title: Nanothin Coculture Membranes with Tunable Pore Architecture and Thermoresponsive Functionality for Transfer-Printable Stem Cell-Derived Cardiac Sheets.
abstract: Coculturing stem cells with the desired cell type is an effective method to promote the differentiation of stem cells. The features of the membrane used for coculturing are crucial to achieving the best outcome. Not only should the membrane act as a physical barrier that prevents the mixing of the cocultured cell populations, but it should also allow effective interactions between the cells. Unfortunately, conventional membranes used for coculture do not sufficiently meet these requirements. In addition, cell harvesting using proteolytic enzymes following coculture impairs cell viability and the extracellular matrix (ECM) produced by the cultured cells. To overcome these limitations, we developed nanothin and highly porous (NTHP) membranes, which are ∼20-fold thinner and ∼25-fold more porous than the conventional coculture membranes. The tunable pore size of NTHP membranes at the nanoscale level was found crucial for the formation of direct gap junctions-mediated contacts between the cocultured cells. Differentiation of the cocultured stem cells was dramatically enhanced with the pore size-customized NTHP membrane system compared to conventional coculture methods. This was likely due to effective physical contacts between the cocultured cells and the fast diffusion of bioactive molecules across the membrane. Also, the thermoresponsive functionality of the NTHP membranes enabled the efficient generation of homogeneous, ECM-preserved, highly viable, and transfer-printable sheets of cardiomyogenically differentiated cells. The coculture platform developed in this study would be effective for producing various types of therapeutic multilayered cell sheets that can be differentiated from stem cells.
authors.forename: Seungmi
authors.initials: S
authors.lastname: Ryu
authors.forename: Jin
authors.initials: J
authors.lastname: Yoo
authors.forename: Yeongseon
authors.initials: Y
authors.lastname: Jang
authors.forename: Jin
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Chemical and Biomolecular Engineering & KI for Nano Century, Korea Advanced Institute of Science and Technology , Daejeon 305-701, Republic of Korea.
authors.forename: Seung Jung
authors.initials: SJ
authors.lastname: Yu
authors.forename: Jooyeon
authors.initials: J
authors.lastname: Park
authors.forename: Seon Yeop
authors.initials: SY
authors.lastname: Jung
authors.forename: Kyung Hyun
authors.initials: KH
authors.lastname: Ahn
authors.affiliation: Department of Chemical and Biomolecular Engineering & KI for Nano Century, Korea Advanced Institute of Science and Technology , Daejeon 305-701, Republic of Korea.
authors.forename: Sung Gap
authors.initials: SG
authors.lastname: Im
authors.forename: Kookheon
authors.initials: K
authors.lastname: Char
authors.forename: Byung-Soo
authors.initials: BS
authors.lastname: Kim
mesh_terms: D000818:Animals; D062028:Bioprinting / Q000295:instrumentation; D002454:Cell Differentiation; D002460:Cell Line; D018920:Coculture Techniques / Q000295:instrumentation*; D006801:Humans; D008567:Membranes, Artificial; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D032446:Myoblasts / Q000166:cytology*; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D016062:Porosity; D051381:Rats; D013696:Temperature
chemical_list: D008567:Membranes, Artificial
keywords: cardiac differentiation; coculture; membrane; mesenchymal stem cells; transfer-printing