Safety and efficacy of transcoronary transfer of human neonatal stem cells to ischemic myocardium using a novel cell-delivery system (CIRCULATE catheter) in swine model of acute myocardial infarction

Agata Bilewska; Mohamed Abdullah; Rachana Mishra; Piotr Musialek; Muthukumar Gunasekaran; Progyaparamita Saha; Artur Stefanowicz; Vivek M Mehta; Sudhish Sharma; Sunjay Kaushal

doi:10.5114/aic.2022.121697

Safety and efficacy of transcoronary transfer of human neonatal stem cells to ischemic myocardium using a novel cell-delivery system (CIRCULATE catheter) in swine model of acute myocardial infarction

Postepy Kardiol Interwencyjnej. 2022 Dec;18(4):431-438. doi: 10.5114/aic.2022.121697. Epub 2022 Nov 30.

Authors

Affiliations

¹ Department of Cardiothoracic Surgery, Ann and Robert H Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
² Department of Cardiology and Internal Diseases, Military Institute of Medicine - National Research Institute, Warsaw, Poland.
³ Icahn School of Medicine at Mount Sinai, New York, United States.
⁴ Department of Cardiothoracic Surgery, Cairo University, Cairo, Egypt.
⁵ Department of Cardiac and Vascular Diseases, John Paul II Hospital, Krakow, Poland.

Abstract

Introduction: Stem cell-based therapies have shown promise in adults with ischemic cardiomyopathy and children with congenital heart diseases, especially those without available therapeutic options. Human neonatal mesenchymal stem cells (nMSCs) have greater regenerative potential than adult stem cells.

Aim: To describe our experience with a novel catheter system for transcoronary delivery of cell-based therapies (CIRCULATE catheter) in the intra-coronary delivery of nMSCs in a swine acute myocardial infarct model.

Material and methods: A newly developed catheter system (CIRCULATE catheter) with several unique features, including an expandable intra-coronary reservoir with spirally placed side holes of varying diameter, was used. nMSCs together with their secretome were used for the treatment. Pigs underwent myocardial infarction by inflating a 2.5 mm angioplasty balloon in the left anterior descending artery for 60 min. After reperfusion, stem cell therapy or placebo was administered via the novel catheter. TTE was performed at baseline, 1 h after the procedure, and before the euthanasia. Troponin blood concertation was evaluated at baseline, and after 48 h. The heart was harvested, sliced, and stained with triphenyl tetrazolium chloride (TTC). Infarct size to area-at-risk ratio was calculated. Troponin was assessed at baseline and after 48 h.

Results: Thirty-nine pigs were operated with the mortality rate of 5.13% (exclusively malignant arrhythmia). Infarct size to area-at-risk ratio was significantly lower in the treatment group. Treated animals had higher ejection fraction than controls.

Conclusions: Intra-coronary delivery of neonatal mesenchymal stem cells reduces the infarct size and restores myocardial function in a swine model. The novel catheter system (CIRCULATE catheter) tested in this study was safe and effective in transcoronary cell delivery of human neonatal mesenchymal stem cells.

Keywords: CIRCULATE catheter; area at risk; infarct size; intra-coronary delivery; myocardial infarction; neonatal mesenchymal stem cells.