The neuroprotective effect of bone marrow stem cells is not dependent on direct cell contact with hypoxic injured tissue
The neuroprotective effect of bone marrow stem cells is not dependent on direct cell contact with hypoxic injured tissue
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DOI：
10.1016/j.expneurol.2008.10.023
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发表时间：
2009-02-01
影响因子：
5.3
通讯作者：
Reymann, Klaus G.
中科院分区：
文献类型：
--
作者：
Sarnowska, Anna;Braun, Holger;Reymann, Klaus G.
骨髓干细胞（BMSCs）在移植到缺血性脑损伤动物体内后能够产生有益的作用。这种作用可能主要是由营养因子的释放引起的，但不能排除死亡的神经细胞被骨髓间充质干细胞取代的可能性。本研究的目的是确定所讨论的神经保护作用是否依赖于骨髓间充质干细胞和损伤组织之间的直接细胞-细胞接触。因此，我们在海马体器官型切片培养（OHCs）的体外模型中研究了这种相互作用，以避免体内移植后免疫排斥过程的干扰。为了进行体外缺血损伤，对OHCs进行了氧-葡萄糖剥夺（OGD）。在损伤24 h后，通过两种实验模式评估骨髓间充质干细胞诱导的可能的直接或间接神经保护作用：(i)细胞移植在ogd处理的OHC上；（ii）细胞培养与OHC空间分离24 h。在这两种模式中，骨髓间充质干细胞治疗对ogd损伤的OHC均产生相当且显著的神经保护作用。通过比较细胞移植和与损伤组织共培养，我们得出结论，缺血后不久（24小时）引起的骨髓间充质干细胞的神经保护作用不依赖于细胞与细胞的接触。此外，经ogd处理的OHC可刺激共培养的骨髓间充质干细胞表达更高水平的bFGF和NGF。最后，缺血海马切片增加了共培养骨髓间充质干细胞中nestin和GFAP的表达，并改变了其形态。(c) 2008爱思唯尔公司版权所有。
Bone marrow stem cells (BMSCs) are able to confer beneficial effects after transplantation into animals with ischemic brain injuries. This effect is probably mainly caused by the release of trophic factors, though the possibility of dead neural cells being replaced by BMSCs cannot be excluded. The aim of this study was to determine whether the neuroprotective effects in question are dependent on direct cell-cell contacts between BMSCs and injured tissue. We therefore investigated that interplay in an in vitro model of hippocampal organotypic slice Cultures (OHCs), in order to avoid the interference due to immunological rejection processes following transplantation in vivo. To perform ischemic injury in vitro, OHCs were made subject to oxygen-glucose deprivation (OGD). The possible direct or indirect neuroprotective effects induced by BMSCs were evaluated 24 h after injury by reference to two experimental paradigms using ischemic injured hippocampal slices:(i) cell transplantation on the top of OGD-treated OHC(ii) co-cultivation of cell culture with OHC space separated for 24 h.In both paradigms, the BMSC treatment induced comparable and significant neuroprotection in OGD-injured OHCs. This effect increased after treatment with serum-deprived BMSCs, enriched with cells expressing nestin and GFAR Comparing cell transplantation and cell co-cultivation with injured tissue, we concluded that the neuroprotective effect of BMSCs evoked shortly after ischemia (24 h) does not depend on cell-cell contacts. Additionally OGD-treated OHC was found to stimulate co-cultured BMSCs into expressing higher levels of bFGF and NGF. Finally, ischemic hippocampal slices increased the expression of nestin and GFAP in co-cultivated BMSCs, as well as changing their morphology. (c) 2008 Elsevier Inc. All rights reserved.