Neurogenic potential of progenitor cells isolated from postmortem human Parkinsonian brains.
The success of cellular therapies for Parkinson's disease (PD) will depend not only on a conducive growth environment in vivo, but also on the ex vivo amplification and targeted neural differentiation of stem/progenitor cells. Here, we demonstrate the in vitro proliferative and differentiation potential of stem/progenitor cells, adult human neural progenitor cells ("AHNPs") isolated from idiopathic PD postmortem tissue samples and, to a lesser extent, discarded deep brain stimulation electrodes. We demonstrate that these AHNPs can be isolated from numerous structures (e.g. substantia nigra, "SN") and are able to differentiate into both glia and neurons, but only under particular growth conditions including co-culturing with embryonic stem cell-derived neural precursors ("ESNPs"); this suggests that PD multipotent neural stem/progenitor cells do reside within the SN and other areas, but by themselves appear to lack key factors required for neuronal differentiation. AHNPs engraft following ex vivo expansion and transplantation into the rodent brain, demonstrating their regenerative potential. Our data demonstrate the presence and capacity of endogenous stem/progenitor cells in the PD brain.
Department of Neurosurgery, The University of Florida, Center for Movement Disorders and Neurorestoration, College of Medicine, Gainesville, FL 32610, USA.
Shanshan
S
Wang
Michael S
MS
Okun
Oleg
O
Suslov
Tong
T
Zheng
Nikolaus R
NR
McFarland
Vinata
V
Vedam-Mai
Kelly D
KD
Foote
Steven N
SN
Roper
Anthony T
AT
Yachnis
Florian A
FA
Siebzehnrubl
Dennis A
DA
Steindler
D000368:Aged; D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D006801:Humans; D020547:Lateral Ventricles / Q000166:cytology; D008297:Male; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology*; D055495:Neurogenesis / Q000502:physiology*; D010300:Parkinson Disease / Q000473:pathology*; D013378:Substantia Nigra / Q000166:cytology*