title: Substrate-dependent modulation of 3D spheroid morphology self-assembled in mesenchymal stem cell-endothelial progenitor cell coculture.
abstract: The structural evolution of three-dimensional spheroids self-assembled from two different types of cells on selective biomaterials is demonstrated in this study. The two types of cells involved in the self-assembly are human mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs). When seeded in different population ratios, they can create a variety of cellular patterns on different biomaterial substrates. When the two populations are matched in initial numbers, they are self-assembled in co-spheroids with different morphologies (i.e. randomly mixed, bumped, or concentric spheroids). The morphologies are influenced by the specific cell-substrate interaction possibly through integrin signaling, as well as a substrate-dependent regulation of heterophilic cell-cell interaction possibly through Notch signaling. In particular, the self-assembled core-shell concentric spheroids from adipose-derived MSCs and EPCs show a greater angiogenic effect in vitro. This study reveals the possibility to modulate the self-assembled morphology as well as the effect of cocultured cells by changing the cell culture substratum.
authors.affiliation: Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan; Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: shhsu@ntu.edu.tw.
authors.forename: Shan-hui
authors.initials: SH
authors.lastname: Hsu
authors.affiliation: Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan.
authors.forename: Tung-Tso
authors.initials: TT
authors.lastname: Ho
authors.affiliation: Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan.
authors.forename: Nien-Chi
authors.initials: NC
authors.lastname: Huang
authors.affiliation: Department of Chemical Engineering and Materials Science, Yuan Ze University, Chung-Li, Taiwan.
authors.forename: Chao-Ling
authors.initials: CL
authors.lastname: Yao
authors.affiliation: Department of Chemical Engineering and Materials Science, Yuan Ze University, Chung-Li, Taiwan.
authors.forename: Luen-Hau
authors.initials: LH
authors.lastname: Peng
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Niann-Tzyy
authors.initials: NT
authors.lastname: Dai
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry*; D002450:Cell Communication; D002465:Cell Movement; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods*; D066026:Endothelial Progenitor Cells / Q000166:cytology* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D016023:Integrins / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D018919:Neovascularization, Physiologic; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction; D018874:Spheroids, Cellular / Q000166:cytology* / Q000378:metabolism; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D016023:Integrins; D051880:Receptors, Notch
keywords: Cell–cell interaction; Coculture; Endothelial progenitor cells (EPCs); Integrin; Mesenchymal stem cells (MSCs); Notch signaling