Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Brain Res. 2019 Jun 1;1712:73-81. doi: 10.1016/j.brainres.2019.02.003. Epub 2019 Feb 5.
Amyotrophic lateral sclerosis (ALS) is a chronic degenerative disease that mainly affects motor neurons, leading to progressive paralysis and death. Recently, cell therapy has emerged as a therapeutic alternative for several neurological diseases, including ALS, and bone-marrow cells are one of the major cell sources. Considering the importance of pre-clinical trials to determine the best therapeutic protocol and the hope of translating this protocol to the clinical setting, we tested bone-marrow mononuclear cell (BMMC) therapy administered by different routes in the SOD1 model of ALS. BMMCs were isolated from non-transgenic, age matched animals and administered intravenously (IV), intramuscularly (IM), and intravenously and intramuscular concomitantly (IV + IM). BMMC therapy had no significant beneficial effects when injected IV or IM, but delayed disease progression when these two routes were used concomitantly. BMMC IV + IM treatment reduced the number of microglia cells in the spinal cord and partially protected of neuromuscular-junction innervation, but had no effect in preventing motor-neuron loss. This study showed that injection of BMMC IV + IM had better results when compared to each route in isolation, highlighting the importance of targeting multiple anatomical regions in the treatment of ALS.
肌萎缩侧索硬化症（ALS）是一种慢性退行性疾病，主要影响运动神经元，导致进行性瘫痪和死亡。最近，细胞疗法已成为包括 ALS 在内的几种神经疾病的治疗选择，骨髓细胞是主要的细胞来源之一。鉴于确定最佳治疗方案的临床前试验的重要性以及将该方案转化为临床环境的希望，我们测试了通过不同途径在 SOD1 模型中进行骨髓单核细胞（BMMC）治疗。BMMC 从非转基因、年龄匹配的动物中分离出来，并通过静脉内（IV）、肌肉内（IM）和静脉内和肌肉内同时（IV+IM）给药。当静脉内或肌肉内注射 BMMC 时，没有明显的有益效果，但当这两种途径同时使用时，可延迟疾病进展。BMMC IV+IM 治疗可减少脊髓中的小胶质细胞数量，并部分保护运动终板神经支配，但对防止运动神经元丢失没有影响。这项研究表明，与单独使用每种途径相比，BMMC IV+IM 注射具有更好的效果，突出了在 ALS 治疗中靶向多个解剖区域的重要性。
