Development of myocardial constructs using modulus-matched acrylated polypropylene glycol triol substrate and different nonmyocyte cell populations

Hudson, James E., Brooke, Gary, Blair, Chris, Wolvetang, Ernst and Cooper-White, Justin John (2011) Development of myocardial constructs using modulus-matched acrylated polypropylene glycol triol substrate and different nonmyocyte cell populations. Tissue Engineering Part A: Tissue Engineering, 17 17-18: 2279-2289. doi:10.1089/ten.tea.2010.0743


Author Hudson, James E.
Brooke, Gary
Blair, Chris
Wolvetang, Ernst
Cooper-White, Justin John
Title Development of myocardial constructs using modulus-matched acrylated polypropylene glycol triol substrate and different nonmyocyte cell populations
Journal name Tissue Engineering Part A: Tissue Engineering   Check publisher's open access policy
ISSN 1937-3341
1937-335X
Publication date 2011-08-25
Sub-type Article (original research)
DOI 10.1089/ten.tea.2010.0743
Volume 17
Issue 17-18
Start page 2279
End page 2289
Total pages 11
Place of publication New Rochelle, NY, U.S.A.
Publisher Mary Ann Liebert, Publishers
Collection year 2012
Language eng
Formatted abstract
Tissue engineering approaches are currently being investigated for the restoration of myocardial function in heart failure patients, most commonly by combining cells with a substrate to form myocardial-like constructs (MCs). The final properties of these constructs are dependant on the characteristics of both the substrate and the cells used for fabrication. To create a construct with the appropriate mechanical properties required for any future therapeutic, we tailored an acrylated polypropylene glycol triol (aPPGT) substrate to the elastic modulus of heart tissue and then investigated the fabrication of MCs. We first assessed the aPPGT substrate alone in vivo, both under normal conditions and in an infarct model in mice, and found that there was a mild foreign body response with good integration of the substrate into the epicardial surface in mice hearts. We next studied the fabrication and properties of MCs by culturing mouse embryonic cardiomyocytes on the aPPGT substrate. To achieve myocardial-like concentrically contractile constructs, cocultures with supportive stromal cells were found to be essential and both mouse heart-derived stromal cells or bone-derived mouse mesenchymal stromal progenitor cells (mMSCs) could be used. These different stromal cell types produced MCs with different properties. The average beating rate of the constructs formed from mouse heart-derived stromal cells was significantly higher those constructs formed using mMSCs. Conversely, the constructs formed using mMSCs had reduced fibrotic extracellular matrix secretion and increased hepatocyte growth factor expression. Both of these mMSC construct properties may enhance integration and therapeutic efficacy of the construct postimplantation on the surface of the infarcted heart. This study thus demonstrates the formation of MCs using mechanically tailored aPPGT substrate and also demonstrates the effects of different stromal cell populations have on the properties of the resultant MCs, both of which are critical for future applications of tissue engineering in heart failure patients.
Keyword Mesenchymal stem-cells
Bioengineered cardiac grafts
Engineered heart-tissue
Growth-factor-1
Functional cardiomyocytes
Embryonic cardiomyocytes
Muscle tissue
Scaffold-free
Expression
Matrix
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

 
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