Neural stem/progenitor cell-laden microfibers promote transplant survival in a mouse transected spinal cord injury model

Neural stem/progenitor cell-laden microfibers promote transplant survival in a mouse transected spinal cord injury model
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DOI:
10.1002/jnr.23636
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发表时间:
2015-12-01
影响因子:
4.2
通讯作者:
Nakamura, Masaya
Nakamura, Masaya
中科院分区:
医学3区
文献类型:
--
作者:
Sugai, Keiko;Nishimura, Soraya;Nakamura, Masaya

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以往的研究表明,神经干/祖细胞(NS/PC)移植到损伤的脊髓可以促进脊髓不完全损伤(SCI)后的功能恢复。然而,由于损伤中心处的差距,这种策略在完全SCI后是不够的。为了在完全SCI的小鼠模型中获得功能恢复,本研究使用新型胶原基微纤维作为移植NS/PC的支架。我们假设NS/PC-微纤维组合将促进横断脊髓中的病变闭合以及移植物存活。NS/PC被接种在新的微纤维内,在那里它们保持其分化和增殖的能力。移植后,载有NS/PC的微纤维成功地桥接了横断脊髓的残端。此外,移植的细胞迁移到宿主脊髓中并分化为三种神经谱系(星形胶质细胞、神经元和少突胶质细胞)。然而,NS/PC负载的支架不能实现损伤的头端和完整的脊髓尾侧区域之间的神经连接,也不能实现运动功能的恢复。为了获得最佳的功能恢复,具有改性组合物的微纤维设计可能是有用的。此外,康复和/或药物的组合疗法也应该被考虑用于基于生物材料/细胞移植的再生医学方法的实际成功。(c)2015 Wiley Periodicals,Inc.
Previous studies have demonstrated that transplantation of neural stem/progenitor cells (NS/PCs) into the lesioned spinal cord can promote functional recovery following incomplete spinal cord injury (SCI) in animal models. However, this strategy is insufficient following complete SCI because of the gap at the lesion epicenter. To obtain functional recovery in a mouse model of complete SCI, this study uses a novel collagen-based microfiber as a scaffold for engrafted NS/PCs. We hypothesized that the NS/PC-microfiber combination would facilitate lesion closure as well as transplant survival in the transected spinal cord. NS/PCs were seeded inside the novel microfibers, where they maintained their capacity to differentiate and proliferate. After transplantation, the stumps of the transected spinal cord were successfully bridged by the NS/PC-laden microfibers. Moreover, the transplanted cells migrated into the host spinal cord and differentiated into three neural lineages (astrocytes, neurons, and oligodendrocytes). However, the NS/PC-laden scaffold could not achieve a neural connection between the rostral end of the injury and the intact caudal area of the spinal cord, nor could it achieve recovery of motor function. To obtain optimal functional recovery, a microfiber design with a modified composition may be useful. Furthermore, combinatorial therapy with rehabilitation and/or medications should also be considered for practical success of biomaterial/cell transplantation-based approaches to regenerative medicine. (c) 2015 Wiley Periodicals, Inc.