Distinct In Vitro Properties of Embryonic and Extraembryonic Fibroblast-Like Cells Are Reflected in Their In Vivo Behavior Following Grafting in the Adult Mouse Brain
Distinct In Vitro Properties of Embryonic and Extraembryonic Fibroblast-Like Cells Are Reflected in Their In Vivo Behavior Following Grafting in the Adult Mouse Brain
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DOI：
10.3727/096368913x676196
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发表时间：
2015-01-01
影响因子：
3.3
通讯作者：
Ponsaerts, Peter
中科院分区：
文献类型：
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作者：
Costa, Roberta;Bergwerf, Irene;Ponsaerts, Peter
虽然各种成纤维细胞（样）细胞群体的脑内移植已被证明是可行的，很少有人知道这些细胞移植物及其环境的实际体内重塑。在这项研究中，我们的目的是比较两个表型相似，但发育不同的成纤维细胞样细胞群，即小鼠胚胎成纤维细胞（mEFs）和小鼠胎儿膜源性基质细胞（mFMSC）的体外和体内的行为。虽然mEF和mFMSC都能够容易地减少LPS/IFN-γ激活的BV-2小胶质细胞的TNF-α分泌，但mFMSC和mEF在正常和炎症条件下就VEGF产生而言显示出惊人相反的行为。mFMSC在与LPS/IFN-γ激活的BV-2小胶质细胞共培养时下调VEGF的产生，而mEFs在LPS/IFN-γ激活的BV-2小胶质细胞存在下上调VEGF的产生。随后，在体内移植的mFMSC和IDEF显示对细胞移植物的小胶质细胞和星形胶质细胞的反应没有差异。然而，与mEF移植物相比，mFMSC移植物显示出较低程度的新血管生成，从而可能解释了能够在mFMSC移植物中存活的较低细胞数量。总之，我们的研究结果表明，成纤维细胞样细胞群体之间的生理差异可能在于在小鼠脑细胞移植后的组织病理学和/或临床结果的变化的基础上。
Although intracerebral transplantation of various fibroblast(-like) cell populations has been shown feasible, little is known about the actual in vivo remodeling of these cellular grafts and their environment. In this study, we aimed to compare the in vitro and in vivo behavior of two phenotypically similar but developmentally distinct fibroblast-like cell populations, namely, mouse embryonic fibroblasts (mEFs) and mouse fetal membrane-derived stromal cells (mFMSCs). While both mEFs and mFMSCs are readily able to reduce TNF-alpha secretion by LPS/IFN-gamma-activated BV-2 microglia, mFMSCs and mEFs display strikingly opposite behavior with regard to VEGF production under normal and inflammatory conditions. Whereas mFMSCs downregulate VEGF production upon coculture with LPS/IFN-gamma-activated BV-2 microglia, mEFs upregulate VEGF production in the presence of LPS/IFN-gamma-activated BV-2 microglia. Subsequently, in vivo grafting of mFMSCs and IDEFs revealed no difference in microglial and astroglial responses toward the cellular grafts. However, mFMSC grafts displayed a lower degree of neoangiogenesis compared to mEF grafts, thereby potentially explaining the lower cell number able to survive in mFMSC grafts. In summary, our results suggest that physiological differences between fibroblast-like cell populations might lie at the basis of variations in histopathological and/or clinical outcome following cell grafting in mouse brain.