I have written about stem cell therapy pretty frequently here for a couple of reasons. I consider it a very promising avenue of investigation based on lab animal and human studies, and I expect someday specific beneficial therapies based on stem cells will be available for dogs and cats. I also believe that stem cell therapies have been marketed aggressively and well beyond the actual evidence concerning risks and benefits. A general rule of medicine, in my opinion, is that any therapy that has real benefits also has real risks, and only rigorous controlled research will elucidate these. A recent review of the current status of research into stem cell therapies for kidney disease in cats illustrates well both the potential benefits and risks of stem cell therapies and the currently inadequate evidence about both that makes use of such treatments only appropriate under experimental conditions.
J.M. Quimby, S.W. Dow. Novel treatment strategies for feline chronic kidney disease: A critical look at the potential of mesenchymal stem cell therapy. The Veterinary Journal 204 (2015) 241–246.
This review briefly outlines different types of stem-cell therapies, such as bone-marrow-derived cells, fat-derived cells, and cells from the patient or from other donor individuals, and discusses the potential advantages and disadvantages of each. This is useful in reminding us that stem-cell therapy is a complex collection of different processes and interventions, and we need good evidence for each specific intervention to make useful judgments about safety and efficacy.
The authors then briefly review the extensive lab animal evidence, which suggests potential benefit for stem cell therapies in animals with kidney disease. They do point out, however, that there are important differences between experimental disease in rats and natural disease in cats, so such studies can only suggest risks and benefits, not conclusively demonstrate them.
Finally, the review looks at the few small studies done to date in cats. These are interesting in their illustration of potential risks and benefits from stem cell therapies and also the complexity of identifying type of cell, route of administration, dose, and measures of effect to demonstrate real clinical impact from these treatments.
One study of 6 cats (2 healthy and 4 with kidney disease) involved injecting either bone-marrow-derived or fat-derived stem cells directly into the kidneys. Some improvement in measures of renal function were seen. However, the study also illustrated that getting cells from old and ill patients was very difficult and that this, along with the expense and risk of the procedure, would likely make this approach impractical in the real world of clinical medicine even if significant clinical benefits were ultimately found.
Three additional small studies have evaluated different doses and forms of fat-derived stem cells given intravenously to cats with stable chronic kidney disease. One group showed statistically significant changes in some bloodwork values, but these were not judged to be large enough to be clinically meaningful. In the other two groups, no significant change was seen in measures of kidney function. However, in one of these two groups, some undesirable adverse effects were noted in most of the cats, possibly due to inflammatory reactions or small clots caused by the stem-cell injections. This illustrates the general principle that any therapy which has significant effects on the body can cause harmful as well as beneficial effects, and the key to making good therapeutic choices is understanding both risks and benefits and being able to compare them in the context of an individual patient’s situation.
Another study of eight cats, this time with randomization, blinding, and a placebo control, investigated intravenous use of stem cells. Over a short-term followup of 6 weeks, no significant effects, for good or ill, were seen, but the study is still ongoing in order to observe any potential effects over a longer term.
From the various pieces of evidence reviewed, these authors draw a conclusion which seems to me to apply well to many potential uses of stem cell therapies in addition to the treatment of kidney disease in cats:
Although it holds much promise, at this time MSC therapy for CKD in cats should still be considered an experimental and unproven therapy. Notably, none of the studies conducted in cats with CKD by our group has been able to replicate the efficacy of MSC treatment reported in numerous rodent models of experimentallyinduced CKD.. Although rodent studies illustrate the impressive potential of MSC treatment for kidney disease, results of these models should be interpreted with caution for the reasons noted above. A conservative interpretation of the available data from studies in cats with CKD is that the current approach of IV administration of allogeneic MSCs is not likely to exert marked clinical benefit, although more animals should be treated before this conclusion can be firmly established.
There are still many questions to be answered regarding the logistics of MSC therapy. The optimal route of MSC administration, the ideal source of MSCs (allogeneic vs. autologous; culture expanded MSCs vs. SVF) and the impact of tissue donor status (attributes such as age, disease status and sex) on MSC function remain to be determined. Studies are currently under way investigating many of these aspects and additional information is eagerly awaited.