INTRAVENOUS INFUSION OF MESENCHYMAL STEM CELLS PROMOTES FUNCTIONAL RECOVERY IN A MODEL OF CHRONIC SPINAL CORD INJURY

INTRAVENOUS INFUSION OF MESENCHYMAL STEM CELLS PROMOTES FUNCTIONAL RECOVERY IN A MODEL OF CHRONIC SPINAL CORD INJURY
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DOI:
10.1016/j.neuroscience.2016.08.037
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发表时间:
2016-10-01
期刊:
影响因子:
3.3
通讯作者:
Honmou, Osamu
Honmou, Osamu
中科院分区:
医学3区
文献类型:
--
作者:
Morita, Tomonori;Sasaki, Masanori;Honmou, Osamu

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静脉输注来源于成人骨髓的间充质干细胞(MSCs)可改善脊髓损伤(SCI)大鼠模型的行为功能。然而,大多数研究都集中在SCI的急性或亚急性期。在本研究中,诱导严重挫伤性SCI后10周,静脉输注大鼠骨髓来源的MSC。开放领域的运动功能进行了评估,每周一次,直到20周后SCI。与溶剂治疗组相比,MSC治疗组的运动恢复更好,在输注后较早时间开始迅速改善。通过静脉输注伊文思蓝(EvB),用分光光度法定量其向实质中的渗漏来评估血脊髓屏障(BSCB)的完整性。在MSC治疗的大鼠中,BSCB渗漏减少。RECA-1和PDGFR-β的免疫组织化学染色显示,MSC治疗的大鼠中微血管形成/修复-新血管形成增加。MSC灌注后,病变中心周围有广泛的髓鞘再生,皮质脊髓束和肾上腺素能纤维的发芽增加。这些结果表明,MSC的全身输注导致与慢性损伤的脊髓中的结构变化相关的功能改善,包括BSCB的稳定、轴突发芽/再生和髓鞘再生。(C)2016年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Intravenous infusion of mesenchymal stem cells (MSCs) derived from adult bone marrow improves behavioral function in rat models of spinal cord injury (SCI). However, most studies have focused on the acute or subacute phase of SCI. In the present study, MSCs derived from bone marrow of rats were intravenously infused 10 weeks after the induction of a severe contusive SCI. Open field locomotor function was assessed weekly until 20 weeks post-SCI. Motor recovery was greater in the MSC-treated group with rapid improvement beginning in earlier post-infusion times than in the vehicle-treated group. Blood spinal cord barrier (BSCB) integrity was assessed by the intravenous infusion of Evans Blue (EvB) with spectrophotometric quantitation of its leakage into the parenchyma. In MSC-treated rats, BSCB leakage was reduced. Immunohistochemical staining for RECA-1 and PDGFR-beta showed increased microvascula ture/repair-neovascularization in MSC-treated rats. There was extensive remyelination around the lesion center and increased sprouting of the corticospinal tract and serotonergic fibers after MSC infusion. These results indicate that the systemic infusion of MSCs results in functional improvement that is associated with structural changes in the chronically injured spinal cord including stabilization of the BSCB, axonal sprouting/regeneration and remyelination. (C) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.