Cell Homing for Pulp Tissue Engineering with Endogenous Dentin Matrix Proteins
Cell Homing for Pulp Tissue Engineering with Endogenous Dentin Matrix Proteins
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DOI：
10.1016/j.joen.2018.02.011
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发表时间：
2018-06-01
影响因子：
4.2
通讯作者：
Galler, Kerstin M.
中科院分区：
文献类型：
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作者：
Widbiller, Matthias;Driesen, Ronald B.;Galler, Kerstin M.
引言：令人信服的证据表明，干细胞移植后的牙髓组织工程是可能的。虽然有趣，但关于临床可行性的严重问题仍然存在。细胞归巢已被提出作为一种可行的替代方案，其中在有益支架中的牙本质衍生的生长因子可以吸引驻留细胞以形成牙髓样组织。在这项研究中，异位动物模型原位牙髓组织工程的开发，以评估是否牙髓样组织形成空根管后，干细胞的吸引是可能的，这是否可以增强牙本质衍生的生长因子。研究方法：三种类型的纤维蛋白（定制的纤维蛋白，纤维蛋白密封剂，血浆中富含生长因子[PRGF]），以及自组装肽进行了评估，在体内的修改牙根模型，使用人类牙齿。用EDTA处理根管牙本质，用含生长因子的支架填充牙根，并将胶原中的牙髓干细胞置于根尖。将构建体植入免疫功能低下的小鼠中4周，随后进行组织学分析。对选定的切片进行微分干涉对比和二次谐波成像。结果如下：对于使用牙本质基质蛋白定制的纤维蛋白和纤维蛋白密封剂，观察到迁移到根部并形成纸浆状组织，而基于肽的支架似乎不太合适。PRGF支持组织的形成，无论牙本质基质蛋白的添加。在实验组与牙本质基质蛋白和EDTA预处理，分化成牙本质细胞样细胞延伸到牙本质小管的细胞突起，这与沉积的新形成的胶原牙本质基质。结论：这种新的细胞归巢模型提供了证据，纤维蛋白衍生物适用的支架和牙本质衍生蛋白诱导趋化性和牙髓样组织形成。
Introduction: 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. Methods: 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. Results: 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. Conclusions: This new cell homing model provides evidence that fibrin derivatives make applicable scaffolds and that dentin-derived proteins induce chemotaxis and pulplike tissue formation.