title: Adipose-derived stem cell adhesion on laminin-coated microcarriers improves commitment toward the cardiomyogenic lineage.
abstract: For tissue-engineering studies of the infarcted heart it is essential to identify a source of cells that may provide cardiomyocyte progenitors, which is easy to amplify, accessible in adults, and allowing autologous grafts. Preclinical studies have shown that human adipose-derived stem cells (ADSCs) can differentiate into cardiomyocyte-like cells and improve heart function in myocardial infarction. We have developed pharmacologically active microcarriers (PAMs) which are biodegradable and biocompatible polymeric microspheres conveying cells on their biomimetic surface, therefore providing an adequate three-dimensional (3D) microenvironment. Moreover, they can release a growth factor in a prolonged manner. In order to implement ADSCs and PAMs for cardiac tissue engineering we first defined the biomimetic surface by studying the influence of matrix molecules laminin (LM) and fibronectin (FN), in combination with growth factors present in the cardiogenic niche, to further enhance the in vitro cardiac differentiation of ADSCs. We demonstrated that LM increased the expression of cardiac markers (Nkx2.5, GATA4, MEF2C) by ADSCs after 2 weeks in vitro. Interestingly, our results suggest that the 3D support provided by PAMs with a LM biomimetic surface (LM-PAMs) further enhanced the expression of cardiac markers and induced the expression of a more mature contractile protein, cardiac troponin I, compared with the 2D differentiating conditions after only 1 week in culture. The enrichment of the growth-factor cocktail with TGF-β1 potentiated the cardiomyogenic differentiation. These results suggest that PAMs offering a LM biomimetic surface may be efficiently used for applications combining adult stem cells in tissue-engineering strategies of the ischemic heart.
authors.affiliation: LUNAM Université, UMR S-1066 F-49933, Angers, France; NSERM U1066, MINT "Micro et nanomédecines biomimétiques,", F-49933, Angers, France; INRC-National Institute for Cardiovascular Research, 40126, Bologna, Italy; Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126, Bologna, Italy.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Karam
authors.forename: Francesca
authors.initials: F
authors.lastname: Bonafè
authors.forename: Laurence
authors.initials: L
authors.lastname: Sindji
authors.forename: Claudio
authors.initials: C
authors.lastname: Muscari
authors.forename: Claudia N
authors.initials: CN
authors.lastname: Montero-Menei
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D015415:Biomarkers / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects*; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D007797:Laminin / Q000494:pharmacology*; D008863:Microspheres; D009206:Myocardium / Q000166:cytology; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D020099:Coated Materials, Biocompatible; D036341:Intercellular Signaling Peptides and Proteins; D007797:Laminin; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1
keywords: 3D cardiomyogenic differentiation; TGF-β1; adipose-derived stem cells; fibronectin; laminin; pharmacologically active microcarriers