Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Harnessing endogenous stem/progenitor cells for tendon regeneration
Chang H. Lee, … , Guodong Yang, Jeremy J. Mao
Chang H. Lee, … , Guodong Yang, Jeremy J. Mao
Published June 8, 2015
Citation Information: J Clin Invest. 2015;125(7):2690-2701. https://doi.org/10.1172/JCI81589.
View: Text | PDF
Research Article

Harnessing endogenous stem/progenitor cells for tendon regeneration

  • Text
  • PDF
Abstract

Current stem cell–based strategies for tissue regeneration involve ex vivo manipulation of these cells to confer features of the desired progenitor population. Recently, the concept that endogenous stem/progenitor cells could be used for regenerating tissues has emerged as a promising approach that potentially overcomes the obstacles related to cell transplantation. Here we applied this strategy for the regeneration of injured tendons in a rat model. First, we identified a rare fraction of tendon cells that was positive for the known tendon stem cell marker CD146 and exhibited clonogenic capacity, as well as multilineage differentiation ability. These tendon-resident CD146+ stem/progenitor cells were selectively enriched by connective tissue growth factor delivery (CTGF delivery) in the early phase of tendon healing, followed by tenogenic differentiation in the later phase. The time-controlled proliferation and differentiation of CD146+ stem/progenitor cells by CTGF delivery successfully led to tendon regeneration with densely aligned collagen fibers, normal level of cellularity, and functional restoration. Using siRNA knockdown to evaluate factors involved in tendon generation, we demonstrated that the FAK/ERK1/2 signaling pathway regulates CTGF-induced proliferation and differentiation of CD146+ stem/progenitor cells. Together, our findings support the use of endogenous stem/progenitor cells as a strategy for tendon regeneration without cell transplantation and suggest this approach warrants exploration in other tissues.

Authors

Chang H. Lee, Francis Y. Lee, Solaiman Tarafder, Kristy Kao, Yena Jun, Guodong Yang, Jeremy J. Mao

×

Figure 5

Proliferation and differentiation of CD146+ cells in vivo tendon healing.

Options: View larger image (or click on image) Download as PowerPoint
Proliferation and differentiation of CD146+ cells in vivo tendon healing...
Ki67+ proliferative CD146+ cells were significantly increased with CTGF delivery by 2 days in comparison with fibrin alone, but there was no difference at 1 week (A). Starting at 1 week, a fraction of CD146+ cells was observed to have be spindle-shaped with aligned collagen fibers in the CTGF-delivered group (B), suggesting that CD146+ cells may undergo tenogenic differentiation. The spindle-shaped tenocyte-like cells derived from CD146+ cells co-expressed COL1A1 and SCX, as demonstrated by immunofluorescence (C–E). (n = 10 randomly selected slides per group; *P < 0.001 compared with control without CTGF.) One-way ANOVA with post-hoc Tukey HSD was performed. All data are presented as mean ± SD. White arrows indicate CD146+ perivascular cells; yellow arrowheads indicate spindle-shaped tenocyte-like CD146+ cells.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts