"We are on the verge of a revolution in medicine: understanding, treating, and ultimately preventing the causes of degenerative aging. But medical revolutions only happen if we all stand up in support of funding and research. We did it for cancer. We're doing it for Alzheimer's. We can do it for aging - and create an era of longer, healthier lives!"

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  • Saturday, August 12, 2006

    What is the Significance of Recent Pluripotency Research?

    As I'm sure you're aware, given the widespread coverage, Japanese scientists may have found the keys to turning adult cells into pluripotent embryonic stem cells. Their initial tests are pretty convincing for a first run out of the gate:

    The researchers found that four of those factors, known as Oct3/4, Sox2, c-Myc, and Klf4, could lend differentiated fibroblast cells taken from embryonic or adult mice the pluripotency normally reserved for embryonic stem cells.

    They further reported that transplantation of the [induced pluripotent stem cells (iPS cells)] under the skin of mice resulted in tumors containing a variety of tissues representing the three primary types found in mammalian embryos. Those primary "germ layers" in embryos eventually give rise to all an animal's tissues and organs.

    Following injection into blastocysts, iPS cells also contributed to mouse embryonic development.

    Looking back a little, you might recall that Oct4 and Sox2 have already been used to prevent differentiation and keep embryonic stem cells pluripotent. Still, there is a certain amount of skepticism in the worldwide audience:

    Personally, I'm skeptical of the claim that reprogramming -- a long sought-after mechanism that would sidestep ethical issues surrounding embryonic cells -- requires such simple steps. Only further experiments will reveal whether four factors are all you need to dive into reprogramming with full gusto.

    And more:

    There are still a lot of unknowns: are the cells truly pluripotent, or do they have some limits on their development that have not yet been identified? What is the risk of abnormal development, mutation, or cancer with these cells? Do human cells use the same proteins? Can cells other than fibroblasts be induced into pluripotency with some or all of these factors? Nevertheless, I think this is an important finding and one that needs to be pursued aggressively.

    This attitude is justified, I think. If there is anything we all know for sure about biochemistry, it is that it is always more complex than you think. We sometimes get lucky, however, and find an important mechanism to be relatively simple - as was the case for progeria, for example. The odds are against that being true here, but you never know.

    It seems to me far more likely that iPS cells have been induced into a state strikingly similar to that of embryonic cells, but different in some important way that will come to light later. I'd be willing to lay odds on issues relating to development, cancer and aging, areas that overlap considerably in terms of cellular biochemistry and genetics. We shall see, and probably very soon. This is the sort of research that will inspire many groups to forge ahead at full steam.

    Randall Parker notes:

    If this approach works for humans as well then some day we'll be able to have pluripotent stem cells made from our own cells. Then those cells could be used to grow replacement parts such as internal organs or injected into joints to supply joint material to those suffering from arthritis.

    The researchers chose factors to introduce into adult cells by looking at which genes are turned on in embryonic stem cells. Note that advances in biotechnology in recent years have made it a lot easier to measure the levels of activity of many genes at once.

    ...

    The researchers still need to repeat this experiment with human cells to find out if this method will work for human cells as well. If they succeed then this discovery could open the gates for much higher levels of research funding for pluripotent stem cells.

    I predict that repeating - and expanding upon - the same work for human cells won't take very long. After that it'll be a longer and more interesting road, but I shouldn't need to elaborate greatly on the enormous benefits that can - and will - can be derived from a low-cost, readily available source of patient-matched pluripotent cells. This is a gateway into an era of expansive, impressively effective regenerative medicine for all forms of damaged tissue.

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