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Replacing dead or dying cells with new, healthy ones is the holy grail of regenerative medicine. Even sustaining damaged cells with toxin-mopping, growth-factor-spewing stem-cell-derived support cells would be a tremendous feat.

But while clinical trials have hinted at stem cell therapy’s tremendous potential to replace parts or at least aid in necessary maintenance, the details of how these cells work their therapeutic magic often fall through the methodological cracks.

It’s all very well to conclude that injecting stem cells into damaged organs does some good. But in order to understand whether these cells are homing to injury sites and setting up shop, or even surviving at all, they have to be traceable.

Let’s look at the heart. A study assessing the acute and long-term effects of intracoronary stem cell transplantation in patients with chronic heart failure (the STAR-heart study), published in the July issue of the European Journal of Heart Failure but re-reported August 29 at the European Society of Cardiology annual meeting in Stockholm, Sweden, suggests the therapy improves ventricular performance, quality of life and survival.

But the mechanism by which 6.6 x 107 bone marrow cells confer protection when injected into damaged hearts is not explained in the report. The researchers posit that the transplant “may overcome the possibly detrimental effects of ventricular remodeling,” but later add that “further studies are required which focus on cell based therapy.”

Not knowing where these cells are going or what type of role they’re taking on not only makes it difficult to optimize the therapy, it also represents a missed opportunity to learn something about the diseases or conditions themselves.

Incorporating reporter genes, magnetic or radioactive labels could allow researchers to follow transplanted cells to their final destination using non-invasive imaging techniques like PET and MRI, offering clues to their newfound function. There are obvious obstacles to consider before applying such approaches widely in humans though, such as immunogenicity of integrated gene products, the possibility that patients might depend on medical devices (such as pacemakers) that preclude them from having MRIs, and radiation exposure.

However, until these marvelous but mysterious cells can be tracked — even just identified in post-mortem tissue — we simply won’t know for sure what they’re doing. This creates problems in the era of stem cell “clinics” selling phony medical miracles based on cell therapies. Clinical trials that show stem cells work but offer no explanation as to how continue to leave open the door for such abuse.

 

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Katie Moisse

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