Repair of infarcted myocardium by skeletal muscle-derived mesenchymal stromal cells delivered by a bioprinted collagen patch

Abstract Mesenchymal stromal cells (MSC) are commonly investigated for post-infarction cardiac repair because of their angiogenic, anti-inflammatory and immunomodulatory properties. However, autologous sources (bone marrow and adipose tissue) require substantially invasive harvest procedures while a...

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Main Authors: Rose Guesdon, Serena Santoro, Audrey Cras, Etienne Pagin, Didier Serteyn, Justine Ceusters, Fabien Guillemot, Albert Hagège, Philippe Menasché
Format: Article
Language:English
Published: BMC 2025-08-01
Series:Stem Cell Research & Therapy
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Online Access:https://doi.org/10.1186/s13287-025-04552-7
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author Rose Guesdon
Serena Santoro
Audrey Cras
Etienne Pagin
Didier Serteyn
Justine Ceusters
Fabien Guillemot
Albert Hagège
Philippe Menasché
author_facet Rose Guesdon
Serena Santoro
Audrey Cras
Etienne Pagin
Didier Serteyn
Justine Ceusters
Fabien Guillemot
Albert Hagège
Philippe Menasché
author_sort Rose Guesdon
collection DOAJ
description Abstract Mesenchymal stromal cells (MSC) are commonly investigated for post-infarction cardiac repair because of their angiogenic, anti-inflammatory and immunomodulatory properties. However, autologous sources (bone marrow and adipose tissue) require substantially invasive harvest procedures while allogeneic MSC from the cord raise the issue of batch to batch variability. This study assessed the effects of another under-investigated cell source: the skeletal muscle whose autologous MSC feature the clinically appealing advantage of being retrievable by a minimally invasive microbiopsy. MSC differentiated from induced pluripotent stem cells (iPSC) were selected as controls as they also look clinically attractive because of their high scalability and high degree of reproducibility. In vitro, muscle-derived (md) MSC exhibited typical MSC features including a tri-lineage differentiation potential and had robust angiogenic, anti-inflammatory, anti-fibrotic and immune-modulatory effects. Overall, they outperformed iPSC-MSC which raised a safety concern linked to the persistence of some pluripotency-associated markers. They were thus chosen for the subsequent in vivo evaluation in a rat model of left ventricular (LV) dysfunction induced by ischemia/reperfusion. To this end, mdMSC were embedded in a collagen bioprinted gel; the resulting epicardially-delivered patch significantly improved LV ejection fraction compared to a cell-free patch and sham-operated controls. Transcriptomic analysis revealed that this benefit was accompanied by a downregulation of fibrosis-, apoptosis-, and inflammation-related genes. This exploratory proof-of-concept study thus suggests that mdMSC offer an attractive alternative because they combine an autologous origin with a minimally invasive harvest procedure. Bioprinting these cells with a collagen bioink allows to generate a patch endowed with cardio-reparative properties.
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spelling doaj-art-10ec6cb8a71940d1bb271b5b4cfe75f82025-08-20T03:46:03ZengBMCStem Cell Research & Therapy1757-65122025-08-0116111410.1186/s13287-025-04552-7Repair of infarcted myocardium by skeletal muscle-derived mesenchymal stromal cells delivered by a bioprinted collagen patchRose Guesdon0Serena Santoro1Audrey Cras2Etienne Pagin3Didier Serteyn4Justine Ceusters5Fabien Guillemot6Albert Hagège7Philippe Menasché8Inserm UMR 970, PARCC, Université Paris CitéInserm UMR 970, PARCC, Université Paris CitéInserm UMR 1342, Centre d’investigation Clinique de Biothérapies CBT501PoietisCentre de L’oxygène R&D, Université de LiègeCentre de L’oxygène R&D, Université de LiègePoietisDepartment of Cardiology, AP-HP, Hôpital Européen Georges PompidouInserm UMR 970, PARCC, Université Paris CitéAbstract Mesenchymal stromal cells (MSC) are commonly investigated for post-infarction cardiac repair because of their angiogenic, anti-inflammatory and immunomodulatory properties. However, autologous sources (bone marrow and adipose tissue) require substantially invasive harvest procedures while allogeneic MSC from the cord raise the issue of batch to batch variability. This study assessed the effects of another under-investigated cell source: the skeletal muscle whose autologous MSC feature the clinically appealing advantage of being retrievable by a minimally invasive microbiopsy. MSC differentiated from induced pluripotent stem cells (iPSC) were selected as controls as they also look clinically attractive because of their high scalability and high degree of reproducibility. In vitro, muscle-derived (md) MSC exhibited typical MSC features including a tri-lineage differentiation potential and had robust angiogenic, anti-inflammatory, anti-fibrotic and immune-modulatory effects. Overall, they outperformed iPSC-MSC which raised a safety concern linked to the persistence of some pluripotency-associated markers. They were thus chosen for the subsequent in vivo evaluation in a rat model of left ventricular (LV) dysfunction induced by ischemia/reperfusion. To this end, mdMSC were embedded in a collagen bioprinted gel; the resulting epicardially-delivered patch significantly improved LV ejection fraction compared to a cell-free patch and sham-operated controls. Transcriptomic analysis revealed that this benefit was accompanied by a downregulation of fibrosis-, apoptosis-, and inflammation-related genes. This exploratory proof-of-concept study thus suggests that mdMSC offer an attractive alternative because they combine an autologous origin with a minimally invasive harvest procedure. Bioprinting these cells with a collagen bioink allows to generate a patch endowed with cardio-reparative properties.https://doi.org/10.1186/s13287-025-04552-7Heart failureStem cell therapyMesenchymal stromal cellsCardiac patch
spellingShingle Rose Guesdon
Serena Santoro
Audrey Cras
Etienne Pagin
Didier Serteyn
Justine Ceusters
Fabien Guillemot
Albert Hagège
Philippe Menasché
Repair of infarcted myocardium by skeletal muscle-derived mesenchymal stromal cells delivered by a bioprinted collagen patch
Stem Cell Research & Therapy
Heart failure
Stem cell therapy
Mesenchymal stromal cells
Cardiac patch
title Repair of infarcted myocardium by skeletal muscle-derived mesenchymal stromal cells delivered by a bioprinted collagen patch
title_full Repair of infarcted myocardium by skeletal muscle-derived mesenchymal stromal cells delivered by a bioprinted collagen patch
title_fullStr Repair of infarcted myocardium by skeletal muscle-derived mesenchymal stromal cells delivered by a bioprinted collagen patch
title_full_unstemmed Repair of infarcted myocardium by skeletal muscle-derived mesenchymal stromal cells delivered by a bioprinted collagen patch
title_short Repair of infarcted myocardium by skeletal muscle-derived mesenchymal stromal cells delivered by a bioprinted collagen patch
title_sort repair of infarcted myocardium by skeletal muscle derived mesenchymal stromal cells delivered by a bioprinted collagen patch
topic Heart failure
Stem cell therapy
Mesenchymal stromal cells
Cardiac patch
url https://doi.org/10.1186/s13287-025-04552-7
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