In 2006 International Society for Cellular Therapy (ISCT) published a position paper on defining a minimal criteria for multipotent mesenchymal stromal cells (MSC). It was very good move! However, since that time, new research data have been published. Some flaws of ISCT definition have been discussed and some statements have been challenged. I think we’re getting to the point when MSC minimal criteria should be revised. I’m starting a discussion with professionals about necessity and content of such revision. Today, I’d like to propose a few positions, which could be considered in revised ISCT statement.
1. The role of ISCT
ISCT is very well respected and trusted organization among professionals. Most of professionals agree with MSC definition, proposed by ISCT. We polled professionals on MSC definition and got the following results:
Therefore, ISCT should continue to take a leading role in discussing and in publishing revised statements.
The current ISCT definition recommends to use term “multipotent mesenchymal stromal cells” (MSC) instead of label “mesenchymal stem cells”. However, my analysis of literature showed that, after 2006 ISCT members (including the authors of MSC position paper) themselves frequently use terms “mesenchymal stromal cells” or “mesenchymal stem cells”. I think, the main point of confusion is a word “multipotent” in ISCT definition. It seem to me that ISCT experts wanted to avoid word “stem” and replaced it by “multipotent”. But “multipotent is actually indicating stem cell nature of the cells. The term “multipotent” was picked based on “tri-lineage differentiation” criteria. But tri-lineage potential is not really reflects multipotency.
I’d propose to remove “multipotent” from revised version and leave “mesenchymal stromal cells” only. Others nomenclature versions should be discussed.
ISCT definition paper doesn’t address the problem of stemness. Are MSC stem cells or progenitors? This is still an ongoing discussion without official ISCT position. Clinical use of MSC has nothing to do with their “stem cell nature”. “Stemness” of MSC could be translated in multilineage differentiation potential. But we mostly use only one-lineage differentiation of MSC in clinic, such as osteogenic/ chondrogenic or don’t use their differentiation potential at all (see “medicinal cells“). Therefore, “multipotency” and “stemness” of MSC doesn’t reflect clinical application. Many academic researchers consider MSC as “progenitors” but not “stem cells”. Some industry developers also call MSC as “mesenchymal progenitor cells” (see Mesoblast).
I’d propose a discussion on this matter with release of ISCT position.
4. Fresh versus cultured MSC
ISCT definition doesn’t address the difference between fresh (native/ freshly isolated) and cultured MSC. The statement covers only MSC expanded ex vivo by defining “plastic adherence” as minimal criteria. This position ignores the fact that properties of native MSC, which reside in tissues, could be completely different from cultured MSC. For example, the recent discussion about CD34 as MSC marker, brought up this issue and highlighted the lack of this information in ISCT definition. Taking in account increasing interest to clinical application of freshly isolated MSC, this issue should be discussed.
I’d propose to address a difference between native and cultured MSC in revised version.
MSC defined by ISCT as positive for CD90, CD105 and CD73. In the light of recent research, some other markers could be considered. For example, MSCA-1, CD271, CD146 and some others. The difference in markers expression should be defined for fresh versus cultured MSC and, also, for MSC isolated from different tissues.
ISCT definition doesn’t address the difference between MSC, isolated from different tissues. The difference could be in markers expression, in differentiation potential and even in naming. For example, if cord blood doesn’t have a stroma, why should it be called MSC? Yet another question is how to define the cells expressing similar markers with MSC (ex: pericytes). I think the questions of heterogeneity should be addressed in the revision.
This is a pilot draft of proposal. Please discuss with me the necessity and content of revised criteria for MSC.