A new paper suggests a hopeful short-term safety profile of laboratory-grown stem cells for treatment of arthritis, but there are some important limitations to the study too.
A debate continues to bubble over whether to classify laboratory-propagated stem cells as biological drugs.
A persistent issue has been whether the growth of stem cells in culture increases risks of negative outcomes for patients including 4 prominent and broadly applicable issues of risk: infection, benign but destructive tissue growth, cancer, and autoimmune reactions.
A fifth concern, particularly in the case of systemic IV administration of stem cell products, is pulmonary embolism (PE) as stem cells in the vascular system tend to trigger clots around themselves and accumulate in the lung rapidly. This could also manifest with local administration of stem cells that escape to the bloodstream via broken blood vessels.
The clinical use of laboratory grown stem cells has a number of potential medical applications including for conditions as diverse as arthritis, cardiovascular disease, and multiple sclerosis just to name three out of a host of others for which interventions are offered.
Published data on the safety of clinical use of laboratory grown stem cells has been rather lacking over the years. For this reason, it was good to see this recent publication specifically on this topic as it relates to treatment of arthritis of the knee and hip:
Safety of intra-articular cell-therapy with culture-expanded stem cells in humans: A systematic literature review
The paper from Peeters, et al. in The Netherlands was published in the journal Osteoarthritis and Cartilage. Figure 1 showing the study design and selection process is above.
The analysis included 8 studies that fulfilled all inclusion criteria and encompassed 844 total procedures. The authors focused primarily on the use of bone marrow-derived MSCs injected into the articular space for the treatment of osteoarthritis.
Encouragingly, serious adverse events (SAE) were relatively uncommon (4 reported equating to <0.5% of procedures) and only a subset (2) of those was definitely attributable to the therapy itself.
One PE and one case of infection were therapy-related.
Twenty nine additional potentially events were possibly related to the stem cell therapy. Therefore, if there were 30 possible adverse events related to the stem cell therapy out of 844 procedures that is a rate of 3.6%.
The authors conclude that this kind of stem cell therapy is probably safe, however there are several important limitations to this paper that lower its impact.
- One is the relatively short term follow up: a mean of only 21 months. While acute adverse events seem to be rare with the use of propagated stem cells injected into joints, longer term side effects (e.g. many kinds of tumors would be likely to manifest after years, not months) cannot be reasonably evaluated from this analysis.
- A second issue is that variability in methods amongst the 8 studies makes analysis more difficult. Some studies followed patients for only months, while others followed them for years. Some studies used bovine serum for cell expansion, while others did not. There were other differences as well.
- The authors also discuss the likely possibility of publication bias due to studies that have adverse events being more likely to remain unpublished or excluded. This is a serious challenge without a ready solution.
The authors of the systematic analysis paper pointed out the limitations mentioned above themselves, for which they should be commended.
Overall, I would say this study is encouraging in terms of short-term safety with the limitations mentioned above and a note to readers added that this study does not prove efficacy.
The more data that is published in this area the greater clarity we will all have the strengths and weaknesses of this kind of stem cell therapeutic approach.