Evaluation of the safety and tolerability of a high-dose intravenous infusion of allogeneic mesenchymal precursor cells.

ABSTRACT

BACKGROUND AIMS: Over the past decade, mounting evidence has shown that mesenchymal stromal cells have the potential to exert protective and reparative effects in a variety of disease settings. Clinical trials are being increasingly established to investigate the therapeutic potential of these cells; however, several safety concerns remain to be addressed, of which dosage safety for intravenous administration is paramount. Published safety studies thus far have predominantly been carried out in small-animal models, whereas data for high-dose allogeneic intravenous administration in large-animal models are limited. This study investigates the safety and tolerability of a single high-dose intravenous infusion of 450 million allogeneic ovine mesenchymal precursor cells (oMPCs) in adult sheep. METHODS: Allogeneic oMPCs (n = 450 million) were intravenously administered to 2-year-old castrated male sheep through the use of three different infusion rates. Sheep were intensively monitored for 7 days by means of vital physiological observations (temperature, blood pressure, heart rate, respiratory rate and oxygen saturation) as well as venous and arterial blood analysis. In addition, full post mortem examination was performed in all animals. RESULTS: A single high dose of intravenously administered cells was well tolerated, with no serious adverse effects reported. No physiologically significant changes in vital signs, oxygen saturation, blood gas analysis or clinical pathology were observed over the duration of the study. CONCLUSIONS: Intravenous delivery of a single high-dose infusion of oMPCs is well tolerated in a large animal model. This study provides additional safety evidence for their intravenous use in future human clinical trials.