Human autologous iPSC-derived dopaminergic progenitors restore motor function in Parkinson's disease models.

Tytuł:: Human autologous iPSC-derived dopaminergic progenitors restore motor function in Parkinson's disease models.
Autorzy:: Song B; Department of Psychiatry and.; Molecular Neurobiology Laboratory, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, USA.
Cha Y; Department of Psychiatry and.; Molecular Neurobiology Laboratory, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, USA.
Ko S; Department of Psychiatry and.; Molecular Neurobiology Laboratory, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, USA.
Jeon J; Department of Psychiatry and.; Molecular Neurobiology Laboratory, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, USA.
Lee N; Department of Psychiatry and.; Molecular Neurobiology Laboratory, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, USA.
Seo H; Department of Psychiatry and.; Molecular Neurobiology Laboratory, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, USA.; Department of Molecular and Life Sciences, Hanyang University, Ansan, Korea.
Park KJ; Department of Psychiatry and.
Lee IH; Department of Pediatrics.; Computational Health Informatics Program, Boston Children's Hospital, and.
Lopes C; Department of Psychiatry and.; Molecular Neurobiology Laboratory, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, USA.
Feitosa M; Department of Psychiatry and.; Molecular Neurobiology Laboratory, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, USA.
Luna MJ; Department of Psychiatry and.; Molecular Neurobiology Laboratory, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, USA.
Jung JH; Department of Psychiatry and.; Molecular Neurobiology Laboratory, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, USA.
Kim J; Department of Psychiatry and.; Molecular Neurobiology Laboratory, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, USA.; Department of Molecular and Life Sciences, Hanyang University, Ansan, Korea.
Hwang D; Department of Psychiatry and.; Molecular Neurobiology Laboratory, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, USA.
Cohen BM; Department of Psychiatry and.
Teicher MH; Department of Psychiatry and.
Leblanc P; Department of Psychiatry and.; Molecular Neurobiology Laboratory, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, USA.
Carter BS; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Kordower JH; Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA.
Bolshakov VY; Department of Psychiatry and.
Kong SW; Department of Pediatrics.; Computational Health Informatics Program, Boston Children's Hospital, and.
Schweitzer JS; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Kim KS; Department of Psychiatry and.; Molecular Neurobiology Laboratory, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, USA.
Źródło:: The Journal of clinical investigation [J Clin Invest] 2020 Feb 03; Vol. 130 (2), pp. 904-920.
Typ publikacji:: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Publication: 1999- : Ann Arbor, MI : American Society for Clinical Investigation
Original Publication: New Haven [etc.] American Society for Clinical Investigation.
MeSH Terms:: Induced Pluripotent Stem Cells*/metabolism
Induced Pluripotent Stem Cells*/pathology
Induced Pluripotent Stem Cells*/transplantation
Motor Activity*
Parkinson Disease, Secondary*/metabolism
Parkinson Disease, Secondary*/pathology
Parkinson Disease, Secondary*/therapy
Recovery of Function*
Stem Cell Transplantation*
Animals ; Autografts ; Humans ; Male ; Rats ; Rats, Nude
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Grant Information:: R01 NS070577 United States NS NINDS NIH HHS; R01 NS084869 United States NS NINDS NIH HHS; R24 OD024622 United States OD NIH HHS
Contributed Indexing:: Keywords: Neuroscience; Parkinson’s disease; Stem cell transplantation; Stem cells
Entry Date(s):: Date Created: 20191113 Date Completed: 20200914 Latest Revision: 20200929
Update Code:: 20240105
PubMed Central ID:: PMC6994130
DOI:: 10.1172/JCI130767
PMID:: 31714896
: Czasopismo naukowe

Parkinson's disease (PD) is a neurodegenerative disorder associated with loss of striatal dopamine, secondary to degeneration of midbrain dopamine (mDA) neurons in the substantia nigra, rendering cell transplantation a promising therapeutic strategy. To establish human induced pluripotent stem cell-based (hiPSC-based) autologous cell therapy, we report a platform of core techniques for the production of mDA progenitors as a safe and effective therapeutic product. First, by combining metabolism-regulating microRNAs with reprogramming factors, we developed a method to more efficiently generate clinical-grade iPSCs, as evidenced by genomic integrity and unbiased pluripotent potential. Second, we established a "spotting"-based in vitro differentiation methodology to generate functional and healthy mDA cells in a scalable manner. Third, we developed a chemical method that safely eliminates undifferentiated cells from the final product. Dopaminergic cells thus express high levels of characteristic mDA markers, produce and secrete dopamine, and exhibit electrophysiological features typical of mDA cells. Transplantation of these cells into rodent models of PD robustly restores motor function and reinnervates host brain, while showing no evidence of tumor formation or redistribution of the implanted cells. We propose that this platform is suitable for the successful implementation of human personalized autologous cell therapy for PD.

Comment in: J Clin Invest. 2020 Feb 3;130(2):601-603. (PMID: 31929191)

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