When adult stem cells won’t work

Stem cells have been, and will continue to be, all over the news. Cells that can make any part of the body could, if deployed properly, totally revolutionize medicine. Lose a kidney? Grow a new one. Brain cells dying off due to Parkinson’s or Alzheimer’s? Just let us inject some happy stem cells in there and, mirabile dictu, you’re back to normal! I truly am in awe of the possibilities. These potentially miraculous cells can be obtained from two sources: derived from embryos, either natural or cloned, or derived from adult tissues. Setting aside for the moment the ethical quandaries associated with making cells from human embryos or creating cloned embryos for the purpose of making stem cells, there are a couple of questions that must be answered before either embryonic or adult stem cells could ever be used in the clinic. On the embryonic side, how do you control the embryonic cells to produce exactly the tissue/organ you want–and not ones you don’t? And, on the adult side, can adult cells actually be made to produce any tissue or organ? Solve either or both of those issues, and I propose you have a remarkable new therapy.

It is the adult stem cell side of the aisle that I want to examine more carefully. In a talk given this afternoon, Dr. Doug Melton described for a few hundred of us his newest discoveries on the development of the pancreas. In people with Type I (insulin-dependent) diabetes, the cells in the pancreas (called beta cells) that produce the essential hormone insulin have been destroyed by their own bodies. Without insulin to regulate sugar metabolism (among its many actions), the symptoms of diabetes result. Dr. Melton’s two children both have this horrible, lifelong and life-threatening disease, and it is his life’s work to find a cure. He rightly concluded that the key to such a cure is understanding the development of the pancreas in order to eventually be able to produce new beta cells to replace the ones that were lost.

Immediately, this brings to mind stem cells as a potential mediator of such therapy. So, the questions above come back into play: how do you make embryonic stem cells into beta cells, or how do you find adult stem cells that could make beta cells? Toward the end of this essay, I’ll return to the ethical dimension of the former, but Dr. Melton has addressed the latter question in great detail. He and his laboratory studied genetically-modified mice in order to look for adult stem cells and the regenerative capacity of the pancreas. First, he established that the “progenitor cells”–that is, the cells that will eventually form the pancreas–are only produced in a small window of time during mouse embryonic development. Deprive the mouse of the ability to make those cells until later in development, and no pancreas will form. This implies, sadly, that there is no capacity to grow a pancreas beyond a certain time in development, and makes the existence of a pool of cells elsewhere in the body that could migrate and form a pancreas much less likely. Second, in a brilliantly simple model, he created a mouse with its beta cells, and nothing else, labelled from birth with a gene that can be easily measured because it reacts with a chemical to produce a deep blue color. He then monitored the mice over time. If there were adult stem cells capable of producing beta cells floating around, as the originally-labelled beta cells died off, then populations of colorless beta cells would result. That didn’t happen. The percentage of colored beta cells stayed constant over time, which meant that the beta cells maintained themselves by dividing, not through stem cells repopulating them. In a diabetic with all his beta cells gone, there is nothing left from which to regenerate anything. Through all his experiments, Dr. Melton has found absolutely no evidence whatsoever of a beta-cell stem cell in the adult mouse. None. Since you can’t prove a negative, there may still be an elusive stem cell out there somewhere, but it isn’t likely.

So what does this mean for folks with Type I diabetes? Sadly, it doesn’t look like adult stem cells will be able to regenerate their beta cells. If we are going to be able to regenerate them, it will have to be via transplantation (which is very promising, if limited in numbers and rather risky) or via those troublesome embryonic stem cells. It is plainly obvious from the state of embryonic stem cell research (ESCR) that their clinical use is years, if not decades, away, but it is never safe to bet against the ingenuity of science to find a way to do something. Dr. Melton is a passionate advocate for ESCR, but he brushes aside the ethical dilemmas that it presents. He makes the valid and disturbing point that we have millions of frozen embryos that will eventually be “discarded”–so why not use them for something good?

Why we shouldn’t use frozen embryos for such a purpose, since it’s still killing them, is a subject far beyond the scope of this essay. And, why we shouldn’t even be creating said embryos in the first place is something that should be self-evident to every Catholic, indeed every Christian. But, here in the year of Our Lord 2006, in the United States of America, we must face the truth that ESCR is here, and it is likely here to stay. That is, unless we start engaging the ethical issues involved on a broad scale. And even if we do, I wonder how successful we’ll be, seeing as how the other side, exemplified by the brilliant and passionate Dr. Doug Melton, can cart out millions of diabetics that their morally repugnant treatments may very well have the ability to save.

8 Responses to “When adult stem cells won’t work”

  1. 1 Fred K. April 19, 2006 at 10:19 am

    excellent questions. Very helpful, thanks.

  2. 2 Edmund C. April 19, 2006 at 10:31 am

    You’re welcome. I hope I didn’t get too technical–it’s hard to translate jargon well.

  3. 3 Bekah S. April 21, 2006 at 11:23 am

    I don’t know too much about the etiology of type 1 diabetes, but it sounds like it is an auto-immune type disease process. If so, then what happens if and when science discovers how to replace the cells? Is there already a solution to how to stop the body from attacking the cells again, or is this a question yet to be answered?

    These things are really interesting in the theoretical aspect, but positively horrifying in reality. Can you imagine being the parent of one of these children, having this therapy available that could be such a transformation in their lives, and have to deny it because of the methodologies used (never mind the ick factor of you child living off the death of another child!).

  4. 4 Edmund C. April 21, 2006 at 11:32 am

    That’s a great question, Bekah. There are ways, albeit not very good ones, to limit autoimmune processes. If you were to give a child a beta-cell transplant, which has been done, then to prevent destruction of those cells, you would have to do immunosuppressant therapy. That, of course, has its own very serious problems.

    But you’re right: that’s the real crux of the matter with Type I diabetes: that even if we were to have wonderful stem cell therapies, there isn’t much beyond suppressing the immune system that we can currently do to prevent those new cells from being destroyed.

    The guy who spoke brushed aside those concerns by saying something to the extent that stem cells would allow us eventually to understand immune system development as well, and provide us a way to turn off the system that is attacking the pancreatic islets in diabetics. It sounds like a panacea, doesn’t it?

  5. 5 Bekah S. April 21, 2006 at 2:57 pm

    It soujnds like this gentleman is grasping. I think his proximity to the fate of his children is blinding him to some extent. It was the same with Christopher Reeve, starting his foundation. They want so badly to cure these evils, but in the process are overlooking the evil they will do, or will allow, and so they choose not to think to long or hard about inherent problems in the therapy. Is it so much better to be consigned to a lifetime of immuno-suppressant therapy than insulin? Each have different risks/benefits, but in the long run, neither is truly healthy, are they? I think this gentleman has rose-colored glasses on.

  6. 6 dcs April 24, 2006 at 4:07 pm

    Is it so much better to be consigned to a lifetime of immuno-suppressant therapy than insulin?

    Immunosuppressant drugs have one advantage over insulin therapy — they can be administered orally. And insulin therapy is not the only issue with type I diabetes — diabetics are more at risk for blindness and kidney disease, among other things.

  7. 7 Edmund C. April 24, 2006 at 6:30 pm

    1. Inhaled insulin is already available and other new therapies are on the way, I’m sure. Never underestimate modern medicine.

    2. Immunosuppressants have the nasty side effect of suppressing the immune system, leading to opportunistic infections. Take, for example, one of my best friends who died 5 years after receiving a double lung transplant. The culprit was a viral infection that we would have been able to fight, but he was unable to on account of the drugs he had to take in order to keep his new lungs functioning. He had no choice in the matter, but diabetics do. The other risks of diabetes are certainly risks, but are lessened with good control of blood glucose. There is no simple solution, to be sure.

  8. 8 Bekah S. April 24, 2006 at 6:36 pm

    Ed, those are exactly the risks/benefits I was alluding to. A permanently suppressed immune system is not an easy situation to live. I’m not sure it is preferable to insulin dependent diabetes at this point in time.

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