CTGF directs fibroblast differentiation from human mesenchymal stem/stromal cells and defines connective tissue healing in a rodent injury model.
J Clin Invest
; 120(9): 3340-9, 2010 Sep.
Article
em En
| MEDLINE
| ID: mdl-20679726
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 alpha-SMA-, differentiating into alpha-SMA+ myofibroblasts only when stimulated subsequently with TGF-beta1, 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cicatrização
/
Diferenciação Celular
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Fator de Crescimento do Tecido Conjuntivo
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Células-Tronco Mesenquimais
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Animals
/
Humans
/
Male
Idioma:
En
Revista:
J Clin Invest
Ano de publicação:
2010
Tipo de documento:
Article