Department of Otolaryngology Head and Neck Surgery, the Affiliated Hospital of Qingdao University, Qingdao, China.
Eur Rev Med Pharmacol Sci. 2019 Jan;23(1):277-288. doi: 10.26355/eurrev_201901_16774.
To investigate the effect and the underlying mechanisms of combined transplantation of Schwann cells (Scs) and Mesenchymal stem cells (MSCs) on optic nerve injury in rats.
A total of 160 normal healthy adult rats were randomly divided into 4 groups: optic nerve injury group, optic nerve injury + Sc transplantation group, optic nerve injury + MSC transplantation group and optic nerve injury + Sc + MSC transplantation group. The optic nerve in the left eye of each rat was damaged via clamping to establish a model of optic nerve injury, and the right eye was used as self-control. Scs + MSCs, Scs alone, MSCs alone and normal saline were injected into the vitreous space, respectively. After the treatment, the optic nerve tissues were collected and subjected to hematoxylin-eosin (HE) staining. Next, the morphologic and pathological changes of rats in each group were observed. Retrograde labeling was utilized to count the number of retinal ganglion cells (RGCs) in the optic nerve tissues. The apoptosis of RGCs was detected using flow cytometry. Western blot was carried out to measure the protein expression level of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax). The expression and distribution of brain-derived neurotrophic factor (BDNF) and growth associated protein-43 (GAP-43) in the optic nerve of rats in each group were detected by immunohistochemistry.
Transplantation of Scs and MSCs could maintain the morphological structures of the retina and optic nerve of rats, increase the amount of RGCs in optic nerve tissues, reduce the apoptosis of RGCs, promote the expression of the Bcl-2 protein and decrease the expression of Bax protein. In addition, our joint transplantation strategy also showed an important role in repairing optic nerve injury by clearly promoting the secretion and expression of BDNF and GAP-43, which indicated a better curative effect than that of separate application of Scs or MSCs.
Therapy with combined use of Scs and MSCs has a significant therapeutic effect in repairing optic nerve injury.
探讨雪旺细胞(SCs)与间充质干细胞(MSCs)联合移植对大鼠视神经损伤的作用及机制。
将 160 只正常健康成年大鼠随机分为 4 组:视神经损伤组、视神经损伤+SCs 移植组、视神经损伤+MSCs 移植组和视神经损伤+SCs+MSCs 移植组。采用夹伤左眼视神经的方法建立大鼠视神经损伤模型,右眼作为自身对照。分别向玻璃体腔注射 Scs+MSCs、SCs 单独、MSCs 单独和生理盐水。治疗后,收集视神经组织行苏木精-伊红(HE)染色,观察各组大鼠视神经组织形态学和病理学变化,逆行标记计数视神经组织中视网膜神经节细胞(RGCs)数量,流式细胞术检测 RGCs 凋亡情况,Western blot 法检测 B 细胞淋巴瘤 2(Bcl-2)和 Bcl-2 相关 X 蛋白(Bax)蛋白表达水平,免疫组化法检测各组大鼠视神经中脑源性神经营养因子(BDNF)和生长相关蛋白-43(GAP-43)的表达和分布。
SCs 和 MSCs 联合移植可维持大鼠视网膜和视神经的形态结构,增加视神经组织中 RGCs 数量,减少 RGCs 凋亡,促进 Bcl-2 蛋白表达,降低 Bax 蛋白表达,且联合移植策略在修复视神经损伤方面的作用明显优于单独应用 Scs 或 MSCs,可明显促进 BDNF 和 GAP-43 的分泌和表达。
SCs 与 MSCs 联合应用治疗视神经损伤具有显著的治疗效果。