November 30, 2020

The Niche

Knoepfler lab stem cell blog

Interview with Arnold Caplan Part 2

Arnold Caplan
Professor Arnold Caplan.

I recently interview Arnold Caplan, the father of the MSC field, and published part 1 of the interview (you can read it here).

Today in part 2 we cover more topics of great importance related to MSCs including propagation, placebos, and patients as well as publishing.

A hot topic in the stem cell world more generally, but especially in the MSC field is what happens to stem cells when they are grown in a lab. Many important questions are being asked. Are the propagated stem cells basically the same as the starting stem cells? If not, how are they different? Should people be concerned about getting transplants of propagated cells?

I asked Caplan about how MSCs react to growth in culture. He acknowledged that MSCs grown in culture do change. “The longer you culture MSCs, the less they can differentiate,” said Caplan, “however, the MSCs retain their ability to inhibit immunosurveillance and to secrete trophic factors”. As discussed in the first segment of this interview, Caplan’s view is that it is these two functions rather than any stem cell-related properties of MSCs that are of the greatest therapeutic importance.

Caplan also mentioned another way in which culturing might change MSCs and in this case have clinical significance. After transplantation, high passage MSCs are more likely to become coated with clotting factor in the donor’s body and become trapped in the lung, reducing their efficacy. Thus, perhaps as is true with so many types of stem cells, lower passage is likely to be safer and more effective.

We also discussed how MSCs are likely to work clinically. One topic was the very important 2012 paper from Katarina LeBlanc’s team on autopsy data from patients who had received MSC transplants. The paper argued for quite limited engraftment of MSCs in support of the idea that nearly all transplanted MSCs do not engraft and rather function in a “hit and run” way to aid patients.

Caplan also acknowledged that many patients receiving MSC transplants (or transplants of other stem cells or even other kinds of medical interventions) definitely experience a significant placebo effect. The placebo effect that some patients experience with treatments can be substantial, up to 30%. However, Caplan passed on the experience of many physicians who are transplanting MSCs in RCTs where, according to Caplan, the doctors can easily tell which patients received placebo and which received stem cells, because those who received MSCs are doing so much better.

Interestingly, Caplan also pointed out that paradoxically for some patients, allogeneic MSC transplants might be more promising than autologous. In this regard, he mentioned how MSCs from healthy people appear to be more functional than MSCs from multiple sclerosis (MS) patients.

Caplan mentioned that there are 100s of patients receiving MSCs worldwide. I asked him why then are there so few publications. Caplan responded, “if only they would publish it would help everyone and the field.” I also would like to see more publications in this area.

Stay tuned for part III of the interview coming up in a few days.

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