Open AccessHyaline cartilage differentiation of fibroblasts in regeneration and regenerative medicine
Author(s) -
Ling Yu,
YuLieh Lin,
Mingquan Yan,
Tao Li,
Emily Wu,
Katherine Zimmel,
Osama Qureshi,
Alyssa Falck,
Kirby M Sherman,
Shan Huggins,
Daniel Osorio,
Larry J. Suva,
Dana Gaddy,
James J. Cai,
Regina Brunauer,
Lindsay Dawson,
Ken Muneoka
Publication year - 2022
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.15
H-Index - 36
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.200249
Subject(s) - hyaline cartilage , chondrogenesis , biology , cartilage , regeneration (biology) , chondrocyte , microbiology and biotechnology , regenerative medicine , hyaline , progenitor cell , wound healing , pathology , stem cell , anatomy , immunology , osteoarthritis , medicine , articular cartilage , botany , alternative medicine
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.