title: Small molecules affect human dental pulp stem cell properties via multiple signaling pathways.
abstract: One fundamental issue regarding stem cells for regenerative medicine is the maintenance of stem cell stemness. The purpose of the study was to test whether small molecules can enhance stem cell properties of mesenchymal stem cells (MSCs) derived from human dental pulp (hDPSCs), which have potential for multiple clinical applications. We identified the effects of small molecules (Pluripotin (SC1), 6-bromoindirubin-3-oxime and rapamycin) on the maintenance of hDPSC properties in vitro and the mechanisms involved in exerting the effects. Primary cultures of hDPSCs were exposed to optimal concentrations of these small molecules. Treated hDPSCs were analyzed for their proliferation, the expression levels of pluripotent and MSC markers, differentiation capacities, and intracellular signaling activations. We found that small molecule treatments decreased cell proliferation and increased the expression of STRO-1, NANOG, OCT4, and SOX2, while diminishing cell differentiation into odonto/osteogenic, adipogenic, and neurogenic lineages in vitro. These effects involved Ras-GAP-, ERK1/2-, and mTOR-signaling pathways, which may preserve the cell self-renewal capacity, while suppressing differentiation. We conclude that small molecules appear to enhance the immature state of hDPSCs in culture, which may be used as a strategy for adult stem cell maintenance and extend their capacity for regenerative applications.
authors.affiliation: Department of Endodontics, Henry M. Goldman School of Dental Medicine, Boston University, Boston, Massachusetts, USA.
authors.forename: Mey
authors.initials: M
authors.lastname: Al-Habib
authors.forename: Zongdong
authors.initials: Z
authors.lastname: Yu
authors.forename: George T-J
authors.initials: GT
authors.lastname: Huang
mesh_terms: D000293:Adolescent; D000954:Antigens, Surface / Q000096:biosynthesis; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003782:Dental Pulp / Q000166:cytology* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D018398:Homeodomain Proteins / Q000096:biosynthesis; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis; D010091:Oximes / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D055748:SOXB1 Transcription Factors / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D055815:Young Adult; D020703:ras GTPase-Activating Proteins / Q000378:metabolism
chemical_list: C483321:6-bromoindirubin-3'-oxime; D000954:Antigens, Surface; D015415:Biomarkers; D018398:Homeodomain Proteins; D007166:Immunosuppressive Agents; D007211:Indoles; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; D010091:Oximes; C494173:POU5F1 protein, human; D011720:Pyrazoles; D011743:Pyrimidines; C515825:SC1 compound; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; C525591:STRO-1 antigen, human; D020703:ras GTPase-Activating Proteins; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D020123:Sirolimus