Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Xi'an, Shaanxi, China.
Department of Periodontology, College of Stomatology, Xi'an Jiaotong University, Xi Wu Road No.98, Xi'an, Shaanxi, 710004, China.
Stem Cell Res Ther. 2017 Sep 29;8(1):198. doi: 10.1186/s13287-017-0648-5.
Traumatic brain injury (TBI) is one of the major causes of mortality and disability for all ages worldwide. Mesenchymal stem cells (MSCs)-originated exosomes have provided therapeutic effects. However, as an indispensable component of MSCs, whether odontogenic stem cell-generated exosomes could benefit TBI is still unclear. Thus we aimed to explore the potential of stem cells from human exfoliated deciduous teeth-originated exosomes (SHED-Ex) for the management of TBI.
First, a transwell system was used to co-culture activated BV-2 microglia cells with SHED. The secretion levels of neuroinflammatory factors and nitrite were evaluated by enzyme-linked immunosorbent assay (ELISA) and Griess assay. Furthermore, purified SHED-Ex were co-cultured with activated BV-2. ELISA, Griess assay, flow cytometry, immunofluorescence, and qRT-PCR were performed to test the levels of inflammatory factors as well as the microglia phenotype. Finally, SHED and SHED-Ex were locally injected into TBI rat models. Basso, Beattie, and Bresnahan (BBB) scores were chosen to evaluate the motor functional recovery. Histopathology and immunofluorescence were performed to measure the lesion volume and neuroinflammation.
As a result, SHED-Ex could reduce neuroinflammation by shifting microglia polarization. The administration of SHED-Ex improves rat motor functional recovery and reduces cortical lesion compared with the control group 2 weeks post-injury (P < 0.05).
The current study demonstrates for the first time that SHED-Ex contribute a therapeutic benefit to TBI in rats, at least in part by shifting microglia polarization to reduce neuroinflammation. The use of odontogenic stem cells, and indeed their exosomes, may be expanded for the treatment of TBI or other neurological disorders.
创伤性脑损伤（TBI）是全球各年龄段人群死亡和残疾的主要原因之一。间充质干细胞（MSCs）衍生的外泌体已显示出治疗效果。然而，作为 MSCs 的不可或缺组成部分，牙源性干细胞产生的外泌体是否对 TBI有益尚不清楚。因此，我们旨在探讨人脱落乳牙来源的间充质干细胞（SHED）衍生的外泌体（SHED-Ex）治疗 TBI 的潜力。
首先，使用 Transwell 系统将激活的 BV-2 小胶质细胞与 SHED 共培养。通过酶联免疫吸附测定（ELISA）和 Griess 测定评估神经炎症因子和亚硝酸盐的分泌水平。此外，将纯化的 SHED-Ex 与激活的 BV-2 共培养。通过 ELISA、Griess 测定、流式细胞术、免疫荧光和 qRT-PCR 检测炎症因子水平以及小胶质细胞表型。最后，将 SHED 和 SHED-Ex 局部注射到 TBI 大鼠模型中。Basso、Beattie 和 Bresnahan（BBB）评分用于评估运动功能恢复情况。进行组织病理学和免疫荧光检查以测量病变体积和神经炎症。
结果表明，SHED-Ex 通过改变小胶质细胞极化来减轻神经炎症。与对照组相比，SHED-Ex 给药可改善 TBI 大鼠的运动功能恢复，并减少皮质损伤（损伤后 2 周，P<0.05）。
本研究首次表明，SHED-Ex 对 TBI 大鼠具有治疗作用，至少部分通过改变小胶质细胞极化来减轻神经炎症。牙源性干细胞及其外泌体的使用可能会扩展到 TBI 或其他神经疾病的治疗中。
