Epicardial transplantation of autologous atrial appendage micrografts-evaluation of safety and feasibility in pigs after coronary artery occlusion

Nummi, A.; Pätilä, T.; Mulari, S.; Lampinen, M.; Nieminen, T.; Mäyränpää, M. I.; Vento, A.; Harjula, A.; Kankuri, E.; Sari Kivistö, Erika Wilkman, Kari Teittinen, Mika Laine, Markku Kupari, Juha Sinisalo, Mat,

doi:10.1101/2021.10.18.464894

bioRxiv · 10.1101/2021.10.18.464894

Epicardial transplantation of autologous atrial appendage micrografts-evaluation of safety and feasibility in pigs after coronary artery occlusion

Nummi, A.·Pätilä, T.·Mulari, S.·Lampinen, M.·Nieminen, T.·Mäyränpää, M. I.·Vento, A.·Harjula, A.·Kankuri, E.·Sari Kivistö, Erika Wilkman, Kari Teittinen, Mika Laine, Markku Kupari, Juha Sinisalo, Mat,

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Abstract

Several approaches devised for clinical utilization of cell-based therapies for heart failure often suffer from complex and lengthy preparation stages. Epicardial delivery of autologous atrial appendage micrografts (AAMs) with a clinically used extracellular matrix (ECM) patch provides a straightforward therapy alternative. We evaluated the operative feasibility and the effect of micrografts on the patch-induced epicardial foreign body inflammatory response in a porcine model of myocardial infarction. Right atrial appendages were harvested and mechanically processed into AAMs. The left anterior descending coronary artery was ligated to generate acute infarction. Patches of ECM matrix with or without AAMs were transplanted epicardially onto the infarcted area. Four pigs received the ECM and four received the AAMs patch. Cardiac function was studied by echocardiography both preoperatively and at three weeks follow-up. The primary outcome measures were safety and feasibility of the therapy administration and the secondary outcome was the inflammatory response to ECM. Neither AAMs nor ECM patch-related complications were detected during the follow-up time. AAMs patch preparation was feasible according to time and safety. Inflammation was greatly reduced in AAMs as compared to ECM patches as measured by the amount of infiltrated inflammatory cells and area of inflammation. Immunohistochemistry demonstrated an increased CD3+ cell density in the AAMs patch infiltrate. Epicardial AAMs transplantation demonstrated safety and clinical feasibility. The use of micrografts significantly inhibited ECM-induced foreign body inflammatory reactivity. Transplantation of AAMs shows good clinical applicability as adjuvant therapy to cardiac surgery and can suppress acute inflammatory reactivity.

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Nummi, A., Pätilä, T., Mulari, S., Lampinen, M., Nieminen, T., Mäyränpää, M. I., Vento, A., Harjula, A., Kankuri, E., Sari Kivistö, Erika Wilkman, Kari Teittinen, Mika Laine, Markku Kupari, Juha Sinisalo, Mat,. 2021-10-18. Epicardial transplantation of autologous atrial appendage micrografts-evaluation of safety and feasibility in pigs after coronary artery occlusion. https://doi.org/10.1101/2021.10.18.464894

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