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SCORING METHODS

Note: This section contains technical data and explanations of procedures

Stem cells are present in most tissues. In the past the most commonly used source has been bone marrow. In 2001 Patricia Zuk published her landmark paper demonstrating the presence of stem cells in fat. Fat is now recognised to be a richer source of stem cells than bone marrow. Stem cell numbers in fat do not reduce with age as they do in bone marrow. Fat has become an extremely popular source of stem cells. It is easy to harvest with minimal adverse events associated with the harvesting and often significant improvement in health because of the harvesting. Fat is often present in large volumes.

How refined do stem cells need to be?

If we transfer stem cells as intact fat grafts from liposuction (lipoaspirate) the stem cell concentration will be approximately half that which was present in the original donor site. I.E. Liposuction removes twice as many Adipocytes (fat cells) than stem cells. This means that after liposuction the remaining fat is stem cell enriched, less inflamed and healthier. This stem cell poor lipoaspirate is still potent enough to produce new nerve growth, fibroblast and collagen, new capillaries, etc.

If we reduce the number of fat cells in the lipoaspirate but retain the stem cell numbers we then have condensed lipoaspirate. This is thought to be associated with fewer adverse events than lipoaspirate. When it becomes possible to selectively remove adipocytes we will have stem cells attached to their own scaffold. The advantages of this include easier cell preparation which means less cost to the patient and we know that as the cells are anchored to their scaffold they will not migrate and be lost to the target.

Separating the cells from fat and adding them to lipoaspirate gives stem cell enriched lipoaspirate which can usefully contain 300% more cells.

Dissolving the collagen structure that holds all the cells together allows cell separation in a centrifuge. This will yield a Stromal Vascular Fraction (SVF) pellet of cells. This pellet of SVF cells is proving to be more potent than pure adipose derived stem cells. We have used this SVF pellet to treat Osteoarthritis of the knee with great success. Other groups using pure stem cells to treat OA have been dissappointed1. This appears to indicate that the stem cells work better when accompanied by all the other cells present in the SVF. Purifying stem cells involved expanding the cells in culture. This is expensive, takes time and introduces the risk of infection and a theoretical risk of mutation during cell multiplication. Stem cells from bone marrow are present in such small numbers that they must be expanded in culture to be a clinically useful treatment.

Are all cells stem cells

At a Stem Cell Conference in Korea in October 2009 Arnold Kaplan, stem cell scientist of more than 30 years and an icon in the industry stated that he was wrong. There was no such thing as a stem cell! Instead we have a bag of DNA that changes nature freely. Cells can move from embryonic to mature somatic cells such as skin, muscle or fat and can dedifferentiate all the way back to embryonic (Induced Pluripotent Stem Cell iPSC). They can also move sideways – Myoblasts can become Osteoblasts etc. As these cells change we are presented with windows of opportunity within which to manipulate or influence their level of activity and future direction of differentiation.

1Kang Sup Yoon et al; Autologous adipose tissue derived mesenchymal stem cells: clinical trials for osteoarthritis. IFATS 2009.

Cellular Therapy in context

Cellular therapy is any treatment that has an effect on cells. Cell therapy is the use of cells to treat cells.

Colostrums contain a lot of maternal antibodies and some growth factors. In particular TGF (Transforming growth Factor) has the ability to attract stem cells.

Platelet Rich Plasma is a rich source of growth factors. They have direct stimulatory and inhibitory actions on tissues as well as attracting stem cells (TGF)

Stromal Vascular Fraction Cells contain stem cells, progenitor cells, pericytes, granulocytes, etc. They are capable of secreting a wide range of growth factors and cytokines.

Cultured Stem Cells are single cells that have been multiplied in culture dishes to obtain large numbers.

We are still seeing clinical trials using Colostrum, PRP, or SVF cells which demonstrate zero efficacy when we know they can work. These trials fuel criticism of these treatments.

We still need to define the optimal formulation and dosage of these products. Often no data is collected on the patients with regard to what is actually put into the patient in terms of total platelet concentration, or white blood cell concentration, or immunoglobulin mix, or cell numbers and viability. Importantly, we also need a better understanding of the mechanisms behind each constituent. Immunoglobulin numbers and mix vary with the health and medical history of the maternal donor. Platelet numbers vary month by month. The cell numbers recovered from the fat of patients varies widely. It is not yet possible to predict what number of immunoglobulins or cells that will be recovered. It is very important that we know how many cells we have used and what percentage were viable. It is only with this data that we will begin to understand why treatments are very successful, only slightly successful or not successful at all.

PRP Criticism

Category : Medicine
Posted on : February 23, 2010 3:35 PM, by PalMD

Several months ago, Dr. Val Jones wrote about a growing fad in the treatment of musculoskeletal disorders. The therapy, called platelet rich plasma (PRP) injection, involves taking a small amount of blood from a patient, spinning it down in a centrifuge, and then injecting the plasma component into…somewhere. This treatment is becoming increasingly popular, and can be very lucrative for doctors. But does it work? Blood platelets are very biologically active particles and plasma is not a bland fluid. Platelets and plasma contain many biologically active molecules, some of which may be implicated in “healing”. This gives PRP at least a veneer of plausibility, but like any other treatment, plausibility is only the first step.

There have been a few human studies of PRP. A recent article in the Journal of the American Medical Association (JAMA) showed no difference between PRP and saline injections for chronic Achilles tendon problems.

A small pilot study looked at PRP for the treatment of a particular periodontal disease, and found some possible benefit.

Another interesting study looked at PRPs affect on the healing of anterior cruciate ligament (ACL) grafts in the knee. This study included long term (two year) follow up, and found no benefit.

And that’s really about it. There is little evidence to support platelet rich plasma for the treatment of anything. And yet it is being hyped and sold everywhere as a miracle cure for musculoskeletal injuries. Perhaps more studies will enlighten the issue further, but at this point, PRP is nothing but expensive snake oil, and those who promote and use it should re-examine the data and their ethics.

Answer to Criticism

These are valid points. If we wish to know who will respond and how much or how little improvement they will get we need to collect and publish this data.