TY - JOUR
T1 - Extensive graft-derived dopaminergic innervation is maintained 24 years after transplantation in the degenerating parkinsonian brain.
AU - LI, WEN
AU - Englund, Elisabet
AU - Widner, Håkan
AU - Mattsson, Bengt
AU - van Westen, Danielle
AU - Lätt, Jimmy
AU - Rehncrona, Stig
AU - Brundin, Patrik
AU - Björklund, Anders
AU - Lindvall, Olle
AU - Li, Jia-Yi
PY - 2016
Y1 - 2016
N2 - Clinical trials using cells derived from embryonic ventral mesencephalon have shown that transplanted dopaminergic neurons can survive and function in the long term, as demonstrated by in vivo brain imaging using 18F-fluorodopa and 11C-raclopride positron emission tomography. Here we report the postmortem analysis of a patient with Parkinson’s disease who 24 y earlier underwent unilateral transplantation of embryonic dopaminergic neurons in the putamen and subsequently exhibited major motor improvement and recovery of striatal dopaminergic function. Histopathological analysis showed that a dense, near-normal graft-derived dopaminergic reinnervation of the putamen can be maintained for a quarter of a century despite severe host brain pathology and with no evidence of immune response. In addition, ubiquitin- and α-synuclein–positive inclusions were seen, some with the appearance of typical Lewy bodies, in 11–12% of the grafted dopaminergic neurons, reflecting the spread of pathology from the host brain to the transplants. Because the clinical benefits induced by transplantation in this patient were gradually lost after 14 y posttransplantation, our findings provide the first reported evidence, to our knowledge, that even a viable dopaminergic graft giving rise to extensive striatal reinnervation may lose its efficacy if widespread degenerative changes develop in the host brain.
AB - Clinical trials using cells derived from embryonic ventral mesencephalon have shown that transplanted dopaminergic neurons can survive and function in the long term, as demonstrated by in vivo brain imaging using 18F-fluorodopa and 11C-raclopride positron emission tomography. Here we report the postmortem analysis of a patient with Parkinson’s disease who 24 y earlier underwent unilateral transplantation of embryonic dopaminergic neurons in the putamen and subsequently exhibited major motor improvement and recovery of striatal dopaminergic function. Histopathological analysis showed that a dense, near-normal graft-derived dopaminergic reinnervation of the putamen can be maintained for a quarter of a century despite severe host brain pathology and with no evidence of immune response. In addition, ubiquitin- and α-synuclein–positive inclusions were seen, some with the appearance of typical Lewy bodies, in 11–12% of the grafted dopaminergic neurons, reflecting the spread of pathology from the host brain to the transplants. Because the clinical benefits induced by transplantation in this patient were gradually lost after 14 y posttransplantation, our findings provide the first reported evidence, to our knowledge, that even a viable dopaminergic graft giving rise to extensive striatal reinnervation may lose its efficacy if widespread degenerative changes develop in the host brain.
KW - Parkinson Disease
U2 - 10.1073/pnas.1605245113
DO - 10.1073/pnas.1605245113
M3 - Article
C2 - 27140603
SN - 1091-6490
VL - 113
SP - 6544
EP - 6549
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 23
ER -