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Thread: Embryonic versus Adult Stem Cells and other spinal cord injury therapies

  1. #31
    thank you for the such a quick reply....what is your opinion on the geron's study that i understand is suspended at the moment? have you been a part of it? where and when do you plan to publish your latest work on the umbilical cord cells and is it possible to know more about it at least in general.... thank you,,

  2. #32
    Quote Originally Posted by asoka View Post
    thank you for the such a quick reply....what is your opinion on the geron's study that i understand is suspended at the moment? have you been a part of it? where and when do you plan to publish your latest work on the umbilical cord cells and is it possible to know more about it at least in general.... thank you,,
    Our work has been focused on developing the GMP procedures that would allow the treatment to get into trial. Many laboratories have studied and reported on the beneficial effects of umbilical cord blood mononuclear cells transplanted to the spinal cord. Likewise, many laboratories have studied the effects of lithium on brain and spinal cord. We studied the effects of lithium on umblical cord blood cells and release of neurotrophins by the cells.

    I have posted extensively about all the work here. If you just look for posts by me (Wise Young) on this forum, for example, about lithium or umbilical cord blood, you will find many dozens if not hundreds of posts that I have done.

    Wise.

  3. #33
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    I guess this means I won't be going to the X-Cell Center anytime soon.

  4. #34
    Senior Member lunasicc42's Avatar
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    Quote Originally Posted by lepups3 View Post
    I guess this means I won't be going to the X-Cell Center anytime soon.

    I hope you don't
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  5. #35
    Dr. Wise

    I was thinking about going ahead and get the bone marrow stem cell transplantation. Which hopital you recomend from x-cell in German or Dr. Alok Sharma in India? And how do I check the accreditation for this hospitals?

  6. #36
    Quote Originally Posted by that dude View Post
    Dr. Wise

    I was thinking about going ahead and get the bone marrow stem cell transplantation. Which hopital you recomend from x-cell in German or Dr. Alok Sharma in India? And how do I check the accreditation for this hospitals?

    dude,

    X-cell provides the cells but I don't know who and how the cells will be transplanted. I know several people who have had the procedure without benefit.

    Regarding Alok Sharma, I have visited him and talked to several of his patients. It seems to have helped some of his patients but didn't do much for others. It is not clear what patient will benefit from the therapy.

    Dr. Sharma works at one of the major public hospitals in Bombay. I don't think that acreditation of hospitals mean all that much in India. While I think that he is a good doctor, I am not yet convinced that the treatment is restoring function in chronic spinal cord injury.

    Wise.

  7. #37
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    well for one, there are no such thing as embryonic stem cell therapies, at least for humans. Rats enjoy these benefits, go back to running on their wheel, and have mind-blowing sex.

  8. #38
    Quote Originally Posted by cdurfee99 View Post
    well for one, there are no such thing as embryonic stem cell therapies, at least for humans. Rats enjoy these benefits, go back to running on their wheel, and have mind-blowing sex.
    cdurfee,

    The Geron trial tells us how difficult the task will be for getting the first embryonic stem cell therapy into clinical trial. The IND (Investigational New Drug/Device) application for the clinical trial costed $45 million and had 22,000 pages of safety and other data. It has also taken about ten years to gather all the data.

    Despite all the expense and time, Geron has not yet solved the two major barriers to using the cells in people.
    • The first is immune-compatibility of the cells. The cells of course come form one cell line. The company is assuming that embryonic stem cells or the cells derived from the cell line will not be rejected by the recipients. This was of course reason why Woo-Suk Hwang and so many others tried hard to clone and produce immune-compatible stem cells. The company will be using immunosuppression in the trial, hoping that the time and dose that they chose would be sufficient to keep the cells from being rejected.
    • The second is that the cells will not form tumors or produce inappropriate cells in the spinal cord. To overcome this, Geron had chosen a cell line that has been differentiated to the oligodendroglia and showed no sign dedifferentiating in culture. But, the last animal test that they sent to the FDA suggest that the cells produced microcysts in the spinal cord. To solve this problem, the company found a marker for the cells that produces these cysts and will be selecting out cells that express these markers.

    I am very appreciative of the herculean efforts that Geron has been making on behalf of the spinal cord injury community. Most other companies, faced with such obstacles, would have given up. Most companies would have given up. Geron stayed the course through thick and thin. We have learned a lot about the FDA and its likely approach towards embryonic stem cells. Their first concern is safety of the patients.

    Wise.

  9. #39
    Dr Young, With the announcement from the Salk Institute concerning the ability to now get embryonic like cells from umbilical cord blood...how will this discovery affect stemcyte and possibly the future therapies devised for SCI using UCB cells?

  10. #40
    Quote Originally Posted by GRAMMY View Post
    Dr Young, With the announcement from the Salk Institute concerning the ability to now get embryonic like cells from umbilical cord blood...how will this discovery affect stemcyte and possibly the future therapies devised for SCI using UCB cells?
    It is a very important development (Source). Please understand, however, that they are not the first ones to do this. Two other groups have reported successful induction of umbilical cord blood into pluripotent stem cells. The Salk Institute is the third.

    http://www.salk.edu/news/pressreleas...p?press_id=380
    "Patient-specific iPS lines have been advocated as a theoretically ideal clinical option to regenerate tissue but from a practical and cost-benefit aspect, this approach may not be feasible," says Izpisúa Belmonte. He hopes that the "large scale production and banking of cord blood-derived iPS lines in a publically available network could be a viable alternative for future clinical applications."

    With this in mind, Belmonte and his colleagues set out to transform hematopoietic stem cells isolated from cord blood into iPS cells. They not only successfully converted them using only two out of the four most commonly used factors—OCT4 and SOX2—but also in less time than any other previously published methodology require. No matter, whether the researchers started with freshly collected cord blood or previously frozen samples, the resulting iPS cells were indistinguishable from human embryonic stem cells.

    "The population of cord blood cells used for reprogramming express reprogramming/stem cell factors at higher levels than those found in other adult somatic cells, which could explain why cord blood cells can be reprogrammed with less factors and in less time," says Izpisúa Belmonte. "It's almost like they are already half-way there."

    In addition, the cord blood-derived iPS cells, CBiPS cells for short, passed all standard tests for pluripotency: The gave rise to stem cell tumors known as teratomas and differentiated into derivatives of the three embryonic tissue layers, including rhythmically beating cardiomyocytes and dopamine-producing neurons.

    Izpisúa Belmonte's next goal is to convince cord blood cells to turn back time using methods that are considered safe for clinical applications in humans. The original protocols for producing iPS cells—including the one used by Belmonte and his team—rely on the integration of foreign "reprogramming" genes into the host-cell genome, a process associated with risks including mutation and the development of cancers after iPS-cell transplantation, limiting their therapeutic value.

    But researchers are hard at work to develop alternative methods that allow them to reprogram cells without leaving any genetic traces, such as simply exposing differentiated cells to small molecules. "Several studies have already shown that this could be possible," says Izpisúa Belmonte. "If we can show they also work for cord blood cells, this certainly could be a step forward towards the clinical application of iPS cells. We should focus our efforts on this particular cell source, CBiPS cells, at least in the near future."
    Let me review the history of IPS cells and discuss why this work is important. In 2006, Yamanaka, et al. at Kyoto University found that insertion of four genes into fibroblasts (skin cells) can convert the fibroblasts into pluripotent embryonic stem cell like cells. The cells not only behave like embryonic stem cells but several groups reported that mouse fibroblasts induced with these four genes can produce other mice. By 2007, both Yamanaka's group and Thomson's group in Wisconsin showed that the same could be done with human cells.

    Everybody was very excited because this suggests that pluripotent stem cells can be cloned from skin cells of an individual, giving rise to the vision of individualized personal stem cell lines for everybody. But, a little bit of arithmetic tells you that this is not going to be feasible economically. Inducing IPS is still a fairly inefficient process. Even with the most efficient viral transduction methods, probably less than 10 out of a million tranfected cells turned out to be pluripotent. So, if one starts out with several million cells, one can isolate a small number of colonies of cells. If one puts in a fluorescent marker, these colonies can be readily identified, isolated and tested for pluripotency, genetic integrity, and other qualities. Such testing may take many weeks or months, because human cells grow relatively slowly.

    At the present, even the most efficient laboratory take 3 months and probably over $100,000 to create a well-characterized IPS cell. Let us suppose that we were to create an industry that is capable to making 1000 IPS cell lines per day. This is an enormous number, by the way, but let us assume that such an industry exists and that it costs $100,000 to make and validate each cell line for treatment. This industry would be able to make at most 365,000 cell lines per year. In order to treat 1% of the U.S. population by 2020, this industry would require 10 years and $365 billion to create 3.65 millon IPS cell lines. To treat 1% of the world's population require over 100 years and over $4 trillion. So, IPS cells will not be a treatment for common people.

    The only way around this is to create a library of IPS cells that can be HLA-matched to potential recipients. We know that a library of about 30,000 umbilical cord blood cells can be matched 4:6 HLA and engraft in 80% of the population of the United States. The same industry mentioned above should be able to create 30,000 IPS cell lines in a month for about $30 billion, well within the realms of possibility. By the way, while this approach would circumvent the need to use embryonic stem cells (ESC) for therapeutic purposes, it would not eliminate the need for access to embryonic stem cell lines to compare IPS and ESC cells.

    I was attending the New York Stem Cell Foundation meeting and was impressed by Kevin Egan (a Harvard stem cell scientist who is the chief scientific officer for the NYSCF) saying that we continue to need to study embryonic stem cells because they are the real thing and IPS cells are just facsimiles of ESC. We know so little about ESC and will need to compare the two and figure out both similarities and differences. Regarding application to humans, several hurdles still must be overcome before IPS cells can be applied to humans. First, the tendency of the cells to become teratomas (pluripotent stem cell tumors) must be controlled. IPS cells are even more likely than ESC cells to become teratomas, because the genes may not be as well controlled. Second, efficient non-viral means of inducing the cells must be developed. At the present, most laboratories still use viruses.

    The exciting thing about this discovery from the Salk Institute is that they need to use only two of the four genes to induce umbilical cord blood cells. This could have been predicted because many studies indicate that a particularly type of umbilical cord blood cells that are positive for CD133 also express SOX2 and OCT3/4, two of the pluripotency genes used by Yamanaka and Thomson (Source).

    Several years from now, historians will all be looking back at this time, puzzling what the fuss was all about regarding embryonic stem cells. Even back in 2001, when Bush restricted the research, many scientists (including myself) had predicted that we would be able to create IPS cells. After all, a stem cell is only a cell that is expressing certain genes. Once those genes were found, IPS cells could be created from any cell. It turned out to be simpler than any of us could have imagined. At the same time, the simplicity is misleading and it is probably more complicated that any of use can imagine.

    I predict that Yamanaka and Thomson will get the Nobel Prize for this work.

    Wise.
    Last edited by Wise Young; 12-25-2009 at 05:25 PM.

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