title: Matrix rigidity-modulated cardiovascular organoid formation from embryoid bodies.
abstract: Stem cell clusters, such as embryoid bodies (EBs) derived from embryonic stem cells, are extensively studied for creation of multicellular clusters and complex functional tissues. It is common to control phenotypes of ES cells with varying molecular compounds; however, there is still a need to improve the controllability of cell differentiation, and thus, the quality of created tissue. This study demonstrates a simple but effective strategy to promote formation of vascularized cardiac muscle-like tissue in EBs and form contracting cardiovascular organoids by modulating the stiffness of a cell adherent hydrogel. Using collagen-conjugated polyacrylamide hydrogels with controlled elastic moduli, we discovered that cellular organization in a form of vascularized cardiac muscle sheet was maximal on the gel with the stiffness similar to cardiac muscle. We envisage that the results of this study will greatly contribute to better understanding of emergent behavior of stem cells in developmental and regeneration process and will also expedite translation of EB studies to drug-screening device assembly and clinical treatments.
authors.affiliation: Department of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
authors.forename: Artem
authors.initials: A
authors.lastname: Shkumatov
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
authors.forename: Kwanghyun
authors.initials: K
authors.lastname: Baek
authors.affiliation: Department of Chemical and Biomolecular Engineering, Department of Pathobiology, Institute of Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
authors.forename: Hyunjoon
authors.initials: H
authors.lastname: Kong
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D000818:Animals; D001921:Brain / Q000378:metabolism; D002319:Cardiovascular System; D002460:Cell Line; D049109:Cell Proliferation; D003094:Collagen / Q000737:chemistry; D046508:Culture Techniques; D058732:Embryoid Bodies / Q000502:physiology*; D020100:Hydrogels / Q000737:chemistry*; D007150:Immunohistochemistry; D051379:Mice; D008855:Microscopy, Electron, Scanning; D009206:Myocardium / Q000378:metabolism; D009940:Organoids / Q000502:physiology*; D012038:Regeneration; D012984:Software; D013234:Stem Cells / Q000166:cytology; D000099166:Polyacrylamides
chemical_list: D000180:Acrylic Resins; D003094:Collagen; D020100:Hydrogels; D000099166:Polyacrylamides
references.citation: Cell Biol Int. 2007 Mar;31(3):269-78
references.pmid: 17241790
references.citation: Cell Death Differ. 2008 Sep;15(9):1417-28
references.pmid: 18497758
references.citation: Biomaterials. 2011 Dec;32(35):9308-15
references.pmid: 21911252
references.citation: Stem Cells Dev. 2006 Dec;15(6):889-904
references.pmid: 17253951
references.citation: Circulation. 2003 Jun 3;107(21):2733-40
references.pmid: 12742992
references.citation: Toxicol In Vitro. 1995 Aug;9(4):477-88
references.pmid: 20650116
references.citation: Biomaterials. 2003 Oct;24(22):4023-9
references.pmid: 12834597
references.citation: Science. 2005 Nov 18;310(5751):1139-43
references.pmid: 16293750
references.citation: Nature. 1982 Sep 9;299(5879):165-7
references.pmid: 7110336
references.citation: Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10733-8
references.pmid: 11535818
references.citation: Cardiovasc Res. 2010 Jun 1;86(3):365-73
references.pmid: 20071355
references.citation: Nat Med. 2008 Feb;14(2):134-43
references.pmid: 18204461
references.citation: Proc Natl Acad Sci U S A. 2006 Dec 5;103(49):18534-9
references.pmid: 17124175
references.citation: Biotechnol Bioeng. 2002 May 20;78(4):442-53
references.pmid: 11948451
references.citation: Stem Cells. 2007 Sep;25(9):2224-34
references.pmid: 17585171
references.citation: Cell Stem Cell. 2008 Nov 6;3(5):508-18
references.pmid: 18983966
references.citation: Nature. 1972 Sep 22;239(5369):200-2
references.pmid: 4562729
references.citation: Tissue Eng. 2002 Aug;8(4):551-9
references.pmid: 12201995
references.citation: Crit Rev Oncol Hematol. 1993 Oct;15(2):149-71
references.pmid: 8117416
references.citation: J Mol Cell Cardiol. 1997 Jun;29(6):1525-39
references.pmid: 9220339
references.citation: J Cell Sci. 2008 Nov 15;121(Pt 22):3794-802
references.pmid: 18957515
references.citation: Nature. 2000 Nov 2;408(6808):92-6
references.pmid: 11081514
references.citation: J Biomech. 2010 Jan 5;43(1):93-8
references.pmid: 19819458
references.citation: Cells Tissues Organs. 2012;195(5):377-91
references.pmid: 21860211
references.citation: Science. 2009 Jun 26;324(5935):1673-7
references.pmid: 19556500