The Side Population Cells Isolated from Porcine Dental Pulp Tissue with Self-renewal and Multipotency for Dentinogenesis, Chondrogenesis, Adipogenesis and Neurogenesis

¹ Laboratory of Oral Disease Research, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Aichi, Japan
² Department of First Anatomy, National Defense Medical College, Tokorozawa, Japan
³ Department of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, Japan

^* To whom correspondence should be addressed. E-mail: misako{at}nils.go.jp.

	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 compared to the non-SP cells and primary pulp cells. Bmi1 was continuously expressed in SP cells, suggesting longer proliferative life span and self-renewal capacity of SP cells. Next, the maintenance of the multi-lineage 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 PPAR and P2, showing adipogenic conversion. Expression of mRNA and proteins of neurofilament and neuromodulin confirmed neurogenic conversion (90%). These results demonstrate that pulp SP cells maintain multi-lineage differentiation potential. We further examined whether bone morphogenetic protein 2 (BMP2) could induce differentiation of pulp SP cells into odontoblasts. The 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.

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