Tremendous Promise and Tragic Carelessness
The excitement surrounding the potential for stem cell therapeutics in AMD, and many other diseases, in understandable. Great advances have been made in the last decade in discerning the mechanisms to derive pluripotency and to direct differentiation. It seems plausible that any diseased tissue can be replaced with autologously produced healthy cells, thereby protecting them from immune attack and restoring function. In AMD for example, we could simply replace the diseased RPE, and voila, we have a cure. It is so elegant and easy to explain; it is no surprise that patients are eager for this approach to become a reality.
Last month in the New England Journal of Medicine, back-to-back papers were published that demonstrate the extremes of all of this excitement. In a seminal study, Mandai et al. (link to paper) report a single case of successful transplantation of a sheet of RPE cells derived from autologous fibroblasts. The study was meticulously designed and executed, with extensive characterization of the cells at each step prior to and following the surgery. Although the vision did not improve, the study is a landmark in the feasibility of this approach.
In the accompanying article, Kuriyan et al. (link to paper) report 3 cases of bilateral intravitreal injections of minimally processed adipose-derived stem-cells in patients with AMD. Although all 6 eyes had at least ambulatory vision prior to the intervention (ranging from 20/30 to 20/200), all but 1 eye ended up with hand motion vision or worse. All of these cases were performed in patient-sponsored clinical trials.
These studies illustrate the stark contrast of careful science versus exploitation. Clearly, high-quality evidence-based medicine can only come from rigorous preclinical evidence, clinical trials, and regulatory review. Both of these studies provide valuable lessons, including what it takes to make real scientific progress, and what can tragically happen with careless shortcuts.