Regenerative therapy for horse laminitis

Regenerative therapy for horse laminitis Grolli Stefano Department of Veterinary Science, University of Parma, Italy Abstract Laminitis is a highly debilitating disease of the foot of the ungulates and is considered one of the most important horse diseases. Laminitis can occur subacutely, acutely or chronically, and it is characterized by pathological changes of the complex lamellar structures that maintain the appendicular skeleton within the hoof. This results in foot pain, lameness, gait abnormalities. In chronic cases, the distant phalanx may penetrate the sole of the hoof. The prognosis in severe cases is poor because the changes become irreversible and secondary infections are common. Laminitis is a multifactorial disease that involve perturbation of the vascular, haematological and inflammatory homeostasis of the foot. Digestive disorders, septic or non-septic endotoxiemia, metabolic syndromes (insulin resistance, obesity), and trauma have been associated with the onset of the disease. Interestingly, the pathogenesis of laminar failure resembles what is observed in metabolic syndromes and sepsis-induced organ failure in human. At the molecular and cellular level, the key factors involved in laminitis include leukocytes infiltration, pro-inflammatory cytokines secretion, local inflammation, extracellular matrix degradation, and endothelial/vascular dysfunction. Since the vascular bed is incapsulated between the distal phalanx bone and the hoof wall, this results in increased tissue pressure, oedema, and veno-constriction. A “gold standard” therapy is not available for laminitis. Current therapies include identification and treatment of the underlying disease, systemic anti-inflammatory medications, appliances changing the biomechanical forces on the digit. Mesenchymal Stem Cells (MSCs) and Platelet Rich Plasma (PRP) are gaining popularity in the treatment of equine tendonitis and soft tissue healing, where different authors report positive results. We hypothesized that the administration of MSCs and PRP could contribute an anti-inflammatory and pro-angiogenic environment, as well as a stimulus to injured tissue regeneration via direct (MSCs replication) as well as indirect (paracrine effects, microvesicles release, etc.) mechanisms. An experimental protocol based on the local intravenous administration of MSCs and PRP in horses affected by chronic laminitis was developed. Seven horses with severely compromised venogram (grade III and IV) were enrolled. The patients had been previously treated by conventional therapies but had poor prognosis. Following loco-regional analgesia, MSCs and PRP ( 15-20x106 cells in 15 ml of PRP) were injected into the lateral or medial digital vein. The inoculation was repeated three times, at 1-month intervals. The first inoculation was performed using allogeneic MSCs, while the second and third inoculation used autologous MSCs. The outcome was evaluated in the short term to assess the safety of the treatment, and in the long term (6-18 month) to evaluate its clinical efficacy. Although the number of animals enrolled is limited, both clinical observation and venography demonstrated an improvement of the general conditions of all horses. No adverse events were reported during the follow-up and the horses returned to walk and graze in comfortable conditions.