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Pharmacological Retention of Oral Mucosa Progenitor/Stem Cells

¹ Section of Oral and Maxillofacial Surgery,
² Section of Plastic and Reconstructive Surgery, Department of Surgery,
³ Life Sciences Institute, and
⁴ Department of Molecular and Integrative Physiology, University of Michigan, A560 MSRB 2, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0654, USA; and
⁵ Division of Oral Anatomy, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

Correspondence: ^* Department of Surgery, 1500 E. Medical Center Drive, Room B1-208 TC, Box 0018, Ann Arbor, MI 48109-0018, USA; sefein{at}med.umich.edu

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.

Key Words: oral keratinocyte • progenitor/stem cell • mTOR • rapamycin

This version was published on December 1, 2009

Journal of Dental Research, Vol. 88, No. 12, 1113-1118 (2009)
DOI: 10.1177/0022034509350559


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