Promotion of spinal cord regeneration by neural stem cell-secreted trimerized cell adhesion molecule L1.
Promotion of spinal cord regeneration by neural stem cell-secreted trimerized cell adhesion molecule L1.
复制标题
DOI：
10.1371/journal.pone.0046223
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Schachner M
中科院分区：
文献类型：
--
作者：
He X;Knepper M;Ding C;Li J;Castro S;Siddiqui M;Schachner M
L1细胞粘附分子在嗜同性和嗜异性相互作用中促进神经突生长和神经元存活，并以嗜同性方式，即通过自我结合，促进神经突生长和神经元存活。我们研究了是否利用嗜同性和可能也嗜异性的机制，神经干细胞过表达全长跨膜L1和分泌三聚体，以表达其胞外结构域，将比只过表达全长L1的干细胞或亲本非工程细胞更有利于成年小鼠脊髓受压损伤的功能恢复。本研究报告表明，与仅过表达全长L1或亲本干细胞相比，表达三聚体和全长L1的干细胞在促进运动恢复方面确实更有效。表达三聚体的干细胞在减少胶质瘢痕体积和硫酸软骨素和硫酸软骨素蛋白聚糖NG2的表达方面也更有效。它们在促进再生/发芽和/或保存血清素能轴突，以及髓鞘再生和/或髓鞘保留方面也更有效。此外，表达三聚体的干细胞更能防止皮质脊髓轴突的变性/死背。这些结果鼓励了这样一种观点，即通过嗜同性和嗜异性相互作用来驱动L1有益功能的干细胞在功能上是优化的，因此可能具有治疗价值。
The L1 cell adhesion molecule promotes neurite outgrowth and neuronal survival in homophilic and heterophilic interactions and enhances neurite outgrowth and neuronal survival homophilically, i.e. by self binding. We investigated whether exploitation of homophilic and possibly also heterophilic mechanisms of neural stem cells overexpressing the full-length transmembrane L1 and a secreted trimer engineered to express its extracellular domain would be more beneficial for functional recovery of the compression injured spinal cord of adult mice than stem cells overexpressing only full-length L1 or the parental, non-engineered cells. Here we report that stem cells expressing trimeric and full-length L1 are indeed more efficient in promoting locomotor recovery when compared to stem cells overexpressing only full-length L1 or the parental stem cells. The trimer expressing stem cells were also more efficient in reducing glial scar volume and expression of chondroitin sulfates and the chondroitin sulfate proteoglycan NG2. They were also more efficient in enhancing regrowth/sprouting and/or preservation of serotonergic axons, and remyelination and/or myelin sparing. Moreover, degeneration/dying back of corticospinal cord axons was prevented more by the trimer expressing stem cells. These results encourage the view that stem cells engineered to drive the beneficial functions of L1 via homophilic and heterophilic interactions are functionally optimized and may thus be of therapeutic value.
登录
查看更多内容
影响因子：
46.9
作者：
Lee, SH;Lumelsky, N;McKay, RD
通讯作者：
McKay, RD
软骨素酶ABC促进脊髓损伤后完整和受伤的脊柱系统的发芽。
DOI：
10.1523/jneurosci.2980-06.2006
发表时间：
2006-10-18
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Barritt AW;Davies M;Marchand F;Hartley R;Grist J;Yip P;McMahon SB;Bradbury EJ
通讯作者：
Bradbury EJ
影响因子：
11.4
作者：
Castellani, V;De Angelis, E;Rougon, G
通讯作者：
Rougon, G
影响因子：
14.5
作者：
Guseva, Daria;Angelov, Doychin N.;Schachner, Melitta
通讯作者：
Schachner, Melitta
影响因子：
5.2
作者：
Dihne, Marcel;Bernreuther, Christian;Schachner, Melitta
通讯作者：
Schachner, Melitta