Abstract
Degenerative lesions of the equine foot and hoof, which include laminitis, navicular and deep digital flexor tendon (DDFT) injuries, are common debilitating diseases in horses. These lesions can be difficult to diagnose and treat in part due to the underlying pathology being multifactorial and complex. Accurate diagnosis requires costly high-level imaging and can lead to invasive surgical intervention. The use of blood biomarkers is becoming a reliable, noninvasive diagnostic adjunct for detecting local, tissue-specific diseases and disorders. The growing number of investigations of biomarkers may expound on the underlying causes of diseases and serve as a method to monitor treatment response. Biomarkers associated with inflammation, vascularity and cellular adhesion will serve as measurable mediators that can be monitored before and after cellular based treatments. Mesenchymal stem cells (MSCs) exhibit anti-inflammatory proprieties which act through a predominantly paracrine signaling fashion. In horses specifically, MSCs from various tissue sources inhibit inflammation through a prostaglandin mediated pathway. However, evidence relating to the efficacy of MSC therapy in equine patients is not well elucidated in literature. The objective of this project was to determine if blood collected from the jugular vein or the digital vein, that drains directly into the equine foot, contains detectable biomarkers of inflammation and vascular dysfunction in a disease specific manner. With these data, the next aim of this study is to use these biomarkers for the detection and monitoring of degenerative lesions in response to autologous MSC therapy. In this study we have measured baseline concentrations of cells and mediators (biomarkers) sampled from the jugular and digital vein in normal healthy horses, and in horses with inflammatory hoof and foot lesions (DDFT, navicular or laminitis). We have chosen biomarkers available in horses that are associated with inflammation, vascular permeability and cellular adhesion. Our data suggests that biomarkers in the digital vein are comparable to those sampled from the jugular vein in nearly every biomarker assessed. Each disease has unique characteristics that were used to create tentative biomarker panels. Preliminary data collected suggests laminitis to be a very inflammatory disease, demonstrating increased levels of IL-8 and CCL2. Navicular disease alternatively, demonstrated increased levels of the regulatory mediators PGE2 and IL-6, which were not noted in other disease groups. Horses sampled with DDFT injuries had the most vasculature properties, and is the only disease type with detectable levels of circulating VEGF. With this data, one horse from every disease group has been injected with autologous adipose derived MSCs. These results suggest there is a unique disease response to MSC administration, which is comparable in the jugular and digital vein. This varied response to MSC therapy highlights the distinct disease properties found through initial biomarker screening. Though preliminary, it is apparent that the disease response to MSC therapy is distinct for each disease investigated. This study is the first of its kind to attempt to understand the biological response in vivo to stem cell therapy in horses and may be directly applicable to the veterinary and human medicine.