A latent Axin2 + /Scx + progenitor pool is the central organizer of tendon healing.

Autor: Grinstein M; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA.; Department of Orthopedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; Harvard Stem Cell Institute, Cambridge, MA, USA., Tsai SL; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA.; Department of Orthopedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; Harvard Stem Cell Institute, Cambridge, MA, USA., Montoro D; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA.; Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Freedman BR; John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA., Dingwall HL; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA.; Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, USA., Villaseñor S; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA., Zou K; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA., Sade-Feldman M; The Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Tanaka MJ; Department of Orthopedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Mooney DJ; John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA., Capellini TD; Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, USA.; Broad Institute of Harvard and MIT, Cambridge, MA, USA., Rajagopal J; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA.; Harvard Stem Cell Institute, Cambridge, MA, USA.; Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Galloway JL; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA. jenna_galloway@hms.harvard.edu.; Department of Orthopedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. jenna_galloway@hms.harvard.edu.; Harvard Stem Cell Institute, Cambridge, MA, USA. jenna_galloway@hms.harvard.edu.
Jazyk: angličtina
Zdroj: NPJ Regenerative medicine [NPJ Regen Med] 2024 Oct 17; Vol. 9 (1), pp. 30. Date of Electronic Publication: 2024 Oct 17.
DOI: 10.1038/s41536-024-00370-2
Abstrakt: A tendon's ordered extracellular matrix (ECM) is essential for transmitting force but is also highly prone to injury. How tendon cells embedded within and surrounding this dense ECM orchestrate healing is not well understood. Here, we identify a specialized quiescent Scx + /Axin2 + population in mouse and human tendons that initiates healing and is a major functional contributor to repair. Axin2 + cells express stem cell markers, expand in vitro, and have multilineage differentiation potential. Following tendon injury, Axin2 + -descendants infiltrate the injury site, proliferate, and differentiate into tenocytes. Transplantation assays of Axin2-labeled cells into injured tendons reveal their dual capacity to significantly proliferate and differentiate yet retain their Axin2 + identity. Specific loss of Wnt secretion in Axin2 + or Scx + cells disrupts their ability to respond to injury, severely compromising healing. Our work highlights an unusual paradigm, wherein specialized Axin2 + /Scx + cells rely on self-regulation to maintain their identity as key organizers of tissue healing.
(© 2024. The Author(s).)
Databáze: MEDLINE
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