Are Mesenchymal Stem Cells Really Stem Cells?

Guess what? Some of the most versatile cells used in Regenerative Medicine that are used to treat a host of chronic conditions may not be the stem cells we thought they were. So if mesenchymal stem cells (MSCs) are not stem cells, then what are they? And, how do they work?

MSCs can be found in several tissues in the body including adipose (fat tissue), bone marrow, muscle, tendon, intervertebral disk, dental pulp, and more. For stem cell therapies they are most frequently harvested and isolated from adipose tissue and bone marrow.

To review, stem cells have two qualities that separate them from the other 200+ types of cells found in the human body. Stem cells can:

self renew
they can differentiate into other more specialized cells or tissues.

Self renew means a stem cell can divide without limit and produce cells identical to itself. Differentiate means a stem cell can change into a more specialized cell. One thing that is not quite understood is how a stem cell stays undifferentiated until needed to differentiate. That may not seem important to you, but it is. What is called the stem cell niche seems serves to keep a stem cell in undifferentiated state. How it does that is not entirely clear, though.

But, mesenchymal stem cells do not actually differentiate into specialized tissues – as they may not be stem cells in the truest sense. Why is that?

Well, it turns out that MSCs in vitro (in the lab) do differentiate into more specialized tissues, but they do not or rarely differentiate into more specialized cells in vivo (when transplanted into the human body). Knowing this does not, however, take away from the importance of these cells.

Arnold Caplan, PhD at Case Western University has recommend the mescencymal stem cells (MSCs) be more appropriately referred to a Medicinal Signaling Cells (MSCs). Here is an important quote from him published in this paper called Mesenchymal Stem Cells: Time to Change the Name.

Unfortunately, the fact that MSCs are called “stem cells” is being used to infer that patients will receive direct medical benefit, because they imagine that these cells will differentiate into regenerating tissue-producing cells. Such a stem cell treatment will presumably cure the patient of their medically relevant difficulties ranging from osteoarthritic (bone-on-bone) knees to various neurological maladies including dementia.

I now urge that we change the name of MSCs to Medicinal Signaling Cells to more accurately reflect the fact that these cells home in on sites of injury or disease and secrete bioactive factors that are immunomodulatory and trophic (regenerative) meaning that these cells make therapeutic drugs in situ that are medicinal. It is, indeed, the patient’s own site-specific and tissue-specific resident stem cells that construct the new tissue as stimulated by the bioactive factors secreted by the exogenously supplied MSCs.

What this means is this. MSCs can be harvested from one’s own fat or bone marrow than transplanted into a joint, the heart, brain, lungs, etc. But, they don’t turn into cartilage, heart, brain, or lung tissue, but rather stimulate the stem cells native or resident to that tissue or site in question to differentiate into more specialized cells to repair and regenerate tissue. I hope that make sense.

Here’s what is interesting. Dr. Caplan is the person responsible for calling MSCs “mesenchymal stem cells”. Here is another quote from Dr. Caplan.

If should be permissible for the person who named MSCs to drop the stem cell nomenclature because it is scientifically and therapeutically misleading. In 2010, I proposed that we call them medicinal signaling cells. That is what these do…. I was wrong….I take back the name that I gave these hugely important cells. Call them MSCs, but please, not stem cells.

It is rare in science or medicine for someone to say he was “wrong”. Mesenchymal “stem cells” are derived from pericytes which are contractile cells that wrap around blood vessels and protrude into the lumen of blood vessels where they monitor and react to systemic signals.

How Do MSCs Work?

Mesenchymal stem cells are immunomodulatory and trophic (tissue growth and repair) as Dr. Caplan states. And, they are also potent antimicrobials.

Immune Modulation

MSCs secrete various anti-inflammatory molecules. In the case of arthritic joints this leads to rather prompt pain relief and creates an environment for trophic (regenerative changes) to occur. They also inhibit an autoimmune response. Autoimmune response is when the body
“attacks itself” following damage to tissue. This autoimmune protection is referred to as the MSC curtain.

Trophic Effects

MSCs create a zone of regeneration through several mechanisms. First, they inhibit apoptosis which is programmed cell death. So they prevent it – cells from dying. They stimulate the formation of new blood vessels which delivers nutrients and oxygen to damaged tissue. They trigger tissue specific stem cells to divide to regenerate/repair tissue and they prevent scar formation (non-functional tissue).

Antimicrobial Effects

MSCs secrete proteins that are antibacterial. One of them, LL37 kills E. coli, Pseudomonas, and Staphylococcus on contact. This reduces the chance of infection at sites of tissue repair.

MSCs – they may not be stem cells in the truest sense, but despite Dr. Caplan’s plea not to refer them as stem cells is not likely to occur anytime soon. And, in a way it doesn’t matter. MSCs are vital to tissue repair and regeneration. Like the photo above MSCs have medicinal properties.

In the end, MSCs are the body’s natural drugstore.