Department of Conservative Dentistry and Periodontology, University Hospital Regensburg, Regensburg, Germany.
Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.
J Endod. 2018 Jun;44(6):956-962.e2. doi: 10.1016/j.joen.2018.02.011. Epub 2018 Mar 29.
Compelling evidence pinpoints that pulp tissue engineering after the transplantation of stem cells is possible. Although intriguing, severe problems regarding clinical feasibility remain. Cell homing has been proposed as a viable alternative in which dentin-derived growth factors in a conducive scaffold may attract resident cells to form pulplike tissue. In this study, an ectopic animal model for in situ dental pulp tissue engineering was developed to evaluate whether pulplike tissue formation in empty root canals after the attraction of stem cells was possible and whether this could be enhanced by dentin-derived growth factors.
Three types of fibrin (custom-made fibrin, fibrin sealant, and plasma rich in growth factors [PRGF]) as well as a self-assembling peptide were evaluated in vivo in a modified tooth root model using human teeth. Root canal dentin was conditioned with EDTA, tooth roots were filled with growth factor-laden scaffolds, and dental pulp stem cells in collagen were placed at the root tip. Constructs were implanted into immunocompromised mice for 4 weeks and subsequently analyzed histologically. Differential interference contrast and second harmonic generation imaging were performed for selected sections.
For custom-made fibrin and fibrin sealant with dentin matrix proteins, migration into the roots and the formation of a pulplike tissue were observed, whereas the peptide-based scaffold appeared less suitable. PRGF supported tissue formation regardless of the addition of dentin matrix proteins. In the test groups with dentin matrix proteins and EDTA conditioning, differentiated odontoblastlike cells extended cellular processes into the dentinal tubules, which coincided with the deposition of the newly formed collagenous dentin matrix.
This new cell homing model provides evidence that fibrin derivatives make applicable scaffolds and that dentin-derived proteins induce chemotaxis and pulplike tissue formation.
有确凿证据表明,干细胞移植后牙髓组织工程是可行的。尽管这很吸引人,但临床可行性方面仍存在严重问题。细胞归巢被认为是一种可行的替代方法,其中在有利的支架中的牙本质衍生生长因子可能吸引常驻细胞形成牙髓样组织。在这项研究中,开发了一种异位动物模型,用于原位牙髓组织工程,以评估在吸引干细胞后空根管中是否有可能形成牙髓样组织,以及牙本质衍生生长因子是否可以增强这种形成。
在使用人牙的改良牙根模型中,体内评估了三种类型的纤维蛋白(定制纤维蛋白、纤维蛋白密封剂和富含生长因子的血浆[PRGF])以及自组装肽。用 EDTA 处理根管牙本质,用生长因子负载的支架填充牙根,并将胶原蛋白中的牙髓干细胞置于根尖处。将构建体植入免疫功能低下的小鼠中 4 周,然后进行组织学分析。对选定的切片进行微分干涉对比和二次谐波产生成像。
对于含有牙本质基质蛋白的定制纤维蛋白和纤维蛋白密封剂,观察到向根部迁移并形成牙髓样组织,而基于肽的支架似乎不太合适。PRGF 支持组织形成,无论是否添加牙本质基质蛋白。在添加牙本质基质蛋白和 EDTA 处理的实验组中,分化的成牙本质细胞将细胞突起延伸到牙本质小管中,这与新形成的胶原性牙本质基质的沉积相吻合。
这个新的细胞归巢模型提供了证据,表明纤维蛋白衍生物可作为适用的支架,牙本质衍生蛋白可诱导趋化性和牙髓样组织形成。