Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.
Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, People's Republic of China.
Development. 2022 Jan 15;149(2). doi: 10.1242/dev.200249. Epub 2022 Jan 28.
Amputation injuries in mammals are typically non-regenerative; however, joint regeneration is stimulated by BMP9 treatment, indicating the presence of latent articular chondrocyte progenitor cells. BMP9 induces a battery of chondrogenic genes in vivo, and a similar response is observed in cultures of amputation wound cells. Extended cultures of BMP9-treated cells results in differentiation of hyaline cartilage, and single cell RNAseq analysis identified wound fibroblasts as BMP9 responsive. This culture model was used to identify a BMP9-responsive adult fibroblast cell line and a culture strategy was developed to engineer hyaline cartilage for engraftment into an acutely damaged joint. Transplanted hyaline cartilage survived engraftment and maintained a hyaline cartilage phenotype, but did not form mature articular cartilage. In addition, individual hypertrophic chondrocytes were identified in some samples, indicating that the acute joint injury site can promote osteogenic progression of engrafted hyaline cartilage. The findings identify fibroblasts as a cell source for engineering articular cartilage and establish a novel experimental strategy that bridges the gap between regeneration biology and regenerative medicine.
哺乳动物的截肢损伤通常不可再生；然而，BMP9 处理可刺激关节再生，表明存在潜在的关节软骨祖细胞。BMP9 在体内诱导一系列软骨生成基因，在截肢伤口细胞的培养中也观察到类似的反应。经过 BMP9 处理的细胞的延长培养导致透明软骨的分化，单细胞 RNAseq 分析鉴定出伤口成纤维细胞对 BMP9 有反应。该培养模型用于鉴定 BMP9 反应性成纤维细胞系，并开发了一种培养策略，用于工程化透明软骨以植入急性损伤关节。移植的透明软骨在植入后存活并保持透明软骨表型，但未形成成熟的关节软骨。此外，在一些样本中鉴定到单个肥大软骨细胞，表明急性关节损伤部位可促进植入的透明软骨的成骨进展。这些发现将成纤维细胞鉴定为工程化关节软骨的细胞来源，并建立了一种新的实验策略，弥合了再生生物学和再生医学之间的差距。
