Department of Restorative Dentistry, Division of Operative Dentistry, Tohoku University Graduate School of Dentistry, Sendai, Japan.
Department of Oral Biology, Division of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai, Japan.
Sci Rep. 2019 Jan 29;9(1):921. doi: 10.1038/s41598-018-37528-0.
The ultimate goal of periodontal disease treatment is the reorganization of functional tissue that can regenerate lost periodontal tissue. Regeneration of periodontal tissues is clinically possible by using autogenic transplantation of MSCs. However, autologous MSC transplantation is limited depending on age, systemic disease and tissue quality, thus precluding their clinical application. Therefore, we evaluated the efficacy of allogeneic transplantation of adipose-derived multi-lineage progenitor cells (ADMPC) in a micro-mini pig periodontal defect model. ADMPC were isolated from the greater omentum of micro-mini pigs, and flow cytometry analysis confirmed that the ADMPC expressed MSC markers, including CD44 and CD73. ADMPC exhibited osteogenic, adipogenic and periodontal ligament differentiation capacities in differentiation medium. ADMPC showed high expression of the immune suppressive factors GBP4 and IL1-RA upon treatment with a cytokine cocktail containing interferon-γ, tumor necrosis factor-α and interleukin-6. Allogeneic transplantation of ADMPC in a micro-mini pig periodontal defect model showed significant bone regeneration ability based on bone-morphometric analysis. Moreover, the regeneration ability of ADMPC by allogeneic transplantation was comparable to those of autologous transplantation by histological analysis. These results indicate that ADMPC have immune-modulation capability that can induce periodontal tissue regeneration by allogeneic transplantation.
牙周病治疗的最终目标是功能性组织的再组织化,以再生丢失的牙周组织。通过使用自体间充质干细胞(MSCs)的自体移植,临床上可以实现牙周组织的再生。然而,自体 MSC 移植受到年龄、系统性疾病和组织质量的限制,因此排除了它们的临床应用。因此,我们在微型猪牙周缺损模型中评估了脂肪来源的多能祖细胞(ADMPC)同种异体移植的疗效。ADMPC 从微型猪的大网膜中分离出来,流式细胞术分析证实 ADMPC 表达 MSC 标志物,包括 CD44 和 CD73。ADMPC 在分化培养基中表现出成骨、成脂和成牙骨质分化能力。ADMPC 在含有干扰素-γ、肿瘤坏死因子-α和白细胞介素-6 的细胞因子鸡尾酒处理下,高表达免疫抑制因子 GBP4 和 IL1-RA。在微型猪牙周缺损模型中进行的 ADMPC 同种异体移植显示出基于骨形态计量学分析的显著骨再生能力。此外,同种异体移植的 ADMPC 的再生能力通过组织学分析与自体移植相当。这些结果表明 ADMPC 具有免疫调节能力,可以通过同种异体移植诱导牙周组织再生。