Yuntao Dai, Hongzhi He, Gary E. Wise, Shaomian Yao

Abstract: Adult stem cells (ASC) have been found in many tis-sues and are of great therapeutic potential due to their capability of differentiation. However, ASC comprise only a small fraction of the tissues. In order to use ASC for therapeutic purposes, it is important to obtain relatively pure stem cells in large quantities. Current methods for stem cell purification are mainly based on marker-dependent cell sorting techniques, which have various technical difficulties. In this study, we have attempted to develop novel conditions to favor the growth of the dental follicle stem cells (DFSC) such that the resultant cell populations are enriched in stem cells. Specifically, a heterogeneous dental follicle cell (H-DFC) population containing stem cells and homogenous non-stem cell dental follicle cell population were cultured at 1% or 5% hypoxic conditions. Only the heterogeneous population could increase proliferation in the hypoxic condition whereas the homogenous DFC did not change their proliferation rate. In addition, when the resultant cells from the heterogonous population were subjected to differentiation, they appeared to have a higher capacity of adipogenesis and osteogenesis as compared to the controls grown in the normal at-mosphere (normoxic condition). These hypoxia- treated cells also express higher levels of some stem cell markers. Together, these data suggest that stem cells are enriched by culturing the heterogeneous cell populations in a reduced O2 condition.

Keywords: Hypoxia; Dental Follicle (DF); Stem Cells; Proliferation; Gene Expression

Cite this paper: nullDai, Y. , He, H. , Wise, G. and Yao, S. (2011) Hypoxia promotes growth of stem cells in dental follicle cell populations. Journal of Biomedical Science and Engineering, 4, 454-461. doi: 10.4236/jbise.2011.46057.

References

[1]   Cahill, D.R. and Marks Jr, S.C. (1980) Tooth eruption: evidence for the central role of the dental follicle. Journal of Oral Pathology, 9, 189-200. doi:10.1111/j.1600-0714.1980.tb00377.x

[2]   Marks Jr, S.C. and Cahill, D.R. (1984) Experimental study in the dog of the non-active role of the tooth in the eruptive process. Archives of Oral Biology, 29, 311-322. doi:10.1016/0003-9969(84)90105-5

[3]   Wise, G.E. and King, G.J. (2008) Mechanisms of tooth eruption and orthodontic tooth movement. Journal of Dental Research, 87, 414-434. doi:10.1177/154405910808700509

[4]   Wise, G.E. (2009) Cellular and molecular basis of tooth eruption. Orthodontics and Craniofacial Research, 12, 67-73. doi:10.1111/j.1601-6343.2009.01439.x

[5]   Yao, S., Pan, F., Prpic, V., et al. (2008) Differentiation of stem cells in the dental follicle. Journal of Dental Research, 87, 767-771. doi:10.1177/154405910808700801

[6]   Bianco, P. and Gehron Robey, P. (2000) Marrow stromal stem cells. Journal of Clinical Investigation, 105, 1663- 1668. doi:10.1172/JCI10413

[7]   Gronthos, S., Mankani, M., Brahim, J., et al. (2000) Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proceedings of the National Academy of Sciences, 97, 13625-13630. doi:10.1073/pnas.240309797

[8]   Miura, M., Gronthos, S., Zhao, M., et al. (2003) SHED: Stem cells from human exfoliated deciduous teeth. Proceedings of the National Academy of Sciences, 100, 5807-5812. doi:10.1073/pnas.0937635100

[9]   ennon, D.P., Edmison, J.M. and Capalan, A.I. (2001) Cultiva-tion of rat marrow-derived mesenchymal stem cells in reduced oxygen tension: effects on in vitro and in vivo osteochondro-genesis. Journal of Cell Physiology, 187, 345-355. doi:10.1002/jcp.1081

[10]   Yoshida, Y., Takahashi, K., Okita, K. et al. (2009) Hypoxia enhances the generation of induced pluripotent stem cells. Cell Stem Cell, 5, 237-241. doi:10.1016/j.stem.2009.08.001

[11]   Wise, G.E., Lin, F. and Fan, W. (1992) Culture and characteri-zation of dental follicle cells from rat molars. Cell Tissue Re-search, 267, 483-492.

[12]   doi:10.1007/BF00319370

[13]   O'Connor, M.D., Kardel, M.D., Iosfina, I., et al. (2008) Alkaline phosphatase-positive colony formation is a sensitive,specific, and quantitative indicator of undifferentiated human embryonic stem cells. Stem Cells, 26, 1109- 1116. doi:10.1634/stemcells.2007-0801

[14]   Yu, J., Vodyanik, M.A., Smuga-Otto, K., et al. (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science, 318, 1917-1920. doi:10.1126/science.1151526

[15]   Aasen, T., Raya, A., Barrero, M.J., et al. (2008) Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes. Nature Biotechnology, 26, 1276-1284. doi:10.1038/nbt.1503

[16]   Yin, A.H., Miraglia, S., Zanjani, E.D., et al. (1997) AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood, 90, 5002-5012.

[17]   Mizrak, D., Brittan, M. and Alison, M.R. (2008) CD133: mo-lecule of the moment. Journal of Pathology, 214, 3-9. doi:10.1002/path.2283

[18]   Uchida, N., Buck, D.W., He, D., et al. (2000) Direct isolation of human central nervous system stem cells. Proceedings of the National Academy of Sciences, 97, 14720-14725. doi:10.1073/pnas.97.26.14720

[19]   Lee, A., Kessler, J.D., Read, T.A., et al. (2005) Isolation of neural stem cells from the postnatal cerebellum. Nature Neuroscience, 8, 723-729. doi:10.1038/nn1473

[20]   Corti, S., Nizzardo, M., Nardini, M., et al. (2007) Isolation and characterization of murine neural stem/progenitor cells based on Prominin-1 expression. Experimental Neurology, 205, 547-562. doi:10.1016/j.expneurol.2007.03.021

[21]   Chen, C.H., Dixon, R.A., Ke, L.Y., et al. (2009) Vascular pro-genitor cells in diabetes mellitus: roles of WNT signaling and negatively charged low-density lipoprotein. Circulation Research, 104, 1038-1040. doi:10.1161/CIRCRESAHA.109.198051

[22]   Barry, F., Boynton, R., Murphy, M., et al. (2001) The SH-3 and SH-4 antibodies recognize distinct epitopes on CD73 from human mesenchymal stem cells. Biochemical and Biophysical Research Communications. 289, 519-524. doi:10.1006/bbrc.2001.6013

[23]   Synnestvedt, K., Furuta, G.T., Comerford, K.M., et al. (2002) Ecto-5'-nucleotidase (CD73) regulation by hypoxia-inducible factor-1 mediates permeability changes in intestinal epithelia. Journal of Clinical Investigation, 110, 993-1002.

[24]   Ledoux, S., Runembert, I., Koumanov, K., et al. (2003) Hypoxia enhances Ecto-5'-Nucleotidase activity and cell surface expression in endothelial cells: role of membrane lipids. Circulation Research, 92, 848-855.doi:10.1161/01.RES.0000069022.95401.FE

[25]   Friedman, G.B., Taylor, C.T., Parkos, C.A., et al. (1998) Epi-thelial permeability induced by neutrophil transmigration is potentiated by hypoxia: role of intracellular cAMP. Journal of Cell Physiology, 176, 76-84. doi:10.1002/(SICI)1097-4652(199807)176:1<76::AID-JCP9>3.0.CO;2-5

[26]   uft, F.C. (2001) Lactic acidosis update for critical care clinicians. Journal of the American Society of Nephrology, 12, S15-19.

[27]   Ye, J., Gao, Z., Yin, J., et al. (2007) Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice. American Journal of Physiology—Endocrinology and Metabolism, 293, E1118-1128. doi:10.1152/ajpendo.00435.2007

[28]   Gonzalez, N.C. and Wood, J.G. (2010) Alveolar hypoxia- in-duced systemic inflammation: what low PO(2) does and does not do. Advances in Experimental Medicine and Biology, 662, 27-32. doi:10.1007/978-1-4419-1241-1_3