Human neural progenitor cells over-expressing IGF-1 protect dopamine neurons and restore function in a rat model of Parkinson's disease

详细信息    查看全文

• 作者：Allison D. Ebert ; Amy J. Beres ; Amelia E. Barber ; Clive N. Svendsen
• 关键词：GDNF ; Lentivirus ; Gene therapy ; 6-Hydroxydopamine ; Stem cells
• 刊名：Experimental Neurology
• 出版年：2008
• 出版时间：January 2008
• 年：2008
• 卷：209
• 期：1
• 页码：213-223
• 全文大小：1370 K

文摘

Growth factors such as glial cell line-derived neurotrophic factor (GDNF) have been shown to prevent neurodegeneration and promote regeneration in many animal models of Parkinson's disease (PD). Insulin-like growth factor 1 (IGF-1) is also known to have neuroprotective effects in a number of disease models but has not been extensively studied in models of PD. We produced human neural progenitor cells (hNPC) releasing either GDNF or IGF-1 and transplanted them into a rat model of PD. hNPC secreting either GDNF or IGF-1 were shown to significantly reduce amphetamine-induced rotational asymmetry and dopamine neuron loss when transplanted 7 days after a 6-hydroxydopamine (6-OHDA) lesion. Neither untransduced hNPC nor a sham transplant had this effect suggesting GDNF and IGF-1 release was required. Interestingly, GDNF, but not IGF-1, was able to protect or regenerate tyrosine hydroxylase-positive fibers in the striatum. In contrast, IGF-1, but not GDNF, significantly increased the overall survival of hNPC both in vitro and following transplantation. This suggests a dual role of IGF-1 to both increase hNPC survival after transplantation and exert trophic effects on degenerating dopamine neurons in this rat model of PD.