Insightful interview with Arnold Caplan: Part 1: MSC history, nomenclature, & properties

A few days ago I had a long, very enjoyable phone conversation with the father of the mesenchymal stem cells (MSC) field, Dr. Arnold Caplan.

Dr. Caplan is Professor of Biology, Director Skeletal Research Center at Case Western. He coined the phrase “mesenchymal stem cell” in the late 1980s.

I’m going to break the interview into 4 parts. Today is Part 1, focused on the history, nomenclature, and properties of MSCs. I learned a lot to put it mildly from talking with him. (See Part 2 of the interview here, covering patients, propagation, publishing, and placebos).

I asked Caplan about the history of the MSC field and he responded that he called the cells by the “MSC” name to be intentionally provocative. According to Caplan, “The dogma of the day was that adult animals only had hematopoietic stem cells, but no other stem cells in other organs.” As a result, the notion that other tissues such as fat or bone marrow could have stem cells such as MSCs was somewhat heretical. I admire Caplan for challenging the orthodoxy. He recalled one seminar he gave at which “esteemed colleagues” in the audience were muttering some not so nice things about his presentation on MSCs.

Of course the new dogma today has caught up with Caplan. It is that every organ and tissue likely has its own compliment of stem cells and most people in the stem cell field believe in MSCs. But I think this scientific history of MSCs is very important to know in order to understand these cells. It also helps us keep an open mind about what we might all consider the new reality in the future that overcame today’s dogma. By the way, what is today’s dogma in the stem cell field? That’s a topic for a whole different blog post I hope to do in the future some day later this year.

Another important issue that we discussed is the inherent heterogeneity of what people call “MSCs”. Just as some folks pronounce “mescenchymal” one way with the accent on the end while others pronounce it with the accent in the middle (see Merriam-Webster here for the different pronunciations), so too do people call very different kinds of cells by that one name. I have heard people say that MSCs are pericytes, fibroblasts, endothelial cells, endothelial cell precursors, adipose progenitor cells….and the list goes on.

I asked Caplan about this and his response was that “I dogmatically say that all MSCs are pericytes.” He went on to explain that in his way of thinking pericytes respond to inflammation or injury by becoming MSCs.

Interestingly, Caplan has now transformed the MSC acronym to stand not for “mesenchymal stem cell”, but rather “medicinal signaling cell”, which he believes is a more accurate name for the cells. He went so far as to say that the therapeutic properties of MSCs are “not connected to stem cells”, but rather “MSCs work by secreting powerful bioactive molecules.”

These molecules have two major areas of action: (1) inhibiting immunosurveillance and (2) trophic effects. The latter function itself manifests in four ways via anti-apoptotic effects, anti-scarring, stimulation of angiogenesis, and mitotic effects on surrounding cells.

The gestalt of MSC function was nicely synthesized by Caplan in another way when he called the cells “a multi-drug site-regulated dispensary”.

Stayed tuned for three more posts on this interview with this leader in the MSC field including tackling key topics such as clinical and regulatory issues related to MSCs.