Embryonic stem cell-derived L1 overexpressing neural aggregates enhance recovery after spinal cord injury in mice.
Embryonic stem cell-derived L1 overexpressing neural aggregates enhance recovery after spinal cord injury in mice.
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DOI：
10.1371/journal.pone.0017126
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发表时间：
2011-03-18
期刊：
影响因子：
3.7
通讯作者：
Bernreuther C
中科院分区：
文献类型：
--
作者：
Cui YF;Xu JC;Hargus G;Jakovcevski I;Schachner M;Bernreuther C
早期干细胞移植到急性损伤的脊髓中的障碍是移植细胞的存活率差。移植胚胎干细胞作为基板贴壁胚胎干细胞衍生的神经聚集体（SENAs）主要由神经元和放射状胶质细胞已被证明，以提高移植细胞在受损小鼠脑的存活。在促进这些SENA的有益功能的尝试中，将组成型过表达神经细胞粘附分子L1的鼠胚胎干细胞分化成SENA，并在压迫损伤后3天移植到脊髓中，所述神经细胞粘附分子L1有利于轴突生长以及移植和危及的细胞在成年哺乳动物中枢神经系统的抑制环境中的存活。与注射野生型SENAs的小鼠相比，移植L1过表达SENAs的小鼠表现出改善的运动功能。L1过表达的SENAs表现出增加的存活细胞的数量，增强神经元分化和减少神经胶质细胞分化移植后相比，SENAs没有工程化过度表达L1。此外，过表达L1的SENA拯救了受威胁的宿主运动神经元和小清蛋白阳性中间神经元，并增加了病变远端的儿茶酚胺能神经纤维的数量。除了鼓励胚胎干细胞用于脊髓损伤后的早期治疗外，L1在受损脊髓微环境中的过表达是其功能的新发现，这将使其在脊髓再生和最有可能的其他神经系统疾病的临床前研究中更具吸引力。
An obstacle to early stem cell transplantation into the acutely injured spinal cord is poor survival of transplanted cells. Transplantation of embryonic stem cells as substrate adherent embryonic stem cell-derived neural aggregates (SENAs) consisting mainly of neurons and radial glial cells has been shown to enhance survival of grafted cells in the injured mouse brain. In the attempt to promote the beneficial function of these SENAs, murine embryonic stem cells constitutively overexpressing the neural cell adhesion molecule L1 which favors axonal growth and survival of grafted and imperiled cells in the inhibitory environment of the adult mammalian central nervous system were differentiated into SENAs and transplanted into the spinal cord three days after compression lesion. Mice transplanted with L1 overexpressing SENAs showed improved locomotor function when compared to mice injected with wild-type SENAs. L1 overexpressing SENAs showed an increased number of surviving cells, enhanced neuronal differentiation and reduced glial differentiation after transplantation when compared to SENAs not engineered to overexpress L1. Furthermore, L1 overexpressing SENAs rescued imperiled host motoneurons and parvalbumin-positive interneurons and increased numbers of catecholaminergic nerve fibers distal to the lesion. In addition to encouraging the use of embryonic stem cells for early therapy after spinal cord injury L1 overexpression in the microenvironment of the lesioned spinal cord is a novel finding in its functions that would make it more attractive for pre-clinical studies in spinal cord regeneration and most likely other diseases of the nervous system.
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影响因子：
4.6
作者：
De Biase, A;Knoblach, SM;Faden, AI
通讯作者：
Faden, AI
影响因子：
5.2
作者：
Dihne, Marcel;Bernreuther, Christian;Schachner, Melitta
通讯作者：
Schachner, Melitta
DOI：
10.1007/bf01183975
发表时间：
1993-01-01
期刊：
JOURNAL OF NEUROCYTOLOGY
影响因子：
--
作者：
CURTIS, R;GREEN, D;WILKIN, GP
通讯作者：
WILKIN, GP
影响因子：
3.4
作者：
Irintchev, A;Simova, O;Schachner, M
通讯作者：
Schachner, M
DOI：
10.1073/pnas.0401103101
发表时间：
2004-05-04
影响因子：
11.1
作者：
Harper, JM;Krishnan, C;Kerr, DA
通讯作者：
Kerr, DA