Transplantation of layer-by-layer assembled neural stem cells tethered with vascular endothelial growth factor reservoir promotes neurogenesis and angiogenesis after ischemic stroke in mice
Transplantation of layer-by-layer assembled neural stem cells tethered with vascular endothelial growth factor reservoir promotes neurogenesis and angiogenesis after ischemic stroke in mice
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移植层层组装的神经干细胞与血管内皮生长因子库连接可促进小鼠缺血性中风后的神经发生和血管生成
DOI：
10.1016/j.apmt.2022.101548
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发表时间：
2022-06-07
影响因子：
8.3
通讯作者：
Feng, Hua
中科院分区：
文献类型：
--
作者：
Ge, Hongfei;Hu, Quan;Feng, Hua
神经干细胞移植是一种很有前途的缺血性脑卒中治疗策略。然而，大多数移植的NSCs很难存活很长时间，并且由于缺血性卒中后恶劣的微环境，移植的NSCs大部分在梗死核心周围分化为星形胶质细胞。因此，探索培养移植的NSCs在敌对生态位中的再生能力是修复病变的可行策略。本研究提出了一种用明胶和透明质酸（HA）进行逐层修饰（LbL-NSCs）接枝的可行方法。结果表明，LbL-NSCs具有生物相容性，并具有促进NSCs向神经元分化的能力。随后，将血管内皮生长因子（vascular endothelial growth factor， VEGF）装入明胶中，生成与VEGF库系在一起的LbL-NSCs [LbL (VEGF)-NSCs]，并在体外pH 7.4条件下持续从LbL (VEGF)-NSCs中释放VEGF。随后，结果表明LbL (VEGF)-NSCs移植促进了植入的NSCs在远端大脑中动脉闭塞（dMCAO）小鼠中的存活和向神经元分化。此外，植入LbL (VEGF)-NSCs可增强dMCAO小鼠的神经发生、血管生成、宿主神经元存活和血脑屏障（BBB）修复，从而通过减少梗死核心的体积来增强功能恢复。本研究提供了一种合适的方法，利用装载VEGF和HA的明胶通过LbL组装来修饰NSCs，以加速移植的NSCs在缺血性卒中后的康复能力。
Transplantation of neural stem cells (NSCs) is a promising therapeutic strategy for ischemic stroke. However, most of engrafted NSCs hardly survive for a long time, and the majority of transplanted NSCs differentiate into astrocytes around infarct core due to harsh microenvironment after ischemic stroke. Therefore, exploring ap-proaches to foster the regenerative ability of transplanted NSCs in hostile niche is a feasible strategy to reha-bilitate lesions. Here, a feasible method for grafted NSCs modified by layer-by-layer (LbL) assembly (LbL-NSCs) using gelatin and hyaluronic acid (HA) was developed. The results indicated the LbL-NSCs were biocompatible, and held the ability of promoting NSCs differentiation into neurons. Subsequently, vascular endothelial growth factor (VEGF) was laden into gelatin to generate LbL-NSCs tethered with VEGF reservoir [LbL (VEGF)-NSCs], and the VEGF releasing from LbL (VEGF)-NSCs was sustained under pH 7.4 in vitro. Afterward, the results demon-strated transplantation of LbL (VEGF)-NSCs facilitated implanted NSCs survival and differentiation into neurons in distal middle cerebral artery occlusion (dMCAO) mice. Additionally, engraftment of LbL (VEGF)-NSCs rein-forced neurogenesis, angiogenesis, survival of host neurons, and blood brain barrier (BBB) repair, thereafter enhancing functional recovery through reducing the volume of infarct core in dMCAO mice. This investigation provides an appropriate approach for modifying NSCs by LbL assembly using gelatin loaded with VEGF and HA to expedite the rehabilitative ability of engrafted NSCs following ischemic stroke.