Antwerp, BelgiumMarch 23-24, 2017From Nutritionto Disease and BackEuropean Equine Health & Nutrition Congress8th Edition
Current use of autologous bone marrow-derived stemcells (BMSCs) for equine joint injury and disease andcomparison of immunomodulatory properties ofequine allogeneic and autologous BMSCsC. Wayne McIlwraith, BVSc, PhD, FRCVS, DACVS, DACVSMRUniversity Distinguished Professor, Barbara Cox Anthony University Chairin Orthopaedics, Orthopaedic Research Center, Colorado State University,USAIntroductionArthroscopic surgery revolutionized our ability to treat joint injuries in the horseand return them to full athletic activity. However, limitations became recognizedin certain situations to achieving this goal including acute articular cartilage loss,soft tissue injuries of intra-articular ligaments and meniscus as well as chronicdisease leading to osteoarthritis (OA). This led to increasing the quest for betterregenerative therapies. New biologic therapies that have increased our ability torehabilitate joint injury and disease include protein therapies (autologousconditioned serum, platelet rich plasma) as well as cellular therapies. Cellulartherapies have revolved around the principal of mesenchymal stem cells (MSCs)and, in particular, our clinical success has been achieved with the use of bonemarrow-derived MSCs (BMSCs). These MSCs exert their effect in dual roles: 1)they can provide replacement units for expired cells and mesenchymal tissuesand, 2) have trophic effects on cells in their vicinity without generating newlydifferentiated mesenchymal phenotypes.Clinical use in the horseThe treatment of equine joint problems started with demonstration in a caprinemodel of OA that an intra-articular dose of 10 million autologous BMSCssuspended in HA compared to HA alone enhanced regeneration of medialmeniscus tissue as well as decrease in degeneration of articular cartilage,osteophyte remodeling and subchondral sclerosis. This led to a clinical studywith intra-articular BMSCs (approximately 20 million cells) injected intraarticularly into femorotibial joints showing a high rate of return to work and, inparticular, 73% success where there was articular cartilage damage and diffusechange on the condyle and 85% returning to work even when full thicknesscartilage damage/eburnation was also present in the articular cartilage1. Thereturn after meniscal tears treated arthroscopically was significantly enhancedwith BMSCs administered intra-articularly. We have also demonstratedaugmentation of healing of full thickness microfractured defects with intraarticular BMSCs.97
The potential for allogenic cellsWe have done two studies at Colorado State University looking at theimmunomodulatory effects of allogeneic BMSCs.3,4 This was because ofconcerns being raised regarding the potential safety and effectiveness ofallogeneic BMSCs including immunologic reaction to allogeneic cells. Weconducted studies to assess the immunologic properties of equine allogeneicBMSCs compared with those of autologous BMSCs. Comparisons were madebetween BMSCs of matched and mismatched donors (Irish Thoroughbreds andConnemara Ponies) in a study in collaboration with Dr. Bea Ranera andProfessor Frank Barry at the University of Galway in Ireland. MismatchedBMSCs inhibited proliferation of stimulated lymphocytes in a dose-dependentmanner with the greater suppression occurring at 1:10 ratio of BM-MSCs toPBMCs. Proliferation of CD4 and CD8 sub population decreased in 1:10 coculture with statistical significance in the case of CD8 cells, while that of theCD4/CD8 double-positive population was similar to the phytohaemagglutinincontrol. These results demonstrate a dose-dependent immunosuppression ofstimulated lymphocytes by mismatched equine BM-MSCs supporting theirfuture application in allo-MSC clinical treatment.3In a second study to assess inherent immunogenicity, the relative ability ofallogeneic and autologous BMSCs to stimulate spontaneous proliferation ofequine lymphocytes was compared4. The immunosuppressive activity of the twocells types was evaluated by adding autologous or allogenic BMSCs to activatedlymphocytes and assessing suppression of lymphocyte proliferation and IFNγproduction. Fifty-six allogeneic and 12 autologous combinations were evaluated.Studies were also done to elucidate mechanisms by which the MSCs suppresslymphocyte function. Potential mechanisms evaluated included production ofprostaglandin E2 (PGE2), nitric oxide, transforming growth factor-β, indoleamine, 2-3-dioxygenase.We found that autologous and allogeneic BMSCs both inhibited mild butequivalent levels of spontaneous lymphocyte activation in vitro. In in vitroassays assessing the ability of BMSCs to suppress activated lymphocytes, bothallogeneic and autologous BMSCs suppressed T-cell proliferation and IFNγproduction to an equal degree. The primary mechanism of equine BMSCsuppression of T-cells was mediated by PGE2. We concluded that allogeneicand autologous BMSCs are equivalent in terms of their immunomodulatoryproperties and stimulated peripheral blood mononuclear cells appear to triggerthe immunosuppressive properties of MSCs. Therefore, both cell types appear tohave equal potency in modulating inflammatory processes related to acute orchronic musculoskeletal injuries in the horse.4In further ongoing work we are showing that the reaction to in vivo intraarticular injection of both autogenous and allogeneic BMSCs to be quitecomparable with no significant increase of reactions in the allogeneic group.3,498
References1.Ferris DJ, Frisbie DD, Kisiday JD, McIlwraith CW, Hague BA, MajorMD, Schneider RK, Zubrod CJ, Kawcak CE, Goodrich LR. Clinicaloutcome after intra-articular administration of bone marrow derivedmesenchymal stem cells in 33 horses with stifle injury. Vet Surg2014;43:255-265. doi: 10.1111/j.1532-950X.2014.12100.x.2.McIlwraith CW, Frisbie DD, Rodkey WG, Kisiday JD, Werpy NM,Kawcak CE, Steadman JR. Evaluation of intra-articular mesenchymalstem cells to augment healing of microfractured chondral defects.Arthroscopy 2011;27:1552-61. doi: 10.1016/j.arthro.2011.06.002.3.Ranera B, Antczak D, Miller D, Doroshenokova T, Ryan A, McIlwraithCW, Barry F. Donor-derived equine mesenchymal stem cells suppressproliferation of mismatched lymphocytes. Equine Vet J 2016;48:253260. doi: 10.1111/evj.12414.4.Colbath AC, Dow SW, Phillips JN, McIlwraith CW, Goodrich LR.Autologous and allogeneic equine mesenchymal stem cells exhibitequivalent immunomodulatory properties in vitro. Stem Cells andDevelopment 2017; In Press.99
The 8th EEHNC is very thankful to:(listed alfabetically / category)Diamond SponsorCavalor / Nutriquinewww.cavalor.comGold SponsorsDSMwww.dsm.comJadis utb-biotanicals.euSilver ji.comRemant Bronze SponsorsAgrolinguawww.agrolingua.comBio igroup.comPhodéwww.phode.comVisit com
conditioned serum, platelet rich plasma) as well as cellular therapies. Cellular therapies have revolved around the principal of mesenchymal stem cells (MSCs) and, in particular, our clinical success has been ach
Atherosclerotic Disease is a Pan Vascular Process Coronary Artery Disease (CAD) Non-coronary Atherosclerosis -Peripheral Artery Disease (PAD) -Lower extremity -Upper extremity (subclavian stenosis) -Carotid artery disease -Renal artery disease -Mesenteric artery disease -Aortic aneurysm -Vasculogenic Erectile Dysfunction Vascular disease is
Nutrition during a woman's life From: ACC/SCN and IFPRI. 4th Report on the World Nutrition Situation: Nutrition Throughout the Life Cycle. Geneva: WHO, 2000. Nutrition during a woman's life From: ACC/SCN and IFPRI. 4th Report on the World Nutrition Situation: Nutrition Throughout the Life Cycle. Geneva: WHO, 2000.
The Nutrition Care Process is defined in four steps: 1. Nutrition Assessment 2. Nutrition Diagnosis 3. Nutrition Intervention 4. Nutrition Monitoring & Evaluation The first component of the “Nutrition Assessment” is a screening of residents for those at risk for nutrition problems and is a candidate for further intervention. One of the
Nutrition Evaluation: the systematic comparison of current findings with the previous status, nutrition intervention goals, effectiveness of overall nutrition care, or a reference standard Nutrition Care Outcomes: the results of nutrition care that are directly related to the nutrition diagnosis and the goals of the intervention plan
Manual of nutrition 12th ed by Department of Health (DOH) Nutrition essentials for nursing practice 6th ed by S G Dudek Medical nutrition and disease: a case-based approach 4th ed. by L Hark Nutrition : a handbook for nurses by C Best Nutrition and mental health: a handbook: an essential guide to the relationship
Basic nutrition overview. Changes in nutritional needs associated to the old age. III. Nutrition and disease. Nutrition-related disorders. Nutrition and feeding in disease management and . Hand, Michael S. and others. 2010. Small Animal Clinical Nutrition, 5th Edition. Mark Morris Asso
Susceptibility or risk predictor biomarkers. Diagnostic biomarker. Individuals at high risk of disease or pre-clinical disease population Diagnostic biomarker. Non-disease population Patients with disease Disease Subtype 1. Disease Subtype 2. Diagnostic biomarker Patients with disease at higher risk of disease-related outcome(s) Prognostic .
Global Nutrition Transition This paper presents the conceptual linkages between food security and nutrition and reviews data on the associations between experience-based measures of food insecurity and nutritional status outcomes in countries at different stages of the nutrition transition. 1. Food security and nutrition - definitions and .