successful use of allogenic umbilical cord-derived stem cells in nonresponsive chronic laminitic...

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[28] de la Rebiere G, Franck T, Deby-Dupont G, et al. Effects of unfrac- tionated and fractionated heparins on myeloperoxidase activity and interactions with endothelial cells: possible effects on the patho- physiology of equine laminitis. Vet J 2008;178:62-9. [29] de la Rebiere de Pouyade G, Grulkle S, Detilleux J, et al. Evaluation of low-molecular-weight heparin for the prevention of equine lami- nitis after colic surgery. J Vet Emerg Crit Care (San Antonio) 2009; 19:113-9. [30] Cohen ND, Parson EM, Seahorn TL, et al. Prevalence and factors associated with development of laminitis in horses with duodenitis/ proximal jejunitis: 33 cases (19851991). J Am Vet Med Assoc 1994; 204:250-4. [31] Peng JS, Zhao XL, Zhan WH, et al. Effect of ecoimmunonutrition on gut barrier function in rats with systemic inammatory response syndrome. [Article in Chinese]. Zhonghua Wei Chang Wai Ke Za Zhi 2005;8:162-4. [32] Bastian L, Weimann A. Immunonutrition in patients after multiple trauma. Br J Nutr 2002;87(Suppl 1):S133-4. [33] Gatt M, Reddy BS, MacFie J. Review article: bacterial translocation in the critically illdevidence and methods of prevention. Aliment Pharmacol Ther 2007;25:741-57. [34] Slotwinski R, Slotwinska S, Kedziora S, et al. Innate immunity signaling pathways: links between immunonutrition and responses to sepsis. Arch Immunol Ther Exp (Warsz) 2011; Feb 6 [Epub ahead of print]. Successful use of allogenic umbilical cord-derived stem cells in nonresponsive chronic laminitic cases Scott Morrison DVM Rood and Riddle Equine Hospital, Lexington KY Take-Home Message: Stem cell therapy, using equine umbilical cord-derived cells, can improve the success rate in horses with chronic refractory laminitis, when used in conjunction with routine treatment procedures and hoof support systems. The cells are delivered directly to the affected foot via regional perfusion using a digital vein. Introduction: Many chronic laminitis cases can be rehabilitated to various degrees of stability or soundness. Foot support systems, deep digital exor tenotomy, and hoof wall resection are commonly used in unstable cases. Success rates for various forms of chronic unstable/uncompensated laminitis have been docu- mented for our caseload and treatment approach (Morrison, 2009). With success rates already established, we were able to begin studying whether the addition of stem cell therapy could improve our success rates. Materials and Methods: Outcome data were reviewed for 12 horses with chronic laminitis that were unresponsive to all other treatments and thus were treated with stem cells. In all cases, routine treatment for laminitis continued and variously included antibiotic therapy, foot casts, deep exor tenotomy, hoof wall resection, and anti-inammatory therapy. The stem cells were derived from equine umbilical cord blood, and an estimated 2025 million cells were administered to each affected foot. The cells were diluted in sterile saline and infused into a digital vein using a technique similar to that described for regional perfusion of antibiotics in horses. Immediately following stem cell infusion, the tourniquet was left in place for 2530 min and the limb intermittently unweighted to facilitate distribution of stem cells to all regions of the foot. The procedure was repeated every 34 weeks as needed. Results: To date 10/12 horses (83%) are doing well. However, long-term success rates still need to be determined. The rst successfulcase is only 14 months out from initial treatment. On average, 3 stem cell infusions were administered per affected foot. Discussion and Conclusions: Stem cell therapy improved the success rate in this group of refractory laminitis cases. Although stem cell therapy potentially is a useful adjunctive treatment to help rehabilitate severe cases, it is important to note that other treatment modalities must also be in place for a successful outcome. Timing of treatment, route of administration, and histological studies of the tissue type generated after stem cell therapy are areas that need further investigation. Practical Laminitis: Progress by Design Metabolic intervention: recognizing and acting on the subtle early warning signs of insulin resistance Donald M. Walsh DVM Homestead Veterinary Hospital, Pacic MO Take-Home Message: Hyperinsulinemia causes changes in hoof growth that are easily detectable by hoof caregivers and veteri- narians. Intervention which normalizes blood insulin concentra- tions can prevent laminitis and restore a normal hoof growth pattern. Introduction: Insulin resistance that results in hyperinsulinemia is associated with laminitis in horses and ponies. The exact mechanism is still under investigation, but recent work has shown that insulin may be activating insulin-like growth factor 1 receptors on epidermal laminar cells. The result is an abnormal proliferation of epidermal cells in the laminae. In the hyper- insulinemic model of laminitis, this proliferation causes the laminae to lengthen and stretch. These same changes are seen in prelaminitic animals that are experiencing abnormally high insulin levels associated with equine metabolic syndrome or equine Cushing's disease. Identifying At-Risk Individuals: It is important to appreciate that even animals with no history of lameness may have abnormal hoof growth patterns related to elevated blood insulin levels. (Normal fasting blood insulin levels are considered to be 1040 mU/ml.) If hyperinsulinemia is not addressed and blood insulin levels normalized, then continued abnormal hoof growth may lead to further weakening of the laminae and the develop- ment of laminitis. However, in cases where diet, exercise, and appropriate medication are able to normalize the insulin levels, over time hoof growth returns to normal and laminitis is averted. Abnormal growth rings in the external hoof wall and separation of the wall from the white line, with the presence of seedy toe, are early signs of the damaging effects of hyperinsulinemia. Often, small areas of hemorrhage are present in the seedy-toe area, caused by damage to the laminar vessels. These changes slowly progress if hyperinsulinemia persists until the laminae can no longer effectively suspend the distal phalanx in its normal posi- tion; consequently, the distal phalanx descends into the sole and the horse now has acute laminitis. This nal insult is caused by very elevated insulin levels, often associated with the intake of a high nonstructural carbohydrate diet, such as spring grasses. These cases are usually conned off the pasture and treated with pain medication. However, the initial clinical response is Abstracts / Journal of Equine Veterinary Science 31 (2011) 562-609 603

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Page 1: Successful use of allogenic umbilical cord-derived stem cells in nonresponsive chronic laminitic cases

Abstracts / Journal of Equine Veterinary Science 31 (2011) 562-609 603

[28] de la Rebiere G, Franck T, Deby-Dupont G, et al. Effects of unfrac-tionated and fractionated heparins on myeloperoxidase activity andinteractions with endothelial cells: possible effects on the patho-physiology of equine laminitis. Vet J 2008;178:62-9.

[29] de la Rebiere de Pouyade G, Grulkle S, Detilleux J, et al. Evaluation oflow-molecular-weight heparin for the prevention of equine lami-nitis after colic surgery. J Vet Emerg Crit Care (San Antonio) 2009;19:113-9.

[30] Cohen ND, Parson EM, Seahorn TL, et al. Prevalence and factorsassociated with development of laminitis in horses with duodenitis/proximal jejunitis: 33 cases (1985–1991). J Am Vet Med Assoc 1994;204:250-4.

[31] Peng JS, Zhao XL, Zhan WH, et al. Effect of ecoimmunonutrition ongut barrier function in rats with systemic inflammatory responsesyndrome. [Article in Chinese]. Zhonghua Wei Chang Wai Ke Za Zhi2005;8:162-4.

[32] Bastian L, Weimann A. Immunonutrition in patients after multipletrauma. Br J Nutr 2002;87(Suppl 1):S133-4.

[33] Gatt M, Reddy BS, MacFie J. Review article: bacterial translocation inthe critically illdevidence and methods of prevention. AlimentPharmacol Ther 2007;25:741-57.

[34] Slotwinski R, Slotwinska S, Kedziora S, et al. Innate immunitysignaling pathways: links between immunonutrition and responsesto sepsis. Arch Immunol Ther Exp (Warsz) 2011; Feb 6 [Epub aheadof print].

Successful use of allogenic umbilical cord-derived stem cellsin nonresponsive chronic laminitic cases

Scott Morrison DVMRood and Riddle Equine Hospital, Lexington KY

Take-Home Message: Stem cell therapy, using equine umbilicalcord-derived cells, can improve the success rate in horses withchronic refractory laminitis, when used in conjunction withroutine treatment procedures and hoof support systems. The cellsare delivered directly to the affected foot via regional perfusionusing a digital vein.

Introduction: Many chronic laminitis cases can be rehabilitatedto various degrees of stability or soundness. Foot support systems,deep digital flexor tenotomy, and hoof wall resection arecommonly used in unstable cases. Success rates for various formsof chronic unstable/uncompensated laminitis have been docu-mented for our caseload and treatment approach (Morrison,2009). With success rates already established, we were able tobegin studying whether the addition of stem cell therapy couldimprove our success rates.Materials and Methods: Outcome data were reviewed for 12horses with chronic laminitis that were unresponsive to all othertreatments and thus were treated with stem cells. In all cases,routine treatment for laminitis continued and variously includedantibiotic therapy, foot casts, deep flexor tenotomy, hoof wallresection, and anti-inflammatory therapy.The stem cells were derived from equine umbilical cord blood,and an estimated 20–25 million cells were administered to eachaffected foot. The cells were diluted in sterile saline and infusedinto a digital vein using a technique similar to that described forregional perfusion of antibiotics in horses. Immediately followingstem cell infusion, the tourniquet was left in place for 25–30 minand the limb intermittently unweighted to facilitate distributionof stem cells to all regions of the foot. The procedurewas repeatedevery 3–4 weeks as needed.Results: To date 10/12 horses (83%) are doing well. However,long-term success rates still need to be determined. The first“successful” case is only 14 months out from initial treatment. Onaverage, 3 stem cell infusions were administered per affected foot.Discussion and Conclusions: Stem cell therapy improved thesuccess rate in this group of refractory laminitis cases. Althoughstem cell therapy potentially is a useful adjunctive treatment tohelp rehabilitate severe cases, it is important to note that othertreatment modalities must also be in place for a successfuloutcome. Timing of treatment, route of administration, andhistological studies of the tissue type generated after stem celltherapy are areas that need further investigation.

Practical – Laminitis: Progress by Design

Metabolic intervention: recognizing and acting on the subtleearly warning signs of insulin resistance

Donald M. Walsh DVMHomestead Veterinary Hospital, Pacific MO

Take-Home Message: Hyperinsulinemia causes changes in hoofgrowth that are easily detectable by hoof caregivers and veteri-narians. Intervention which normalizes blood insulin concentra-tions can prevent laminitis and restore a normal hoof growthpattern.Introduction: Insulin resistance that results in hyperinsulinemiais associated with laminitis in horses and ponies. The exactmechanism is still under investigation, but recent work hasshown that insulin may be activating insulin-like growth factor 1receptors on epidermal laminar cells. The result is an abnormalproliferation of epidermal cells in the laminae. In the hyper-insulinemic model of laminitis, this proliferation causes thelaminae to lengthen and stretch. These same changes are seen inprelaminitic animals that are experiencing abnormally highinsulin levels associated with equine metabolic syndrome orequine Cushing's disease.

Identifying At-Risk Individuals: It is important to appreciatethat even animals with no history of lameness may haveabnormal hoof growth patterns related to elevated blood insulinlevels. (Normal fasting blood insulin levels are considered to be10–40 mU/ml.) If hyperinsulinemia is not addressed and bloodinsulin levels normalized, then continued abnormal hoof growthmay lead to further weakening of the laminae and the develop-ment of laminitis. However, in cases where diet, exercise, andappropriate medication are able to normalize the insulin levels,over time hoof growth returns to normal and laminitis is averted.Abnormal growth rings in the external hoof wall and separationof the wall from thewhite line, with the presence of seedy toe, areearly signs of the damaging effects of hyperinsulinemia. Often,small areas of hemorrhage are present in the seedy-toe area,caused by damage to the laminar vessels. These changes slowlyprogress if hyperinsulinemia persists until the laminae can nolonger effectively suspend the distal phalanx in its normal posi-tion; consequently, the distal phalanx descends into the sole andthe horse now has acute laminitis. This final insult is caused byvery elevated insulin levels, often associated with the intake ofa high nonstructural carbohydrate diet, such as spring grasses.These cases are usually confined off the pasture and treated withpain medication. However, the initial clinical response is