Lineage-restricted neural precursors survive, migrate, and differentiate following transplantation into the injured adult spinal cord
Lineage-restricted neural precursors survive, migrate, and differentiate following transplantation into the injured adult spinal cord
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DOI：
10.1016/j.expneurol.2005.02.020
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发表时间：
2005-07-01
影响因子：
5.3
通讯作者：
Fischer, I
中科院分区：
文献类型：
--
作者：
Lepore, AC;Fischer, I
胚胎14天的胚胎脊髓（E14/FSC）已被用于许多损伤脊髓的移植研究，E14/FSC主要由神经元（NRP）和胶质（GRP）限制的前体组成。因此，我们推断将E14/FSC的命运与限定的谱系限制性前体群体进行比较将测试这些前体在CNS中的体内特性，并使我们能够确定它们移植到损伤的脊髓中后的事件顺序。使用来自表达碱性磷酸酶（AP）标记的转基因大鼠的组织，我们发现E14/FSC在急性移植到部分半切损伤后4天表现出早期细胞丢失，但存活的细胞在3周时扩展到填充整个损伤腔。E14 FSC移植物整合到宿主组织中，分化成神经元、星形胶质细胞和少突胶质细胞，并表现出过程延伸和迁移出移植部位的变异性。在相似的移植条件下，确定的NRP/GRP细胞表现出良好的存活。一致迁移出损伤部位并稳健分化为成熟CNS表型，包括许多神经元。移植物中3周时几乎没有未成熟细胞。这些结果表明，通过结合神经元和胶质限制的前体，有可能产生一个微环境生态位，其中新兴的胶质细胞，衍生自GRP，支持非神经源性和非许可性损伤的成年脊髓内的NRP的存活和神经元分化，即使移植到急性损伤。此外，NRP/GRP移植物比胎儿移植物具有实际优势，使其成为神经细胞替代的有吸引力的候选者。(c)2005年爱思唯尔公司All rights reserved.
Fetal spinal cord from embryonic day 14 (E14/FSC) has been used for numerous transplantation studies of injured spinal cord, E14/FSC consists primarily of neuronal (NRP)- and glial (GRP)-restricted precursors. Therefore, we reasoned that comparing the fate of E14/FSC with defined populations of lineage-restricted precursors will test the in vivo properties of these precursors in CNS and allow us to define the sequence of events following their grafting into the injured spinal cord. Using tissue derived from transgenic rats expressing the alkaline phosphatase (AP) marker, we found that E14/FSC exhibited early cell loss at 4 days following acute transplantation into a partial hemisection injury, but the surviving cells expanded to fill the entire injury cavity by 3 weeks. E14FSC grafts integrated into host tissue, differentiated into neurons, astrocytes, and oligodendrocytes, and demonstrated variability in process extension and migration out of the transplant site. Under similar grafting conditions, defined NRP/GRP cells showed excellent survival. consistent migration Out of the injury site and robust differentiation into mature CNS phenotypes, including many neurons. Few immature cells remained at 3 weeks in either grafts. These results suggest that by combining neuronal and glial restricted precursors, it is possible to generate a microenvironmental niche where emerging glial cells, derived from GRPs, support survival and neuronal differentiation of NRPs within the non-neurogenic and non-permissive injured adult spinal cord, even when grafted into acute injury. Furthermore, the NRP/GRP grafts have practical advantages over fetal transplants, making them attractive candidates for neural cell replacement. (c) 2005 Elsevier Inc. All rights reserved.