title: Tendon progenitor cells in injured tendons have strong chondrogenic potential: the CD105-negative subpopulation induces chondrogenic degeneration.
abstract: To study the cellular mechanism of the tendon repair process, we used a mouse Achilles tendon injury model to focus on the cells recruited to the injured site. The cells isolated from injured tendon 1 week after the surgery and uninjured tendons contained the connective tissue progenitor populations as determined by colony-forming capacity, cell surface markers, and multipotency. When the injured tendon-derived progenitor cells (inTPCs) were transplanted into injured Achilles tendons, they were not only integrated in the regenerating area expressing tenogenic phenotype but also trans-differentiated into chondrogenic cells in the degenerative lesion that underwent ectopic endochondral ossification. Surprisingly, the micromass culture of the inTPCs rapidly underwent chondrogenic differentiation even in the absence of exogenous bone morphogenetic proteins or TGFβs. The cells isolated from human ruptured tendon tissues also showed connective tissue progenitor properties and exhibited stronger chondrogenic ability than bone marrow stromal cells. The mouse inTPCs contained two subpopulations one positive and one negative for CD105, a coreceptor of the TGFβ superfamily. The CD105-negative cells showed superior chondrogenic potential in vitro and induced larger chondroid degenerative lesions in mice as compared to the CD105-positive cells. These findings indicate that tendon progenitor cells are recruited to the injured site of tendons and have a strong chondrogenic potential and that the CD105-negative population of these cells would be the cause for chondroid degeneration in injured tendons. The newly identified cells recruited to the injured tendon may provide novel targets to develop therapeutic strategies to facilitate tendon repair.
authors.affiliation: Translational Research Program in Pediatric Orthopaedics, Division of Orthopaedic Surgery, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Asai
authors.forename: Satoru
authors.initials: S
authors.lastname: Otsuru
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Candela
authors.forename: Leslie
authors.initials: L
authors.lastname: Cantley
authors.forename: Kenta
authors.initials: K
authors.lastname: Uchibe
authors.forename: Ted J
authors.initials: TJ
authors.lastname: Hofmann
authors.forename: Kairui
authors.initials: K
authors.lastname: Zhang
authors.forename: Keith L
authors.initials: KL
authors.lastname: Wapner
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Soslowsky
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Horwitz
authors.forename: Motomi
authors.initials: M
authors.lastname: Enomoto-Iwamoto
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000502:physiology; D000071063:Endoglin; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D010012:Osteogenesis / Q000502:physiology; D013234:Stem Cells / Q000166:cytology*; D013710:Tendons / Q000166:cytology* / Q000378:metabolism
chemical_list: D000071063:Endoglin; C502004:Eng protein, mouse; D047908:Intracellular Signaling Peptides and Proteins
keywords: Chondrogenesis; Injury; Progenitor; TGFβ; Tendon