Industrialized GMP Production of CD34+ Cells (ProtheraCytes®) at Clinical Scale for Treatment of Ischemic Cardiac Diseases Is Feasible and Safe

Abstract

Regenerative medicine now needs to pass a crucial turning point, from academic research to the market. Several sources/types of cells have been experimented with, more or less successfully. CD34⁺ cells have demonstrated multipotent or even pluripotent capacities, making them good candidates for regenerative medicine, particularly for treating heart diseases. Strongly encouraged by the results we achieved in a pilot study using CD34⁺ stem cells in patients with poor-prognosis acute myocardial infarcts (AMIs), we soon began the development of an industrialized platform making use of a closed automated device (StemXpand^®) and a disposable kit (StemPack^®) for the large-scale expansion of CD34⁺ cells with reproducible good manufacturing practice (GMP). This scalable platform can produce expanded CD34⁺ cells (ProtheraCytes^®) of sufficient quality that, interestingly, express early markers of the cardiac and endothelial pathways and early cardiac-mesoderm markers. They also contain CD34⁺ pluripotent cells characterized as very small embryonic-like stem cells (VSELs), capable of differentiating under appropriate stimuli into different tissue lineages, including endothelial and cardiomyocytic ones.