Open AccessProlonged 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
Author(s) -
Doi Daisuke,
Morizane Asuka,
Kikuchi Tetsuhiro,
Onoe Hirotaka,
Hayashi Takuya,
Kawasaki Toshiyuki,
Motono Makoto,
Sasai Yoshiki,
Saiki Hidemoto,
Gomi Masanori,
Yoshikawa Tatsuya,
Hayashi Hideki,
Shinoyama Mizuya,
Refaat Mohamed M.,
Suemori Hirofumi,
Miyamoto Susumu,
Takahashi Jun
Publication year - 2012
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1060
Subject(s) - glial cell line derived neurotrophic factor , biology , neurotrophic factors , dopaminergic , embryonic stem cell , neuroscience , primate , neural stem cell , cell culture , neurotrophin , stem cell , transplantation , parkinson's disease , disease , dopamine , microbiology and biotechnology , pathology , medicine , receptor , genetics , gene
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. S TEM C ELLS 2012;30:935–945