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与恒牙来源的干细胞相比,犬乳牙来源的干细胞的生物学特性和牙髓再生潜力。

Biological characteristics and pulp regeneration potential of stem cells from canine deciduous teeth compared with those of permanent teeth.

机构信息

Regenerative Dental Medicine, National Center for Geriatrics and Gerontology, Research Institute, Geroscience Research Center, 7-430 Morioka, Obu, Aichi, 474-8511, Japan.

Department of Periodontology and Endodontology, Nagasaki University Graduate, School of Biomedical Sciences, Nagasaki, Japan.

出版信息

Stem Cell Res Ther. 2022 Sep 2;13(1):439. doi: 10.1186/s13287-022-03124-3.

Abstract

BACKGROUND

Clinical studies have demonstrated that dental pulp stem cells isolated from permanent teeth (PT-DPSCs) are safe and efficacious for complete pulp regeneration in mature pulpectomized permanent teeth with complete apical closure. Moreover, dental pulp stem cells from deciduous teeth (DT-DPSCs) have also been shown to be useful for pulp regenerative cell therapy of injured immature permanent teeth. However, direct comparisons of the pulp regenerative potential of DT-DPSCs and PT-DPSCs from the same individual have not been performed. This study aimed to compare the differences in stem cell properties and pulp regenerative potential of DT-DPSCs and PT-DPSCs of identical origin.

METHODS

DT-DPSCs and PT-DPSCs were isolated from the same individual dogs at 4 months and 9 months of age, respectively. The expression of cell surface antigen markers, proliferation and migration activities, and gene expression of stem cell markers, angiogenic/neurotrophic factors and senescence markers were compared. The effects of conditioned medium (CM) derived from these cells on cellular proliferation, migration, angiogenesis, neurite outgrowth and immunosuppression were also compared. Autologous transplantation of DT-DPSCs or PT-DPSCs together with G-CSF was performed to treat pulpectomized teeth in individual dogs. The vascularization and reinnervation of the regenerated pulp tissues were qualitatively and quantitatively compared between groups by histomorphometric analyses.

RESULTS

The rates of positive CXCR4 and G-CSFR expression in DT-DPSCs were significantly higher than those in PT-DPSCs. DT-DPSCs migrated at a higher rate with/without G-CSF and exhibited increased expression of the stem cell markers Oct3/4 and CXCR4 and the angiogenic factor VEGF and decreased expression of the senescence marker p16 than PT-DPSCs. DT-DPSC-derived CM promoted increased cell proliferation, migration with G-CSF, and angiogenesis compared with PT-DPSC-derived CM; however, no difference was observed in neurite outgrowth or immunosuppression. The regenerated pulp tissues in the pulpectomized teeth were quantitatively and qualitatively similar between the DT-DPSCs and PT-DPSCs transplant groups.

CONCLUSIONS

These results demonstrated that DT-DPSCs could be a potential clinical alternative to PT-DPSCs for pulp regenerative therapy. DT-DPSCs can be preserved in an individual cell bank and used for potential future pulp regenerative therapy before the supply of an individual's own sound discarded teeth has been exhausted.

摘要

背景

临床研究表明,从恒齿(PT-DPSCs)分离的牙髓干细胞对于完全闭合的成熟恒牙髓腔化的完全牙髓再生是安全有效的。此外,乳牙(DT-DPSCs)的牙髓干细胞也已被证明对受伤的未成熟恒牙髓再生细胞治疗有用。然而,尚未对来自同一个体的 DT-DPSCs 和 PT-DPSCs 的牙髓再生潜力进行直接比较。本研究旨在比较同一来源的 DT-DPSCs 和 PT-DPSCs 的干细胞特性和牙髓再生潜力的差异。

方法

分别从 4 个月和 9 个月大的同一只狗中分离 DT-DPSCs 和 PT-DPSCs。比较细胞表面抗原标志物的表达、增殖和迁移活性以及干细胞标志物、血管生成/神经营养因子和衰老标志物的基因表达。还比较了这些细胞的条件培养基(CM)对细胞增殖、迁移、血管生成、神经突生长和免疫抑制的影响。将 DT-DPSCs 或 PT-DPSCs 与 G-CSF 自体移植到个体狗的牙髓腔化牙齿中。通过组织形态计量学分析,定性和定量比较各组再生牙髓组织的血管化和再神经支配。

结果

DT-DPSCs 中 CXCR4 和 G-CSFR 的阳性表达率明显高于 PT-DPSCs。有/无 G-CSF 时,DT-DPSCs 迁移速度更快,并且表达的干细胞标志物 Oct3/4 和 CXCR4 以及血管生成因子 VEGF 更高,衰老标志物 p16 表达更低。与 PT-DPSC 衍生的 CM 相比,DT-DPSC 衍生的 CM 促进细胞增殖、有 G-CSF 时的迁移和血管生成增加;然而,在神经突生长或免疫抑制方面没有差异。牙髓腔化牙齿中的再生牙髓组织在 DT-DPSCs 和 PT-DPSCs 移植组之间在数量和质量上相似。

结论

这些结果表明,DT-DPSCs 可以成为牙髓再生治疗的一种潜在临床替代物。在个人自身完好的废弃牙齿供应耗尽之前,可以将 DT-DPSCs 保存在个体细胞库中,以备将来可能进行牙髓再生治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb14/9438285/aa8c2712d50e/13287_2022_3124_Fig1_HTML.jpg

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