Abstract

IntroductionIntravenous (IV) injection of mesenchymal stem cells (MSCs) is used to treat systemic human diseases and disorders but is not routinely used in equine therapy. In horses, MSCs are isolated primarily from adipose tissue (AT) or bone marrow (BM) and used for treatment of orthopedic injuries through one or more local injections. The objective of this study was to determine the safety and lymphocyte response to multiple allogeneic IV injections of either AT-derived MSCs (AT-MSCs) or BM-derived MSCs (BM-MSCs) to healthy horses.MethodsWe injected three doses of 25 × 106 allogeneic MSCs from either AT or BM (a total of 75 × 106 MSCs per horse) into five and five, respectively, healthy horses. Horses were followed up for 35 days after the first MSC infusion. We evaluated host inflammatory and immune response, including total leukocyte numbers, serum cytokine concentration, and splenic lymphocyte subsets.ResultsRepeated injection of allogeneic AT-MSCs or BM-MSCs did not elicit any clinical adverse effects. Repeated BM-MSC injection resulted in increased blood CD8+ T-cell numbers. Multiple BM-MSC injections also increased splenic regulatory T cell numbers compared with AT-MSC-injected horses but not controls.ConclusionsThese data demonstrate that multiple IV injections of allogeneic MSCs are well tolerated by healthy horses. No clinical signs or clinico-pathologic measurements of organ toxicity or systemic inflammatory response were recorded. Increased numbers of circulating CD8+ T cells after multiple IV injections of allogeneic BM-MSCs may indicate a mild allo-antigen-directed cytotoxic response. Safety and efficacy of allogeneic MSC IV infusions in sick horses remain to be determined.

Highlights

  • Intravenous (IV) injection of mesenchymal stem cells (MSCs) is used to treat systemic human diseases and disorders but is not routinely used in equine therapy

  • Multiple bone marrow (BM)-MSC injections increased splenic regulatory T cell numbers compared with adipose tissue (AT)-MSC-injected horses but not controls

  • These data demonstrate that multiple IV injections of allogeneic MSCs are well tolerated by healthy horses

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Summary

Introduction

Intravenous (IV) injection of mesenchymal stem cells (MSCs) is used to treat systemic human diseases and disorders but is not routinely used in equine therapy. MSCs are isolated primarily from adipose tissue (AT) or bone marrow (BM) and used for treatment of orthopedic injuries through one or more local injections. Mesenchymal stem cells (MSCs) have been isolated from humans and most veterinary and laboratory animal species, including horses [1,2]. Autologous and Allogeneic MSCs offer considerable advantages over autologous MSCs as they do not require patient-specific tissue harvest, they are available for immediate application, and cell batches can be well characterized, providing a consistent source of multiple cell doses [5].

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