When it comes to stem cell therapy, there is a gray area that many companies across America are exploiting to sell stem cell-based transplants that are not explicitly approved:
“minimally manipulated” cells.
What does “minimally manipulated cells” mean?
Unfortunately, the definition is not clear and this term is interpreted differently depending on whom you ask. Here is a website from the FDA providing guidance, but I found it very confusing.
Here in 21 CFR 1271.3(f) I found an actual definition:
(f)Minimal manipulation means:
(1) For structural tissue, processing that does not alter the original relevant characteristics of the tissue relating to the tissue’s utility for reconstruction, repair, or replacement; and
(2) For cells or nonstructural tissues, processing that does not alter the relevant biological characteristics of cells or tissues.
Companies selling stem cell therapies based on adult stem cells assert that their treatments are indeed “minimally manipulated”, but the FDA requires that cells be proven to be minimally manipulated and without that proof the cell product is by definition not minimally manipulated.
In other words, according to the FDA, companies must conclusively prove minimal manipulation or alternatively by default the cell product in question is going to have to explicitly be vetted and approved by the FDA.
Of course any medical therapy or drug has to eventually be tested in people in order for biomedical scientists to know if it works.
However, there is a tremendous difference between a rigorous scientific clinical trial whose goal is to advance knowledge and a for-profit company transplanting stem cells into patients for the goal of making money.
In the context of a for-profit clinic, I would say patients are guinea pigs in real danger of not only losing their money, but also their health and lives.
For the people running such a clinic, is using human patients literally as experimental guinea pigs ethical?
Are vulnerable patients being maximally manipulated by some of the ever-growing number of companies selling what they call “minimally manipulated” cells? I think the answer is unfortunately clearly “yes” and often patients are convinced to get therapies by emotional patient testimonials and promises of beneficial outcomes when there is no hard science to support such claims. The risks to patients are often downplayed by these clinics as well, but the reality is that the risks are very real and include death.
I applaud the recent actions of the FDA (and FBI) in regulating stem cell therapies, but it would also be extremely helpful if the FDA could provide more guidance on issues such as minimal manipulation including more precise, detailed definitions and real world examples. Sometimes manipulations of cells is obviously more than “minimal”. For example, in the beautiful image at top I have differentiated neural stem cells into glia (green) and neurons (red). That’s clearly more than minimal. But for many procedures we simply do not know if they count as “minimal” or not.
For example, do any of the following make a cellular product more than minimally manipulated?
FACS sorting of a subpopulation of a mixed cellular population? For example, isolation putative MSCs from adipose tissue?
Storing of cell samples for X hours, where x could be anything from 1 to 24 hours or much longer if cryopreserved.
Treatment of a sample with antibiotics? (I’m not sure the clinics even do this, but people have asked me about it)
For some of these questions, potential answers are scattered out there in cyberspace such as hints that storage overnight is viewed by the FDA as automatically not minimally manipulated, but are these anecdotal “answers” correct? Again, it is unclear.
Meanwhile, different debates are underway amongst a variety of scientists in academia in different fields (stem cells, ethics), legal scholars, and the folks running the stem cell clinics. I personally believe that what should not get lost in any of these conversations is the well-being of patients, an issue that is a common thread throughout all these fields and one that should be the main focus for all parties involved.