Key Laboratory of Functional Proteomics of Guangdong Province, Key Laboratory of Mental Health of the Ministry of Education, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
Departments of Mechanical Engineering, Biochemistry and Medical Genetics, University of Manitoba and Manitoba Institute of Child Health, Winnipeg, MB R3T 2N2, Canada.
Mater Sci Eng C Mater Biol Appl. 2019 Jul;100:584-597. doi: 10.1016/j.msec.2019.03.024. Epub 2019 Mar 8.
Parkinson's disease (PD) is a long-term neurodegenerative disorders that characterized by a progressive loss of dopaminergic neurons in substantia nigra pars compacta (SNc). Bone marrow stromal cells (BMSCs) are promising therapeutic agents for neurodegenerative disease due to their multipotent capacity. To promote the potential therapeutic effect of BMSCs on PD, we developed an injectable Gelatin-PANI hydrogels as a novel carrier for delivering BMSCs to the SNc region in mice with PD by stereotactic injection. Histology results showed that the BMSCs-loaded hydrogels lead to increased numbers of tyrosine hydroxylase positive (TH) dopaminergic neurons and fibers in the SNc and striatum, and increased expression of brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) in the SNc. Meanwhile, rotarod and open field evaluation demonstrated BMSCs-loaded hydrogels significantly improved the behavioral performance of PD mice. Importantly, BMSCs-loaded hydrogels imparted more sustained protective effects than BMSCs alone in PD mice. Overall, the current data indicate that the hydrogel serves as a promising carrier to deliver BMSCs to the SNc for the treatment of PD.
帕金森病（PD）是一种长期的神经退行性疾病，其特征是黑质致密部（SNc）中的多巴胺能神经元进行性丧失。骨髓基质细胞（BMSCs）由于其多能性而成为治疗神经退行性疾病的有前途的治疗剂。为了提高 BMSCs 对 PD 的潜在治疗效果，我们开发了一种可注射的明胶-PANI 水凝胶，作为通过立体定向注射将 BMSCs 递送到 PD 小鼠 SNc 区域的新型载体。组织学结果表明，负载 BMSCs 的水凝胶导致 SNc 和纹状体中酪氨酸羟化酶阳性（TH）多巴胺能神经元和纤维的数量增加，并且 SNc 中脑源性神经营养因子（BDNF）和胶质细胞源性神经营养因子（GDNF）的表达增加。同时，旋转杆和开阔场评估表明，负载 BMSCs 的水凝胶显著改善了 PD 小鼠的行为表现。重要的是，负载 BMSCs 的水凝胶在 PD 小鼠中比单独使用 BMSCs 具有更持久的保护作用。总体而言，目前的数据表明该水凝胶可作为将 BMSCs 递送到 SNc 以治疗 PD 的有前途的载体。
