Cyclosporin A increases recovery after spinal cord injury but does not improve myelination by oligodendrocyte progenitor cell transplantation.
Cyclosporin A increases recovery after spinal cord injury but does not improve myelination by oligodendrocyte progenitor cell transplantation.
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环孢素 A 可促进脊髓损伤后的恢复，但不能通过少突胶质祖细胞移植改善髓鞘形成
DOI：
10.1186/1471-2202-11-127
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发表时间：
2010-10-12
期刊：
影响因子：
2.4
通讯作者：
Hu JG
中科院分区：
文献类型：
--
作者：
Lü HZ;Wang YX;Zhou JS;Wang FC;Hu JG
背景少突胶质前体细胞（oligodendrocyte precursor cells，OPCs）移植是治疗脱髓鞘疾病的一种有吸引力的方法。环孢菌素A（CsA）是最重要的免疫抑制剂之一，广泛应用于组织和细胞移植。然而，CsA是否影响移植的OPC在体内的存活和分化尚不清楚。在这项研究中，CsA的形态，功能和免疫方面的影响，以及移植的OPCs在损伤的脊髓explored.ResultsWe移植绿色荧光蛋白（GFP）表达的OPCs（GFP-OPCs）到损伤的大鼠脊髓治疗或不CsA（10 mg/kg）。细胞移植后两周，更多的GFP阳性细胞被发现在CsA治疗的大鼠比在溶剂治疗的。然而，移植的细胞大多分化成星形胶质细胞，但在两组中的少突胶质细胞。与对照组相比，CsA治疗组脊髓病变体积沿着减少，备用髓鞘和神经元增加。这种组织学改善与行为恢复的增加密切相关。进一步研究表明，CsA可抑制损伤脊髓中T细胞的浸润和单核细胞来源的小胶质细胞和/或巨噬细胞的活化，从而促进移植OPCs的存活和脊髓损伤的修复。移植的细胞大多分化为星形胶质细胞，但不是少突胶质细胞。CsA对SCI和移植细胞存活的有益作用可能归因于其神经保护作用。
BackgroundTransplantation of oligodendrocyte precursor cells (OPCs) is an attractive therapy for demyelinating diseases. Cyclosporin A (CsA) is one of the foremost immunosuppressive agents and has widespread use in tissue and cell transplantation. However, whether CsA affects survival and differentiation of engrafted OPCsin vivois unknown. In this study, the effect of CsA on morphological, functional and immunological aspects, as well as survival and differentiation of engrafted OPCs in injured spinal cord was explored.ResultsWe transplanted green fluorescent protein (GFP) expressed OPCs (GFP-OPCs) into injured spinal cords of rats treated with or without CsA (10 mg/kg). Two weeks after cell transplantation, more GFP-positive cells were found in CsA-treated rats than that in vehicle-treated ones. However, the engrafted cells mostly differentiated into astrocytes, but not oligodendrocytes in both groups. In the CsA-treated group, a significant decrease in spinal cord lesion volume along with increase in spared myelin and neurons were found compared to the control group. Such histological improvement correlated well with an increase in behavioral recovery. Further study suggested that CsA treatment could inhibit infiltration of T cells and activation of resident microglia and/or macrophages derived from infiltrating monocytes in injured spinal cords, which contributes to the survival of engrafted OPCs and repair of spinal cord injury (SCI).ConclusionsThese results collectively indicate that CsA can promote the survival of engrafted OPCs in injured spinal cords, but has no effect on their differentiation. The engrafted cells mostly differentiated into astrocytes, but not oligodendrocytes. The beneficial effect of CsA on SCI and the survival of engrafted cells may be attributed to its neuroprotective effect.
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影响因子：
4.2
作者：
Carrico, Kimberly M.;Vaishnav, Radhika;Hall, Edward D.
通讯作者：
Hall, Edward D.
影响因子：
5.8
作者：
Kawanokuchi, J.;Mizuno, T.;Suzumura, A.
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影响因子：
4.2
作者：
GALIANA, E;BERNARD, R;EVRARD, C
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EVRARD, C
影响因子：
5.3
作者：
Keirstead, HS;Nistor, G;Steward, O
通讯作者：
Steward, O
影响因子：
5.3
作者：
Jones, TB;Hart, RP;Popovich, PG
通讯作者：
Popovich, PG