Cardiac Stem Cell Transplant

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Researchers from Osaka University in Japan have announced a success transplant of cardiac stem cells into a patient as part of a clinical trial. While any stem cell advance is potentially exciting, this is also a good opportunity to put this research into perspective.

Like any new medical technology, there is a great deal of hype and hope surrounding the potential of stem cells in medicine. This has lead, unfortunately, to an explosion of fraudulent stem cells clinics, starting in China but then spreading throughout the word. These clinics make promises they can’t keep, exploiting early hype around this new technology.

What is Stem Cell Therapy

Stem cells refers to cells in the body that are able to develop into other specific cell types. This is a normal part of biology. Bone marrow cells, for example, are blood stem cells that can turn into red and white blood cells. “Multipotent” refers to stem cells that can turn into multiple, but not all, different cell types. “Pluripotent” refers to stem cells that can mature into every different cell type in the body, but not placental cells. “Totipotent” refers to embryonic stem cells that can turn into any cell type, including the placenta.

Over the last couple of decades the basic technology of stem cells has increased dramatically, perhaps even exceeding expectations. Scientists are now able to take skin cells, induce them to be pluripotent stem cells, and then coax them into maturing into various different mature cell types – heart, liver, brain, etc. This success has contributed, of course, to the stem cell hype.

But as we always like to point out here at SBM – basic science discoveries and advancements do not always translate into clinical applications. As stem cell basic science is more advanced than anticipated, stem cell clinical applications have proven frustrating. There are two main types of hurdles that researchers are facing – getting the stem cells to do what they want, and keeping them from doing what they don’t want. In the latter category the big problem is that stem cell preparations may contain cancer cells.

Essentially, there is a reason evolution has not equipped us to be flush with stem cells, to regenerate any disease, damage, or degeneration. It’s because of the cancer potential of stem cells, so we have no more than we absolutely need. Transplanting a bolus of stem cells into the body has proven to be a tumor risk, and perhaps an insurmountable one (at least for now).

But also it is extremely challenging, once the stem cells are made, to have them take up shop in the body, make meaningful anatomical connections, to contribute meaningfully to function, and to survive long enough to make the whole thing worth it. The desire to simply be injected with a cocktail of stem cells and supporting factors, and then regenerate your tissues and organs, remains science fiction, as least for now.

In fact clinical translation has been so difficult that researchers at the more pessimistic end of the spectrum worry that such treatments may never pan out. They warn that even saying that stem cell treatments are 20-30 years off is misleading hype. This may prove largely to be a dead end. I am cautious but less pessimistic. Rather, I think it’s likely researchers will pick some low-hanging fruit, and we will have another option for some conditions, but it won’t be the revolution many hoped.

The Current Research

With this as background, what did the current researchers actually do? This is part of a clinical trial, the first of ten planned patients suffering from ischemic cardiomyopathy. These are patients who have lost heart tissue to myocardial infarction, and so their heart muscle is weakened and not able to strongly enough pump blood. The ultimate treatment for these patients is cardiac transplant. While this works, there are a limited number of donor hearts available, and getting such a transplant means a lifetime of anti-rejection drugs. So any new treatment that can spare some patients from needing a transplant is hugely beneficial.

What the researchers did was take the patient’s cells and induce them to become pluripotent. They then coaxed them to become cardiac muscle tissue and created a thin layer (0.1 mm thick) of the cells onto a degradable sheet. The announcement is that they just transplanted the first such sheets into a patient, and the operation itself was an apparent success.

The hope is that these transplanted cells will secrete proteins which act as hormonal signals to induce blood vessel formation. The increased blood supply will then improve cardiac function, perhaps eliminating the need for a transplant. So in essence, the stem cells are being used as a drug delivery system.

This is a good idea, one I have been hearing about for years (mostly in neurological contexts because of my speciality). This gets around the problem of having the stem cells take on the desired function. All they have to do is sit there and be alive, undergoing metabolism and producing the stuff that their kind of cells normally produces. Also, such cells can be genetically tweaked to produce a potentially larger repertoire of biological products.

These cells can function as drug delivery systems, or as support cells – keeping the existing functional cells alive and in good shape longer. I first heard about this concept about 15 years ago, so you can see how long it takes to research even the most watered down application for stem cells. This is not to downplay the this potential application. It has great promise, and should be judged for what it can do, not for what it isn’t designed to do.

But this does put stem cell research into perspective. When I first read this news item I was hoping the transplanted heart cells were functioning as heart muscle, which is not implausible as heart cells will spontaneously synchronize with their neighbors and start beating away. I still think this is one of the more likely functional applications for stem cells in the future. But no – this was just using the stem cells as a drug delivery system. I am still recalibrating my expectations for stem cell research.

I think it’s clear now that the big hopes for stem cells are farther off than most hoped, and certainly than the impression given to the public. It is now so uncertain and far off that the technology may be eclipsed by currently unknown technology. In effect, we cannot make reliable predictions.  There is also still the big problem of preventing tumors from stem cells (a non-trivial problem). But at the same time the more realistic applications are moving ahead, if slowly. This potential should not be ignored or downplayed simply because of the less realistic hype.

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