کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6022402 1580675 2013 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Efficient expansion and dopaminergic differentiation of human fetal ventral midbrain neural stem cells by midbrain morphogens
ترجمه فارسی عنوان
توسعه کارآیی و تمایز دوپامینرژیک سلول های بنیادی عصبی مغز استخوان جنین انسان با مورفوژن های متابولیسمی
کلمات کلیدی
دوپامینرژیک، متوسط ​​بطن مرزی جنین انسان،
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی عصب شناسی
چکیده انگلیسی
Human fetal midbrain tissue grafting has provided proof-of-concept for dopamine cell replacement therapy (CRT) in Parkinson's disease (PD). However, limited tissue availability has hindered the development and widespread use of this experimental therapy. Here we present a method for generating large numbers of midbrain dopaminergic (DA) neurons based on expanding and differentiating neural stem/progenitor cells present in the human ventral midbrain (hVM) tissue. Our results show that hVM neurospheres (hVMN) with low cell numbers, unlike their rodent counterparts, expand the total number of cells 3-fold, whilst retaining their capacity to differentiate into midbrain DA neurons. Moreover, Wnt5a promoted DA differentiation of expanded cells resulting in improved morphological maturation, midbrain DA marker expression, DA release and electrophysiological properties. This method results in cell preparations that, after expansion and differentiation, can contain 6-fold more midbrain DA neurons than the starting VM preparation. Thus, our results provide evidence that by improving expansion and differentiation of progenitors present in the hVM it is possible to greatly enrich cell preparations for DA neurons. This method could substantially reduce the amount of human fetal midbrain tissue necessary for CRT in patients with PD, which could have major implications for the widespread adoption of this approach.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 49, January 2013, Pages 118-127
نویسندگان
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