24 January 2012
Induced pluripotent stem cells (iPSC) are a promising avenue for cell replacement therapy in neurologic diseases. For example, mouse and human iPSCs have been used to generate dopaminergic (DA) neurons that improve symptoms in rat Parkinson’s disease models. Reporting in the current issue of the Journal of Parkinson’s Disease, a group of scientists from Japan evaluated the growth, differentiation, and function of human-derived iPSC-derived neural progenitor cells (NPCs) in a primate model, elucidating their therapeutic potential.
“We developed a series of methods to induce human iPSCs to become NPCs, using a feeder-free culture method, and grafted NPCs at different stages of differentiation into the brain of a monkey PD model,” explains lead investigator Jun Takahashi, MD, PhD, of Kyoto University. “We developed a method to evaluate the growth and DA activity of the grafts using magnetic resonance imaging (MRI), positron emission tomography (PET), immunocytochemistry, and behavioral analyses, all of which will be useful in preclinical research.”
Investigators grafted human iPSCs into the brains of laboratory mice and a monkey treated with MPTP, a neurotoxin that causes Parkinson’s symptoms. They found that iPSCs incubated in feeder-free culture generated functional midbrain DA neurons. “In previous studies, midbrain DA neurons were induced from human iPSCs, but the method required coculture with stromal mouse feeder cells or Matrigel,” noted Dr. Takahashi. “Our feeder-free method would be more suitable for clinical use.”
Pre-treatment with growth factors was required to promote the maturation of functional DA neurons in vivo. MRI and PET imaging allowed real-time monitoring of in vivo cell proliferation and activity. The study demonstrates that dopamine synthesis, transport, and reuptake reflect DA activity in the grafted NPCs, an approach that can also be used in human patients.
“Our results contribute to the evaluation of the survival, differentiation, and function of human iPSC-derived neuronal cells in a primate PD model. Although we have to perform additional preclinical studies using more primate models before clinical application, we believe our findings contribute as the first step for developing a strategy for cell replacement therapy in Parkinson’s disease,” Dr. Takahashi concludes.
The article is “Survial of Human Induced Pluripotent Stem Cell-Derived Midbrain Dopaminergic Neurons into the Brain of a Primate Model of Parkinson’s Disease,” by T. Kikuchi, A. Morizane, D. Doi, H. Onoe, T. Hayashi, T. Kawasaki, H. Saiki, S. Miyamoto, and J. Takahashi. Journal of Parkinson’s Disease. 1(2011) 395-412. DOI: 10.3233/JPD-2011-11070. Published by IOS Press.
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NOTES FOR EDITORS
Full text of the article is available to credentialed journalists. Contact Daphne Watrin, IOS Press, +31 20 688 3355, d.watrin@iospress.nl. Journalists wishing to interview the authors should contact Brian Browne, Communications and Outreach Manager, Banner Research Institute, at 623-875-6536 or Brian.Browne@bannerhealth.com.
ABOUT THE JOURNAL OF PARKINSON’S DISEASE (JPD)
Launched in June 2011 the Journal of Parkinson’s Disease is dedicated to providing an open forum for original research in basic science, translational research and clinical medicine that will expedite our fundamental understanding and improve treatment of Parkinson’s disease. The journal is international and multidisciplinary and aims to promote progress in the epidemiology, etiology, genetics, molecular correlates, pathogenesis, pharmacology, psychology, diagnosis and treatment of Parkinson’s disease. It publishes research reports, reviews, short communications, and letters-to-the-editor and offers very rapid publication and an affordable open access option.
ABOUT IOS PRESS
Commencing its publishing activities in 1987, IOS Press (www.iospress.nl) serves the information needs of scientific and medical communities worldwide. IOS Press now (co-)publishes over 100 international journals and about 130 book titles each year on subjects ranging from computer sciences and mathematics to medicine and the natural sciences.
IOS Press continues its rapid growth, embracing new technologies for the timely dissemination of information. All journals are available electronically and an e-book platform was launched in 2005.
Headquartered in Amsterdam with satellite offices in the USA, Germany, India and China, IOS Press has established several strategic co-publishing initiatives. Notable acquisitions included Delft University Press in 2005 and Millpress Science Publishers in 2008.
