Page 14 - 25 May 2012

Culture expanded bone marrow derived stem cells appear to be the state of the art in equine medicine today.
Dr. David D. Frisbie
Orthopaedic Research Center, College of Veterinary Medicine and Biomedical Sciences, Colorado State University
The use of mesenchymal stem cells has been reported as a treatment for a number of disease processes in both humans and animals. The peer reviewed literature contains a substantial number of scientific studies performed in the laboratory, but there are few clinical reports showing improved outcomes following stem cell treatment, especially in horses.
WHAT ARE STEM CELLS AND HOW DO WE GET THEM?
To help better understand the field, we must define what we call a stem cell. In general terms, a stem
cell can be defined as a master cell that is capable of reproducing itself and that has the potential to become one of the body’s more specific or differentiated cells, of which there are hundreds. It is important to note the adult stem cells differ from fetal or embryonic stem cells, the latter of which is often discussed in the press from an ethical standpoint. In equine medicine, the safety of fetal stem cells is just now being investigated and will need to undergo a more rigorous governmen- tal approval process prior to commercialization. Adult stem cells can be isolated from many of the body’s various tissues, but most research has focused on bone derived cells, which will be the main focus of this article. Fat is also used as an origin of stem cells and was the source used by the first commercial veterinary laboratory. However, two published equine studies found fat derived cells to be inferior when looking
at differentiation into musculoskeletal tissue such as cartilage and tendon. (Vidal et al. 2008; Kisiday et al. 2008). Further, researchers looking into equine stem cells are focusing on bone derived cells suggesting this cell source will be used in the future.
Bone derived cells in horses are most often obtained from an aspirate of either the hip or sternum with apparent minimal discomfort. The procedure typically takes less than 15 minutes and can be done stand-
ing under light sedation. Historic reports suggested direct treatment with an unmodified bone marrow aspirate was considered “stem cell” therapy (Herthel 2001). This is no longer an accepted description given only 0.01% to 0.001% of the mononuclear cells col- lected this way are stem cells. Instead the term “stem cell treatment” is reserved for the process by which the stem cells are selected and then expanded by
cell culture technique to provide adequate numbers. While the absolute number of stems cells required to improve clinical outcomes is not definitively known,
compilation of published laboratory research sug-
gests that 5 million or greater cells are necessary for significant outcomes. To date, obtaining such numbers can only be accomplished through culture expansion techniques. Therefore, the state of art today is to col- lect a low volume bone marrow aspirate and culture expand the stem cells prior to injection into the joint or tendon. This is different from umbilical derived cells from blood or cells from adipose tissue that are injected without culture expansion.
RESULTS OF CLINICAL STUDIES
Reports of long term clinical improvements follow- ing stem cell treatment have been published in the peer reviewed literature by two groups, notably both using bone derived cells. The first group, led by Roger Smith and others from the Royal Veterinary College (RVC), has focused on the treatment of superficial digital
flexor tendon (SDF) injuries. This group has compel- ling evidence that treating injured SDF with stem cells decreases the re-injury rate by almost half, a significant step forward in tendon treatment (Godwin et al. 2012). A similar decrease in re-injury rate with SDF and liga- mentous injuries, including chronic suspensory lesions, has also been observed by researchers at Colorado
State University (CSU). Furthermore, CSU research-
ers have obtained long term follow up on treating joint injury; especially involving the meniscus in the stifle. Specifically, they have shown a significant improvement in grade 3 meniscal tears after injection stem cells after surgery, (60% return to work, Ferris et al. 2011) com- pared to surgery alone (6% return to work, Walmsley et al. 2003). While much more work on dosage and timing of treatments is required, initial results following clinical cases in a CSU study suggest that treating once; at least 30 days post injury and with at least 5 million cells appears to provide good long term outcomes. Recently a randomized controlled study demonstrated waiting lon- ger than 2 weeks post injury was “critical for long-term amelioration of tendinopathy and chondroid metaplasia” in a sheep model utilized to mimic rotor cuff injuries/ tendon injury (Smith et al. 2012). Thus, early treatment with stem cells should be carefully reconsidered.
Also in the area of bone derived stem cell research, investigators at Cornell University found use of stem cells for the treatment of experimental created injuries and have some interesting results for both cartilage and tendon healing; the clinical applications of this work are hopefully forthcoming.
STEM CELLS
The treatment shows promise in horses.
by David D. Frisbie, DVM, PhD, Dipl. ACVS
on behalf of the Equine Research Coordination Group
14 SPEEDHORSE, May 25, 2012
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