Transplantation Of Monkey Embryonic Stem Cells Reverses Parkinson Disease In Primates
Best of Luck,
SS
>>>>>>
bio.com
Transplantation Of Monkey Embryonic Stem Cells Reverses Parkinson Disease In Primates
01/04/05 -- The replenishment of missing neurons in the brain as a treatment for Parkinson disease reached the stage of human trials over 15 years ago, however the field is still in its infancy. Researchers from Kyoto University have now shown that dopamine-producing neurons (DA neurons) generated from monkey embryonic stem cells and transplanted into areas of the brain where these neurons have degenerated in a monkey model of Parkinson disease, can reverse parkinsonism. Their results appear in the January 3 issue of the Journal of Clinical Investigation.
Studies of animal models of Parkinson disease as well as clinical investigations, have shown that transplantation of fetal DA neurons can relieve the symptoms this disease. However the technical and ethical difficulties in obtaining sufficient and appropriate donor fetal brain tissue have limited the application of this therapy.
These researchers previously demonstrated that mouse embryonic stem cells can differentiate into neurons when cultured under specific conditions. These same culture conditions, technically simple and efficient, were recently applied to primate embryonic stem cells and resulted in the generation of large numbers of DA neurons. In their current JCI study, Jun Takahashi and colleagues generated neurons from monkey embryonic stem cells and exposed these cells to FGF20, a growth factor that is produced exclusively in the area of the brain affected by Parkinson disease and is reported to have a protective effect on DA neurons. The authors observed increased DA neuron development and subsequently transplanted these neurons into monkeys treated with an agent called MPTP, which is considered a primate model for Parkinson disease. These transplanted cells were able to function as DA neurons and diminished Parkinsonian symptoms.
In an accompanying commentary, J. William Langston from the Parkinson's Institute, California, describes this study as a milestone in the development of stem cell technology but cautions that while the observations are encouraging, the reported number of surviving DA neurons was very low, only 1--3% of the cells surviving, well below the estimated number of DA neurons that survive after fetal cell transplants (approximately 10%). While this may be a difference observed between transplantation in monkeys and humans, Langston stresses that it may be necessary for far more DA neurons to survive and for that survival to be long lasting in order to render this approach as a useful therapy in humans.
Langston highlights that "clearly the study reported here will advance research aimed at validating the use of stem cells to treat neurodegenerative disease" and this is most welcome particularly as investigators face yet another presidential moratorium endeavoring to limit the number of human stem cell lines that can be used for future research and treatment.
Source: Journal of Clinical Investigation
>>>>
ncbi.nlm.nih.gov
1: J Clin Invest. 2005 Jan 3;115(1):102-109. Related Articles, Links
Dopaminergic neurons generated from monkey embryonic stem cells function in a Parkinson primate model.
Takagi Y, Takahashi J, Saiki H, Morizane A, Hayashi T, Kishi Y, Fukuda H, Okamoto Y, Koyanagi M, Ideguchi M, Hayashi H, Imazato T, Kawasaki H, Suemori H, Omachi S, Iida H, Itoh N, Nakatsuji N, Sasai Y, Hashimoto N.
Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan. Organogenesis and Neurogenesis Group, Center for Developmental Biology, RIKEN, Kobe, Japan. Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan. Department of Experimental Radiology, National Cardiovascular Center, Osaka, Japan. Department of Medical Embryology and Neurobiology and Department of Development and Differentiation, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan. Department of Genetic Biochemistry, Kyoto University Graduate School of Pharmaceutical Sciences, Kyoto, Japan.
Parkinson disease (PD) is a neurodegenerative disorder characterized by loss of midbrain dopaminergic (DA) neurons. ES cells are currently the most promising donor cell source for cell-replacement therapy in PD. We previously described a strong neuralizing activity present on the surface of stromal cells, named stromal cell-derived inducing activity (SDIA). In this study, we generated neurospheres composed of neural progenitors from monkey ES cells, which are capable of producing large numbers of DA neurons. We demonstrated that FGF20, preferentially expressed in the substantia nigra, acts synergistically with FGF2 to increase the number of DA neurons in ES cell-derived neurospheres. We also analyzed the effect of transplantation of DA neurons generated from monkey ES cells into 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated (MPTP-treated) monkeys, a primate model for PD. Behavioral studies and functional imaging revealed that the transplanted cells functioned as DA neurons and attenuated MPTP-induced neurological symptoms.
PMID: 15630449 [PubMed - as supplied by publisher]
Article...
jci.org
Commentary...
jci.org
|
