Article Text

Download PDFPDF

Lower retention after retrograde coronary venous infusion compared with intracoronary infusion of mesenchymal stromal cells in the infarcted porcine myocardium
  1. Wouter A Gathier1,
  2. Mira van der Naald1,
  3. Bas R van Klarenbosch1,
  4. Anton E Tuinenburg1,
  5. John LM Bemelmans2,
  6. Klaus Neef1,3,
  7. Joost PG Sluijter3,4,5,
  8. Frebus J van Slochteren1,
  9. Pieter A Doevendans1,3,5,6,
  10. Steven AJ Chamuleau1,3
  1. 1 Department of Cardiology, Universitair Medisch Centrum Utrecht, Utrecht, Netherlands
  2. 2 Department of Nuclear Medicine, Universitair Medisch Centrum Utrecht, Utrecht, Netherlands
  3. 3 Regenerative Medicine Center Utrecht, Utrecht, Netherlands
  4. 4 Department of Experimental Cardiology, Universitair Medisch Centrum Utrecht, Utrecht, Netherlands
  5. 5 NL-HI (Dutch Heart Institute), Utrecht, Netherlands
  6. 6 Central Military Hospital, Utrecht, Netherlands
  1. Correspondence to Professor Steven AJ Chamuleau; S.A.J.Chamuleau{at}umcutrecht.nl

Abstract

Embedded Image

Background Commonly used strategies for cell delivery to the heart are intramyocardial injection and intracoronary (IC) infusion, both having their advantages and disadvantages. Therefore, alternative strategies, such as retrograde coronary venous infusion (RCVI), are explored. The aim of this confirmatory study was to compare cardiac cell retention between RCVI and IC infusion. As a secondary end point, the procedural safety of RCVI is assessed.

Methods Four weeks after myocardial infarction, 12 pigs were randomised to receive mesenchymal stromal cells, labelled with Indium-111, via RCVI (n=6) or IC infusion (n=6). Four hours after cell administration, nuclear imaging was performed to determine the number of cells retained in the heart both in vivo and ex vivo. Procedure-related safety measures were reported.

Results Cardiac cell retention is significantly lower after RCVI compared with IC infusion (in vivo: RCVI: median 2.89% vs IC: median 13.74%, p=0.002, ex vivo: RCVI: median 2.55% vs IC: median 39.40%, p=0.002). RCVI led to development of pericardial fluid and haematomas on the frontal wall of the heart in three cases. Coronary venous dissection after RCVI was seen in three pigs, of which one also developed pericardial fluid and a haematoma. IC infusion led to no flow in one pig.

Conclusion RCVI is significantly less efficient in delivering cells to the heart compared with IC infusion. RCVI led to more procedure-related safety issues than IC infusion, with multiple cases of venous dissection and development of haematomas and pericardial fluid collections.

  • bmjos
  • mesenchymal stromal cells
  • myocardial infarction
  • stem cell transplantation

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

View Full Text

Statistics from Altmetric.com

Review history and Supplementary material

  • Data Supplement

    Peer review history and previous versions

Footnotes

  • This article has received OSF badges for Open Data, Open Materials and Preregistration.

  • Data availability statement All data relevant to the study are included in the article.

  • Contributors WAG: Data curation (lead), Formal analysis (lead), Investigation (lead), Methodology (supporting), Project administration (equal), Validation (equal), Writing of the original draft (lead). MvdN: Data curation (supporting), Investigation (supporting), Methodology (supporting), Validation (equal), Writing of the original draft (supporting). BRvK: Data curation (supporting), Formal analysis (supporting), Investigation (supporting), Writing of the review and editing (equal). AET: Investigation (supporting), Supervision (supporting), Validation (supporting), Writing of the review and editing (equal). JLMB: Data curation (supporting), Investigation (supporting), Formal analysis (supporting), Writing of the review and editing (equal). KN: Methodology (supporting). JPGS: Resources (supporting), Methodology (supporting), Writing of the review and editing (equal). FJvS: Supervision (supporting), Methodology (supporting). PAD: Funding acquisition (equal), Resources (equal), Writing of the review and editing (equal). SAJC: Conceptualization (Lead), Funding acquisition (equal), Methodology (lead), Resources (equal), Supervision (lead), Validation (equal), Writing of the review and editing (lead), Project administration (equal).

  • Funding This research is part of Cardiovasculair Onderzoek Nederland (grant number: CVON2011-12), an initiative of the Dutch Heart Foundation, Netherlands Federation of University Medical Centres (NFU), Royal Netherlands Academy of Arts and Science (KNAW) and NWO/ZonMW.

  • Competing interests WAG, MvdN, KN, JPGS, PAD and SAJC report grants from the Netherlands CardioVascular Research Initiative (CVON): the Dutch Heart Foundation, Dutch Federations of University Medical Centers, the Netherlands Organization for Health Research and Development, and the Royal Netherlands Academy of Sciences, during the conduct of the study. JPGS reports grants from Horizon2020 ERC-2016-COG EVICARE, grants from Technobeat, grants from the Project SMARTCARE-II of the BioMedicalMaterials institute, co-funded by the ZonMw‐TAS program, grants from the Dutch Ministry of Economic Affairs, Agriculture and Innovation, during the conduct of the study. WAG, FJvS and SAJC report non-financial support from Cook Regentec, 1102 Indiana Avenue Indianapolis, USA, during the conduct of the study. Catheters for RCVI were provided by Cook Regentec, 1102 Indiana Avenue Indianapolis, USA. On-site training with these catheters was facilitated by Cook Regentec. The authors did not receive payment from Cook Regentec to perform this study. Neither do the authors have stock options in Cook Regentec. Cook Regentec reviewed the manuscript prior to submission. BRvK, AET and JLMB declare no conflict of interest.

  • Ethics approval The study protocol was approved by the Animal Experiment Committee of the University of Utrecht and the governing national Central Animal Experiment Committee (AVD115002015257, 1 05 119–2).

  • Provenance and peer review Not commissioned, externally peer reviewed.

  • Open data Open data are available at https://osf.io/n8wg4/?view_only=55de4fda913d450899e95c3052dcf79b.

  • Open material All materials have been made publicly available at https://www.protocols.io/view/labeling-of-porcine-mesenchymal-stromal-cells-mscs-mr9c596.

  • Preregistration Study design has been preregistered and is publicly available at https://preclinicaltrials.eu/#recordpage, ID: PCTE0000104.

  • Open peer review Prepublication and Review History is available online at http://dx.doi.org/10.1136/bmjos-2018-000006.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.