Department of Stem Cell Biology and Regenerative Medicine, National Center for Geriatrics and Gerontology, Research Institute, 7-430 Morioka, Obu, Aichi, 474-8511, Japan.
Drug Safety Research Laboratories, Shin Nippon Biomedical Laboratories Ltd, Kagoshima, Japan.
Stem Cell Res Ther. 2018 Apr 27;9(1):116. doi: 10.1186/s13287-018-0855-8.
We recently demonstrated that autologous transplantation of mobilized dental pulp stem cells (MDPSCs) was a safe and efficacious potential therapy for total pulp regeneration in a clinical study. The autologous MDPSCs, however, have some limitations to overcome, such as limited availability of discarded teeth from older patients. In the present study, we investigated whether MDPSCs can be used for allogeneic applications to expand their therapeutic use.
Analysis of dog leukocyte antigen (DLA) was performed using polymerase chain reaction from blood. Canine allogeneic MDPSCs with the matched and mismatched DLA were transplanted with granulocyte-colony stimulating factor in collagen into pulpectomized teeth respectively (n = 7, each). Results were evaluated by hematoxylin and eosin staining, Masson trichrome staining, PGP9.5 immunostaining, and BS-1 lectin immunostaining performed 12 weeks after transplantation. The MDPSCs of the same DLA used in the first transplantation were further transplanted into another pulpectomized tooth and evaluated 12 weeks after transplantation.
There was no evidence of toxicity or adverse events of the allogeneic transplantation of the MDPSCs with the mismatched DLA. No adverse event of dual transplantation of the MDPSCs with the matched and mismatched DLA was observed. Regenerated pulp tissues including neovascularization and neuronal extension were quantitatively and qualitatively similar at 12 weeks in both matched and mismatched DLA transplants. Regenerated pulp tissue was similarly observed in the dual transplantation as in the single transplantation of MDPSCs both with the matched and mismatched DLA.
Dual allogeneic transplantation of MDPSCs with the mismatched DLA is a safe and efficacious method for total pulp regeneration.
我们最近的研究表明，自体动员牙髓干细胞（MDPSCs）移植是一种安全有效的牙髓再生的潜在疗法，已在临床试验中得到验证。然而，自体 MDPSCs 存在一些局限性，如老年患者废弃牙齿的来源有限。在本研究中，我们研究了 MDPSCs 是否可用于同种异体应用，以扩大其治疗用途。
从血液中提取犬白细胞抗原（DLA），采用聚合酶链反应进行分析。将匹配和不匹配 DLA 的同种异体 MDPSCs 与粒细胞集落刺激因子一起移植到牙髓切断的牙齿中（n=7，每组）。移植后 12 周，通过苏木精和伊红染色、Masson 三色染色、PGP9.5 免疫染色和 BS-1 凝集素免疫染色评估结果。第一次移植中使用的相同 DLA 的 MDPSCs 进一步移植到另一个牙髓切断的牙齿中，并在移植后 12 周进行评估。
没有证据表明不匹配 DLA 的 MDPSCs 同种异体移植存在毒性或不良事件。未观察到匹配和不匹配 DLA 的 MDPSCs 双重移植的不良事件。在 12 周时，匹配和不匹配 DLA 移植的再生牙髓组织均表现出类似的定量和定性的血管生成和神经元延伸。在匹配和不匹配 DLA 的 MDPSCs 的双重移植和单次移植中，均观察到类似的再生牙髓组织。
不匹配 DLA 的 MDPSCs 双重同种异体移植是一种安全有效的牙髓再生方法。
