print 2021 May.
Generating phenotypic chondrocytes from pluripotent stem cells is of great interest in the field of cartilage regeneration. In this study, we differentiated human induced pluripotent stem cells into the mesodermal and ectomesodermal lineages to prepare isogenic mesodermal cell-derived chondrocytes (MC-Chs) and neural crest cell-derived chondrocytes (NCC-Chs), respectively, for comparative evaluation. Our results showed that both MC-Chs and NCC-Chs expressed hyaline cartilage-associated markers and were capable of generating hyaline cartilage-like tissue ectopically and at joint defects. Moreover, NCC-Chs revealed closer morphological and transcriptional similarities to native articular chondrocytes than MC-Chs. NCC-Ch implants induced by our growth factor mixture demonstrated increased matrix production and stiffness compared to MC-Ch implants. Our findings address how chondrocytes derived from pluripotent stem cells through mesodermal and ectomesodermal differentiation are different in activities and functions, providing the crucial information that helps make appropriate cell choices for effective regeneration of articular cartilage.
从多能干细胞生成表型软骨细胞在软骨再生领域具有重要意义。在本研究中，我们将人诱导多能干细胞分化为中胚层和外胚层谱系，分别制备同基因中胚层细胞来源的软骨细胞（MC-Chs）和神经嵴细胞来源的软骨细胞（NCC-Chs），用于比较评价。结果表明，MC-Chs 和 NCC-Chs 均表达透明软骨相关标志物，能够异位和在关节缺损处生成透明软骨样组织。此外，NCC-Chs 在形态和转录水平上比 MC-Chs 更接近天然关节软骨细胞。与 MC-Ch 植入物相比，我们的生长因子混合物诱导的 NCC-Ch 植入物显示出增加的基质生成和硬度。我们的研究结果解决了通过中胚层和外胚层分化从多能干细胞衍生的软骨细胞在活性和功能上的差异，为有效的关节软骨再生提供了有助于做出适当细胞选择的关键信息。
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