Side population cells isolated from porcine dental pulp tissue with self-renewal and multipotency for dentinogenesis, chondrogenesis, adipogenesis, and neurogenesis

Koichiro Iohara, Li Zheng, Masataka Ito, Atsushi Tomokiyo, Kenji Matsushita, Misako Nakashima

Research output: Contribution to journalArticle

196 Citations (Scopus)

Abstract

Dental pulp has the potential to form dentin as a regenerative response to caries. This regeneration is mediated by stem/progenitor cells. Thus, stem cell therapy might be of potential utility in induction of reparative dentin. We isolated side population (SP) cells from dental pulp based on the exclusion of the DNA binding dye Hoechst 33342 by flow cytometry and compared its self-renewal capacities and multipotency with non-SP cells and primary pulp cells. The cumulative cell number of the SP cells was greater than the non-SP cells and primary pulp cells. Bmi1 was continuously expressed in SP cells, suggesting longer proliferative lifespan and self-renewal capacity of SP cells. Next, the maintenance of the multilineage differentiation potential of pulp SP cells was investigated. Expression of type II collagen and aggrecan confirmed chondrogenic conversion (30%) of SP cells. SP cells expressed peroxisome proliferator-activated receptor γ and adaptor protein 2, showing adipogenic conversion. Expression of mRNA and proteins of neurofilament and neuromodulin confirmed neurogenic conversion (90%). These results demonstrate that pulp SP cells maintain multilineage differentiation potential. We further examined whether bone morphogenetic protein 2 (BMP2) could induce differentiation of pulp SP cells into odontoblasts. BMP2 stimulated the expression of dentin sialophosphoprotein (Dspp) and enamelysin in three-dimensional pellet cultures. Autogenous transplantation of the Bmp2-supplemented SP cells on the amputated pulp stimulated the reparative dentin formation. Thus, adult pulp contains SP cells, which are enriched for stem cell properties and useful for cell therapy with BMP2 for dentin regeneration.

Original languageEnglish
Pages (from-to)2493-2503
Number of pages11
JournalStem Cells
Volume24
Issue number11
DOIs
Publication statusPublished - Nov 8 2006

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Dentinogenesis
Side-Population Cells
Chondrogenesis
Dental Pulp
Adipogenesis
Neurogenesis
Swine
Dentin
Bone Morphogenetic Protein 2
Stem Cells
Cell- and Tissue-Based Therapy
Matrix Metalloproteinase 20
Regeneration
GAP-43 Protein
Odontoblasts
Neurofilament Proteins
Aggrecans
Peroxisome Proliferator-Activated Receptors
Collagen Type II
Population

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Cite this

Side population cells isolated from porcine dental pulp tissue with self-renewal and multipotency for dentinogenesis, chondrogenesis, adipogenesis, and neurogenesis. / Iohara, Koichiro; Zheng, Li; Ito, Masataka; Tomokiyo, Atsushi; Matsushita, Kenji; Nakashima, Misako.

In: Stem Cells, Vol. 24, No. 11, 08.11.2006, p. 2493-2503.

Research output: Contribution to journalArticle

Iohara, Koichiro ; Zheng, Li ; Ito, Masataka ; Tomokiyo, Atsushi ; Matsushita, Kenji ; Nakashima, Misako. / Side population cells isolated from porcine dental pulp tissue with self-renewal and multipotency for dentinogenesis, chondrogenesis, adipogenesis, and neurogenesis. In: Stem Cells. 2006 ; Vol. 24, No. 11. pp. 2493-2503.
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