The neurotrophic effects of different human dental mesenchymal stem cells.
The neurotrophic effects of different human dental mesenchymal stem cells.
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DOI：
10.1038/s41598-017-12969-1
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发表时间：
2017-10-03
影响因子：
4.6
通讯作者：
Kelk P
中科院分区：
文献类型：
--
作者：
Kolar MK;Itte VN;Kingham PJ;Novikov LN;Wiberg M;Kelk P
目前周围神经损伤的金标准治疗是神经移植，但这有缺点，如供区发病率。新技术的重点是用生长因子和/或各种细胞类型（如间充质干细胞（MSC））增强的神经导管替代这些移植物。牙本质间充质干细胞（D-MSCs）包括从根尖乳头获得的干细胞（SCAP）、牙髓干细胞（DPSC）和牙周膜干细胞（PDLSC），是用于神经修复的MSCs的潜在来源。在这里，我们提出了不同的D-MSC的表征从相同的人供体周围神经再生。SCAP、DPSC和PDLSC表达BDNF、GDNF、NGF、NTF 3、ANGPT 1和VEGFA生长因子转录本。在体外试验中，来自D-MSC的条件培养基增强了神经突生长。中和抗体的应用表明，脑源性神经营养因子在D-MSCs刺激神经突起生长中起重要作用。在大鼠坐骨神经损伤模型中，使用SCAP、DPSC和PDLSC治疗10 mm神经间隙缺损。两周后，所有类型的干细胞均显著促进轴突再生，并对背根神经节神经元表现出神经保护作用。总的来说，结果表明SCAP是周围神经修复的最佳牙科干细胞类型。
The current gold standard treatment for peripheral nerve injury is nerve grafting but this has disadvantages such as donor site morbidity. New techniques focus on replacing these grafts with nerve conduits enhanced with growth factors and/or various cell types such as mesenchymal stem cells (MSCs). Dental-MSCs (D-MSCs) including stem cells obtained from apical papilla (SCAP), dental pulp stem cells (DPSC), and periodontal ligament stem cells (PDLSC) are potential sources of MSCs for nerve repair. Here we present the characterization of various D-MSCs from the same human donors for peripheral nerve regeneration. SCAP, DPSC and PDLSC expressed BDNF, GDNF, NGF, NTF3, ANGPT1 and VEGFA growth factor transcripts. Conditioned media from D-MSCs enhanced neurite outgrowth in an in vitro assay. Application of neutralizing antibodies showed that brain derived neurotrophic factor plays an important mechanistic role by which the D-MSCs stimulate neurite outgrowth. SCAP, DPSC and PDLSC were used to treat a 10 mm nerve gap defect in a rat sciatic nerve injury model. All the stem cell types significantly enhanced axon regeneration after two weeks and showed neuroprotective effects on the dorsal root ganglia neurons. Overall the results suggested SCAP to be the optimal dental stem cell type for peripheral nerve repair.
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