Department of Integrative Medical Biology, Section for Anatomy, Umeå University, Umeå, Sweden.
Department of Surgical & Perioperative Sciences, Section for Hand and Plastic Surgery, Umeå University, Umeå, Sweden.
Sci Rep. 2017 Oct 3;7(1):12605. doi: 10.1038/s41598-017-12969-1.
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.
目前治疗周围神经损伤的金标准是神经移植，但这种方法有供体部位发病率高等缺点。新技术的重点是用神经导管替代这些移植物，这些神经导管通过生长因子和/或各种细胞类型（如间充质干细胞[MSCs]）得到增强。牙髓间充质干细胞（DPSC）、根尖乳头间充质干细胞（SCAP）和牙周膜干细胞（PDLSC）等牙源性间充质干细胞（D-MSCs）是用于神经修复的 MSC 的潜在来源。在这里，我们展示了来自同一供体的不同 D-MSCs 对周围神经再生的特性。SCAP、DPSC 和 PDLSC 表达 BDNF、GDNF、NGF、NTF3、ANGPT1 和 VEGFA 生长因子转录本。D-MSCs 的条件培养基在体外试验中增强了神经突的生长。中和抗体的应用表明，脑源性神经营养因子通过刺激神经突生长发挥重要的机制作用。SCAP、DPSC 和 PDLSC 用于治疗大鼠坐骨神经损伤模型中的 10mm 神经间隙缺损。所有干细胞类型在两周后均显著增强了轴突再生，并对背根神经节神经元表现出神经保护作用。总体而言，结果表明 SCAP 是用于周围神经修复的最佳牙源性干细胞类型。
