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TISSUE-SPECIFIC STEM CELLS

A Novel Stem Cell Source for Vasculogenesis in Ischemia: Subfraction of Side Population Cells from Dental Pulp

^aDepartment of Oral Disease Research, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan;
^bDepartment of Developmental Physiology, National Institute for Physiological Sciences, Okazaki, Aichi, Japan;
^cDepartment of Developmental Anatomy and Regenerative Medicine, National Defense Medical College, Tokorozawa, Saitama, Japan;
^dDepartment of Vascular Dementia Research, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan;
^eDepartment of Endodontics, School of Dentistry, Aichigakuin University, Nagoya, Aichi, Japan

Key Words. Dental pulp stem cells • Side population cells • CD31 • Limb ischemia • Vasculogenesis • Angiogenesis

Correspondence: Correspondence: Misako Nakashima, Ph.D., Department of Oral Disease Research, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8522, Japan. Telephone: 0562-44-5651 ext. 5063; Fax: 0562-46-8684; e-mail: misako{at}nils.go.jp

Received on April 21, 2008; accepted for publication on June 18, 2008.

First published online in STEM CELLS EXPRESS  June 26, 2008.

Cell therapy with stem cells and endothelial progenitor cells (EPCs) to stimulate vasculogenesis as a potential treatment for ischemic disease is an exciting area of research in regenerative medicine. EPCs are present in bone marrow, peripheral blood, and adipose tissue. Autologous EPCs, however, are obtained by invasive biopsy, a potentially painful procedure. An alternative approach is proposed in this investigation. Permanent and deciduous pulp tissue is easily available from teeth after extraction without ethical issues and has potential for clinical use. We isolated a highly vasculogenic subfraction of side population (SP) cells based on CD31 and CD146, from dental pulp. The CD31^–;CD146^– SP cells, demonstrating CD34⁺ and vascular endothelial growth factor-2 (VEGFR2)/Flk1⁺, were similar to EPCs. These cells were distinct from the hematopoietic lineage as CD11b, CD14, and CD45 mRNA were not expressed. They showed high proliferation and migration activities and multilineage differentiation potential including vasculogenic potential. In models of mouse hind limb ischemia, local transplantation of this subfraction of SP cells resulted in successful engraftment and an increase in the blood flow including high density of capillary formation. The transplanted cells were in proximity of the newly formed vasculature and expressed several proangiogenic factors, such as VEGF-A, G-CSF, GM-CSF, and MMP3. Conditioned medium from this subfraction showed the mitogenic and antiapoptotic activity on human umbilical vein endothelial cells. In conclusion, subfraction of SP cells from dental pulp is a new stem cell source for cell-based therapy to stimulate angiogenesis/vasculogenesis during tissue regeneration.

Disclosure of potential conflicts of interest is found at the end of this article.