How do Stem Cells work to make patients feel better ?


The only honest answer to this fundamental question is we don't know for sure. The initial excitement and interest in stem cells for orthopedic conditions came out of the understanding of their ability to differentiate into various cell types as seen in the figure above showing an overview of the Mesengenic process where "Pericytes" become MSC's (mesenchymal stem cells) which then can become muscle,tendon, bone, fat, marrow or cartilage cells. This has been observed in the laboratory, in vitro (in a test tube or petri dish)  with cell culture. This has not, I repeat has not been proven to occur with any of the same day in office type procedures. The lab results are exciting, but still a long way to go, since so far these cells are only basic cartilage or tendon, they haven't been proven to be the more specific type of cartilage in say a meniscus of the knee.  

This does not necessarily mean pericytes don't have some benefit, but it does mean that based on the current scientific understanding none of the same day in office procedures can produce cells that can turn into another cell type such as bone, cartilage or tendon. 

The next big question is what are these Pericytes and what do they do to help tissues heal. Pericytes it turns out live on blood vessels, where they have several functions, of our interest is in how these cells respond to tissue injury and what role they play in tissue healing and regeneration. The following image summarizes some of the current thinking of how these cells respond, and according to Dr. Caplan these pericytes behave more like Medicinal Signaling cells (MSC) rather than the traditional Mesenchymal Stem Cell (MSC). 

What do we do ?


We don't do any "Stem Cell" procedures, and in my opinion neither does anyone else.  I have been trained on how to obtain msc's or pericytes, but once I explain how none of these procedures are really a stem cell treatment and what it cost no one wants to do it.  There is no convincing evidence that any of these same day transferred cells differentiate into anything, they may have a role as a signaling cell, but not a "stem cell".  Who wants to have a liposuction procedure or holes drilled into their pelvic bone for just a signaling cell ? Now a true stem cell, that can be shown to differentiate into cartilage specific to a joint or tendon would be awesome, but we don't know scientifically how to do that. Someday in the future, a laboratory will figure out how to manipulate these cells  in culture.  But the interesting point is that the FDA has the opinion that cells cultured or manipulated in a lab are a drug. Therefore these cells have to be further studied to prove they are safe and effective, just like any other drug that gets approved by the FDA. This takes on average 10 years or more and 1 billion dollars, yes billion with a B, now the bummer is some said 10 years ago that we would have these therapies today but we don't.  My best guess is it will be another 10 years before we see anything make it through the FDA approval process, I am sure it will be expensive and wonder what the insurance coverage will be like if any. 

I think the next best alternative is PRP or platelet rich plasma. PRP can be thought of as an activator of the cartilage/tendon/ligament cells that are already there, it is part of your body's natural response to injury. When you have a soft tissue injury that causes bleeding, platelets react to this and clump together at the injury site to stop the bleeding, if this isn't successful then nothing else really matters, when you bleed out you die. I must say it was very clever to package growth factors for repair in the alpha granules of platelets, much like granular fertilizer these granules are now concentrated at the sight of injury, and will release their growth factors over the days following injury to promote repair and healing. The cool thing is that it only requires a blood draw to get these platelets and their alpha granules, so click on my PRP page to learn more.

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THE MSC: AN INJURY DRUGSTORE
ARNOLD I. CAPLAN, Ph.D. and DIEGO CORREA, M.D., Ph.D.

 
Dr. Caplan suggest we think of these cells as injury drug stores, and it seems their first response is to protect the damaged tissue from an overzealous immune response, and to secrete a number of different bio-molecules and growth factors that work together to promote regeneration of tissue, creating what he calls a "Regenerative Microenvironment". Most likely this microenvironment is also important in working along side the growth factors released from the alpha granules in Platelets that is obtained from Platelet Rich Plasma (PRP). He thinks of the PRP as a MSC/Pericyte activator.  The following article from 2015 provides further evidence of this growth factor release and cell to cell communication.
 
​The paracrine effect of adipose-derived stem cells inhibits osteoarthritis progression (Sept 2015)
This is a fascinating study that gives some insight as to the why and how Stem Cells work to help osteoarthritis
these cells homed to the synovium (joint capsule) and ligament, but not to the cartilage
the cells released a liquid factor that decreased cartilage degeneration in a rabbit knee with a lab created anterior cruciate ligament transection
there was no evidence the implanted stem cells differentiating into new cartilage/tendon/ligament/bone cells 
 
What happens after this initial regenerative microenvironment is created is not completely understood. Dr. Caplan does not believe that some of these Pericytes go on to become other cell types, such as muscle,cartilage,tendon, bone, but they just simply go back to being pericytes on a blood vessel, or just die because they couldn't find a blood vessel to live on.  It will be fascinating to see how the science improves our understanding of how our bodies heal and repair, and how we can use the bodies own intrinsic healing strategies to improve patient outcomes.​

Stem Cells (Pericytes)

 

What is a Stem Cell ?

 

An adult stem cell is an undifferentiated cell, one of the body’s most important natural repair mechanisms. They repair organs, muscles, heart, lungs, skin, and nerves by replacing old, dead, or diseased cells throughout the body.​ They are characterized by the cell's ability to renew itself through cell division and differentiate into specialized cells. Stem Cell therapies were initially developed in the 70's and 80's in the form of a Bone Marrow Transplant.

 

Different Stem Cell types 

 

Embryonic Stem Cells

  1. The first Human Embryonic Stem Cell line was derived at University of Wisconsin in 1998
  2. 2001 Cloned "Dolly the Sheep"These cells are highly controversial and Politically Sensitive
  3. These are not used in Regenerative Orthopedic Procedures

 

Induced Pluripotent Stem Cell

  1. These are essentially Adult Cells that have been reprogrammed to become pluripotent and behave like Embryonic Stem Cells
  2. These also are not being used in Regenerative Orthopedic Procedures

 

Adult Stem Cell

  1. Can come from different tissues bone, fat, placenta, amniotic fluid, cord blood, synovium, bursae etc.
  2. have been successfully used to treat cancer through Bone Marrow Transplants since the 60's
  3. Advantages are that the Adult Stem Cells are not controversial like the Embryonic Stem Cells 
  4. There are Autologous Adult Stem Cells meaning the patients own cells usually taken from either Bone Marrow or Fat
  5. There are Allogenic Stem Cells meaning taken from another human such as cord blood or amniotic fluid
  6. Mesenchymal Adult Stem Cells can form bone,fat,cartilage,muscle,heart,kidney,blood vessels,nerves
  7. Hematopoietic Stem Cells can form the various types of blood cells RBC's,WBC's,Platelets, etc.