When the results of clinical trials do not live up to expectations from pre-clinical studies in animals it can be all too easy to ascribe the divergence to species differences, however scientists are increasingly aware that in many, even most cases, the problem may not be species differences but rather differences in the design of studies in animals and humans. Identifying what those differences are and how they affect the outcome of a study is vital if future treatments are to be more successful.
An excellent example of this process in action is provided by a paper published this week in the Journal Science Translational Medicine. Seeking to understand why the benefits seen in clinical trials of stem cell therapy for heart attack were far more modest than those seen when the same approach was evaluated in mice, a team led by Professor Xiaoyin Wang of the University of California, San Francisco UCSF looked to the source of the stem cells used in the transplants.
They noticed that the stem cells used in the mouse studies had been taken from young healthy mice, while those used in the clinical trials had been taken from the patients themselves, an older population who had suffered heart attacks before their stem cells were harvested. To test whether the health of the stem cell donor made a difference they compared the outcome when they transplanted stem cells from healthy mice into mice with induced heart attacks, with that when the transplanted cells were taken from mice that had suffered a heart attack, and found that in the latter case the therapeutic efficiency of the transplanted cells was greatly reduced. Further experiments enabled them to identify the cause of this reduction and evaluate potential solutions.
You can read more about the work of the UCSF team in this excellent summary on UCSF News, which includes an interview with Prof. Wang
It’s a very nice piece of research, and one that may well in the next few years result in the availability of effective stem cell treatments to promote recovery after heart attack. It is also an excellent example of how thoughtful research can maximize the synergy between laboratory and clinical research.