Regulation of chondrogenesis by transforming growth factor-beta 3 and insulin-like growth factor-1 from human mesenchymal umbilical cord blood cells

• Published in: Journal of rheumatology 2010-07, Vol.37 (7), p.1519-1526
• Main Authors: Mara, Cristiane S, Duarte, Adriana S S, Sartori, Angelica, Luzo, Angela C, Saad, Sara T O, Coimbra, Ibsen B
• Format: Article
• Language: English
• Subjects: Aggrecans - genetics; Aggrecans - metabolism; Cell Differentiation - drug effects; Cells, Cultured; Chondrogenesis - drug effects; Chondrogenesis - physiology; Collagen Type II - genetics; Collagen Type II - metabolism; Fetal Blood - cytology; Humans; Insulin-Like Growth Factor I - pharmacology; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - drug effects; Mesenchymal Stromal Cells - physiology; SOX9 Transcription Factor - genetics; SOX9 Transcription Factor - metabolism; Transforming Growth Factor beta3 - pharmacology
• ISSN: 0315-162X
• DOI: 10.3899/jrheum.091169

Mature articular cartilage is vulnerable to injuries and disease processes that cause irreversible tissue damage because of its limited capacity for self-repair. Umbilical cord blood is a source of mesenchymal stem cells, which can give rise to cells of different lineages, including cartilage, bone, and fat. Cellular condensation is a required step in the initiation of mesenchymal chondrogenesis. We attempted to differentiate cells from umbilical cord blood into chondrocytes with insulin-like growth factor 1 (IGF-1) and transforming growth factor-ss3 (TGF-ss3). Cells were grown in high density micromass and monolayer culture systems and then evaluated for expression of type II collagen, aggrecan, and Sox9. Umbilical cord blood from 130 patients was harvested. Expression of type II collagen, aggrecan, and Sox9 was detected after 14 days in TGF-ss3- and IGF-1-stimulated cells in both types of culture (monolayer and micromass). On Day 21 in the micromass culture, expression levels were greater than they were at 14 days for all genes. TGF-ss3 was found to be more efficient at promoting chondrogenesis than IGF-1. By western blot, we also found that after 3 weeks, the expression of type II collagen was greater in micromass culture with TGF-ss3. TGF-ss3 used in micromass culture is the best growth factor for promoting the proliferation and differentiation of mesenchymal cells from umbilical cord blood during chondrogenesis. This approach may provide an alternative to autologous grafting.