Engineering of Pulsatile Conduits from Human Pluripotent Stem Cell Derived Cardiomyocytes
Technical Report,01 Jun 2016,31 May 2017
Yale University New Haven United States
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We have derived cardiomyocytes heart cells with high purity using an optimized approach that can coax human induced pluripotent stem cells hiPSCs into heart cells in combination with a two-day lactate selection method that can remove non-cardiomyocytes from the culture. With the availability of robust hiPSC-derived cardiomyocytes hiPSC-CMs, we have compared different supporting scaffolds and established a highly effective system that enables robust pulsatile tissue formation. Specifically, a novel approach for developing robustly contractile tissue constructs was established by seeding hiPSC-CMs onto a laser-cut, thin sections of decellularized porcine myocardium that enable the alignment of the seeded cells along native collagen fiber for efficient cell-cell contact and gap junction formation. Moreover, human cardiac fibroblasts have been shown to improve the even distribution of hiPSC-CMs in the tissue constructs and to enhance the contractile force. Furthermore, decellularized human umbilical arteries HUAs, readily available and mechanically robust tubular scaffolds that can endure high blood pressure in humans, have been successfully developed and utilized for wrapping the pulsatile tissue constructs with the goal of generating tubular pulsatile conduits. We anticipate that novel and effective tissue-engineered pulsatile conduits will be established for comprehensive functional studies in vitro and in vivo in the coming research period.
- Medicine and Medical Research