Hyaline cartilage differentiation of fibroblasts in regeneration and regenerative medicine.

Abstract

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.

• Authors: Ling Yu, Yu-Lieh Lin, Mingquan Yan, Tao Li, Emily Y Wu, Katherine Zimmel, Osama Qureshi, Alyssa Falck, Kirby M Sherman, Shannon S Huggins, Daniel Osorio Hurtado, Larry J Suva, Dana Gaddy, James Cai, Regina Brunauer, Lindsay A Dawson, Ken Muneoka
• Journal: Development (Cambridge, England) (Development) Vol. 149 Issue 2 (01 15 2022) ISSN: 1477-9129 [Electronic] England
• PMID: 35005773 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2022. Published by The Company of Biologists Ltd.

Chemical References

• Gdf2 protein, mouse
• Growth Differentiation Factor 2

Topics

• Animals
• Cell Differentiation
• Cells, Cultured
• Chondrocytes (cytology, drug effects)
• Chondrogenesis
• Fibroblasts (cytology, drug effects)
• Growth Differentiation Factor 2 (pharmacology)
• Hyaline Cartilage (cytology, metabolism, physiology)
• Mice
• Mice, Inbred C57BL
• Mice, Inbred NOD
• Mice, SCID
• Regeneration
• Tissue Engineering (methods)