Murakami Masashi, Hayashi Yuki, Iohara Koichiro, Osako Yohei, Hirose Yujiro, Nakashima Misako
Department of Dental Regenerative Medicine, Center of Advanced Medicine for Dental and Oral Diseases, National Center for Geriatrics and Gerontology, Research Institute, Obu, Japan.
Cell Transplant. 2015;24(9):1753-65. doi: 10.3727/096368914X683502. Epub 2014 Jul 30.
Dental pulp stem cell (DPSC) subsets mobilized by granulocyte-colony-stimulating factor (G-CSF) are safe and efficacious for complete pulp regeneration. The supply of autologous pulp tissue, however, is very limited in the aged. Therefore, alternative sources of mesenchymal stem/progenitor cells (MSCs) are needed for the cell therapy. In this study, DPSCs, bone marrow (BM), and adipose tissue (AD)-derived stem cells of the same individual dog were isolated using G-CSF-induced mobilization (MDPSCs, MBMSCs, and MADSCs). The positive rates of CXCR4 and G-CSFR in MDPSCs were similar to MADSCs and were significantly higher than those in MBMSCs. Trophic effects of MDPSCs on angiogenesis, neurite extension, migration, and antiapoptosis were higher than those of MBMSCs and MADSCs. Pulp-like loose connective tissues were regenerated in all three MSC transplantations. Significantly higher volume of regenerated pulp and higher density of vascularization and innervation were observed in response to MDPSCs compared to MBMSC and MADSC transplantation. Collagenous matrix containing dentin sialophosphoprotein (DSPP)-positive odontoblast-like cells was the highest in MBMSCs and significantly higher in MADSCs compared to MDPSCs. MBMSCs and MADSCs, therefore, have potential for pulp regeneration, although the volume of regenerated pulp tissue, angiogenesis, and reinnervation, were less. Thus, in conclusion, an alternative cell source for dental pulp/dentin regeneration are stem cells from BM and AD tissue.
粒细胞集落刺激因子（G-CSF）动员的牙髓干细胞（DPSC）亚群对牙髓完全再生安全且有效。然而，在老年人中，自体牙髓组织的供应非常有限。因此，细胞治疗需要间充质干/祖细胞（MSC）的替代来源。在本研究中，使用G-CSF诱导动员（MDPSC、MBMSC和MADSC）从同一只犬分离出DPSC、骨髓（BM）和脂肪组织（AD）来源的干细胞。MDPSC中CXCR4和G-CSFR的阳性率与MADSC相似，且显著高于MBMSC。MDPSC对血管生成、神经突延伸、迁移和抗凋亡的营养作用高于MBMSC和MADSC。在所有三种MSC移植中均再生出牙髓样疏松结缔组织。与MBMSC和MADSC移植相比，MDPSC移植后观察到再生牙髓体积显著更大，血管化和神经支配密度更高。含有牙本质涎磷蛋白（DSPP）阳性成牙本质细胞样细胞的胶原基质在MBMSC中最高，在MADSC中比MDPSC显著更高。因此，MBMSC和MADSC具有牙髓再生的潜力，尽管再生牙髓组织的体积、血管生成和神经再支配较少。因此，总之，BM和AD组织来源的干细胞是牙髓/牙本质再生的替代细胞来源。
