Pharmacological retention of oral mucosa progenitor/stem cells.
Oral mucosa progenitor/stem cells reside as a small-sized cell population that eventually differentiates concurrently with an increase in cell size. Activation of the mammalian target of rapamycin (mTOR) leads to an increase in cell size. We hypothesized that rapamycin, a specific inhibitor of mTOR, will maintain primary human oral keratinocytes as a small-sized, undifferentiated cell population capable of retaining their proliferative capacity. Primary, rapamycin-treated (2 nM, 20 nM) oral keratinocytes showed a diminished cell size that correlated with a higher clonogenicity, a longer-term proliferative potential, and a slower cycling cell population concurrent with decreased expression of a differentiation marker when compared with untreated cells. Only the 2-nM rapamycin-treated oral keratinocytes maintained their ability to regenerate oral mucosa in vitro after 15 weeks of culture. Rapamycin, a Food and Drug Administration-approved drug, may have applicability for use in creating a highly proliferative cell population for use in regenerative medicine.
Izumi
K
K
Section of Oral and Maxillofacial Surgery, Department of Surgery, Life Sciences Institute, University of Michigan, A560 MSRB 2, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0654, USA.
Inoki
K
K
Fujimori
Y
Y
Marcelo
C L
CL
Feinberg
S E
SE
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D002999:Clone Cells / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000502:physiology; D009061:Mouth Mucosa / Q000166:cytology / Q000187:drug effects*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011494:Protein Kinases / Q000187:drug effects; D012038:Regeneration / Q000187:drug effects / Q000502:physiology; D019893:Ribosomal Protein S6 Kinases / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology; D058570:TOR Serine-Threonine Kinases
D000900:Anti-Bacterial Agents; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011494:Protein Kinases; C546842:MTOR protein, human; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus