Implantation of BM mesenchymal stem cells into injured spinal cord elicits de novo neurogenesis and functional recovery:: evidence from a study in rhesus monkeys
Implantation of BM mesenchymal stem cells into injured spinal cord elicits de novo neurogenesis and functional recovery:: evidence from a study in rhesus monkeys
复制标题
DOI：
10.1080/14653240600760808
复制
发表时间：
2006-05-01
期刊：
影响因子：
4.5
通讯作者：
Zhou, G-Q
中科院分区：
文献类型：
--
作者：
Deng, Y-B;Liu, X-G;Zhou, G-Q
骨髓间充质干细胞（MSC）移植治疗脊髓损伤（SCI）已被证实是一种有效的治疗方法。然而，在MSC临床应用于patients.Methods从恒河猴骨髓分离MSC，并体外诱导分化为神经系细胞之前，还需要进一步的灵长类动物模型研究。用Hoechst 33342标记诱导的细胞，并将其注射到恒河猴SCI模型的损伤部位。采用Tarlov行为评估、感觉反应以及皮质体感诱发电位（CSEP）和运动诱发电位（MEP）的电生理测试来评估受损脊髓的功能。Hoechst 33342标记的细胞中存在神经细胞标志物，证明了植入细胞的体内分化。轴突通路的重建证明了使用真蓝（TB）氯化物逆行追踪study.Results猴达到Tarlov等级2-3和接近正常的感觉反应细胞移植后3个月。CSEP和MEP均表现出恢复特征。在大约10%的Hoechst 33342标记细胞中观察到神经细胞标记物神经丝（NF）、神经特异性烯醇化酶（NSE）和胶质细胞酸性蛋白（GFAP）的存在。TB，最初注射在尾侧受伤的网站，是可追溯的喙胸脊髓，红核和感觉运动cortex.Discussion我们的研究结果表明，MSC衍生细胞eldibrant从头神经发生和功能恢复的非人灵长类动物SCI模型的植入，并应利用骨髓MSC在SCI患者的临床应用。
Background Transplantation of mesenchymal stem cells (MSC) in rodent models has proved to be an effective therapeutic approach for spinal cord injury (SCI). However, further studies in primate models are still needed before clinical application of MSC to patients.Methods MSC were isolated from rhesus monkey BM and induced ex vivo to differentiate into neural lineage cells. Induced cells were labeled with Hoechst 33342 and injected into the injured sites of rhesus SCI models. Function of the injured spinal cord was assessed using Tarlov behavior assessment, sensory responses and electrophysiologic tests of cortical somatosensory-evoked potential (CSEP) and motor-evoked potential (MEP). In vivo differentiation of the implanted cells was demonstrated by the presence of neural cell markers in Hoechst 33342-labeled cells. The re-establishment of the axonal pathway was demonstrated using a true blue (TB) chloride retrograde tracing study.Results Monkeys achieved Tarlov grades 2-3 and nearly normal sensory responses 3 months after cell transplantation. Both CSEP and MEP showed recovery features. The presence of the neural cell markers neurofilament (NF), neuro-specific enolase (NSE) and glial fibrillary acidic protein (GFAP) was observed in approximately 10% of Hoechst 33342-labeled cells. TB, originally injected at the caudal side of injured sites, was traceable in the rostral thoracic spinal cord, red nucleus and sensory motor cortex.Discussion Our results suggest that the implantation of MSC-derived cells elicits de novo neurogenesis and functional recovery in a non-human primate SCI model and should harness the clinical application of BM MSC in SCI patients.