Dori Ioanna, Petrakis Spyros, Giannakopoulou Aggeliki, Bekiari Chryssa, Grivas Ioannis, Siska Evangelia K, Koliakos Georgios, Papadopoulos Georgios C
Laboratory of Anatomy, Histology and Embryology, School of Veterinary Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Biohellenika, Pylaia, Thessaloniki, Greece.
Histol Histopathol. 2017 Oct;32(10):1041-1055. doi: 10.14670/HH-11-864. Epub 2016 Dec 30.
Mesenchymal stromal cells (MSC) have been suggested to have beneficial effects on animal models of traumatic brain injury (TBI), owing to their neurotrophic and immunomodulatory properties. Adipose tissue-derived stromal cells (ASCs) are multipotent MSC that can be harvested with minimally invasive methods, show a high proliferative capacity, low immunogenicity if allogeneic, and can be used in autologous or heterologous settings. In the present study ASCs were genetically labelled using the Sleeping Beauty transposon to express the fluorescent protein Venus. Venus+ASCs were transplanted intra-cerebroventricularly (ICV), on a rat TBI model and their survival, fate and effects on host brain responses were examined at seven days post-injury (7dPI). We provide evidence that Venus+ASCs survived, migrated into the periventricular striatum and were negative for neuronal or glial lineage differentiation markers. Venus+ASCs stimulated the proliferation of endogenous neural stem cells (NSCs) in the brain neurogenic niches, the subventricular zone (SVZ) and the hippocampal dentate gyrus (DG). It was also evident that Venus+ASCs modify the host brain's cellular microenvironment both at the injury site and at their localization area by promoting a significant reduction of the lesion area, as well as altering the post-injury, pro-inflammatory profile of microglial and astrocytic cell populations. Our data support the view that ICV transplantation of ASCs induces alterations in the host brain's cellular response to injury that may be correlated to a reversal from a detrimental to a beneficial state which is permissive for regeneration and repair.
间充质基质细胞（MSC）因其神经营养和免疫调节特性，已被证明对创伤性脑损伤（TBI）动物模型具有有益作用。脂肪组织来源的基质细胞（ASC）是多能MSC，可通过微创方法获取，具有高增殖能力，异体时免疫原性低，可用于自体或异体移植。在本研究中，使用睡美人转座子对ASC进行基因标记以表达荧光蛋白维纳斯。将维纳斯阳性的ASC经脑室内（ICV）移植到大鼠TBI模型上，并在损伤后7天（7dPI）检查其存活、命运以及对宿主脑反应的影响。我们提供的证据表明，维纳斯阳性的ASC存活下来，迁移到脑室周围纹状体，并且神经元或神经胶质谱系分化标志物呈阴性。维纳斯阳性的ASC刺激了脑源性神经干细胞（NSC）在脑源性神经发生微环境、脑室下区（SVZ）和海马齿状回（DG）中的增殖。同样明显的是，维纳斯阳性的ASC通过促进损伤面积的显著减少，以及改变损伤后小胶质细胞和星形胶质细胞群体的促炎特征，在损伤部位及其定位区域改变了宿主脑的细胞微环境。我们的数据支持这样一种观点，即ASC的ICV移植会诱导宿主脑对损伤的细胞反应发生改变，这可能与从有害状态转变为有利于再生和修复的有益状态相关。
