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Bone Marrow

Bone Marrow Aspirate Concentrate (BMAC)

BMAC was the first to be used for regenerative medicine primarily because scientists were not aware that mesenchymal stem cells (MSCs) were accessible in other tissues. Studies then showed that fat or adipose tissue contains 3-500 times more MSCs than fat.1,2,3   While the “soup” that MSCs of BMAC are floating around in contain growth factors that aid in natural healing and decrease inflammation, current techniques do not purify the BMAC to remove cells that are inflammatory such as red blood cells (RBCs) and white blood cells (WBCs). In the photos below, BMAC the red BMAC indicates the large concentration of RBCs. The yellow adipose indicates a pure product without RBCs.

BMAC

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ADIPOSE

Number of Nucleated Cells does not Equal Number of MSCs

Many studies using BMAC are deceiving as they count the total number or nucleated cells inferring that this qualifies their product as a “stem cell” procedure when in fact, very few nucleated cells are MSCs in patients over the age of 50. What is a nucleated cell?  RBCs, WBCs, synoviocytes and MSCs are all nucleated cells. A study published by Arnold Caplan, PhD, one of the world’s leading researchers in MSCs found that the number of MSCs in bone marrow sharply declines with age

For example, a 60 year old has 1 MSC per 1 million nucleated cells. There are 5 million nucleated cells per milliliter of bone marrow. So, a 60 year old has 5 MSCs/ml of bone marrow. The number of MSCs in adipose remains the same with age. A 60 year old has between 3,000-10,000 MSCs/ml of adipose.5 Why do the number of MSCs in bone marrow decline with age? Bone marrow is a cell factory. It produces 200 billion new red blood cells every day, along with white blood cells and platelets. The machines in the factory wear down over time and produce far fewer MSCs. While the size of the fat cells in adipose can increase, the number of MSCs remain constant.

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Recent Studies Show That Bone Marrow Does Not Contain Stem Cells and Results are Inconsistent When Used to Treat Cartilage Defects

In an analysis published in June 2019 of current available data on the use of bone marrow aspirate concentrate, authors reviewed 23 studies; 10 animal and 13 human. They found that cells in BMAC did not meet criteria for qualify them as MSCs and that studies have shown inconsistent outcomes with most studies using poor methodology and “low scientific rigor.” https://www.ncbi.nlm.nih.gov/pubmed/30871903

BMAC Harvest

Research shows that BMAC is clinically effective in certain circumstances, but harvesting is painful requiring the use of anesthesia or sedation and is technique-dependent. If not done correctly, blood, not bone marrow is harvested. There is also a risk of nerve injury. 6

Conclusion

While BMAC had its place in the past, current scientific evidence shows that adipose is clinically effective and has more MSCs. It is also easier to harvest and results in a product which far fewer inflammatory cells than BMAC. For these reasons, most of the recent studies published in orthopedic regenerative medicine use adipose.

References

1.Hass, Ralf, Cornelia Kasper, Stefanie Böhm, and Roland Jacobs. Different Populations and Sources of Human Mesenchymal Stem Cells (MSC): A Comparison of Adult and Neonatal Tissue-derived MSC. Cell Commun Signal Cell Communication and Signaling. 2011;9.1: 12.

2.Caplan A. Mesenchymal stem cells environmentally responsive therapeutics for regenerative medicine. Experimental & Molecular medicine. 2013;45(11):e54.

3.0Vangsness, et. A;. Umbilical cord tissue offers the greatest number of harvestable mesenchymal stem cells for research and clinical application: A literature review of different harvest sites. Arthroscopy. 2015; Sep; 31(9):1836-43

4.Caplan, A. Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J Cell  Physiol. 2007; 213(2):341-7

5.Choudry, et al. Subcutaneous Adipose Tissue–Derived Stem Cell Utility Is Independent of Anatomical Harvest Site. BioRes Open Access. 2015;4(1):131-145.

6. Irving I1Cooper MDurrant S. Sciatic nerve compression following bone marrow harvest. Bone Marrow Transplant.2000 Sep;26(6):705-6.