A novel stem cell source for vasculogenesis in ischemia: Subfraction of side population cells from dental pulp

Koichiro Iohara, Li Zheng, Hiroaki Wake, Masataka Ito, Junichi Nabekura, Hideaki Wakita, Hiroshi Nakamura, Takeshi Into, Kenji Matsushita, Misako Nakashima

Research output: Contribution to journalArticle

163 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2408-2418
Number of pages11
JournalStem Cells
Volume26
Issue number9
DOIs
Publication statusPublished - 01-09-2008

Fingerprint

Side-Population Cells
Dental Pulp
Stem Cells
Ischemia
Granulocyte-Macrophage Colony-Stimulating Factor
Cell- and Tissue-Based Therapy
Vascular Endothelial Growth Factor A
Tooth Extraction
Regenerative Medicine
Human Umbilical Vein Endothelial Cells
Granulocyte Colony-Stimulating Factor
Conditioned Culture Medium
Ethics
Adipose Tissue
Regeneration
Extremities
Transplantation
Bone Marrow
Biopsy
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Cite this

Iohara, Koichiro ; Zheng, Li ; Wake, Hiroaki ; Ito, Masataka ; Nabekura, Junichi ; Wakita, Hideaki ; Nakamura, Hiroshi ; Into, Takeshi ; Matsushita, Kenji ; Nakashima, Misako. / A novel stem cell source for vasculogenesis in ischemia : Subfraction of side population cells from dental pulp. In: Stem Cells. 2008 ; Vol. 26, No. 9. pp. 2408-2418.
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Iohara, K, Zheng, L, Wake, H, Ito, M, Nabekura, J, Wakita, H, Nakamura, H, Into, T, Matsushita, K & Nakashima, M 2008, 'A novel stem cell source for vasculogenesis in ischemia: Subfraction of side population cells from dental pulp', Stem Cells, vol. 26, no. 9, pp. 2408-2418. https://doi.org/10.1634/stemcells.2008-0393

A novel stem cell source for vasculogenesis in ischemia : Subfraction of side population cells from dental pulp. / Iohara, Koichiro; Zheng, Li; Wake, Hiroaki; Ito, Masataka; Nabekura, Junichi; Wakita, Hideaki; Nakamura, Hiroshi; Into, Takeshi; Matsushita, Kenji; Nakashima, Misako.

In: Stem Cells, Vol. 26, No. 9, 01.09.2008, p. 2408-2418.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A novel stem cell source for vasculogenesis in ischemia

T2 - Subfraction of side population cells from dental pulp

AU - Iohara, Koichiro

AU - Zheng, Li

AU - Wake, Hiroaki

AU - Ito, Masataka

AU - Nabekura, Junichi

AU - Wakita, Hideaki

AU - Nakamura, Hiroshi

AU - Into, Takeshi

AU - Matsushita, Kenji

AU - Nakashima, Misako

PY - 2008/9/1

Y1 - 2008/9/1

N2 - 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.

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