Postdoctoral Fellow Massachusetts General Hospital Melrose, Massachusetts, United States
Introduction: Morphogenesis is a major developmental process forming proper structures through a series of highly coordinated structural deformations. There have been limited models of morphogenesis due to the complexity of the hierarchical change. In this study, we looked to create a tissue model of cardiac morphogenesis in an approach called directed morphogenesis. In development, the embryonic heart undergoes a complex morphogenesis, known as looping, transforming the primordial tube to four-chambered organ. A model of looping could provide unique insights into this phase of development and improve understanding of congenital defect generation.
Materials and
Methods: Embryonic heart tubes (EHT) were engineered using a casting method with iPS derived cardiomyocytes, mimicking the in vivo anatomy. In the developing heart, looping is driven through both internal and external forces, leading to elongation of the tube resulting in a rightward rotation at the cranial end of the embryo and a dorsal deflection at the caudal end. To mimic this, we designed a bioreactor system that would illicit such deformations onto the EHTs.
Results, Conclusions, and Discussions: EHTs were looped and maintained for seven days via perfusion culture. EHTs looped in the bioreactor recapitulated embryonic structures such as intraventricular septum formation, cellular orientations matching measured angles within mammalian hearts, and ventricular shapes resembling native heart. Biomolecular investigation of looped EHTs found an upregulation of genes implicated in cardiac morphogenesis. In conclusion, through directed morphogenesis, a model of cardiogenesis was created. Directed morphogenesis could be translated to other organ types to generate three-dimensional embryogenesis models.
