Arnold Caplan is a scientist, who coined a term “mesenchymal stem cells” in 1991 for the type of bone marrow cells, previously known as “stromal stem cells”. This term became widely adopted. He gave a very interesting talk during plenary session of Till & McCulloch Meetings. I’ll try to summarize his current view on “Mesenchymal Stem Cells” (MSC) biology and clinical applications.
Caplan said that a term “Mesenchymal Stem Cells” got him in trouble later, because not everyone believed in their “stemness”. More than a year ago he proposed to use an alternative term “Medicinal Signaling Cells” instead of “Mesenchymal Stem Cells”. According our recent poll, professionals didn’t adapt yet a new MSC’s name.
Caplan believes that MSC are progeny of pericytes – the cells, attached to blood vessel’s wall in all tissues and organs. So, they are not stem cells, but progenitors. Ironically, nobody call pericytes as “stem cells”, even though they are MSC’s ancestors. Importantly, he thinks that cell definition should be functional – based on biological role in vivo. Right after blood vessel injury, pericytes give MSC progeny. MSC get activated in inflammatory environment and express their “medicinal” functions – immunomodulatory and trophic. So, MSC’s biological function has nothing to do with “stemness”. He noted: “We should focus on what these cells can do medicinally instead of what they can differentiate to”. Also, Caplan thinks that MSC have nothing to do with stroma. So, no to “stem” no to “stromal” in definition. As he said: “Turn your “stem cell brains” off and think!”
I’d argue, that in normal condition, bone marrow MSC have a stromal/ structural role as hematopoietic stem cell niche. Unfortunately, Caplan completely ignored this very basic MSC function, described by Alexander Friedenstein and Joseph Chertkov more than 30 years ago. I don’t think we can define and name a cell type, based only on their function in pathological conditions. Should it be two different names – “stromal” for normal condition and “medicinal” (activated stromal) for pathology? It is very confusing!
Caplan views MSCs as a “drugstores”, which can produce 10-20 biologically active substances. He thinks that FDA standards should not be applied to “live drugstores”. He said: “We can’t use Pharma logic in regenerative medicine”. I was thinking – why every MSC-based therapy developer trying to show “tri-lineage differentiation assay” in preclinical protocol and put it in product characterization? Based on medicinal signaling cell logic, it doesn’t make any sense. Almost all clinical trials in regenerative medicine currently assess medicinal functions of MSC, which have nothing to do with “stemness”. So, probably just one good potency assay is enough for product characterization. Ironically, everyone call it “stem cell therapy”.
From the recent therapeutic trends, Caplan is really excited by antibacterial function of MSCs. These cells can make natural antibiotic-like substances (LL37) in contact with bacteria. His data confirm and complement of studies by Matthay’s group. He also impressed by use of MSC in veterinary medicine. He credited Vet-Stem, which have treated more than 5000 horses for tendons injuries with 75% of cure rate. Finally, as a founder of Osiris, he noted: “Osiris data on Crohn’s disease is spectacular!”
Caplan concluded that we have to accept the paradigm shift from MSC characterization in vitro (tri-lineage differentiation) to medicinal function, which is irrelevant to concept of “stemness”.