Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
Neurosci Lett. 2011 Jul 1;498(1):15-9. doi: 10.1016/j.neulet.2011.04.050. Epub 2011 Apr 27.
Most of the transplanted cells within central nervous system (CNS) undergo extensive cell death. Preventing the death of stem cell-derived neuron-like cells within adult CNS would enhance the efficiency of transplantation in clinics. We have employed an interfering RNA (RNAi) approach to elevate the survival rate of neurally differentiated bone marrow stromal stem cells (BMSCs), by means of suppressing p75NTR expression. Our data revealed that stably overexpressing a specific shRNA against p75NTR transcript could effectively reduce the expression of endogenous p75NTR in neurally differentiated BMSCs. As p75NTR can induce neuronal death in target cells, its suppression is followed by a significant reduction of apoptosis in neural-like cells derived from BMSCs. Thus, our data provides a method to increase the survival of stem cells being employed in transplantation within CNS and hence increase the success rate of cell-based therapies in damaged area of brain and spinal cord.
中枢神经系统（CNS）内的大多数移植细胞都会发生广泛的细胞死亡。防止成年 CNS 内干细胞源性神经元样细胞的死亡将提高移植在临床上的效率。我们已经采用干扰 RNA（RNAi）方法通过抑制 p75NTR 表达来提高神经分化骨髓基质干细胞（BMSC）的存活率。我们的数据表明，稳定过表达针对 p75NTR 转录本的特异性 shRNA 可以有效地降低神经分化 BMSC 中内源性 p75NTR 的表达。由于 p75NTR 可以诱导靶细胞中的神经元死亡，因此其抑制作用伴随着源自 BMSC 的神经样细胞中凋亡的显著减少。因此，我们的数据提供了一种增加 CNS 内移植中使用的干细胞存活率的方法，从而提高脑和脊髓损伤区域细胞治疗的成功率。
