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 includedin 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+CD45dim (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 upregulatedat T1 are CD45dim clusters, confirming our results. In conclusion, using a flow cytometry approach, we demonstrated in A-TAH-transplanted patients a significant mobilization of Lin-CD34+CD45dim 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+CD45dim 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.
Highlights
The Aeson® total artificial heart (A-TAH, Carmat, Velisy Villacoublay, France) has been developed as a total heart replacement for patients at risk of death from biventricular failure [1]
As the A-TAH hybrid membrane has been described as being endothelialized after several months of implantation [7], we decided to explore the phenotype of circulating stem cells after implantation in order to hypothesize the cell origin of these newly formed endothelial tissues
When CD133 or c-Kit were positive, we always observed a significant increase in stem cells after implantation, whereas there was no significant difference after A-TAH implantation in the Lin-CD34+CD45dimCD133−c-Kit− population
Summary
The Aeson® total artificial heart (A-TAH, Carmat, Velisy Villacoublay, France) has been developed as a total heart replacement for patients at risk of death from biventricular failure [1]. The endothelial phenotype was confirmed with vascular endothelial (VE)-cadherin expression and the presence of tight junctional structures observed by electron microscopy [7] The origin of these endothelial cells remains unknown. These cells shall originate from the circulating blood, since there is no physical connection between the endothelialized hybrid membrane and the patient’s blood vessels This could be linked to circulating endothelial progenitor cells (EPCs) or very small embryonic-like stem cells (VSELs) [1]. A multidimensional proteomic approach of circulating cells allowed us to fully characterize stem and progenitor cells in peripheral blood that could be at the origin of the endothelial cells This extensive phenotyping enabled us to demonstrate that non-KDR cells with immaturity markers can be mobilized and confirmed the absence of KDR on circulating stem/progenitor cells [11]. VSELs are able to give rise to endothelial cells and promote postischemic revascularization [15, 16]
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