Do subchondral bone and cartilage follow a common pathway in early stage post-traumatic osteoarthritis?
Dr. A Cruz
This study will investigate the changes occurring in cartilage and SCB in early stages of arthritis using a post-traumatic osteoarthritis model.
Chip fractures and arthritis are the most common causes of lameness costing the horse industry close to $1 billion. The bone immediately beneath the cartilage known as the subchondral bone (SCB) is thought to play an important role in the disease mechanism, but it is uncertain whether cartilage or SCB injury is the primary player.
In many cases, horses had well-established arthritis without detectable SCB lesions, while others had severely affected SCB without cartilage lesions. To understand the significance of an early diagnosis of SCB disease, it would be advantageous to identify the sequence of events leading to arthritis and how SCB and cartilage respond to impact trauma.
Understanding the mechanisms leading to irreversible arthritis and correlating them with biomarkers in synovial fluid will allow us to identify very early disease and in this manner draft potential interventions to prevent it.
Functions of Equine Clara Cell Secretory Protein
Dr. D. Bienzle
This study will investigate why horses are particularly prone to lung inflammation associated with RAO and how the condition could be best diagnosed and treated early on.
Horses that are stabled indoors are prone to develop a lung disease called Recurrent Airway Obstruction (RAO) or “heaves”. This disease is caused be an allergic-type reaction to mould spores and bacterial components in dusty air associated with poor quality hay or bedding. Affected horses have lung inflammation that subsides when they are housed outdoors or treated with specific drugs, and recurs when they are exposed to dusty air.
A key protein, CCSP has been identified and is involved in countering lung inflammation. CCSP is markedly decreased in horses with RAO. Most unusually, horses have 3 copies of the gene for CCSP, and each produces a slightly different protein. This study will determine which CCSP genes are expressed in the lung, what the functions of the different proteins are, and why inflammation progresses in horses despite extra copies of CCSP. It is a belief that horses that develop RAO express a gene that is not effective in countering lung inflammation.
Proliferative potential, tri-lineage potency and allogenic immunogenic evaluation of equine cord blood stem cells
Dr. D. Betts
This study will investigate the most suitable stem cell to treat joint cartilage defects in horses.
It is generally recognized that cartilage lesions over a certain size do not heal spontaneously and that there is no universal treatment for cartilage defects. Comparative studies of human stem cells from bone marrow, fat and cord blood have shown that cord blood stem cells are difficult to isolate, but may be less immunogenic, more potent and have a longer life span than stem cells from fat and bone marrow.
Stem cells from foal umbilical cord blood were recently isolated and have demonstrated their potential to form bone, cartilage and fat in petri dishes. The studies outlined in this proposal aim to optimize the procedures for the isolation of equine mesenchymal stem cells (eMSCs) from umbilical cord blood.
MSCs from cord blood will be compared to MSC derived from adipose tissue and bone marrow in terms of its proliferation and differentiation potential. These three different stem cell sources will be evaluated for their immunological profile and immunigenicity and for potential allogenic (use in another horse than the one donating the stem cells) stem cell-based therapies in the horse.
The effect of racetrack characteristics on the horse-hoof-track interaction in Standardbred horses
Dr. J. Thomason
This study will evaluate the variation in track hardness and surface roughness, changes in track profile from straight to curve, and test whether these track measurements affects two important measurements of loading on the hoof: the accelerations of the hoof at impact and the peak forces at midstance.
How much do racing and training track surfaces contribute to injury and lameness in Standardbred horses? It is known that training intensity, hoof shape, conformation, shoe type, and the different properties of training and racing tracks are among the many factors that predispose an animal for injury.
Data from the track will be combined with laboratory studies that mimic the loading conditions on cadaver limbs and determine corresponding stresses and strains in the bones of the foot (cannon, long pastern). The outcome of this study will be a better understanding in the role of the racetrack in lameness and breakdown of harness horses.
The role of vascular wall strain in arterial calcification in horses
Dr. J. Runciman
This study will determine the mechanical effects of arterial geometry and calcification on the pulmonary artery wall. MR images of an artery under pressure (during exercise and at rest) will be taken to develop computer models. This model will then be used to investigate detailed wall stresses and strains in the pulmonary artery.
Pulmonary artery calcification is a process where calcium is deposited within the walls of the pulmonary artery found in the horse’s lung. In one recent study 27% of all surveyed thoroughbreds were found to have the condition.
Calcium deposits tend to stiffen the artery wall and have been linked to premature death in horses. The mechanism regulating calcification of the artery is not currently known although current hypotheses include biochemical factors, a high calcium diet, and arterial geometry. The pulmonary artery is a highly branched structure having areas of increased stress and strain within its walls.
Magnetic Resonance Imaging evaluation of SPIO labeled Equine Mesenchymal Stem Cells and in vivo tracking SPIO labeled Equine Stem Cell Therapy in a tendonitis model
Dr. R. Cruz
This study will evaluate the feasibility of labeling equine bone marrow derived mesenchymal stem cells with SPIO and to evaluate the applicability of MRI to monitor and track SPIO labeled cells after transplantation into live horses with a tendon injury.
Previously, the only way to evaluate the location and viability of transplanted cells was by means of surgery or final euthanasia of experimental animals. Magnetic Resonance Imaging (MRI) is currently widely used for clinical diagnosis due to its exquisite property to image and show differences among different kinds of soft tissues as well as skeletal tissue and associated structures.
MRI imaging is based on changes in magnetic characteristics of soft tissues and certain substances. Soft tissue cells can be labeled with Superparamagnetic iron oxide (SPIO) and identified by MRI. Therefore soft tissue cells such as Mesenchymal Stem Cells (MSCs) and other pluripotential stem cells can be labeled with SPIO and then transplanted into an animal model to track the localization of the cells by means of MRI.
Comparison of cardiovascular function in isoflurane-anesthetized horses administered lidocaine and medetomidine constant rate infusions during elective and emergency surgery
Dr. A. Valverde
This study will compare cardiovascular function in sick and healthy horses undergoing general anesthesia with an anesthetic protocol that combines injectable and inhalational anesthetics.
General anesthesia in horses is associated with significant risk. Anesthetic deaths have been estimated at approximately 1 case for every 100 anesthetics when inhalational anesthetics are used as the main component to maintain general anesthesia, whereas injectable anesthetics alone decrease mortality 3-fold. In addition, mortality is 9 times higher in sick (e.g., colic) than in healthy anesthetized horses.
Mortality associated with general anesthesia is usually due to cardiac arrest and fractures. Since mortality is lower in horses that are anesthetized and maintained with injectable anesthetics, it is possible that a combination of injectable anesthetics, throughout the anesthetic period, with inhalation anesthesia will result in a more stable cardiovascular system in horses compromised due to disease.
Determination of the presence of opioid receptors on bone tissue in horses and their binding to morphine
Dr. A. Valverde
This study will investigate the feasibility of morphine administration to bones of horses’ extremities in exerting an analgesic effect as it has been described for people.Orthopedic pain is a common occurrence in horses that suffer from a wide range of injuries including fractures, tendon and ligament breakdowns, and synovial sepsis. Controlling pain is of paramount importance for the welfare of the horse. Several modalities of analgesia are available if pain originates in the hindlimbs, including peripheral nerve blocks, systemic analgesics, and epidural techniques. The latter modality is the most effective in avoiding whole body effects from the drugs and providing analgesic effects of long duration.
Currently the only available method of providing analgesic management to the forelimbs and thereby avoiding systemic side effects is with peripheral nerve blocks. Although peripheral nerve blocks with local anesthetic agents completely desensitise the leg, this can lead to the horse taking a bad step and potentially causing an injury.
Modern techniques used in people for pain control originating from extremities involve the use of low dose of opioid analgesics administered topically on bones and joints. This could represent an alternative pain therapy for horses to avoid interference with leg mobility but allow effective pain control
Evaluation of broad range real time polymerase chain reaction (PCR) for diagnosis of septic arthritis
Dr. S. Weese
This study will use real time PCR and DNA sequencing to detect bacterial DNA in samples from septic joints.
Septic arthritis, a bacterial infection of the joint, is a common and potentially devastating problem in adult horses and foals. Rapid institution of appropriate therapy is critical.
An important factor is prompt identification of the bacterium that is causing the infection, so that an appropriate antibiotic therapy can be started. However, bacterial culture can often be falsely negative with long wait times for culture results. Molecular diagnostic methods may be better alternatives to traditional culture tests.
This method allows for detection of small numbers of bacteria, bacteria that cannot be grown using standard culture methods and bacteria that may be poorly viable in a sample but still the cause of infection.
If validated, real time PCR and sequencing could provide accurate and rapid testing for the cause of joint infections, and facilitate timely use of appropriate antibiotic therapy.
Mechanisms of maintenance and loss of early pregnancy
Dr. K. Betteridge
This study investigates how the horse embryo attaches to the endometrium (lining of the uterus) during the critical third week of pregnancy in order to understand the mechanism behind embryo attachment in the mare.
At this stage the embryo is still enclosed in a ‘capsule’ and is known as a conceptus.During the study, conceptuses and endometrium will be collected from both normal and “failing” pregnancies in order to identify changes in proteins, steroid hormones and other molecules that change in the conceptus and uterus during this period.
Previous studies have identified target molecules that help us understand how the embryo exchanges signals with the mare and allows the embryo to attach to the uterus. Analyzing the presence and absence of the target molecules in normal and failing pregnancies will help assess the significance of any differences found.
The work will help explain conceptus interaction with the endometrium that is essential to pregnancy maintenance and which, when disrupted, results in pregnancy failure. This will be key to the development of diagnostic tests of reproductive health and, possibly, to new treatments for infertility.