Multiple intravenous injections of allogeneic equine mesenchymal stem cells do not induce a systemic inflammatory response but do alter lymphocyte subsets in healthy horses

Multiple intravenous injections of allogeneic equine mesenchymal stem cells do not induce a systemic inflammatory response but do alter lymphocyte subsets in healthy horses

Stem Cell Research & Therapy, April 2015

25888916

Amir Kol, Joshua A Wood, Danielle D Carrade Holt, Jessica A Gillette, Laurie K Bohannon-Worsley, Sarah M Puchalski, Naomi J Walker, Kaitlin C Clark, Johanna L Watson, Dori L Borjesson

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. In horses, MSCs are primarily isolated from adipose tissue (AT) or bone marrow (BM) and used for treatment of orthopedic injuries through one or more local injections. The objectives of this study were to determine safety and lymphocyte response to multiple allogeneic IV injections of either AT-MSCs or BM-MSCs to healthy horses. We injected 3 doses of 25 x 10(6) allogeneic MSCs from either AT or BM (a total of 75 x 10(6) MSCs per horse) into 5 and 5, respectively, healthy horses. Horses were followed up for 35 days after the first MSC infusion. We evaluated host inflammatory and immune response including total leukocytes numbers, serum cytokine concentration and splenic lymphocyte subsets. Repeated 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 T regulatory cell numbers compared to AT-MSC injected horses but not controls. These 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 cell after multiple IV injections of allogeneic BM-MSC may indicate a mild allo-antigen-directed cytotoxic response. Safety and efficacy of allogeneic MSC IV infusions in sick horses remains to be determined.