Horses are predisposed to traumatic wounds that can be labor intensive and expensive to manage. Skin has a considerable potential for efficient and functional repair however, while cutaneous repair is a regenerative process in the fetus, this capability declines in late gestation as inflammation and scarring alter the outcome of healing. The historical gold standard for replacement of lost skin is the autologous skin graft. However, the horse's lack of redundant donor skin limits the practicality of full-thickness grafting to smaller wounds; moreover, graft failure is relatively common in equine patients as a result of infection, inflammation, fluid accumulation beneath the graft, and motion. Tissue engineering has emerged as an interdisciplinary field with the aim to regenerate new biological material for replacing diseased or damaged tissues or organs. In the case of skin, the ultimate goal is to rapidly create a construct that effects the complete regeneration of functional skin, including all its layers and appendages. Moreover, an operational vascular and nervous network, with scar-free integration within the surrounding host tissue, is desirable. For this to be achieved, not only is an appropriate source of cells required, but also a scaffold designed from natural or synthetic polymers. The newly created tissue might finally meet the numerous needs and expectations of practitioners and surgeons managing a catastrophic wound in a horse.
Summary Reasons for performing study : Marginal osteophytes represent a well known component of osteoarthritis in man and animals. Conversely, central subchondral osteophytes (COs), which are commonly present in human knees with osteoarthritis, have not been reported in horses. Objectives : To describe and compare computed radiography (CR), single‐slice computed tomography (CT), 1.5 Tesla magnetic resonance imaging (MRI), and histological features of COs in equine metacarpophalangeal joints with macroscopic evidence of naturally‐occurring osteoarthritis. Methods : MRI sequences (sagittal spoiled gradient recalled echo [SPGR] with fat saturation, sagittal T2‐weighted fast spin echo with fat saturation [T2‐FS], dorsal and transverse T1‐weighted gradient‐recalled echo [GRE], and sagittal T2*‐weighted gradient echo with fast imaging employing steady state acquisition [FIESTA]), as well as transverse and reformatted sagittal CT, and 4 computed radiographic (CR) views of 20 paired metacarpophalangeal joints were acquired ex vivo. Following macroscopic evaluation, samples were harvested in predetermined sites of the metacarpal condyle for subsequent histology. The prevalence and detection level of COs was determined for each imaging modality. Results : Abnormalities consistent with COs were clearly depicted on MRI, using the SPGR sequence, in 7/20 (35%) joints. They were identified as a focal hypointense protuberance from the subchondral plate into the cartilage, at the palmarodistal aspect (n = 7) and/or at the very dorsal aspect (n = 2) of the metacarpal condyle. COs were visible but less obvious in 5 of the 7 joints using FIESTA and reformatted sagittal CT, and were not identifiable on T2‐FS, T1‐GRE or CR. Microscopically, they consisted of dense bone protruding into the calcified cartilage and disrupting the tidemarks, and they were consistently associated with overlying cartilage defects. Conclusions : Subchondral osteophytes are a feature of osteoarthritis of equine metacarpophalangeal joints and they may be diagnosed using 1.5 Tesla MRI and CT. Potential relevance : Central subchondral osteophytes on MRI represent indirect evidence of cartilage damage in horses.
Abstract Objective —To clone full-length equine pigment epithelium-derived factor (PEDF) complementary DNA (cDNA) and to evaluate its temporal expression during repair of wounds in horses. Animals —4 clinically normal 2-to 3-year-old Standardbred mares. Procedures —Full-length equine PEDF cDNA was cloned by screening size-selected cDNA libraries derived from biopsy specimens obtained from the wound edge 7 days after experimental creation of a 6.25-cm 2 full-thickness wound in the skin of the lateral thoracic wall. Expression was evaluated in normal skin and in biopsy specimens obtained weekly from experimentally induced wounds on the trunk and limbs of horses. Temporal gene expression was determined by use of reverse transcriptase PCR assay. Results — Equine PEDF shared 87% sequence and 88% peptide homology with human PEDF. Wounding caused upregulation of PEDF mRNA, which did not return to baseline by the end of the study in either anatomic location. Relative overexpression was evident in wounds on the trunk, compared with expression for wounds on the limbs. Conclusions and Clinical Relevance —This study characterized full-length equine cDNA for PEDF and determined that the gene for PEDF appeared to be upregulated in response to dermal wounding. Although the cause of exuberant granulation tissue is probably multifactorial, these data suggested that PEDF, via its potent antiangiogenic capabilities, may contribute to superior healing in wounds on the trunks of horses by protecting such wounds from excessive formation of vascular granulation tissue that characterizes wounds on the limbs of this species.
Wounds in horses often exhibit sustained inflammation and inefficient vascularization, leading to excessive fibrosis and clinical complications such as "proud flesh". Orf virus-derived proteins, vascular endothelial growth factor (VEGF)-E and interleukin (ovIL)-10, enhance angiogenesis and control inflammation and fibrosis in skin wounds of laboratory animals.The study aimed to determine if equine dermal cells respond to VEGF-E and ovIL-10. Equine dermal cells are expected to express VEGF and IL-10 receptors, so viral protein treatment is likely to alter cellular gene expression and behaviour in a manner conducive to healing.Skin samples were harvested from the lateral thoracic wall of two healthy thoroughbred horses.Equine dermal cells were isolated using a skin explant method and their phenotype assessed by immunofluorescence. Cells were treated with recombinant proteins, with or without inflammatory stimuli. Gene expression was examined using standard and quantitative reverse transcriptase PCR. Cell behaviour was evaluated in a scratch assay.Cultured cells were half vimentin(+ve) fibroblasts and half alpha smooth muscle actin(+ve) and vimentin(+ve) myofibroblasts. VEGF-E increased basal expression of IL-10 mRNA, whereas VEGF-A and collagenase-1 mRNA expression was increased by ovIL-10. In cells exposed to inflammatory stimulus, both treatments dampened tumour necrosis factor mRNA expression, and ovIL-10 exacerbated expression of monocyte chemoattractant protein. Neither viral protein influenced cell migration greatly.This study shows that VEGF-E and ovIL-10 are active on equine dermal cells and exert anti-inflammatory and anti-fibrotic effects that may enhance skin wound healing in horses.
We compared the ability of 1.5 T magnetic resonance imaging (MRI), computed tomography (CT), and computed radiography (CR) to evaluate noncartilaginous structures of the equine metacarpophalangeal joint (MCP), and the association of imaging changes with gross cartilage damage in the context of osteoarthritis. Four CR projections, helical single-slice CT, and MRI (T1-weighted gradient recalled echo [GRE], T2*-weighted GRE with fast imaging employing steady-state acquisition [FIESTA], T2-weighted fast spin echo with fat saturation, and spoiled gradient recalled echo with fat saturation [SPGR-FS]) were performed on 20 racehorse cadaver forelimbs. Osteophytosis, synovial effusion, subchondral bone lysis and sclerosis, supracondylar lysis, joint fragments, bone marrow lesions, and collateral desmopathy were assessed with each modality. Interexaminer agreement was inferior to intraexaminer agreement and was generally moderate (i.e., 0.4<κ<0.6). Subchondral bone sclerosis scores using CT or MRI were correlated significantly with the reference quantitative CT technique used to assess bone mineral density (P<0.0001). Scores for subchondral lysis and osteophytosis were higher with MRI or CT vs. CR (P<0.0001). Although differences between modalities were noted, osteophytosis, subchondral sclerosis, and lysis as well as synovial effusion were all associated with the degree of cartilage damage and should be further evaluated as potential criteria to be included in a whole-organ scoring system. This study highlights the capacity of MRI to evaluate noncartilaginous changes in the osteoarthritic equine MCP joint.
Abstract Veterinarians and veterinary medicine have been integral to the development of stem cell therapies. The contributions of large animal experimental models to the development and refinement of modern hematopoietic stem cell transplantation were noted nearly five decades ago. More recent advances in adult stem cell/regenerative cell therapies continue to expand knowledge of the basic biology and clinical applications of stem cells. A relatively liberal legal and ethical regulation of stem cell research in veterinary medicine has facilitated the development and in some instances clinical translation of a variety of cell‐based therapies involving hematopoietic stem cells and mesenchymal stem cells, as well as other adult regenerative cells and recently embryonic stem cells and induced pluripotent stem cells. In fact, many of the pioneering developments in these fields of stem cell research have been achieved through collaborations of veterinary and human scientists. This review aims to provide an overview of the contribution of large animal veterinary models in advancing stem cell therapies for both human and clinical veterinary applications. Moreover, in the context of the “One Health Initiative,” the role veterinary patients may play in the future evolution of stem cell therapies for both human and animal patients will be explored.
