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Review Article – Trying to Shed Light on the Use of Stem Cells in Equine Orthopaedics

Take Home Message

The field of mesenchymal stem cell research is an ever evolving science and much work is still needed in the clinical application of this treatment modality. Some good basic science studies have been done over recent years but equally importantly, clinicians need to continue communicate openly on the success and failures with this emerging modality under evidence-based (EBM) conditions.
 
Given the amount of information and misconception that has been introduced into the veterinary and lay press, Drs. Frisbie and Roger Smith of the Royal Veterinary College, London published a review article to try and clarify key points of the stem cell technology and research. The following is a summary of that publication.
 
The manuscript focused on the clinical use of mesenchymal stem cells (MSCs) in horses and the justification for, as well as issues surrounding, their use. Many of the early reports used bone marrow as a source of these cells, but other sources have been more recently demonstrated. For example, muscle, cartilage, and adipose tissue all have been shown to contain multipotent MSCs. Direct comparisons of the two most commonly used clinical sources of cells, bone marrow and fat derived, have shown superior cells from bone marrow when tested in a joint environment. Work to compare the best source for tendon is yet to be published; however, work done after the current publication suggests bone marrow may be better for tendon repair as well.
 
Various methods of preparing stem cells from bone marrow aspirates have been used. They range from injecting the raw aspirate to picking out stem cells and culture expanding them. While the direct injection of aspirate was first labeled as stem cell treatment it has been shown only 2,000 stem cells/ml are contained in such a preparation, thus significantly below what is believed to be needed (1-5 million cells). More recently bone marrow concentration has been proposed. This method concentrated the stem cells found in the raw aspirate approximately 12 times however, given the initial volume limitations the final number of cells is usually in the hundreds of thousands, not millions. Thus culture expanding the stem cells to provide adequate stem cell numbers is still the gold standard. While some have looked at using allogeneic cells or cells derived from another horse, this process has not been approved by the Food and Drug Administration (FDA).
 
Research has been done looking at horses with experimental osteoarthritis, in this study published in the Journal of Orthopaedic Research a significant decrease in PGE2 (an inflammatory mediator) was seen in response to a single treatment with bone marrow derived stem cells. While this is encouraging, it is not clear given the cost of stem cell treatment that the improvement warrants the expense. Stem cells have also been used to treat clinical cases of joint disease. A group of horses that have undergone surgery to ascertain a definitive diagnosis as well as determine the degree of pathology were followed for almost two years. The majority of these horses had meniscal damage and were treated surgically, as well as with bone derived culture expanded stem cells. These horses were more likely to go back to work compared to a previously published group of horses that received surgery alone, especially in cases of severe damage. These results have provided encouragement for continued intraarticular treatment of horses with stem cells.
 
The publication also detailed reports of horses that sustained tendon or ligamentous injuries that were treated with rehabilitation and stem cells and then compared to those treated with rehabilitation alone. It has been shown that stem cells can help these horses go back to work and in flat racing horses decrease the incidence of re-injury after they have gone back to work, when compared to rehabilitation alone.
 
In conclusion, the field of stem cell research is an ever evolving science and much work is still needed in the clinical application of this treatment modality. It is important for clinicians to continue to communicate openly on the success and failures with the emerging modality, under evidence-based (EBM) conditions.

References

  1. Frisbie D.D., Smith R.W. Review Article Clinical update on the use of mesenchymal stem cells in equine orthopaedics. Equine Vet J, 2010; 42:86-89.
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