title: Evaluation of polyelectrolyte complex-based scaffolds for mesenchymal stem cell therapy in cardiac ischemia treatment.
abstract: Three-dimensional (3D) scaffolds hold great potential for stem cell-based therapies. Indeed, recent results have shown that biomimetic scaffolds may enhance cell survival and promote an increase in the concentration of therapeutic cells at the injury site. The aim of this work was to engineer an original polymeric scaffold based on the respective beneficial effects of alginate and chitosan. Formulations were made from various alginate/chitosan ratios to form opposite-charge polyelectrolyte complexes (PECs). After freeze-drying, the resultant matrices presented a highly interconnected porous microstructure and mechanical properties suitable for cell culture. In vitro evaluation demonstrated their compatibility with mesenchymal stell cell (MSC) proliferation and their ability to maintain paracrine activity. Finally, the in vivo performance of seeded 3D PEC scaffolds with a polymeric ratio of 40/60 was evaluated after an acute myocardial infarction provoked in a rat model. Evaluation of cardiac function showed a significant increase in the ejection fraction, improved neovascularization, attenuated fibrosis as well as less left ventricular dilatation as compared to an animal control group. These results provide evidence that 3D PEC scaffolds prepared from alginate and chitosan offer an efficient environment for 3D culturing of MSCs and represent an innovative solution for tissue engineering.
authors.affiliation: Université de Toulouse, CIRIMAT, UPS-INPT-CNRS, Faculté de Pharmacie, F-31062 Toulouse, France; INSERM, UMR 1048, F-31432 Toulouse, France. Electronic address: caroline.ceccaldi@inserm.fr.
authors.forename: Caroline
authors.initials: C
authors.lastname: Ceccaldi
authors.affiliation: Université de Toulouse, CIRIMAT, UPS-INPT-CNRS, Faculté de Pharmacie, F-31062 Toulouse, France; INSERM, UMR 1048, F-31432 Toulouse, France.
authors.forename: Raya
authors.initials: R
authors.lastname: Bushkalova
authors.affiliation: INSERM, UMR 1048, F-31432 Toulouse, France.
authors.forename: Chiara
authors.initials: C
authors.lastname: Alfarano
authors.affiliation: INSERM, UMR 1048, F-31432 Toulouse, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lairez
authors.affiliation: INSERM, UMR 1048, F-31432 Toulouse, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Calise
authors.affiliation: EFS, Laboratoire de thérapie cellulaire, F-31027 Toulouse, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bourin
authors.affiliation: INSERM, UMR 1048, F-31432 Toulouse, France.
authors.forename: Celine
authors.initials: C
authors.lastname: Frugier
authors.affiliation: INSERM, UMR 1048, F-31432 Toulouse, France; CHU Toulouse, Service de Pharmacie Hospitalière, F-31432 Toulouse, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Rouzaud-Laborde
authors.affiliation: INSERM, UMR 1048, F-31432 Toulouse, France; Université de Toulouse, UPS, Faculté des Sciences Pharmaceutiques, F-31062 Toulouse, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Cussac
authors.affiliation: INSERM, UMR 1048, F-31432 Toulouse, France; Université de Toulouse, UPS, Faculté des Sciences Pharmaceutiques, F-31062 Toulouse, France; CHU Toulouse, Service de Pharmacie Hospitalière, F-31432 Toulouse, France.
authors.forename: Angelo
authors.initials: A
authors.lastname: Parini
authors.affiliation: INSERM, UMR 1048, F-31432 Toulouse, France; Université de Toulouse, UPS, Faculté des Sciences Pharmaceutiques, F-31062 Toulouse, France; CHU Toulouse, Service de Pharmacie Hospitalière, F-31432 Toulouse, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Sallerin
authors.affiliation: Université de Toulouse, CIRIMAT, UPS-INPT-CNRS, Faculté de Pharmacie, F-31062 Toulouse, France.
authors.forename: Sophie Girod
authors.initials: SG
authors.lastname: Fullana
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D004573:Electrolytes / Q000737:chemistry*; D005260:Female; D005355:Fibrosis; D006334:Heart Function Tests; D006801:Humans; D055595:Mechanical Phenomena / Q000187:drug effects; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D017202:Myocardial Ischemia / Q000503:physiopathology / Q000628:therapy*; D019899:Paracrine Communication / Q000187:drug effects; D019736:Prostheses and Implants; D051381:Rats; D011917:Rats, Inbred Lew; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D000464:Alginates; D001672:Biocompatible Materials; D004573:Electrolytes; D048271:Chitosan
keywords: Alginate; Cell therapy; Chitosan; Mesenchymal stem cells; Myocardial infarction