Cells are also beginning to be investigated in the laboratory but have not yet been applied to the bmjopen-2016-011824 clinical 2-(2,4-Dichloro-5-fluorophenyl)oxirane scenario.Culture-expanded bone marrow-derived mesenchymal stem cellsBone marrow-derived mesenchymal stem cells (BMMSCs) have the advantages of being easily and relatively noninvasively obtained and have a greater capacity to differentiate into tissue types of the musculoskeletal system in comparison with other MSCs [8-10]. Furthermore, BM-MSCs have received the most scientific attention and hence are the best characterized. One disadvantage of culture-expanded BM-MSCs is the time lag of 3 to 6 weeks from bone marrow aspirate until treatment. This time lag is necessitated by the time required to grow the MSCs. Bone marrow is collected from the sternum or the tuber coxae of horses under sedation or can be collected intraoperatively if the horse is already anesthetized. The horse has seven marrow spaces in the sternum, and marrow spaces 3 to 5 are the largest (up to 5 cm in diameter). Ultrasonography can be used to isolate the marrow space but is not necessary if one is familiar with the regional anatomy. Bone marrow is typically aspirated from the proximal humerus, proximal femur, or tuber coxae in dogs.TendonitisBM-MSCs was first reported in 2003 [15]. More recently, a small case control study (n = 11) demonstrated that, as a result of BM-MSCs, 90 of treated horses successfully returned to pre-injury athletic function and race horses suffered no re-injury of the superficial digital flexor tendon after 2 years whereas Methyl 4-chloro-5-fluoroanthranilate all of the horses of a control population suffered from re-injury [16]. In an unblinded, uncontrolled case series, Godwin and Smith [17] reported on 141 horses treated with cultured BM-MSCs with at PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/9144744 least a 3-year follow-up. The authors reported a significant PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/24083752 decrease in re-injury rate for National Hunt race horses but not flat-track Thoroughbred race horses treated with BM-MSCs when compared with conventionally treated historical controls (23 to 66 ). To date, preclinical and clinical studies have focused on the ability of stem cells to enhance tissue regeneration and have not investigated the potential immunomodulatory roles of stem cells for tendon repair. This is most likely simply a matter of timing, with the concept of immunomodulation being more recent than the more traditional paradigm of stem cells differentiating and functioning as tissuespecific cells. Although the above-mentioned studies have documented stemness of the cells to varying degrees, tumor, ectopic bone, or cartilage formation has not been observed in either clinical or research investigations.Cartilage injury/osteoarthritisThe use of culture-expanded BM-MSCs for the treatment of tendon injuries is supported by experimental investigations in horses and laboratory animals in which MSCs were implanted in surgically or collagenase-induced tendon lesions. These studies have shown favorable effects on tissue organization, composition, and mechanics of MSC-implanted tendons and ligaments [11-14]. These studies vary in experimental design with respect to the number of BM-MSCs implanted (0.5 to 10 ?106), vehicle for suspension (plasma, phosphate-buffered saline, bone marrow supernatant), and time post-injury to injection (up to 2 weeks). The clinical application ofCulture-expanded BM-MSCs have been evaluated in an equine model of acute cartilage injury in which 15-mmdiameter full-thickness articular cartilage defects were created on the lateral trochlea.