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 ...
    • Pancreatic Cancer (Jul 2025)
    • 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)
    • 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
CTGF directs fibroblast differentiation from human mesenchymal stem/stromal cells and defines connective tissue healing in a rodent injury model
Chang H. Lee, … , Eduardo K. Moioli, Jeremy J. Mao
Chang H. Lee, … , Eduardo K. Moioli, Jeremy J. Mao
Published August 2, 2010
Citation Information: J Clin Invest. 2010;120(9):3340-3349. https://doi.org/10.1172/JCI43230.
View: Text | PDF | Erratum
Research Article Article has an altmetric score of 7

CTGF directs fibroblast differentiation from human mesenchymal stem/stromal cells and defines connective tissue healing in a rodent injury model

  • Text
  • PDF
Abstract

Fibroblasts are ubiquitous cells that demonstrate remarkable diversity. However, their origin and pathways of differentiation remain poorly defined. Here, we show that connective tissue growth factor (CTGF; also known as CCN2) is sufficient to induce human bone marrow mesenchymal stem/stromal cells (MSCs) to differentiate into fibroblasts. CTGF-stimulated MSCs lost their surface mesenchymal epitopes, expressed broad fibroblastic hallmarks, and increasingly synthesized collagen type I and tenacin-C. After fibroblastic commitment, the ability of MSCs to differentiate into nonfibroblastic lineages — including osteoblasts, chondrocytes, and adipocytes — was diminished. To address inherent heterogeneity in MSC culture, we established 18 single MSC–derived clones by limiting dilution. CTGF-treated MSCs were α-SMA–, differentiating into α-SMA+ myofibroblasts only when stimulated subsequently with TGF-β1, suggestive of stepwise processes of fibroblast commitment, fibrogenesis, and pathological fibrosis. In rats, in vivo microencapsulated delivery of CTGF prompted postnatal connective tissue to undergo fibrogenesis rather than ectopic mineralization. The knowledge that fibroblasts have a mesenchymal origin may enrich our understanding of organ fibrosis, cancer stroma, ectopic mineralization, scarring, and regeneration.

Authors

Chang H. Lee, Bhranti Shah, Eduardo K. Moioli, Jeremy J. Mao

×

Figure 1

CTGF-mediated fibroblastic differentiation of MSCs.

Options: View larger image (or click on image) Download as PowerPoint
CTGF-mediated fibroblastic differentiation of MSCs.
(A) Bone marrow MSCs...
(A) Bone marrow MSCs were isolated and culture expanded. (B) CTGF treatment (100 ng/ml) prompted substantial collagen synthesis (Masson trichrome) compared with MSCs without CTGF treatment (A). (C and D) Col-I (C) and Tn-C (D) contents of CTGF-treated MSCs cells were significantly higher than MSCs without CTGF treatment at the 2- and 4-week time points (n = 5), as determined by ELISA. (E) Collagen deposition increased with increasing CTGF doses from 0 to 100 ng/ml (Goldner trichrome). (F) Levels of MSC surface epitopes were gradually attenuated, including CD29, CD44, CD105, CD106, CD117, BMPR1A, and Sca1 upon 2 and 4 weeks of CTGF treatment. (G) Concurrently, levels of fibroblastic markers gradually increased, including Col-I, Col-III, Tn-C, fibronectin (FN), MMP-1, FSP1, and vimentin (VIM) upon 4 weeks of CTGF treatment. The chondrogenic marker Col-II and myofibroblastic marker α-SMA were undetectable, whereas the osteogenic marker osteocalcin (OC) was minimally expressed (G). Scale bars: 100 μm. Data represent mean ± SD. *P < 0.05.

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

Sign up for email alerts

Referenced in 7 patents
Highlighted by 1 platforms
214 readers on Mendeley
1 readers on CiteULike
See more details