Survival, differentiation, and migration of bioreactor-expanded human neural precursor cells in a model of Parkinson disease in rats.
OBJECTIVE
Fetal tissue transplantation for Parkinson disease (PD) has demonstrated promising results in experimental and clinical studies. However, the widespread clinical application of this therapeutic approach is limited by a lack of fetal tissue. Human neural precursor cells (HNPCs) are attractive candidates for transplantation because of their long-term proliferation activity. Furthermore, these cells can be reproducibly expanded in a standardized fashion in suspension bioreactors. In this study the authors sought to determine whether the survival, differentiation, and migration of HNPCs after transplantation depended on the region of precursor cell origin, intracerebral site of transplantation, and duration of their expansion.


METHODS
Human neural precursor cells were isolated from the telencephalon, brainstem, ventral mesencephalon, and spinal cord of human fetuses 8-10 weeks of gestational age, and their differentiation potential characterized in vitro. After expansion in suspension bioreactors, the HNPCs were transplanted into the striatum and substantia nigra of parkinsonian rats. Histological analyses were performed 7 weeks posttransplantation.


RESULTS
The HNPCs isolated from various regions of the neuraxis demonstrated diverse propensities to differentiate into astrocytes and neurons and could all successfully expand under standardized conditions in suspension bioreactors. At 7 weeks posttransplantation, survival and migration were significantly greater for HNPCs obtained from the more rostral brain regions. The HNPCs differentiated predominantly into astrocytes after transplantation into the striatum or substantia nigra regions, and thus no behavioral improvement was observed.


CONCLUSIONS
Understanding the regional differences in HNPC properties is prerequisite to their application for PD cell restoration strategies.
Mukhida
Karim
K
Division of Neurosurgery, Department of Surgery, Cell Restoration Laboratory, Dalhousie Medical School, Halifax, Nova Scotia, Canada.
Baghbaderani
Behnam A
BA
Hong
Murray
M
Lewington
Matthew
M
Phillips
Timothy
T
McLeod
Marcus
M
Sen
Arindom
A
Behie
Leo A
LA
Mendez
Ivar
I
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D019149:Bioreactors; D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D002470:Cell Survival; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology; D000697:Central Nervous System Stimulants; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000502:physiology*; D005260:Female; D005333:Fetus; D006801:Humans; D009474:Neurons / Q000502:physiology*; D010300:Parkinson Disease / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy; D051381:Rats; D017208:Rats, Wistar; D033581:Stem Cell Transplantation / Q000379:methods
D000697:Central Nervous System Stimulants; D000661:Amphetamine