I spent a few years anxiously waiting while scientists chased rainbows before I turned my attention back to just trying to find enjoyment in life. This news thrills me though. These scientists are colleagues of Dr. Yamanaka who got the Nobel prize for work in IBS and now they turn their attention to dopamine producing cells! This is the best article I could find in English so far. Will keep looking. See following post for link.

Sounds good. Your link didn't get posted however.

http://news.google.com/news/url?sa=t...sease-in-works

Kyoto University Hospital is expected to use the new technology to transplant nerve cells produced from iPS cells of Parkinson’s disease patients to the patients as early as 2016.

“If all goes as planned, we want to complete studies on the technology’s safety and efficiency this year and apply for clinical research to the health ministry in fiscal 2014,” said Jun Takahashi, a professor at Kyoto University’s Center for iPS Cell Research and Application and a member of the research team.

Kyoto University Hospital will prepare to set up a third-party committee to examine the research plan in June at the earliest.

Under the plan, tens of millions of nerve cells will be transplanted to each of the six patients of non-hereditary Parkinson’s disease. It will require nine months to produce nerve cells and make other preparations.

The finding will be published in Stem Cell Reports, a U.S. scientific journal, on March 7.

http://www.cira.kyoto-u.ac.jp/e/pres...07-084337.html

March 07, 2014
Establishment of protocol brings the clinical application of iPS cell transplantation for Parkinson's disease a step closer

A CiRA research team has developed a method of producing human iPS cell-derived dopaminergic neural progenitor cells that brings closer the prospect of clinical application. The team, which carried out joint research with Osaka University and KAN Research Institute, Inc., included researcher Daisuke Doi and Professor Jun Takahashi, both members of CiRA's Department of Clinical Application. The findings of their research were published in the U.S. scientific journal Stem Cell Reports on March 6, 2014 at noon (U.S. Eastern time).

Parkinson's disease is an intractable and progressive disease of the nervous system in which depletion of the dopaminergic neurons, which project from the midbrain substantia nigra into the corpum striatum, leads to reduced levels of dopamine in the brain, causing limb tremor and stiffness and resulting in reduced mobility and other symptoms. The therapies applied up till now, based on drug treatment and electrode therapy, may relieve symptoms, but have proved unable to halt the depletion of dopaminergic neurons. The result is that it becomes increasingly difficult to lessen symptoms as the pathology progresses. Hopes have therefore become focused on a therapy with the more radical approach of replacing the lost dopaminergic neurons through cell transplantation, thereby promoting the formation of new neural pathways to restore brain function. Human iPS cells are looked to as one potential source of the transplant cells.

Previous reports had indicated that transplantation of dopaminergic neurons induced from human iPS cells can improve motor function in a rat model of Parkinson's disease. However, it was recognized that clinical application would require development of a large-scale culture method and the exclusion of cells that carry the risk of tumor formation. One of the characteristics of iPS cells is their high proliferative ability. The converse of this is that, when implanted in patients as a graft, there is a risk that a residue of cells with proliferative potential may cause tumors to form. Takahashi and his team had previously carried out experiments in which human ES cell-derived neurons were transplanted into primates. Their findings showed that large numbers of the ES cell-derived dopaminergic neurons became viable in the brain and produced improvement of neurological symptoms (Doi et al., Stem Cells, 2012). Although no surviving residue of human ES cells was observed in the study, immature neurons were found to have displayed slight proliferation. The other disadvantage of this earlier method was that the graft contained a mixture of various cell types, with a relatively low proportion of the dopaminergic neurons required for Parkinson's disease treatment.

Clinical application therefore demanded that cells with proliferative potential be excluded and the proportion of dopaminergic neurons increased. It also required a large number of cells, from 10 million to 100 million or more, which had to be cultured under conditions free of animal-derived substances. A new culture method therefore had to be developed. To resolve these issues, the team experimented with modified methods of inducing cell differentiation and the use of cell sorting by FACS (fluorescence-activated cell sorting) to screen the dopaminergic neural progenitor cells.

Under the newly developed method, which involves adhesion culture using synthetic laminin, recombinant laminin 511E8 fragments developed by the Osaka University Institute for Protein Research, cell culture at more than 20 times the previous concentration became possible, while screening and concentration of the dopaminergic neural progenitor cells was made possible by the use of cell sorting based on an anti-CORIN antibody developed by KAN Research Institute, Inc. When cells generated using this method were transplanted into the brain of a rat model of Parkinson's disease, motor function was improved without tumor formation, indicating that this is a safer and more efficient method of dopaminergic neuron transplantation.

In iPS cell-based cell transplantation therapy, the risk of tumors arising in the graft from residues of proliferative cells has been a problem. In the present study, cell sorting using the anti-CORIN antibodies allowed the researchers to exclude cells that presented a tumor risk and also increased the proportion of midbrain dopaminergic neurons in the graft, enabling safer and more efficient transplantation. Previously, iPS cell culture and neural induction required the use of mouse-derived feeder cells. Neural induction could be achieved using suspension cell culture, but this method was not suitable for large-scale culture. The use of the recombinant laminin 511E8 fragments in the present study, in place of mouse-derived feeder cells, has made possible the large-scale culture of cells that are suitable for clinical use. These improvements are significant for having allowed the establishment of a protocol that brings closer the prospect of clinical application.

In the present study, the rat model was observed for four months after transplantation before the protocol was established. Before commencing clinical application, the researchers plan to carry out transplantation to a primate model of cells prepared using this protocol, followed by a longer observation period to confirm safety and efficacy in greater detail. Meanwhile, it has been demonstrated that autologous transplantation of iPS cells_derived functional cells is possible, and investigation is now needed to test whether dopaminergic cells induced using iPS cells generated from Parkinson's disease patients can function within the brain. Once these issues have been dealt with, researchers will be in a position to proceed toward clinical application.

SCR_JT_Fig3A.png
Figure: Brain sections immunostained with dopaminergic cell marker (TH)
Grafts made with sorted cells contained numerous viable dopaminergic neurons with neurites extending into the surrounding brain tissue. CORIN+: with cell sorting; Unsorted: no cell sorting.

<Journal Information>
Title of Paper
"Isolation of Human Induced Pluripotent Stem Cell-derived Dopaminergic Progenitors by Cell Sorting for Successful Transplantation"

Authors
Daisuke Doi1, Bumpei Samata1, Mitsuko Katsukawa1, Tetsuhiro Kikuchi1, Asuka Morizane1, Yuichi Ono2, Kiyotoshi Sekiguchi3, Masato Nakagawa1, Malin Parmar4, and Jun Takahashi1, 5, 6

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If you are interested in better understanding Yamanaka's Nobel prize iPS work which laid the groundwork for the dopamine producing cell research at Takahashi lab, watch these next week (in English). Note need to change from JST to your local time. Fascinating.

from cira facebook page
NHK World will rerun three programs featuring iPS cells in this March.
You can watch them at http://www3.nhk.or.jp/nhkworld/ as scheduled below.

■Part 1
The iPS Cell Revolution: A Discussion with Dr. Yamanaka

March 11(Tues) at 23:30 JST
March 12(Wed) at 3:30 7:30 11:30 15:30 19:30 JST (Originally broadcasted on May 25, 2012)

■Part 2
The Future of iPS Cells: ISSCR in Yokohama

March 18(Tues) at 23:30 JST
March 19(Wed) at 3:30 7:30 11:30 15:30 19:30 JST (Originally broadcasted on July 13, 2012)

■Part 3
The Nobel Prize: Shinya Yamanaka
The Genealogy of iPS Cells

March 25(Tues) at 23:30 JST
March 26(Wed) at 3:30 7:30 11:30 15:30 19:30 JST (Originally broadcasted on December 7, 2012)

Similar work being done at Scripps:

http://www.summit4stemcell.com/
http://www.scripps.edu/loring/