Nov 15 2011

Stem Cells for Heart Function

Stem Cells have been one of the biggest science news stories of the decade, for many reasons. There is the controversy surrounding stem cell research, sparked by President Bush’s ban on federal funding for such research outside of existing cell lines. This controversy has quietly faded away as advances have rendered the core issue mostly obsolete – embryonic stem cells from aborted fetal tissue are still a great source of potent stem cells, but researchers have figured out several methods for deriving stem cells from adult tissue, and even tweaking them so that they have similar potential to embryonic-derived  cells.

There is also the scandal surrounding the creation of many stem cell clinics around the world, most notably in China, but they have cropped up anywhere where regulations are lax. These clinics are mostly peddling hype and false promises, preying on desperate patients with very premature offers of stem cell cures.

Meanwhile real research into stem cells continues, and has the potential to usher in a new age of medicine. Stem cell technology is potentially a game-changer for many serious illnesses, but this technology will take years to develop to the point that stem cell treatment will become routine. (I am not talking about old treatments like bone marrow transplant, which are technically stem cell treatments, but rather fixing or replacing tissue and organs with engineered stem cells.) We are on the brink of picking the lowest hanging fruit on the stem cell tree, and a new study published in the Lancet takes us one big step closer.

Researchers removed a small piece of heart tissue from patients who were undergoing bypass surgery. These patients all have heart failure secondary to ischemic disease – heart attacks. They used this small piece of heart tissue to culture cardiac stem cells.

1 million autologous CSCs were administered by intracoronary infusion at a mean of 113 days (SE 4) after surgery; controls were not given any treatment. Although the study was open label, the echocardiographic analyses were masked to group assignment. The primary endpoint was short-term safety of CSCs and the secondary endpoint was efficacy.

In the patients who received the autologous stem cells their left ventricular ejection fraction, a measure of heart contractions, increased from 30.3% to 38.5% at 4 months after infusion. The control group experienced no increase in ejection fraction. Normal ejection fraction is 50-70%, so their heart function is still far from normal. But an increase of 8% is physiologically significant, and will likely improve the quality of life for these patients. This is also an ongoing study, so these patients will be followed to see if the results last, and perhaps even improve.

Of course this is a preliminary open-label study (a phase I trial mostly about the safety of the procedure in humans, but with some measure of efficacy as well). Further study is required, but these results are very encouraging. I also think this is the likely easiest application of this type of stem cell therapy. Heart cells automatically sync up with each other (beat in unison with the surrounding heart cells), and as long as the heart structure is intact adding more heart muscle cells should improve the strength of the contraction. It’s a pretty straightforward application.

We are still likely several years away from this therapy being approved and adopted as standard procedure, but I see no major hurdles at this point. Also, researchers are working on ways to develop cardiac stem cells from other tissue sources, like bone marrow, so they will not have to be harvested during surgery. Such a therapy has the potential of improving quality of life, extending life expectancy, and perhaps even avoiding cardiac transplant for many heart failure patients.

Researchers generally have a low threshold for concluding that their topic of study “deserves further research.” In this case, however, I complete agree that this treatment should be a high research priority.

Incidentally, another stem cell application that I feel is likely to be low-hanging fruit is the use of neuronal stem cells for stroke and injury recovery. The brain already recruits native neuronal stem cells to repair damage, and injecting additional stem cells will provide more raw material for repair – so they will easily plug into an existing repair mechanism. The major hurdle with this application is keeping the stem cells from developing into a tumor. I do not know how much of a problem this will be. If it turns out not to be a serious problem then this therapy could be available within 10 years (as a rough guess).  More sophisticated applications, like replacing organs or diseases tissues, are further away, and I don’t think we can yet predict how long it will take to develop these treatments.

The stem cell therapy saga has a few lessons – it is fine to hope and to look forward to future potential technologies, but you have to have patience, and beware premature hype.

4 responses so far

4 Responses to “Stem Cells for Heart Function”

  1. gerastuffon 15 Nov 2011 at 4:01 pm

    “Incidentally, another stem cell application that I feel is likely to be low-hanging fruit is the use of neuronal stem cells for stroke and injury recovery. The brain already recruits native neuronal stem cells to repair damage, and injecting additional stem cells will provide more raw material for repair – so they will easily plug into an existing repair mechanism.”

    Stem Cell brain grafts have been tried for some obvious neurological applications such as Parkinson’s Disease (there was a pilot research using fetal grafts implants in Sweden about 10 years ago), I’m lucky enough to be working on that field, 10 years seems about right to possible clinical therapies based on this; but I respectfuly disagree that it is one of the “low-hanging fruit” applications. On the contrary, I do think that functional and safe neuronal stem cells implantation is harder than almost any other application of stem cells (for instance insulin-producing cells, or whole estructures derived from stem cells such as trachea replacements, whole bone grafts )

    I’m really not sure if the tumorogenic potential of stem cells in neural transplants is the principal limitation, and from what literature describes I’d say that one of the main issues right now (and the one the lab I work for focuses on) is the correct differentiation of stem cells into specific types of neurons, because unfortunately stem cells grafted in neural tissue left by their own devices, have a strong preference to differentiate into glial phenotypes (Astrocytes, microglia) much more than to the needed neuronal phenotype for the area.

    To further complicate matters, it is not enough for the new neurons to survive and be neurochemically functional, they would have to integrate to the “brain circuitry” for a real clinical difference, and to date there are very few examples in animal models that this is possible. (this is because it is hard to say in rodents, when the transplanted stem cells are responsible for any measured improvement since they exhibit a much more strong and efficient endogenous neural regeneration of the brain)

    Just wanted to add my 2 cents…

  2. lucicapon 15 Nov 2011 at 9:30 pm

    Thanks for the update. I will have to check out the article tommorrow when I have access to the full version. That is amazing news and hopefully it will mature into a treatment for cardiac disease. With such a short supply of hearts for transplantion, if this became a viable option many lives would be spared. Fascinating.

  3. Kawarthajonon 16 Nov 2011 at 11:45 am

    While I agree that we have to be careful about stem-cell hype, it seems to me that right to life lobby in the USA is really holding up this research and we could have been much further ahead in terms of clinical applications if Bush had not suspended funding. I would imagine that potential researchers or commercial labs are reluctant to endeavour on future research for fear that a yet to be elected president will ban this research sometime down the road, which would ruin any current investment in stem-cells. A risky endeavour from a financial perspective.

  4. ConspicuousCarlon 16 Nov 2011 at 4:33 pm

    I thought heart attacks left you with scar tissue built up on the heart muscle. Is the effect of the stem cells’ adding more muscle tissue limited in part by the lack of a good way to get rid of the leftover junk?

Trackback URI | Comments RSS

Leave a Reply

You must be logged in to post a comment.