A Novel Combinatorial Therapy With Pulp Stem Cells and Granulocyte Colony-Stimulating Factor for Total Pulp Regeneration
A Novel Combinatorial Therapy With Pulp Stem Cells and Granulocyte Colony-Stimulating Factor for Total Pulp Regeneration
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DOI：
10.5966/sctm.2012-0132
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发表时间：
2013-07-01
影响因子：
6
通讯作者：
Nakashima, Misako
中科院分区：
文献类型：
--
作者：
Iohara, Koichiro;Murakami, Masashi;Nakashima, Misako
深龋伴牙髓炎的治疗是牙科学的一个重大挑战。干细胞疗法代表了一种潜在的策略，以再生牙本质牙髓复合体，使牙齿的保护和修复。本研究的目的是评估牙髓干细胞移植的有效性和安全性，作为即将进行的临床试验的前奏。临床级牙髓干细胞根据良好的生产实践条件进行分离和扩增。免疫缺陷小鼠移植后无污染、核型异常/畸变和肿瘤形成，确保了良好的质量控制。将牙髓干细胞与粒细胞集落刺激因子（G-CSF）联合自体移植于犬去髓牙后，再生的牙髓组织（包括血管和神经支配）完全填充根管，在冠部形成再生的牙本质，并防止了微渗漏，移植时间可达180 d。牙髓干细胞与G-CSF联合移植较单纯干细胞或G-CSF移植产生更大量的再生牙本质牙髓复合体。同样值得注意的是，与没有G-CSF的结果相比，炎性细胞和凋亡细胞的数量减少，神经突生长显著增加。移植的干细胞表达血管生成/神经营养因子。G-CSF与牙髓干细胞条件培养液联合应用，在体外刺激牙髓干细胞迁移和突起生长，防止细胞死亡，促进免疫抑制等方面具有重要意义。此外，没有证据表明存在毒性或不良事件。总之，牙髓干细胞和G-CSF的组合营养效应对于牙髓/牙本质再生具有直接效用，证明了对于临床应用至关重要的安全性和有效性的先决条件。
Treatment of deep caries with pulpitis is a major challenge in dentistry. Stem cell therapy represents a potential strategy to regenerate the dentin-pulp complex, enabling conservation and restoration of teeth. The objective of this study was to assess the efficacy and safety of pulp stem cell transplantation as a prelude for the impending clinical trials. Clinical-grade pulp stem cells were isolated and expanded according to good manufacturing practice conditions. The absence of contamination, abnormalities/aberrations in karyotype, and tumor formation after transplantation in an immunodeficient mouse ensured excellent quality control. After autologous transplantation of pulp stem cells with granulocyte-colony stimulating factor (G-CSF) in a dog pulpectomized tooth, regenerated pulp tissue including vasculature and innervation completely filled in the root canal, and regenerated dentin was formed in the coronal part and prevented microleakage up to day 180. Transplantation of pulp stem cells with G-CSF yielded a significantly larger amount of regenerated dentin-pulp complex compared with transplantation of G-CSF or stem cells alone. Also noteworthy was the reduction in the number of inflammatory cells and apoptotic cells and the significant increase in neurite outgrowth compared with results without G-CSF. The transplanted stem cells expressed angiogenic/neurotrophic factors. It is significant that G-CSF together with conditioned medium of pulp stem cells stimulated cell migration and neurite outgrowth, prevented cell death, and promoted immunosuppression in vitro. Furthermore, there was no evidence of toxicity or adverse events. In conclusion, the combinatorial trophic effects of pulp stem cells and G-CSF are of immediate utility for pulp/dentin regeneration, demonstrating the prerequisites of safety and efficacy critical for clinical applications.