Extensive cell migration, axon regeneration, and improved function with polysialic acid-modified Schwann cells after spinal cord injury.
Extensive cell migration, axon regeneration, and improved function with polysialic acid-modified Schwann cells after spinal cord injury.
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DOI：
10.1002/glia.22330
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发表时间：
2012-05
期刊：
影响因子：
6.2
通讯作者：
Pearse, Damien Daniel
中科院分区：
文献类型：
--
作者：
Ghosh, Mousumi;Tuesta, Luis M.;Puentes, Rocio;Patel, Samik;Melendez, Kiara;El Maarouf, Abderrahman;Rutishauser, Urs;Pearse, Damien Daniel
脊髓损伤(SCI)后植入雪旺细胞(SC)可促进轴突再生、再生髓鞘修复和功能恢复。然而，由于干细胞不能从病变植入部位向外迁移，修复效果可能是有限的。已有研究表明，通过过度表达聚唾液酸(PSA)来改变SC细胞表面的性质可以促进SC的迁移。在目前的研究中，我们利用脊髓挫伤来评估与聚唾液酸转移酶(PST)过度表达的SCs(PST-GFP SCs)或对照(GFP SCs)相关的迁移、脊髓上轴突生长支持和功能恢复。与仍然局限于损伤中心注射部位的GFP SCs相比，PST-GFP SCs在邻近宿主组织内跨越病变：宿主脊髓界面迁移长达4.4 mm。此外，对于PST-GFP SCs，植入体内有广泛的5-羟色胺能和皮质脊髓轴突生长，这在GFP SC对照组中是有限的。PST-GFP SCs的迁移增强伴随着这些轴突向损伤尾侧的显著生长。与GFP SC对照组相比，接受PST-GFP SCs的动物在开阔场地和网格行走测试中的功能结果都有所改善。目前的研究首次表明，干细胞缺乏迁移可能会阻碍其修复功能，细胞表面PSA的过表达增强了植入的干细胞与皮质脊髓轴突结合和支持生长的能力。这些结果进一步表明，PSA修饰的SCs将是一种有效的脊髓损伤修复方法。
Schwann cells (SC) implantation after spinal cord injury (SCI) promotes axonal regeneration, remyelination repair and functional recovery. Reparative efficacy, however, may be limited due to the inability of SCs to migrate outward from the lesion-implant site. Altering SC cell surface properties by over-expressing polysialic acid (PSA) has been shown to promote SC migration. In the current study, a SCI contusion was used to evaluate the migration, supraspinal axon growth support and functional recovery associated with polysialyltransferase (PST)-over-expressing SCs (PST-GFP SCs) or controls (GFP SCs). Compared to GFP SCs, which remained confined to the injection site at the injury center, PST-GFP SCs migrated across the lesion:host cord interface for distances of up to 4.4 mm within adjacent host tissue. In addition, with PST-GFP SCs, there was extensive serotonergic and corticospinal axon in-growth within the implants that was limited in the GFP SC controls. The enhanced migration of PST-GFP SCs was accompanied by significant growth of these axons caudal to lesion. Animals receiving PST-GFP SCs exhibited improved functional outcome, both in the open-field and on the gridwalk test, over modest improvements provided by GFP SC controls. The current study for the first time demonstrates that a lack of migration by SC may hinder their reparative benefits and that cell surface overexpression of PSA enhances the ability of implanted SCs to associate with and support the growth of corticospinal axons. These results provide further promise that PSA modified SCs will be a potent reparative approach for SCI.
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影响因子：
2.5
作者：
Hunanyan, Arsen S.;Alessi, Valentina;Arvanian, Victor L.
通讯作者：
Arvanian, Victor L.
影响因子：
5.3
作者：
Arvanian, Victor L.;Schnell, Lisa;Lou, Li;Golshani, Roozbeh;Hunanyan, Arsen;Ghosh, Arko;Pearse, Damien D.;Robinson, John K.;Schwab, Martin E.;Fawcett, James W.;Mendell, Lorne M.
通讯作者：
Mendell, Lorne M.
影响因子：
3.5
作者：
Fairless, R;Frame, MC;Barnett, SC
通讯作者：
Barnett, SC
影响因子：
6.2
作者：
Lavdas, AA;Franceschini, I;Matsas, R
通讯作者：
Matsas, R
影响因子：
3
作者：
Metz, GA;Whishaw, IQ
通讯作者：
Whishaw, IQ