CXCL14 and MCP1 are potent trophic factors associated with cell migration and angiogenesis leading to higher regenerative potential of dental pulp side population cells

CXCL14 and MCP1 are potent trophic factors associated with cell migration and angiogenesis leading to higher regenerative potential of dental pulp side population cells

Stem Cell Research & Therapy, May 2015

26021377

Y Hayashi, M Murakami, R Kawamura, R Ishizaka, O Fukuta, M Nakashima

The release of trophic factors from mesenchymal stem cells (MSCs) is critical for tissue regeneration. A systematic investigation of the regenerative potential of trophic factors from different MSCs, however, has not been performed. Thus, in the present study, the regenerative potential of conditioned medium (CM) from dental pulp, bone marrow and adipose tissue-derived CD31(-) side population (SP) cells from an individual source was compared in an ectopic tooth transplantation model. The tooth root transplantation in an ectopic site model was used for investigation of the regenerative potential and trophic effects in vivo. Either pulp CD31(-) SP cell populations, 1 × 10(6) cells, at the third to fourth passage or 5 μg/ml of CM from dental pulp, bone marrow and adipose stem cells from 4 different individuals were injected into the root with collagen TE. Each root was transplanted subcutaneously in 5-week-old SCID mice. Each root with surrounding tissue was harvested for histology on days 7, 21 and 28, and for western blot analysis and real-time RT-PCR analysis on day 28. Furthermore, the trophic factors responsible for the regenerative potential were identified as the up-regulated genes present in pulp CD31(-) SP cells when compared to the genes in both bone marrow and adipose CD31(-) SP cells using microarray analysis, real-time RT-PCR and western blot analysis. Transplantation of pulp CM yielded increased volume of pulp regeneration, more BrdU-positive migrated cells and fewer Caspase 3-positive cells in the regenerated pulp compared to the others. Pulp CM also demonstrated significantly increased cell migration, anti-apoptosis and angiogenesis in C2C12 cells. Higher expression of CXCL14, MCP1 in pulp SP cells suggested candidate trophic factors. The stimulatory effects on both migration and angiogenesis of CXCL14 and MCP1 were demonstrated in vitro. In the regenerated tissue, BrdU-positive migrated cells expressed CXCR4 and CCR2, receptors for CXCL14 and MCP1, respectively. The higher regenerative potential of pulp SP cells may be due to potent trophic factors, including CXCL14 and MCP1 which promote migration and angiogenesis.