Glial cell line-derived neurotrophic factor-secreting human neural progenitors show long-term survival, maturation into astrocytes, and no tumor formation following transplantation into the spinal cord of immunocompromised rats.
Glial cell line-derived neurotrophic factor-secreting human neural progenitors show long-term survival, maturation into astrocytes, and no tumor formation following transplantation into the spinal cord of immunocompromised rats.
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DOI：
10.1097/wnr.0000000000000092
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发表时间：
2014-04-16
期刊：
影响因子：
1.7
通讯作者：
Svendsen CN
中科院分区：
文献类型：
--
作者：
Gowing G;Shelley B;Staggenborg K;Hurley A;Avalos P;Victoroff J;Latter J;Garcia L;Svendsen CN
来自胎儿皮质的人类神经祖细胞（hNPC）可以在体外扩增，并通过慢病毒转导进行基因修饰，以分泌生长因子，在神经系统疾病的动物模型中显示出具有神经营养作用。 hNPCs 移植到大型和小型动物（包括肌萎缩侧索硬化症大鼠模型）的中枢神经系统后能够存活并成熟。在此，我们报道，被设计表达胶质细胞源性神经营养因子（GDNF）的hNPCs在移植到无胸腺裸鼠的脊髓后可以长期存活（7.5个月），并继续分泌GDNF。细胞增殖下降，而星形胶质细胞数量增加，表明细胞随着时间的推移在体内最终成熟。这些数据共同表明，产生 GDNF 的 hNPC 可作为细胞来源，将星形胶质细胞和 GDNF 长期递送至受损的中枢神经系统。
Human neural progenitor cells (hNPCs) derived from the fetal cortex can be expanded in vitro and genetically modified through lentiviral transduction to secrete growth factors shown to have a neurotrophic effect in animal models of neurological disease. hNPCs survive and mature following transplantation into the central nervous system of large and small animals including the rat model of amyotrophic lateral sclerosis. Here we report that hNPCs engineered to express glial cell line-derived neurotrophic factor (GDNF) survive long-term (7.5 months) following transplantation into the spinal cord of athymic nude rats and continue to secrete GDNF. Cell proliferation declined while the number of astrocytes increased, suggesting final maturation of the cells over time in vivo. Together these data show that GDNF-producing hNPCs may be useful as a source of cells for long-term delivery of both astrocytes and GDNF to the damaged central nervous system.