A critical need in tissue engineering is a means to create the equivalent of a microvasculature within relatively thick and/or metabolic engineered tissues, such as engineered myocardium. This proposal combines the use of stem cells from convenient autologous sources and the technology of guided cell assembly via cell entrapment in and subsequent remodeling of fibrin gel into aligned tissue in order to create a perfusable and beating engineered myocardium. Perfusable tissue constructs will be fabricated from blood outgrowth endothelial cells and pericytes. Beating tissue constructs will be fabricated from induced pluripotent stem cell (iPS)-derived cardiomyocytes. Perfusable and beating engineered myocardium will then be fabricated by co-entrapment of the three cell types using the same guided cell assembly methods, which are based on mechanically-constrained cell contraction and alignment of fibrin gel. These tissue constructs will be extensively characterized in vitro and then assessed in an infarcted rat heart model for improved functional outcomes. The results from this research will be both enabling technology for many engineered tissues - a means to create a functional microvasculature - and the basis for a functional heart patch that can treat myocardial infarcts and potentially prevent onset of congestive heart failure.

Public Health Relevance

A critical need in tissue engineering is a means to create the equivalent of a microvasculature within relatively thick and/or metabolic engineered tissues, such as engineered heart tissue. This proposal combines stem cells from convenient autologous sources and the technology of guided self-assembly of aligned tissues from cell entrapment in and subsequent remodeling of fibrin gel to create a perfusable and beating heart patch that may ultimately treat patients with damaged heart tissue following a heart attack, precluding the onset of heart failure.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL108670-02
Application #
8328585
Study Section
Special Emphasis Panel (ZHL1-CSR-N (M1))
Program Officer
Lundberg, Martha
Project Start
2011-09-05
Project End
2015-05-31
Budget Start
2012-06-01
Budget End
2013-05-31
Support Year
2
Fiscal Year
2012
Total Cost
$744,371
Indirect Cost
$183,764
Name
University of Minnesota Twin Cities
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
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Schaefer, Jeremy A; Tranquillo, Robert T (2016) Tissue Contraction Force Microscopy for Optimization of Engineered Cardiac Tissue. Tissue Eng Part C Methods 22:76-83
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Morin, Kristen T; Carlson, Paul D; Tranquillo, Robert T (2015) Automated image analysis programs for the quantification of microvascular network characteristics. Methods 84:76-83
Wendel, Jacqueline S; Ye, Lei; Tao, Ran et al. (2015) Functional Effects of a Tissue-Engineered Cardiac Patch From Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in a Rat Infarct Model. Stem Cells Transl Med 4:1324-32
Barry, David M; Xu, Ke; Meadows, Stryder M et al. (2015) Cdc42 is required for cytoskeletal support of endothelial cell adhesion during blood vessel formation in mice. Development 142:3058-70
Morin, Kristen T; Dries-Devlin, Jessica L; Tranquillo, Robert T (2014) Engineered microvessels with strong alignment and high lumen density via cell-induced fibrin gel compaction and interstitial flow. Tissue Eng Part A 20:553-65
Lalit, Pratik A; Hei, Derek J; Raval, Amish N et al. (2014) Induced pluripotent stem cells for post-myocardial infarction repair: remarkable opportunities and challenges. Circ Res 114:1328-45
Morin, Kristen T; Smith, Annie O; Davis, George E et al. (2013) Aligned human microvessels formed in 3D fibrin gel by constraint of gel contraction. Microvasc Res 90:12-22

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