Embryonic stem cells differentiate into oligodendrocytes and myelinate in culture and after spinal cord transplantation
Embryonic stem cells differentiate into oligodendrocytes and myelinate in culture and after spinal cord transplantation
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DOI：
10.1073/pnas.97.11.6126
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发表时间：
2000-05-23
影响因子：
11.1
通讯作者：
McDonald, JW
中科院分区：
文献类型：
--
作者：
Liu, S;Qu, Y;McDonald, JW
脱髓鞘导致中枢神经系统（CNS）损伤后的功能丧失。通过移植髓鞘生成细胞来增强髓鞘再生可能为恢复有意义的神经功能提供一种实用的方法。适用于这种移植治疗的无限来源的细胞可以源自胚胎干（ES）细胞，其是多能的和遗传柔性的。在本文中，我们表明，少突胶质细胞培养物可以可靠地产生从视黄酸诱导的ES细胞，这些少突胶质细胞可以髓鞘轴突在体外。进一步开发了通过额外的培养步骤产生高度富集的少突胶质细胞培养物的方法，产生中间“少突球”阶段。为检测ES细胞能否在成年大鼠中枢神经系统脱髓鞘区存活、迁移和分化为成熟的髓鞘生成细胞，将ES细胞移植到化学脱髓鞘3天后的成年大鼠脊髓背柱中，在脱髓鞘部位，大量ES细胞存活并初步分化为能够髓鞘化轴突的成熟少突胶质细胞。当将少突胶质球细胞移植到髓鞘缺乏的shiverer（shi/shi）突变小鼠的脊髓中时，ES细胞衍生的少突胶质细胞迁移到宿主组织中，产生髓鞘和有髓鞘的宿主轴突。这些研究表明ES细胞来源的少突胶质细胞能够在培养中使轴突髓鞘化，并能够替代损伤的成人CNS中丢失的髓鞘。ES细胞移植可能是治疗成人CNS中原发性和继发性脱髓鞘疾病的实用方法。
Demyelination contributes to the loss of function consequent to central nervous system (CNS) injury. Enhanced remyelination through transplantation of myelin-producing cells may offer a pragmatic approach to restoring meaningful neurological function. An unlimited source of cells suitable for such transplantation therapy can be derived from embryonic stem (ES) cells, which are both pluripotent and genetically flexible. In this paper we show that oligodendrocyte cultures can be reliably produced from retinoic acid-induced ES cells and that these oligodendrocytes can myelinate axons in vitro. Methods were further developed for generating highly enriched cultures of oligodendrocytes through an additional culturing step, producing an intermediate "oligosphere" stage. To test whether ES cells can survive, migrate, and differentiate into mature myelin-producing cells in areas of demyelination in the adult CNS, ES cells were transplanted into the dorsal columns of adult rat spinal cord 3 days after chemical demyelination, In the demyelination site, large numbers of ES cells survived and differentiated primarily into mature oligodendrocytes that were capable of myelinating axons, Furthermore, when oligosphere cells were transplanted into the spinal cords of myelin-deficient shiverer (shi/shi) mutant mice, the ES cell-derived oligodendrocytes migrated into the host tissue, produced myelin and myelinated host axons. These studies demonstrate the ability of ES cell-derived oligodendrocytes to myelinate axons in culture and to replace lost myelin in the injured adult CNS, Transplantation of ES cells may be a practical approach to treatment of primary and secondary demyelinating diseases in the adult CNS.