Transplanted neural progenitor cells expressing mutant NT3 promote myelination and partial hindlimb recovery in the chronic phase after spinal cord injury
Transplanted neural progenitor cells expressing mutant NT3 promote myelination and partial hindlimb recovery in the chronic phase after spinal cord injury
复制标题
DOI：
10.1016/j.bbrc.2010.02.088
复制
发表时间：
2010-03-19
影响因子：
3.1
通讯作者：
Okawa, Atsushi
中科院分区：
文献类型：
--
作者：
Kusano, Kazuo;Enomoto, Mitsuhiro;Okawa, Atsushi
中性粒细胞营养素-3（NT 3）通过与trk受体相互作用在受损的中枢神经系统组织中起保护作用。为了增强受损组织的再生，正在开发细胞移植和神经营养素的联合疗法。我们研究了移植分泌NT 3/D15 A的神经祖细胞（NPC）是否会增强受损组织的修复和脊髓损伤慢性期的功能恢复，NT 3/D15 A是一种能够结合trkB和trkC的多神经营养因子。在初始胸部损伤后6周，将含有GFP或NT 3/D15 A的慢病毒载体的培养的NPC移植到挫伤的脊髓中。移植后8周，NT 3/D15 A移植物显示出比GFP移植物更好的存活率，并且它们表现出增强的髓鞘形成和后肢功能的部分改善。我们的研究表明，NT 3/D15 A即使在慢性期也对受损的脊髓产生积极影响。这些作用表明NT 3/D15 A增强的神经营养因子-trk信号传导。(C)2010年爱思唯尔公司All rights reserved.
Neutrotrophin-3 (NT3) plays a protective role in injured central nervous system tissues through interaction with trk receptors. To enhance the regeneration of damaged tissue, a combination therapy with cell transplantation and neurotrophins has been under development. We examined whether the transplantation of neural progenitor cells (NPCs) secreting NT3/D15A, a multi-neurotrophin with the capacity to bind both trkB and trkC, would enhance the repair of damaged tissues and the functional recovery in a chronic phase of spinal cord injury. The cultured NPCs with lentiviral vector containing either GFP or NT3/D15A were transplanted into the contused spinal cord at 6 weeks after the initial thoracic injury. Eight weeks after the transplantation, the NT3/D15A transplants displayed better survival than the GFP transplants, and they exhibited enhanced myelin formation and partial improvement of hindlimb function. Our study revealed that NT3/D15A produced positive effects in injured spinal cords even in the chronic phase. These effects suggest an enhanced neurotrophin-trk signaling by NT3/D15A. (C) 2010 Elsevier Inc. All rights reserved.