Successful function of autologous iPSC-derived dopamine neurons following transplantation in a non-human primate model of Parkinson's disease

Cell Stem Cell
Penelope J HallettOle Isacson

Abstract

Autologous transplantation of patient-specific induced pluripotent stem cell (iPSC)-derived neurons is a potential clinical approach for treatment of neurological disease. Preclinical demonstration of long-term efficacy, feasibility, and safety of iPSC-derived dopamine neurons in non-human primate models will be an important step in clinical development of cell therapy. Here, we analyzed cynomolgus monkey (CM) iPSC-derived midbrain dopamine neurons for up to 2 years following autologous transplantation in a Parkinson's disease (PD) model. In one animal, with the most successful protocol, we found that unilateral engraftment of CM-iPSCs could provide a gradual onset of functional motor improvement contralateral to the side of dopamine neuron transplantation, and increased motor activity, without a need for immunosuppression. Postmortem analyses demonstrated robust survival of midbrain-like dopaminergic neurons and extensive outgrowth into the transplanted putamen. Our proof of concept findings support further development of autologous iPSC-derived cell transplantation for treatment of PD.

References

Oct 1, 1989·Experimental Neurology·G DoucetA Björklund
Oct 29, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Bruce G JenkinsOle Isacson
Aug 28, 2010·Proceedings of the National Academy of Sciences of the United States of America·Gunnar HargusOle Isacson
Jul 20, 2011·Proceedings of the National Academy of Sciences of the United States of America·Fredrik H SterkyNils-Göran Larsson

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Citations

Feb 24, 2016·Journal of Animal Science and Biotechnology·J OgorevcP Dovč
Feb 18, 2016·Stem Cells International·Nina Xie, Beisha Tang
Feb 18, 2016·Neural Plasticity·François-Xavier Blaudin de ThéRajiv L Joshi
Dec 22, 2015·Trends in Immunology·Kathryn J WoodJoanna Hester
Sep 4, 2015·Journal of Internal Medicine·O Lindvall
Mar 2, 2016·Biochemical and Biophysical Research Communications·Michela Deleidi, Cong Yu
Sep 30, 2015·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Olle Lindvall
Jun 23, 2015·Movement Disorders : Official Journal of the Movement Disorder Society·Dustin R Wakeman
Aug 5, 2015·Nature Reviews. Neurology·Roger A BarkerMalin Parmar
Sep 5, 2015·Translational Neurodegeneration·Fabin HanQingfa Chen
Jul 3, 2015·Open Biology·Lauren M WatsonEsther B E Becker
Apr 8, 2015·Proceedings of the National Academy of Sciences of the United States of America·Ole Isacson
May 4, 2016·Expert Review of Neurotherapeutics·Ting ShenBaorong Zhang
Jun 12, 2016·Trends in Molecular Medicine·Clara Soria-Valles, Carlos López-Otín
Jan 30, 2016·The International Journal of Neuroscience·Bangfu ZhuBing Song
Aug 11, 2016·Molecular Therapy : the Journal of the American Society of Gene Therapy·So Gun HongJizhong Zou
Aug 20, 2016·Journal of Internal Medicine·S GrealishM Parmar
Aug 16, 2016·Current Opinion in Organ Transplantation·Marta VadoriEmanuele Cozzi
Nov 26, 2016·Clinical Hemorheology and Microcirculation·Zhengdong LiAndreas Lendlein
Dec 3, 2016·Regenerative Medicine·Erin A Kimbrel, Robert Lanza
Jun 28, 2016·Stem Cells Translational Medicine·Douglas A GrowChristopher S Navara
Dec 18, 2016·The European Journal of Neuroscience·Rafieh AlizadehMahmoudreza Hadjighassem
Feb 9, 2017·Stem Cells Translational Medicine·Scott BellCarl Ernst
Mar 23, 2017·Journal of Neural Transmission·Scott C Vermilyea, Marina E Emborg
Feb 6, 2017·Frontiers in Cell and Developmental Biology·Mohamad KhazaeiMichael G Fehlings
Jan 7, 2017·Cell Stem Cell·Teresia Osborn, Penelope J Hallett
Mar 18, 2017·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Andrew R Bassett
Sep 17, 2016·Cell Transplantation·Scott C VermilyeaMarina E Emborg
Dec 29, 2017·Neuroscience Bulletin·Zhen-Yang LiuJian Wang
Mar 31, 2018·International Journal of Molecular Sciences·Marina GazdicMiodrag Stojkovic
May 3, 2018·Advanced Healthcare Materials·Shupei QiaoWeiming Tian
Feb 18, 2017·American Journal of Physiology. Gastrointestinal and Liver Physiology·Lincon A Stamp
Nov 9, 2017·Cell Transplantation·Takao YasuharaIsao Date

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