Prolonged maturation culture favors a reduction in the tumorigenicity and the dopaminergic function of human ESC-derived neural cells in a primate model of Parkinson's disease

Stem Cells
Daisuke DoiJun Takahashi

Abstract

For the safe clinical application of embryonic stem cells (ESCs) for neurological diseases, it is critical to evaluate the tumorigenicity and function of human ESC (hESC)-derived neural cells in primates. We have herein, for the first time, compared the growth and function of hESC-derived cells with different stages of neural differentiation implanted in the brains of primate models of Parkinson's disease. We herein show that residual undifferentiated cells expressing ESC markers present in the cell preparation can induce tumor formation in the monkey brain. In contrast, a cell preparation matured by 42-day culture with brain-derived neurotrophic factor/glial cell line-derived neurotrophic factor (BDNF/GDNF) treatment did not form tumors and survived as primarily dopaminergic (DA) neurons. In addition, the monkeys with such grafts showed behavioral improvement for at least 12 months. These results support the idea that hESCs, if appropriately matured, can serve as a source for DA neurons without forming any tumors in a primate brain.

References

Aug 1, 1992·Cancer·S ItoM S Edwards
Jan 1, 1986·Seminars in Nuclear Medicine·A AlaviM Reivich
Dec 1, 1985·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·C S Patlak, R G Blasberg
Mar 10, 2001·The New England Journal of Medicine·C R FreedS Fahn
Aug 23, 2001·Medical Image Analysis·M Jenkinson, S Smith
Oct 23, 2002·Human Brain Mapping·Stephen M Smith
Sep 4, 2003·Annals of Neurology·C Warren OlanowThomas B Freeman
Aug 18, 2004·Proceedings of the National Academy of Sciences of the United States of America·Anselme L PerrierLorenz Studer
Oct 27, 2004·NeuroImage·Stephen M SmithPaul M Matthews
Nov 13, 2004·Stem Cells·Xianmin ZengWilliam J Freed
Jan 5, 2005·The Journal of Clinical Investigation·Yasushi TakagiNobuo Hashimoto
Feb 18, 2005·Journal of Neurochemistry·Chang-Hwan ParkSang-Hun Lee
Jan 18, 2006·Progress in Neurobiology·Simone M SmitsMarten P Smidt
May 19, 2006·Biochemical and Biophysical Research Communications·Hirofumi SuemoriNorio Nakatsuji
Nov 23, 2006·Clinical Nuclear Medicine·Tsuneo SagaKaori Togashi
May 29, 2007·Nature Biotechnology·Kiichi WatanabeYoshiki Sasai
Jun 19, 2007·Nature Biotechnology·UNKNOWN International Stem Cell InitiativeWeidong Zhang
Jun 26, 2007·Proceedings of the National Academy of Sciences of the United States of America·D Eugene RedmondEvan Y Snyder
Jan 25, 2008·The European Journal of Neuroscience·Hideki HayashiJun Takahashi
Nov 11, 2008·Biochimica Et Biophysica Acta·Nicola Pavese, David J Brooks
May 22, 2010·Journal of Neuroscience Methods·Hidemoto SaikiJun Takahashi
Aug 28, 2010·Proceedings of the National Academy of Sciences of the United States of America·Gunnar HargusOle Isacson
May 17, 2011·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Tadayuki TakashimaYasuyoshi Watanabe

❮ Previous
Next ❯

Citations

Feb 26, 2013·Veterinary Research Communications·Yasutaka OdaYasuho Taura
Aug 8, 2013·Nature Medicine·Andrew S LeeJoseph C Wu
Mar 26, 2013·The Journal of Clinical Investigation·Lu CuiYing Jin
Mar 26, 2013·The Journal of Clinical Investigation·Hong OuyangKang Zhang
Oct 31, 2013·BioMed Research International·Nopporn Jongkamonwiwat, Parinya Noisa
Sep 23, 2014·Cell Reports·Elisa OricchioHans-Guido Wendel
Dec 3, 2014·Stem Cells and Development·Marcel M DaadiRobert E Lanford
Dec 3, 2013·Rinshō shinkeigaku = Clinical neurology·Jun Takahashi
Jan 21, 2014·Expert Opinion on Biological Therapy·Maria Sundberg, Ole Isacson
Nov 12, 2013·Expert Opinion on Biological Therapy·Takuya Hayashi, Hirotaka Onoe
Feb 3, 2016·Molecular Therapy. Nucleic Acids·Andriana G KotiniEirini P Papapetrou
Jan 23, 2016·Stem Cells International·Antonio Romito, Gilda Cobellis
Dec 17, 2015·Molecular Therapy. Nucleic Acids·Narumi UnoMitsuo Oshimura
Dec 15, 2015·Stem Cell Research & Therapy·Laia TolosaAnne Dubart-Kupperschmitt
Feb 26, 2016·Neurologia Medico-chirurgica·Asuka Morizane, Jun Takahashi
Dec 30, 2014·Movement Disorders : Official Journal of the Movement Disorder Society·Björn BrändlFranz-Josef Müller
Jul 25, 2015·Journal of Tissue Engineering and Regenerative Medicine·Masaaki IshikawaTakayuki Nakagawa
May 9, 2015·Biochimica Et Biophysica Acta·Mitsue KomatsuHiroo Iwata
Feb 2, 2013·Biological & Pharmaceutical Bulletin·Kaneyasu Nishimura, Jun Takahashi
Apr 29, 2015·Neurobiology of Disease·Lachlan H Thompson, Anders Björklund
Jun 3, 2015·Proceedings of the National Academy of Sciences of the United States of America·Eric B KeverneInna Tabansky
Jul 16, 2016·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Suzanne E PetersonJeanne F Loring
Mar 10, 2015·Neurologia Medico-chirurgica·Takao YasuharaIsao Date
Mar 1, 2013·Asia-Pacific Journal of Ophthalmology·Jiagang ZhaoKang Zhang
Jun 24, 2016·Stem Cells Translational Medicine·Gaia BarazzettiAlexandre Mauron
Apr 3, 2015·Stem Cells Translational Medicine·Erin M KroppRebekah L Gundry

❮ Previous
Next ❯

Related Concepts

Related Feeds

Allogenic & Autologous Therapies

Allogenic therapies are generated in large batches from unrelated donor tissues such as bone marrow. In contrast, autologous therapies are manufactures as a single lot from the patient being treated. Here is the latest research on allogenic and autologous therapies.

Astrocytes in Parkinson Disease

Parkinson's disease (PD) is a neurodegenerative disorder caused by the progressive loss of dopaminergic neurons. Some PD-genes may be associated with astrocyte dysfunction. Discover the latest research on astrocytes in Parkinson's disease here.