Exosomes secreted by stem cells from human exfoliated deciduous teeth contribute to functional recovery after traumatic brain injury by shifting microglia M1/M2 polarization in rats.
Exosomes secreted by stem cells from human exfoliated deciduous teeth contribute to functional recovery after traumatic brain injury by shifting microglia M1/M2 polarization in rats.
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DOI：
10.1186/s13287-017-0648-5
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发表时间：
2017-09-29
影响因子：
7.5
通讯作者：
Li A
中科院分区：
文献类型：
--
作者：
Li Y;Yang YY;Ren JL;Xu F;Chen FM;Li A
创伤性脑损伤（TBI）是全世界所有年龄段死亡和残疾的主要原因之一。间充质干细胞（MSC）来源的外泌体提供了治疗效果。然而，作为骨髓间充质干细胞不可或缺的组成部分，牙源性干细胞产生的exosomes是否可以有益于TBI仍不清楚。因此，我们的目的是探索来自人类脱落乳牙源性外泌体（SHED-Ex）的干细胞用于TBI管理的潜力。首先，使用transwell系统将活化的BV-2小胶质细胞与SHED共培养。采用酶联免疫吸附试验（ELISA）和Griess法检测神经炎性因子和亚硝酸盐的分泌水平。此外，将纯化的SHED-Ex与活化的BV-2共培养。采用ELISA、Griess试验、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。选择Basso、Beattie和Bresnahan（BBB）评分来评估运动功能恢复。组织学和免疫荧光法测量病变体积和神经炎症。因此，SHED-Ex可以通过改变小胶质细胞极化来减少神经炎症。与对照组相比，伤后2周给予SHED-Ex可促进大鼠运动功能恢复，减少皮层损伤（P < 0.05）。目前的研究首次证明，SHED-Ex对大鼠TBI有治疗益处，至少部分是通过改变小胶质细胞极化来减少神经炎症。牙源性干细胞及其外泌体的使用可能会扩大到TBI或其他神经系统疾病的治疗。
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.
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影响因子：
3.7
作者：
Ma L;Makino Y;Yamaza H;Akiyama K;Hoshino Y;Song G;Kukita T;Nonaka K;Shi S;Yamaza T
通讯作者：
Yamaza T
影响因子：
2.9
作者：
Shear, DA;Tate, MC;Stein, DG
通讯作者：
Stein, DG
影响因子：
7.6
作者：
Huang GT;Gronthos S;Shi S
通讯作者：
Shi S
影响因子：
5.3
作者：
Brites D;Fernandes A
通讯作者：
Fernandes A
影响因子：
4.5
作者：
Kanafi, Mohammad Mahboob;Rajeshwari, Yajaman Bajjappa;Bhonde, Ramesh Ramchandra
通讯作者：
Bhonde, Ramesh Ramchandra