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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. 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

What is Stem Cell Therapy ?

 

A Stem Cell can be used to generate healthy and functioning specialized cells which can then replace diseased or dysfunctional cells. Some of the Potential diseases currently being treated or studied with Stem Cells are:

  • Retinal Degeneration
  • Alzheimer's disease
  • Parkinsons disease
  • Muscular Dystrophies
  • Arthritis
  • Diabetes
  • Spinal Cord Injury
  • Blood Disorders
  • Congestive Heart Failure and Myocardial Infarction

 

Stem Cells for Regenerative Orthopedic Injections

 

Recent studies have focused on the use of adult stem cells for disorders such as osteoarthritis. Mesenchymal stem cells (MSCs) are non-hematopoietic, multipotent progenitor cells, which can be isolated from various human adult tissues. The potential to form cells of chondrogenic (Cartilage) lineage has indicated the potential of these cells in cases of osteoarthritis. In recent years, MSCs have been shown to possess broad range of regenerative capabilities, modulating disease progression improving cartilage lesions closely associated with osteoarthritis.

 

There is much debate in the Regenerative Medicine World regarding Adipose Vs Bone Marrow Derived Stem Cells. Bone Marrow Stem cells have been around and known about since the 60's, therefore there has historically been more research and treatment with Bone Marrow Stem Cells, large amounts of Mesenchymal Stem Cells were discovered in Adipose (Fat) Tissue much later.

 

Adipose Derived Stem Cells Advantages over Bone Marrow Derived Stem Cells

 

  • A study published in the European Heart Journal 2007 demonstrated about 500 times more stem cells from Adipose as compared to Bone Marrow, estimating 30 million stem cells within 60cc of Fat
  • Adipose can be obtained in larger quantities by a less invasive method over Bone Marrow. Mol Biol Cell 2002. 13:4279-4295
  • It is technically very difficult to obtain large quantities of stem cells in Bone Marrow Aspirates, as only the first 5-7cc of aspirate contain Stem Cells after that is primarily peripheral blood and the needle must be advanced within the bone to continue aspirating stem cells

 

Supporting Studies for Adipose over Bone Marrow Stem Cells:

 

Comparative analysis of mesenchymal stem cells from bone marrow, cartilage, and adipose tissue.
  • Adipose Stem Cells grew at a faster rate
  • Adipose possessed greater proliferation potential


Autologous point-of-care cellular therapies variably induce equine mesenchymal stem cell migration, proliferation and cytokine expression

  • compared Bone Marrow Mononuclear Cells , PRP and SVF (Adipose Derived Stromal Vascular Fraction) and there affect on stem cell function in vitro
  • all increased Stem Cell proliferation, but highest in SVF
  • only SVF stimulated chemotaxis or cell migration siginficantly
  • SVF and cord blood increased IL-6 which is believed important in a healing response
  • TGF Beta controls cell proliferation and differentiation and was highest with PRP supporting why you should include PRP with Stem Cells (PRP acts as the fertilizer for Stem Cells)
  • Prostaglandin E3 important for cell to cell communication and stimulation (paracrine effect) , and was higher with SVF over BMMN  

 

Adipose tissue-derived multipotent stromal cells have a higher immunomodulatory capacity than their bone marrow-derived counterparts (June 2013)
  • Adipose cells were better at decreasing inflammation
  • Adipose showed higher IL-10 anti-inflammatory cytokine expression
  • Adipose showed higher gene activation for anti-inflammatory cytokines

 

Characterization of adipose tissue-derived stromal vascular fraction for clinical application to cartilage regeneration.​ (Feb 2015)

  • comparison of bone marrow derived vs adipose derived stem cells
  • Adipose had 6 fold less nucleated cells - therefore should be less inflammatory
  • Adipose has 4 times greater adherent cells - suggests are more likely to adhere to damaged tissue and initiate a repair
  • Adipose cells showed chondrogenesis where the bone marrow cells did not - new cartilage formation

 

​​Do Stem Cells help Osteoarthritis ?

 

Autologous adipose tissue-derived stromal vascular fraction cells application in patients with osteoarthritis (Jan 2015)

  • Large joint arthritis mainly knee and hip 
  • 75% improvement in clinical modified KOOS score was seen in 63% of patients
  • 50% improvement was seen in 91% of patients
  • obesity and worse arthritis was associated with slower healing

 

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,ligament, bone, fat, marrow or cartilage cells. This has been observed in the laboratory with cell culture. The interesting point is that the FDA does not allow stem cells to be cultured and then injected into a patient, the only option is to process the stem cells in a minimally manipulated way such as centrifugation, or possibly mechanical or enzymatic separation and then must be injected into the patient the same day. Most likely this does not allow the Pericytes time to differentiate into anything, so 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). 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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), which is why we always include PRP with our stem cell/Pericyte procedures. 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. A really big but still unanswered question is whether the clinical improvement seen is due to the implanted stem cells differentiating into new cartilage/tendon/ligament/bone cells or is it cell to cell signaling (paracrine)  effects that lead to improvement, or some combination of both. This study answers part of the question that cell to cell signaling is atleast part of why patients improve.

 

What happens after this initial regenerative microenvironment is created is not completely understood. It could be that some of these Pericytes go on to become other cell types, such as muscle,cartilage,tendon, bone, or just simply continue to send signals to the cells already present in the tissue of interest to continue to respond, regenerate and remodel. I suspect it is some combination of both. 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.

 

What we do

 

Our current opinion is that Adipose Derived Stem Cells when isolated down to the Stromal Vascular Fraction gives the largest number of Cells for regenerative potential. ​​Some providers are simply doing a whole fat graft and calling this a stem cell procedure, this is not what we do. We take additional steps to isolate the progenitor stem cell from the whole fat, to yield only the stromal vascular fraction. We then combine this with a leukocyte-poor and red blood cell poor Platelet-Rich Plasma.

 

This is all done by a simple in-office Lipo-aspiration procedure under local anesthetic and blood draw to obtain the PRP. Then the PRP/Stem Cell SVF sample is immediately  injected into the pathologic area that same day. We are careful to stay within the FDA Guidelines of minimal manipulation and do not do any kind of stem cell culture and expansion, as this is currently not allowed in the United States by the FDA.

 

Please call our office 501-673-3116 or enter your information on our contact page to schedule an appointment so we can evaluate you and see if you would be a candidate for this procedure.