Neural cells from primary human striatal xenografts migrate extensively in the adult rat CNS.
Primary neural cells do not appear to migrate significantly following transplantation into the adult rodent CNS, which is in contrast to expanded neural precursor cells where migration is well-documented. However, most transplant studies of primary neural tissue have been performed in an allograft situation in which it is difficult to identify graft-derived cells. We have, therefore, used a xenograft paradigm to investigate the potential for cells derived from grafts of primary human fetal striatal tissue (gestational age of 66-72 days) to migrate following intrastriatal transplantation in an athymic adult rat model of Huntington's disease. The use of an antibody specific to human nuclear antigen enabled clear identification of graft-derived cells within the host brain, and specific neural phenotypes were determined using human-specific tau for neurons, glial fibrillary acidic protein for mature astrocytes and Ki67 for proliferative cells. At 6 weeks, the graft mass was very dense with a high proliferative index, few cells had migrated away from the graft, and the cells that had differentiated both within and away from the graft were mainly neurons. In contrast, at 6 months, the graft core was dispersed significantly more and a large number of graft-derived cells had migrated throughout the brain as far rostral as the olfactory bulb and as caudal as the substantia nigra. Cells had differentiated into both neurons and astrocytes and the level of proliferation was significantly lower within the graft. These results demonstrate that primary neural xenografts contain proliferative cells that possess the ability to migrate and differentiate into both neurons and astrocytes, and suggest that these cells could contribute to normal graft function. This property may be a consequence of the xenograft situation and could potentially be exploited to provide the opportunity to target regions of distant pathology in neurodegenerative diseases using xenotransplantation of embryonic neural tissue.
Hurelbrink
Carrie B
CB
Cambridge Centre for Brain Repair, Forvie Site, Robinson Way, Cambridge CB2 2PY, UK. cbh20@cam.ac.uk
Armstrong
Richard J E
RJ
Dunnett
Stephen B
SB
Rosser
Anne E
AE
Barker
Roger A
RA
D000818:Animals; D016380:Brain Tissue Transplantation / Q000379:methods*; D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D005333:Fetus; D006085:Graft Survival / Q000502:physiology; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D017072:Neostriatum / Q000166:cytology / Q000196:embryology / Q000637:transplantation*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D009498:Neurotoxins / Q000494:pharmacology; D011247:Pregnancy; D017378:Quinolinic Acid / Q000494:pharmacology; D051381:Rats; D011923:Rats, Nude; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014183:Transplantation, Heterologous / Q000379:methods*
D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D017378:Quinolinic Acid