Central Laboratory, First Affiliated Hospital of Bengbu Medical College, Anhui 233004, China.
BMC Neurosci. 2010 Oct 12;11:127. doi: 10.1186/1471-2202-11-127.
Transplantation 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 OPCs in vivo is 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.
We 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).
These 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.
少突胶质前体细胞（OPCs）移植是脱髓鞘疾病的一种有吸引力的治疗方法。环孢素 A（CsA）是一种主要的免疫抑制剂，广泛应用于组织和细胞移植。然而，CsA 是否影响体内移植的 OPCs 的存活和分化尚不清楚。在这项研究中，探讨了 CsA 对损伤脊髓中移植的 OPCs 的形态、功能和免疫学方面以及存活和分化的影响。
我们将表达绿色荧光蛋白（GFP）的 OPCs（GFP-OPCs）移植到用或不用 CsA（10mg/kg）处理的大鼠损伤脊髓中。细胞移植后 2 周，CsA 处理组大鼠中发现的 GFP 阳性细胞比对照组多。然而，在两组中，移植的细胞大多分化为星形胶质细胞，而不是少突胶质细胞。与对照组相比，CsA 处理组脊髓损伤体积明显减小，髓鞘和神经元保留增加。这种组织学改善与行为恢复增加密切相关。进一步的研究表明，CsA 处理可抑制 T 细胞浸润和损伤脊髓中浸润单核细胞来源的固有小胶质细胞和/或巨噬细胞的激活，这有助于移植的 OPCs 的存活和脊髓损伤（SCI）的修复。
这些结果表明，CsA 可以促进损伤脊髓中移植的 OPCs 的存活，但对其分化没有影响。移植的细胞大多分化为星形胶质细胞，而不是少突胶质细胞。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。
