Grafts of EGF-responsive neural stem cells derived from GFAP-hNGF transgenic mice: Trophic and tropic effects in a rodent model of Huntington's disease

作者：Jeffrey H. Kordower, Er‐Yun Chen, Christian Winkler, Rose A. Fricker, Vinod Charles, Albee Messing, Elliott J. Mufson, Shou C. Wong, Jeffrey M. Rosenstein, A. Bj�rklund, Dwaine F. Emerich, Joseph P. Hammang, Melissa K. Carpenter · 发表于：The Journal of Comparative Neurology · 年份：1997 · DOI：10.1002/(sici)1096-9861(19971013)387:1<96::aid-cne8>3.0.co;2-i · 被引用次数：107 · 研究领域：Genetic Neurodegenerative Diseases、Nerve injury and regeneration、Pluripotent Stem Cells Research

The present study examined whether implants of epidermal growth factor (EGF)-responsive stems cells derived from transgenic mice in which the glial fibrillary acid protein (GFAP) promoter directs the expression of human nerve growth factor (hNGF) could prevent the degeneration of striatal neurons in a rodent model of Huntington's disease (HD). Rats received intrastriatal transplants of GFAP-hNGF stem cells or control stem cells followed 9 days later by an intrastriatal injection of quinolinic acid (QA). Nissl stains revealed large striatal lesions in rats receiving control grafts, which, on average, encompassed 12.78 mm3. The size of the lesion was significantly reduced (1.92 mm3) in rats receiving lesions and GFAP-hNGF transplants. Rats receiving QA lesions and GFAP-hNGF-secreting grafts stem cell grafts displayed a sparing of striatal neurons immunoreactive (ir) for glutamic acid decarboxylase, choline acetyltransferase, and neurons histochemically positive for nicotinamide adenosine diphosphate. Intrastriatal GFAP-hNGF-secreting implants also induced a robust sprouting of cholinergic fibers from subjacent basal forebrain neurons. The lesioned striatum in control-grafted animals displayed numerous p75 neurotrophin-ir (p75NTR) astrocytes, which enveloped host vasculature. In rats receiving GFAP-hNGF-secreting stem cell grafts, the astroglial staining pattern was absent. By using a mouse-specific probe, stem cells were identified in all animals. These data indicate that cellu...