A role for c-Kit in the maintenance of undifferentiated human mesenchymal stromal cells.
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.
Section of Periodontology, Department of Hard Tissue Engineering, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan; Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University (TWIns), 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan; Global Center of Excellence Program, International Research Center for Molecular Science in Tooth and Bone Diseases (GCOE Program), Tokyo Medical and Dental University, Japan.
Supreda
S
Suphanantachat
Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University (TWIns), 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. Electronic address: iwata.takanori@twmu.ac.jp.
Takanori
T
Iwata
Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University (TWIns), 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan; Division of Cellular Therapy, The Institute of Medical Science, The University of Tokyo (IMSUT), 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Jun
J
Ishihara
Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University (TWIns), 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
Masayuki
M
Yamato
Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University (TWIns), 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. Electronic address: okano.teruo@twmu.ac.jp.
Teruo
T
Okano
Section of Periodontology, Department of Hard Tissue Engineering, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan; Global Center of Excellence Program, International Research Center for Molecular Science in Tooth and Bone Diseases (GCOE Program), Tokyo Medical and Dental University, Japan.
Yuichi
Y
Izumi
D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics; D000469:Alkaline Phosphatase / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D019089:Stem Cell Factor / Q000235:genetics / Q000378:metabolism
D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017468:Receptors, Fibroblast Growth Factor; D018125:Receptors, Transforming Growth Factor beta; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit; D000469:Alkaline Phosphatase
Cell differentiation; Growth factors; Mesenchymal stromal cells; Periodontal ligament; Stem cell factor; c-Kit receptor