Lower retention after retrograde coronary venous infusion compared with intracoronary infusion of mesenchymal stromal cells in the infarcted porcine myocardium

Gathier, Wouter; Naald, Mira van der; Klarenbosch, Bas R van; Tuinenburg, Anton E.; Bemelmans, John Lm; Neef, Klaus; Sluijter, Joost P.G.; Slochteren, Frebus J. van; Doevendans, Pieter A.; Chamuleau, Steven A.J.

doi:10.1136/bmjos-2018-000006

Cited by 5 publications

(4 citation statements)

References 43 publications

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“…We observed in these 4 pigs that the cardiac retention is limited (3-5%), both in our control and UPy-gel group, and lower compared to previous work 3,4,13,14 . Clearly, this study was not completed and no definite conclusions can be drawn about cardiac retention.…”

Section: Relatively Lower Cardiac Retentioncontrasting

confidence: 62%

“…The protocol was approved by the Animal Experiments Committee of the Utrecht University (AVD115002015257) and registered at www.preclinicaltrials.eu (PCTE0000105). Protocols of comparable experiments are available online 3,4,6,7 .…”

Section: Methods Ethical Statementmentioning

confidence: 99%

“…One possible explanation for the observed low efficacy could be inefficient cell delivery. We previously showed that cardiac retention after intracoronary infusion or intramyocardial injection of bone marrow derived mesenchymal stromal cells (MSC) is limited to 10-15% 3,4 . Additionally, we showed that retrograde coronary venous infusion does not improve cardiac retention 4 .…”

Section: Introductionmentioning

confidence: 99%

“…We previously showed that cardiac retention after intracoronary infusion or intramyocardial injection of bone marrow derived mesenchymal stromal cells (MSC) is limited to 10-15% 3,4 . Additionally, we showed that retrograde coronary venous infusion does not improve cardiac retention 4 . In this study we aim to test if delivery with a cell carrier improves cardiac retention.…”

Section: Introductionmentioning

confidence: 99%

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Report of unexpected findings after cardiac stem cell injections in a preclinical model

Naald

Broek

Bemelmans

et al. 2021

Preprint

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Introduction Cardiac regenerative therapy is a proposed therapy for ischemic heart disease. So far efficacy has been low and this might partly be explained by low cardiac cell retention. In this study we aimed to investigate if cardiac cell retention improves using ureido-pyrimidinone units (UPy-gel) as a cell carrier. Methods We used an ischemia-reperfusion model. Pigs were randomized to intramyocardial injections with mesenchymal stromal cells (MSC) labelled with both Indium-111 and a fluorescent tracer in either PBS or in the UPy-gel. After 4 hours, a total body scintigraphy was performed to determine the cardiac cell retention and histology was obtained. Results In the first 4 pigs, we noticed focused areas of radio activity (hotspots) outside the heart in both the control and UPy-gel arm, and decided to interrupt the study. At histology we confirmed one hotspots to be located in a lymph node. No satisfactory explanation for these, potentially harmful, hotspots was found. Conclusion This study was interrupted due to unexpected extra-cardiac hotspots. Although we do not have a conclusive explanation for these findings, we find that sharing these results is important for future research. We recommend to use total body imaging in future retention studies to confirm of reject the occurrence of extra-cardiac cell accumulation after intramyocardial cell injection and discover the pathophysiology and its clinical implications.

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Section: Relatively Lower Cardiac Retentioncontrasting

confidence: 62%