Of stem cell-based technologies in veterinary medicine was first used by Herthel [3] to treat equine suspensory ligament desmitis. This application involved direct injection of large volumes (20 to 60 mL) of na e bone marrow aspirate obtained from the PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/14960617 sternum into an injured ligament. In this report of an uncontrolled, nonrandomized case series, the technique appeared to improve return to athletic function rates over conventional therapies. However, it is unlikely that the observed results were due to stem cells, as it became known that there are very few stem cells in bone marrow aspirate. Mesenchymal stem cells (MSCs) represent a very small fraction of the total population of nucleated cells from bone marrow from humans [4] and cats [5] and are presumed to be similar in other species, including the horse. These studies indicate that 0.001 to 0.01 of mononuclear cells isolated from a Ficoll density gradient of bone marrow aspirate are MSCs. The percentage of MSCs in raw bone marrow aspirate would be less than 0.001 to 0.01 because the technique of Ficoll density gradient isolation omits several types of nucleated cells, including granulocytes and immature myeloid precursors. Any clinical effect of bone marrow aspirate might be attributed to the numerous bioactive substances in the acellular fraction such as growth factors produced by cells or platelets. For example, bone marrow aspirate that is rendered acellular through freeze-thaw has some stimulatory effects on matrix synthesis when applied in vitro to tendons and ligaments [6,7].Stem cell products in clinical useThe clinical applications of stem cells At present, stem cell therapies in veterinary patients are not rigorously 3-Nitro-6-(trifluoromethyl)pyridin-2(1H)-one supervised by regulatory agencies in any country [1]. Unfortunately, this has led to the implementation of some therapies that have not demonstrated efficacy in vitro or 1-(Cyclopropylsulfonyl)-1,4-diazepane in preclinical animal studies. In general, the therapeutic role of stem cells in regenerative medicine is not fully understood. It is unclear whether stem cells journal.pone.0168728 ultimately function once differentiated into a tissue-specific cell such as a tenocyte or whether they primarily improve tissue repair through secretion of immunomodulatory and bioactive trophic factors or whether a combination of the two mechanisms occurs*Correspondence: laf4@cornell.edu 1 Department of Clinical Sciences, Cornell University, VMC C3-181, Ithaca, NY 14850, USA Full list of author information is available at the end of the article?2010 PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/9544797 BioMed Central Ltd?2011 BioMed Central LtdIn veterinary patients, three MSC-based approaches are currently used for the treatment of tendon, ligament, orFortier and Travis Stem Cell Research Therapy 2011, 2:9 http://stemcellres.com/content/2/1/Page 2 ofcartilage/joint injuries in horses or dogs. As stated previously, there are research-based but no clinical reports that document the use of stem cells to enhance fracture repair, nor are there any reports in cardiovascular, gastrointestinal, or neuroendocrine body systems. The first MSC-based method relies on a culture-expanded cell population derived from bone marrow aspirate, the second is another bone marrow aspirate-based approach using a concentrated mixed cell population derived from bone marrow aspiration, and the third method employs a mixed nucleated cell population derived from adipose tissue. Each technique has its strengths and weaknesses. Embryonic stem (ES) cells, induced pluripotent stem (iPS) cells, and cord bloodderived.