Ghirnikar R S, Eng L F
Department of Pathology, Stanford University, School of Medicine, California, USA.
Glia. 1995 Jun;14(2):145-52. doi: 10.1002/glia.440140209.
Transplantation of Schwann cells (SCs) in the central nervous system (CNS) for remyelination in pathological situations has been considered a promising approach. However, numerous studies have indicated that astrocytes have a restrictive effect on SC migration within the CNS. We have previously established an in vitro model which demonstrates the restrictive effect of astrocytes on SCs (Ghirnikar and Eng, Glia 4:367-377, 1994). Using this culture model, in the present study, we have characterized the molecular basis underlying astrocyte-SC interaction and demonstrated chondroitin sulfate proteoglycan (CSP) staining in the co-cultures. Following 1-2 weeks of incubation, CSP staining was specifically associated with SCs co-cultured with astrocytes. Staining with antibodies specific for the different chondroitin sulfate isomers revealed the presence of both, chondroitin-4- and 6-sulfates in SCs. In contrast, SCs when cultured alone, or in the presence of astrocytes conditioned medium did not show CSP staining. These data suggest that CSP staining is associated with SCs following co-culture with astrocytes and mediated by cell to cell contact. We hypothesize that the CSP, alone or in combination with other molecules expressed by astrocytes and/or SCs, may be involved in the restrictive effects of astrocytes on SCs. Identification of molecules involved in the unfavorable interaction between astrocytes and SCs will have an important bearing on efforts to remyelinate demyelinated axons by SC transplantation within the damaged CNS.
在病理情况下,将雪旺细胞(SCs)移植到中枢神经系统(CNS)以进行髓鞘再生被认为是一种有前景的方法。然而,大量研究表明星形胶质细胞对CNS内SCs的迁移具有限制作用。我们之前建立了一个体外模型,该模型证明了星形胶质细胞对SCs的限制作用(Ghirnikar和Eng,《胶质细胞》4:367 - 377,1994)。在本研究中,利用这个培养模型,我们对星形胶质细胞与SCs相互作用的分子基础进行了表征,并在共培养物中证实了硫酸软骨素蛋白聚糖(CSP)染色。孵育1 - 2周后,CSP染色与与星形胶质细胞共培养的SCs特异性相关。用针对不同硫酸软骨素异构体的特异性抗体染色显示,SCs中同时存在硫酸软骨素-4-硫酸盐和6-硫酸盐。相比之下,单独培养的SCs或在星形胶质细胞条件培养基存在下培养的SCs未显示CSP染色。这些数据表明,CSP染色与SCs和星形胶质细胞共培养后相关,且由细胞间接触介导。我们推测,CSP单独或与星形胶质细胞和/或SCs表达的其他分子结合,可能参与星形胶质细胞对SCs的限制作用。鉴定参与星形胶质细胞与SCs之间不利相互作用的分子,对于通过在受损CNS内进行SCs移植使脱髓鞘轴突重新髓鞘化的努力具有重要意义。