Biomaterials 35, 3618-3626 (2014)
A role for c-Kit in the maintenance of undifferentiated human mesenchymal stromal cells
Suphanantachat S, Iwata T, Ishihara J, Yamato M, Okano T, Izumi Y
Mesenchymal stromal cells,Periodontal ligament,c-Kit receptor,Stem cell factor,Growth factors,Cell differentiation
The multipotency of human mesenchymal stromal cells (hMSCs) and the feasibility of deriving these cells from periodontal ligament hold promise for stem cell-based tissue engineering. However, the regulation of adult hMSCs activity is not well understood. The present study investigated the c-Kit surface receptor and downstream gene expression in hMSCs. The c-Kit-positive population showed increased colony-forming ability rather than differentiation potential. The knockdown of c-Kit and/or stem cell factor (SCF) genes enhanced alkaline phosphatase activity and also upregulated osteoblast- and adipocyte-specific genes, including osteocalcin, runt-related transcription factor 2, osteopontin, peroxisome proliferator-activated receptor-γ, and lipoprotein lipase. Stimulation with growth factors, including fibroblast growth factor-2, transforming growth factor-β1, and enamel matrix derivative significantly suppressed the mRNA expression of c-Kit. These results support an emerging understanding of the roles of the c-Kit/SCF signal in maintaining the undifferentiated stage of hMSCs by inhibiting the expression of lineage-specific genes in hMSCs and regulating the effect of growth factors on the proliferation and differentiation of hMSCs. The modulation of c-Kit/SCF signaling might contribute to future regenerative approaches in controlling both the stemness and differentiation properties of hMSCs.