We report the isolation of a population of immature dental pulp stem cells (IDPSC), which express embryonic stem cell markers Oct-4, Nanog, SSEA-3, SSEA-4, TRA-1-60 and TRA-1-81 as well as several other mesenchymal stem cell markers during at least 25 passages while maintaining the normal karyotype and the rate of expansion characteristic of stem cells. The expression of these markers was maintained in subclones obtained from these cells. Moreover, in vitrothese cells can be induced to undergo uniform differentiation into smooth and skeletal muscles, neurons, cartilage, and bone under chemically defined culture conditions. After in vivo transplantation of these cells into immunocompromised mice, they showed dense engraftment in various tissues. The relative ease of recovery and the expression profiles of various markers justify further exploration of IDPSC for clinical therapy.

Bissell, M.J., M.A. Lafarge (2005) Context, tissue plasticity, and cancer: are tumor stem cells also regulated by the microenvironment? Cancer Cell 7: 17–23.
Caplan, A.I. (1991) Mesenchymal stem cells. J Orthop Res 9: 641–650.
Caplan, A.I. (2000) Tissue engineering design for the future: new logics, old molecules. Tissue Eng 6: 1–8.
Caplan, A.I. (2003) Design parameters for function tissue engineering; in Guilak, F., D.L. Butler, S.A. Goldstein, D.J. Mooney (eds): Functional Tissue Engineering. New York, Springer, pp 129–138.
Caplan, A.I. (2004) Mesenchymal stem cells; in Lanza, R. (ed): Handbook of Stem Cells. New York, Academic Press, vol 2, pp 299–308.
Caplan, A.I. (2005) Mesenchymal stem cells; cell-based reconstructive therapy in orthopedics. Tissue Eng 11: 1198–1211.
Caplan, A.I., S.P. Bruder (2001) Mesenchymal stem cells: building blocks for molecular medicine in the 21st century. Trends Mol Med 6: 259–264.
Chambers, I., D. Colby, M. Robertson, J. Nichol, S. Lee, S. Tweedie, A. Smith (2003) Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell 113: 643–655.
Cheshier, S., S.J. Morrison, X. Liao, I.L. Weissman (1999) In vivo proliferation and cell cycle kinetics of long-term self-renewing hematopoietic stem cells. Proc Natl Acad Sci USA 96: 3120–3125.
Constantinescu, S. (2003) Stemness, fusion and renewal of hematopoietic and embryonic stem cells. J Cell Mol Biol 7: 103–112.
Dartsch, P.C., H.D. Weiss, E. Betz (1990) Human vascular smooth muscle cells in culture: growth characteristics and protein pattern by use of serum-free media supplements. Eur J Cell Biol 51: 285–294.
Fleming, W.H., E.J. Alpern, N. Uchida, K. Ikuta, G.J. Spangrude, I.L. Weissman (1993) Functional heterogeneity is associated with the cell cycle status of murine hematopoietic stem cells. J Cell Biol 122: 897–902.
Fraichard, A., O. Chassande, G. Bilbaut, C. Dehay, P. Savatier, J. Samarut (1995) In vitro differentiation of embryonic stem cells into glial cells and functional neurons. J Cell Sci 108: 3181–3188.
Gronthos, S., M. Mankani, J. Brahim, P.G. Robey, S. Shi (2002) Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci USA 97: 13625–13630.
Harlow, E., D. Lane (1988) Antibodies: A Laboratory Manual. Cold Spring Harbor, Cold Spring Harbor Laboratory Press, pp 726.
Houghton J., C. Stoicov, S. Nomura, A.B. Rogers, J. Carlson, H. Li, X. Cai, J.G. Fox, J.R. Goldenring, T.C. Wang (2004) Gastric cancer originating from bone marrow-derived cells. Science 306: 1568–1571.
Jiang Y, B.N. Jahagirdar, R.L. Reinhardt, R.E. Schwartz, C.D. Keene, X.R. Ortiz-Gonzalez, M. Reyes, T. Lenvik, T. Lund, M Blackstad, J. Du, S. Aldrich, A. Lisberg, W.C. Low, D.A. Largaespada, C.M. Verfaillie (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418: 41–49.
Kirchhof, N., J.W. Carnwath, E. Lemme, K. Anastassiadis, H. Schole, H. Niemann (2000) Expression pattern of Oct-4 in preimplantation embryos of different species. Biol Reprod 63: 1698–1705.
Kuehle I., M.A. Goodell (2002) The therapeutic potential of stem cells from adults. BMJ 325: 372–376.
Laino, G., A. Graziano, R. d’Aquino, G. Pirozzi, V. Lanza, S. Valiante, A. De Rosa, F. Naro, E. Vivarelli, G. Papaccio (2006) An approachable human adult stem cell source for hard-tissue engineering. J Cell Physiol 3: 693–701.
Lan, C.W., F.F. Wang, Y.J. Wang (2003) Osteogenic enrichment of bone-marrow stromal cells with the use of flow chamber and type I collagen-coated surface. J Biomed Mater Res 66A: 38–46.
Laslett, A.L., A.A. Filipczyk, M.F. Pera (2003) Characterization and culture of human embryonic stem cells. Trends Cardiovasc Med 13: 295–301.
Mann, L.M., D.P. Lennon, A.I. Caplan (1996) Cultured rat pulp cells have the potential to form bone, cartilage, and dentin in vivo; in Davidovitch, Z., L.A. Norton (eds): Biological Mechanisms of Tooth Movement and Craniofacial Adaptation. Boston, Harvard Society of the Advancement of Orthodontics, pp 7–10.
Miki, T., T. Lehmann, H. Cai, D.B. Stolz, S.C. Strom (2005) Stem cell characteristics of amniotic epithelial cells. Stem Cells 23: 1549–1559.
Mitsui, K., Y. Tokuzawa, H. Itoh, K. Segawa, M. Murakami, K. Takahashi, M. Maruyama, M. Maeda, S. Yamanaka (2003) The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell 113: 631–642.
Miura M, S. Gronthos, M. Zhao, B. Lu, L.W. Fisher, P.G. Robey, S. Shi (2003) SHED: stem cells from human exfoliated deciduous teeth. Proc Nat Acad Sci USA 100: 5807–5812.
Pierdomenico, L., L. Bonsi, M. Calvitti, D. Rondelli, M. Arpinati, G. Chirumbolo, E. Becchetti, C. Marchionni, F. Alviano, V. Fossati, N. Staffolani, M. Franchina, A. Grossi, G.P. Bagnara (2005) Multipotent mesenchymal stem cells with immunosuppressive activity can be easily isolated from dental pulp. Transplantation 80: 836–842.
Pittenger, M.F., B.J. Martin (2004) Mesenchymal stem cells and their potential as cardiac therapeutics. Circ Res 95: 9–20.
Reyes, M., T. Lund, T. Lenvik, D. Aguiar, L. Koodie, C.M. Verfaillie (2001) Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells. Blood 98: 2615–2625.
Reubinoff, B.E., M.F. Pera, C.Y. Fong, A. Trounson, A. Bongso (2000) Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro. Nat Biotechnol 18: 399–404.
Rohwedel, J., K. Guan, A.M. Wobus (1999) Induction of cellular differentiation by retinoic acid in vitro. Cell Tissues Org 165: 190–202.
Sambrook, J., E.F. Fritsch, T. Maniatis (1989) Molecular Cloning: A Laboratory Manual, ed 2. Cold Spring Harbor, Cold Spring Harbor Laboratory Press, pp 7.71–7.78.
Schor, A.M., T.D. Allen, A.E. Canfield, P. Sloan, S.L. Schor (1990) Pericytes derived from the retinal microvasculature undergo calcification in vitro. J Cell Sci 97: 449–461.
Schwartz, R.E., C.M. Verfaillie (2005) Adult stem cells plasticity; in J. Odorico, S.C. Zhang, R. Pedersen (eds): Human Embryonic Stem Cells. New York, Garland Science/BIOS Scientific Publisher, pp 45–60.
Sheehan, D., B. Hrapchak (1980) Theory and Practice of Histotechnology, ed 2. Columbus Richland, Battelle Press, pp 226–227.
Talbot, N.C., C.E. Rexrod, V. Pursel, A.M. Powell (1993) Alkaline phosphatase staining of pig and sheep epiblast cells in culture. Mol Reprod Dev 36: 139–147.
Ward, C.M., K. Barrow, A.M. Woods, P.L. Stern (2003) The 5T4 oncofoetal antigen is an early differentiation marker of mouse ES cells and its absence is a useful means to assess pluripotency. J Cell Sci 116: 4533–4542.
Zuk, P.A., M. Zhu, P. Ashjian, D.A. De Ugarte, J.I. Huang, H. Mizuno, Z.C. Alfonso, J.K. Fraser, P. Benhaim, M.H. Hedrick (2002). Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13: 4279–4295.
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