The first assay-based definition of stem cell – the history told by Jim Till

by Alexey Bersenev on August 28, 2012 · 0 comments

in hematopoietic, interviews

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James Till is a part of the famous Canadian duo (with Ernest McCulloch), which identified and assayed stem cells for the first time. Recently I was really enjoying watching an interview with Jim Till, where he discussed the history of the first stem cell assays and definition made in 1960s. The interview was recorded in April, 2012.

He describes a history of identification so-calleld “colony-forming units” in the spleen, which later they started to call “stem cells”. There were very few important moments for me in his talk, so I made a quick transcript of one part:

We still didn’t know that we were dealing with a stem cells. The concept of stem cell have been around for a long time. Could be traced back in 1800s, not necessarily mean the same thing, but the term was used for a long time. But attempts to identify them were based on visual microscopy primarily.

Nobody could find anything distinctive that would say “that a stem cell”.

… That says individual cells, which form colonies can give rise to more than one kind of specialized cells. That answers the question, which been around since early 1900s. A name most attached to it is usually Maximow, who postulated that different kind of blood cells all come from common progenitor. The opposition to that was well, each one has it’s own – a separate progenitor. We showed that in mice at least, in our experiential conditions, Maximow was right! That answered the question in hematology, which has been around for quite long time.

He describes in details the first self-renewal assay, performed by Siminovitch. This assay led to final definition of “stem cell”:

That provides the strong evidence, of course, that these colony-forming units could self-renew. They could produce more colony-forming units. At that point we thought maybe we’re really dealing with stem cells here. Because we have been calling them colony-forming units, so we wouldn’t prejudge what it was and what we looking at. We defined them operationally by what we could actually see – which were the colonies. That fits the definition of stem cells. But what is a definition of stem cell? We look at literature and we could not find any definition. We had to make one up! Which was: they be capable of self-renew and they be capable to give rise to differentiated cells, preferably more than one kind and they be capable to extensive proliferation. Well, extensive proliferation is kind of build-in in self-renew criterion. So, those two major criteria – that’s all we use. We made them up and published in 1963 in the Journal of Cellular Physiology and the word “stem cell” for the first time.

He also discussed the issues of reproducibility, publishing and computational models. Great interview! Must watch!

Also see the history of hematopoietic stem cell assays.
Also see Stem Cell Assays history channel

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