Elevated Circulating Stem Cells Level is Observed One Month After Implantation of Carmat Bioprosthetic Total Artificial Heart

Abstract

The Aeson® total artificial heart (A-TAH) has been developed as a total heart replacement for patients at risk of death from biventricular failure. We previously described endothelialization of the hybrid membrane inside A-TAH probably at the origin of acquired hemocompatibility. We aimed to quantify vasculogenic stem cells in peripheral blood of patients with long-term A-TAH implantation. Four male adult patients were included in this study. Peripheral blood mononuclear cells were collected before A-TAH implantation (T0) and after implantation at one month (T1), between two and five months (T2), and then between six and twelve months (T3). Supervised analysis of flow cytometry data confirmed the presence of the previously identified Lin^-CD133⁺CD45^- and Lin^-CD34⁺ with different CD45 level intensities. Lin^-CD133⁺CD45^-, Lin^-CD34⁺CD45^- and Lin^-CD34⁺CD45⁺ were not modulated after A-TAH implantation. However, we demonstrated a significant mobilization of Lin^-CD34⁺CD45^dim (p = 0.01) one month after A-TAH implantation regardless of the expression of CD133 or c-Kit. We then visualized data for the resulting clusters on a uniform manifold approximation and projection (UMAP) plot showing all single cells of the live Lin^- and CD34⁺ events selected from down sampled files concatenated at T0 and T1. The three clusters upregulated at T1 are CD45^dim clusters, confirming our results. In conclusion, using a flow cytometry approach, we demonstrated in A-TAH-transplanted patients a significant mobilization of Lin^-CD34⁺CD45^dim in peripheral blood one month after A-TAH implantation. Using a flow cytometry approach, we demonstrated in A-TAH transplanted patients a significant mobilization of Lin^-CD34⁺CD45^dim in peripheral blood one month after A-TAH implantation. This cell population could be at the origin of newly formed endothelial cells on top of hybrid membrane in Carmat bioprosthetic total artificial heart.

Keywords: Aeson; Endothelial progenitors; Mobilization; Stem cells; Total artificial heart; Transplantation.