title: Matrix production and remodeling capacity of cardiomyocyte progenitor cells during in vitro differentiation.
abstract: Cell-based therapy has emerged as a treatment modality for myocardial repair. Especially cardiac resident stem cells are considered a potential cell source since they are able to differentiate into cardiomyocytes and have improved heart function after injury in a preclinical model for myocardial infarction. To avoid or repair myocardial damage it is important not only to replace the lost cardiomyocytes, but also to remodel and replace the scar tissue by "healthy" extracellular matrix (ECM). Interestingly, the role of cardiac stem cells in this facet of cardiac repair is largely unknown. Therefore, we investigated the expression and production of ECM proteins, matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in human cardiomyocyte progenitor cells (CMPCs) undergoing differentiation towards the cardiomyogenic lineage. Our data suggest that CMPCs have the capacity to synthesize and modulate their own matrix environment, especially during differentiation towards the cardiomyogenic lineage. While undifferentiated CMPCs expressed collagen I, III, IV and fibronectin, but no elastin, during the process of differentiation the expression of collagen I, III, IV and fibronectin increased and interestingly also elastin expression was induced. Furthermore, undifferentiated CMPCs express MMP-1 -2 and -9 and upon differentiation the expression of MMP-1 decreased, while the expression of MMP-2 and MMP-9, although the latter only in the early stage of differentiation, increased. Additionally, the expression of TIMP-1, -2 and -4 was induced during differentiation. This study provides new insights into the matrix production and remodeling capacity of human CMPCs, with potential beneficial effects for the treatment of cardiac injury.
authors: Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
authors: Noortje A M
authors: NA
authors: Bax
authors: Mieke H
authors: MH
authors: van Marion
authors: Bhakti
authors: B
authors: Shah
authors: Marie-José
authors: MJ
authors: Goumans
authors: Carlijn V C
authors: CV
authors: Bouten
authors: Daisy W J
authors: DW
authors: van der Schaft
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D004549:Elastin / Q000096:biosynthesis; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis*; D005353:Fibronectins / Q000096:biosynthesis; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D009203:Myocardial Infarction / Q000378:metabolism / Q000628:therapy; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism*; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism
chemical_list: D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D019714:Tissue Inhibitor of Metalloproteinases; D003094:Collagen; D004549:Elastin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1