Ribeiro Thiago B, Duarte Adriana S S, Longhini Ana Leda F, Pradella Fernando, Farias Alessandro S, Luzo Angela C M, Oliveira Alexandre L R, Olalla Saad Sara Teresinha
Hematology and Hemotherapy Center-University of Campinas/Hemocentro-Unicamp, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, São Paulo, Brazil.
Neuroimmunomodulation Group, Dept. Genetics, Evolution and Bioagents, University of Campinas, Campinas, Brazil.
Sci Rep. 2015 Nov 9;5:16167. doi: 10.1038/srep16167.
The present study investigates the effects of xenotransplantation of Adipose Tissue Mesenchymal Stem Cells (AT-MSCs) in animals after ventral root avulsion. AT-MSC has similar characteristics to bone marrow mesenchymal stem cells (BM-MSCs), such as immunomodulatory properties and expression of neurotrophic factors. In this study, Lewis rats were submitted to surgery for unilateral avulsion of the lumbar ventral roots and received 5 × 10(5) AT-MSCs via the lateral funiculus. Two weeks after cell administration, the animals were sacrificed and the moto neurons, T lymphocytes and cell defense nervous system were analyzed. An increased neuronal survival and partial preservation of synaptophysin-positive nerve terminals, related to GDNF and BDNF expression of AT-MSCs, and reduction of pro-inflammatory reaction were observed. In conclusion, AT-MSCs prevent second phase neuronal injury, since they suppressed lymphocyte, astroglia and microglia effects, which finally contributed to rat motor-neuron survival and synaptic stability of the lesioned motor-neuron. Moreover, the survival of the injected AT- MSCs lasted for at least 14 days. These results indicate that neuronal survival after lesion, followed by mesenchymal stem cell (MSC) administration, might occur through cytokine release and immunomodulation, thus suggesting that AT-MSCs are promising cells for the therapy of neuronal lesions.
本研究调查了脂肪组织间充质干细胞(AT-MSCs)异种移植对腹根撕脱术后动物的影响。AT-MSC具有与骨髓间充质干细胞(BM-MSCs)相似的特性,如免疫调节特性和神经营养因子的表达。在本研究中,将Lewis大鼠进行单侧腰腹根撕脱手术,并通过外侧索给予5×10(5)个AT-MSCs。细胞给药两周后,处死动物并分析运动神经元、T淋巴细胞和细胞防御神经系统。观察到神经元存活率增加、与AT-MSCs的GDNF和BDNF表达相关的突触素阳性神经末梢部分保留以及促炎反应减少。总之,AT-MSCs可预防二期神经元损伤,因为它们抑制了淋巴细胞、星形胶质细胞和小胶质细胞的作用,最终有助于大鼠运动神经元存活和损伤运动神经元的突触稳定性。此外,注射的AT-MSCs存活至少持续14天。这些结果表明,损伤后给予间充质干细胞(MSC)后神经元存活可能通过细胞因子释放和免疫调节发生,因此表明AT-MSCs是治疗神经元损伤的有前景的细胞。