Sulfatase-mediated manipulation of the astrocyte-Schwann cell interface.
Sulfatase-mediated manipulation of the astrocyte-Schwann cell interface.
复制标题
硫酸酯酶介导的星形胶质细胞-雪旺细胞界面的操作。
作者：
O'Neill P;Lindsay SL;Pantiru A;Guimond SE;Fagoe N;Verhaagen J;Turnbull JE;Riddell JS;Barnett SC
脊髓损伤后的雪旺细胞（SC）移植可能具有治疗潜力。然而，由于SC与宿主星形胶质细胞的相互作用较差以及星形胶质细胞增生的诱导，功能恢复有限。嗅鞘细胞（OECs）与SC密切相关，但在培养中更容易与星形胶质细胞混合，诱导较少的星形胶质细胞增生。我们先前证明，OEC表达比SC更高水平的硫酸酯酶，从硫酸乙酰肝素蛋白聚糖中去除6-O-硫酸酯基团的酶，并且硫酸酯酶的RNAi敲低阻止了OEC-星形胶质细胞的体外混合。由于人类OEC难以大量培养，我们使用慢病毒载体对SC进行基因工程改造以表达硫酸酯酶1和2（SC-S1 S2），并评估其与星形胶质细胞相互作用的能力。我们证明，在星形胶质细胞存在的情况下，SC-S1 S2通过调节NRG和FGF受体相关的PI 3 K/AKT细胞内信号传导增加了整合素依赖性运动，并且在培养物中不与星形胶质细胞形成边界。SC-星形胶质细胞混合依赖于局部NRG浓度，我们认为硫酸酯酶影响NRG配体的生物利用度，从而影响SC行为。我们进一步证明，将表达硫酸酯酶的SC注射到脊髓白色物质中导致比对照SC注射的神经胶质反应性更低，与OEC注射的神经胶质反应性相当。我们的数据表明，硫酸酯酶介导的细胞外基质的修饰可以影响胶质细胞与星形胶质细胞的相互作用，并且被工程化以表达硫酸酯酶的SC在性质上可能更像OEC。这种方法可能有利于细胞移植介导的脊髓修复。2017年第65届中国国际汽车工业展览会;65：19-33
Schwann cell (SC) transplantation following spinal cord injury (SCI) may have therapeutic potential. Functional recovery is limited however, due to poor SC interactions with host astrocytes and the induction of astrogliosis. Olfactory ensheathing cells (OECs) are closely related to SCs, but intermix more readily with astrocytes in culture and induce less astrogliosis. We previously demonstrated that OECs express higher levels of sulfatases, enzymes that remove 6‐O‐sulfate groups from heparan sulphate proteoglycans, than SCs and that RNAi knockdown of sulfatase prevented OEC‐astrocyte mixing in vitro. As human OECs are difficult to culture in large numbers we have genetically engineered SCs using lentiviral vectors to express sulfatase 1 and 2 (SC‐S1S2) and assessed their ability to interact with astrocytes. We demonstrate that SC‐S1S2s have increased integrin‐dependent motility in the presence of astrocytes via modulation of NRG and FGF receptor‐linked PI3K/AKT intracellular signaling and do not form boundaries with astrocytes in culture. SC‐astrocyte mixing is dependent on local NRG concentration and we propose that sulfatase enzymes influence the bioavailability of NRG ligand and thus influence SC behavior. We further demonstrate that injection of sulfatase expressing SCs into spinal cord white matter results in less glial reactivity than control SC injections comparable to that of OEC injections. Our data indicate that sulfatase‐mediated modification of the extracellular matrix can influence glial interactions with astrocytes, and that SCs engineered to express sulfatase may be more OEC‐like in character. This approach may be beneficial for cell transplant‐mediated spinal cord repair. GLIA 2016 GLIA 2017;65:19–33
影响因子：
7.8
作者：
RATNER, N;BUNGE, RP;GLASER, L
通讯作者：
GLASER, L