大鼠骨髓间充质干细胞源性神经元促进脊髓横断性损伤的神经功能恢复  

Functional improvement of neuro in the transectional spinal cord seeded with rat bone marrow mesenchymal stem cells (rMSCs)

作　　者：黎国强 杨海华[2] 徐评议[2] 李毅[2] 朱雯[2] 刘焯霖[2] 

机构地区：[1]广东新兴县人民医院,527400 [2]中山大学附属第一医院神经内科,广州510080

出　　处：《中华神经医学杂志》2006年第4期353-359,共7页Chinese Journal of Neuromedicine

基　　金：国家自然科学基金(30370509,30570645);留学回国人员基金(2003-406)

摘　　要：目的探讨干细胞治疗外伤性脊髓损伤的策略。方法体外分离纯化成年SD大鼠骨髓MSCs,并在体外培养过程中加入麝香多肽(Musk-1)将其诱导分化为神经前体细胞,再定向将神经前体细胞植入经显微外科手术建立的大鼠横断性脊髓损伤病灶中。结果与对照组大鼠相比,植入的rMSCs源性神经元可明显促进脊髓损伤后的神经功能恢复(P<0．05;有效观察期90 d)。组织学和免疫细胞组化分析进一步证实了植入rMSCs源性神经元在移植区域大量成活,并向损伤区域四周的邻近组织迁移约6 mm。荧光金逆行追踪分析显示在大鼠脊髓头侧、中脑红核和大脑感觉运动皮层等区域均可检测到荧光金标记阳性的运动神经元,推测脊髓损伤侧的皮层脊髓束发生了再生并穿越横断性病灶达到了脊髓尾侧。结论作为干细胞替代治疗的新策略,rMSCs源性神经元可在横断性脊髓损伤病灶中成活、迁移、整合,以及具备修补脊髓功能的潜在可能性。Objective Explore an approach with which stem cell can be used to cure traumatic spinal cord. Methods To better repair spinal cord injury, adult Sprague-Dawley （SD） rat MSCs was isolated and induced to differentiate into neuron-like cells with a Chinese medicine, Musk＇s polypeptide named Musk- 1 in vitro and be seeded into microsurgical transectional model of adult rat spinal cord with cell differentiation and transplantation techniques. Results After cell transplantation, animals seeded with the rMSCs-derived neuron-like cells promoted significant improvement in function after spinal cord （P〈0.05, effective observation for 90 days ） when compared to the lesion-control group. Histology and immunocytochemical analysis confirmed a large number of rMSCs-derived neuron-like cells survived well in the transplantation zoon and numerous cells migrated within the host adjacent tissues as far as 6 millimeters above and below the border of the lesion. Fluorescence gold retrograde tract tracing analysis revealed the positive motor neuron of fluorescence gold mark was found in the head side of rat spinal marrow ,corpus rubrum ofmesencephalic and corticospinal tract fibers.This suggested that corticospinal tract fibers of spinal cord area got regeneration and passed through the lession to reach the tail of spinal marrow. Conclusion These findings demonstrated that ＂pre-programmed＂ rMSCs can survive, migrate, integrate as well as restore spinal function and behavior in the microsurgical transectional model of rat spinal cord, and may serve as a suitable approach to traumatic spinal cord injury.

关 键 词：骨髓间充质干细胞 细胞分化 脊髓损伤 细胞移植 

分 类 号：R651.2[医药卫生—外科学]