Rosalinda Madonna1, Lyubomir Petrov2, Maria Anna Teberino3, Lamberto Manzoli4, Jean-Pierre Karam5, Francesca Vera Renna3, Peter Ferdinandy6, Claudia N Montero-Menei5, Seppo Ylä-Herttuala2, Raffaele De Caterina7. 1. Center of Excellence on Aging, 'G. d'Annunzio' University, Chieti, Italy. 2. Biocenter Kuopio, A. I. Virtanen Institute for Molecular Sciences, Kuopio, Finland. 3. Institute of Cardiology, Department of Neurosciences, Imaging, and Clinical Sciences, 'G. d'Annunzio' University, Chieti, Italy. 4. Department of Medicine and Aging Sciences, 'G. d'Annunzio' University, Chieti, Italy. 5. INSERM U 1066, Micro et nanomédecine biomimétiques, LUNAM, Université d'Angers, Angers, France. 6. Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary. 7. Center of Excellence on Aging, 'G. d'Annunzio' University, Chieti, Italy Institute of Cardiology, Department of Neurosciences, Imaging, and Clinical Sciences, 'G. d'Annunzio' University, Chieti, Italy rdecater@unich.it.
Abstract
RATIONALE: Engraftment and survival of transplanted stem or stromal cells in the microenvironment of host tissues may be improved by combining such cells with scaffolds to delay apoptosis and enhance regenerative properties. AIMS: We examined whether poly(lactic-co-glycolic acid) pharmacologically active microcarriers (PAMs) releasing vascular endothelial growth factor (VEGF) enhance survival, differentiation, and angiogenesis of adipose tissue-mesenchymal stromal cells (AT-MSCs). We analysed the efficacy of transplanted AT-MSCs conjugated with PAMs in a murine model of acute myocardial infarction (AMI). METHODS AND RESULTS: We used fibronectin-coated (empty) PAMs or VEGF-releasing PAMs covered with murine AT-MSCs. Twelve-month-old C57 mice underwent coronary artery ligation to induce AMI, and were randomized into five treatment groups: AMI control (saline 20 µL, n = 7), AMI followed by intramyocardial injection with AT-MSCs (2.5 × 10(5) cells/20 µL, n = 5), or concentrated medium (CM) from AT-MSCs (20 µL, n = 8), or AT-MSCs (2.5 × 10(5) cells/20 µL) conjugated with empty PAMs (n = 7), or VEGF-releasing PAMs (n = 8). Sham-operated mice (n = 7) were used as controls. VEGF-releasing PAMs increased proliferation and angiogenic potential of AT-MSCs, but did not impact their osteogenic or adipogenic differentiation. AT-MSCs conjugated with VEGF-releasing PAMs inhibited apoptosis, decreased fibrosis, increased arteriogenesis and the number of cardiac-resident Ki-67 positive cells, and improved myocardial fractional shortening compared with AT-MSCs alone when transplanted into the infarcted hearts of C57 mice. With the exception of fractional shortening, all such effects of AT-MSCs conjugated with VEGF-PAMs were paralleled by the injection of CM. CONCLUSIONS: AT-MSCs conjugated with VEGF-releasing PAMs exert paracrine effects that may have therapeutic applications. Published on behalf of the European Society of Cardiology. All rights reserved.
RATIONALE: Engraftment and survival of transplanted stem or stromal cells in the microenvironment of host tissues may be improved by combining such cells with scaffolds to delay apoptosis and enhance regenerative properties. AIMS: We examined whether poly(lactic-co-glycolic acid) pharmacologically active microcarriers (PAMs) releasing vascular endothelial growth factor (VEGF) enhance survival, differentiation, and angiogenesis of adipose tissue-mesenchymal stromal cells (AT-MSCs). We analysed the efficacy of transplanted AT-MSCs conjugated with PAMs in a murine model of acute myocardial infarction (AMI). METHODS AND RESULTS: We used fibronectin-coated (empty) PAMs or VEGF-releasing PAMs covered with murine AT-MSCs. Twelve-month-old C57 mice underwent coronary artery ligation to induce AMI, and were randomized into five treatment groups: AMI control (saline 20 µL, n = 7), AMI followed by intramyocardial injection with AT-MSCs (2.5 × 10(5) cells/20 µL, n = 5), or concentrated medium (CM) from AT-MSCs (20 µL, n = 8), or AT-MSCs (2.5 × 10(5) cells/20 µL) conjugated with empty PAMs (n = 7), or VEGF-releasing PAMs (n = 8). Sham-operated mice (n = 7) were used as controls. VEGF-releasing PAMs increased proliferation and angiogenic potential of AT-MSCs, but did not impact their osteogenic or adipogenic differentiation. AT-MSCs conjugated with VEGF-releasing PAMs inhibited apoptosis, decreased fibrosis, increased arteriogenesis and the number of cardiac-resident Ki-67 positive cells, and improved myocardial fractional shortening compared with AT-MSCs alone when transplanted into the infarcted hearts of C57 mice. With the exception of fractional shortening, all such effects of AT-MSCs conjugated with VEGF-PAMs were paralleled by the injection of CM. CONCLUSIONS: AT-MSCs conjugated with VEGF-releasing PAMs exert paracrine effects that may have therapeutic applications. Published on behalf of the European Society of Cardiology. All rights reserved.
Authors: Rosalinda Madonna; Linda W Van Laake; Hans Erik Botker; Sean M Davidson; Raffaele De Caterina; Felix B Engel; Thomas Eschenhagen; Francesco Fernandez-Aviles; Derek J Hausenloy; Jean-Sebastien Hulot; Sandrine Lecour; Jonathan Leor; Philippe Menasché; Maurizio Pesce; Cinzia Perrino; Fabrice Prunier; Sophie Van Linthout; Kirsti Ytrehus; Wolfram-Hubertus Zimmermann; Peter Ferdinandy; Joost P G Sluijter Journal: Cardiovasc Res Date: 2019-03-01 Impact factor: 10.787
Authors: Rosalinda Madonna; Linda W Van Laake; Sean M Davidson; Felix B Engel; Derek J Hausenloy; Sandrine Lecour; Jonathan Leor; Cinzia Perrino; Rainer Schulz; Kirsti Ytrehus; Ulf Landmesser; Christine L Mummery; Stefan Janssens; James Willerson; Thomas Eschenhagen; Péter Ferdinandy; Joost P G Sluijter Journal: Eur Heart J Date: 2016-04-07 Impact factor: 29.983