title: Migration-driven aggregate behaviors of human mesenchymal stem cells on a dendrimer-immobilized surface direct differentiation toward a cardiomyogenic fate commitment.
abstract: Dynamic behaviors of cell aggregates on a dendrimer surface were investigated to drive the directed differentiation of human mesenchymal stem cells (hMSCs) toward a cardiomyogenic lineage. Cell aggregates on the polyamidoamine dendrimer surface with fifth-generation (G5) of dendron structure showed dynamic changes in morphology associated with repetitive stretching and contracting during migration. Spatial-temporal observations revealed cellular movement in single aggregates by their morphological change through stretching and contracting on the G5 surface, suggesting that the dynamic behavior of aggregate causes mixing of cells. However, aggregates without cell-substrate adhesions on the low-binding culture surface sustained their spherical morphology without cellular movement within a single aggregate. Furthermore, β-catenin was observed at nuclei in aggregates on the G5 surface, and expression of the cardiomyocyte marker cardiac Troponin T (cTnT) was detected. However, β-catenin localized to the nuclei only in the outer region of the aggregate on the low-binding culture surface, and cTnT expression was restricted at the exterior surface of the aggregates. These observations indicate that cell mixing within aggregates on the G5 surface induced the directed differentiation of hMSCs toward a cardiomyogenic lineage by nuclear translocation of β-catenin through dissociation of cell-cell adhesions. These results suggest that migration-driven aggregate behaviors on the dendrimer surface caused repeated morphological changes of aggregate through stretching and contracting, leading to the directed differentiation of hMSCs toward a cardiomyogenic fate commitment.
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Ogawa
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Mee-Hae
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: kino-oka@bio.eng.osaka-u.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kino-Oka
mesh_terms: D002448:Cell Adhesion; D002449:Cell Aggregation; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D050091:Dendrimers / Q000737:chemistry*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology*; D011073:Polyamines / Q000737:chemistry; D054457:Tissue Scaffolds / Q000737:chemistry*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D050091:Dendrimers; C531249:Poly(amidoamine); D011073:Polyamines; D051176:beta Catenin
keywords: Cardiomyogenic lineage; Cell–cell adhesion; Dendrimer surface; Human mesenchymal stem cells; Migration-driven aggregate behaviors