iPSC-Derived Vascular Cell Spheroids as Building Blocks for Scaffold-Free Biofabrication

Leni Moldovan, April Barnard, Chang Hyun Gil, Yang Lin, Maria B. Grant, Mervin C. Yoder, Nutan Prasain, Nicanor I. Moldovan

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Recently a protocol is established to obtain large quantities of human induced pluripotent stem cells (iPSC)-derived endothelial progenitors, called endothelial colony forming cells (ECFC), and of candidate smooth-muscle forming cells (SMFC). Here, the suitability for assembling in spheroids, and in larger 3D cell constructs is tested. iPSC-derived ECFC and SMFC are labeled with tdTomato and eGFP, respectively. Spheroids are formed in ultra-low adhesive wells, and their dynamic proprieties are studied by time-lapse microscopy, or by confocal microscopy. Spheroids are also tested for fusion ability either in the wells, or assembled on the Regenova 3D bioprinter which laces them in stainless steel micro-needles (the “Kenzan” method). It is found that both ECFC and SMFC formed spheroids in about 24 h. Fluorescence monitoring indicated a continuous compaction of ECFC spheroids, but stabilization in those prepared from SMFC. In mixed spheroids, the cell distribution changed continuously, with ECFC relocating to the core, and showing pre-vascular organization. All spheroids have the ability of in-well fusion, but only those containing SMFC are robust enough to sustain assembling in tubular structures. In these constructs a layered distribution of alpha smooth muscle actin-positive cells and extracellular matrix deposition is found. In conclusion, iPSC-derived vascular cell spheroids represent a promising new cellular material for scaffold-free biofabrication.

Original languageEnglish (US)
Article number1700444
JournalBiotechnology Journal
Volume12
Issue number12
DOIs
StatePublished - Dec 2017

Keywords

  • Kenzan method
  • cell spheroids
  • endothelial colony forming cells
  • iPSC-derived cells
  • scaffold-free biofabrication

ASJC Scopus subject areas

  • Applied Microbiology and Biotechnology
  • Molecular Medicine

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  • Cite this

    Moldovan, L., Barnard, A., Gil, C. H., Lin, Y., Grant, M. B., Yoder, M. C., Prasain, N., & Moldovan, N. I. (2017). iPSC-Derived Vascular Cell Spheroids as Building Blocks for Scaffold-Free Biofabrication. Biotechnology Journal, 12(12), [1700444]. https://doi.org/10.1002/biot.201700444