Open AccessA Novel Stem Cell Source for Vasculogenesis in Ischemia: Subfraction of Side Population Cells from Dental Pulp
Author(s) -
Iohara Koichiro,
Zheng Li,
Wake Hiroaki,
Ito Masataka,
Nabekura Junichi,
Wakita Hideaki,
Nakamura Hiroshi,
Into Takeshi,
Matsushita Kenji,
Nakashima Misako
Publication year - 2008
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2008-0393
Subject(s) - vasculogenesis , biology , angiogenesis , cd34 , stem cell , progenitor cell , cd31 , dental pulp stem cells , population , vascular endothelial growth factor , immunology , bone marrow , endothelial stem cell , microbiology and biotechnology , cancer research , medicine , in vitro , biochemistry , environmental health , vegf receptors
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.