Linqi Jin
BME PhD Defense Presentation

Date: 2026-02-27
Time: 2:00-4:00 PM EST
Location / Meeting Link: HSRB I, W106 (Rollins Auditorium 160); https://emory.zoom.us/j/98833000578

Committee Members:
Vahid Serpooshan, PhD; Sean M. Wu, MD, PhD; Holly Bauser-Heaton, MD, PhD; Lakshmi Prasad Dasi, PhD; Michael E. Davis, PhD


Title: Flow Regulated Pathogenesis of Hypoplastic Left Heart Syndrome in A 3D Bioprinted Model of Developing Human Heart

Abstract:
Hypoplastic left heart syndrome (HLHS) is an etiologically multifactorial congenital heart defect (CHD) characterized by severe underdevelopment of the left heart. Various factors have been identified as critical contributors to the manifestation of HLHS, including intrinsic genetics, cardiac tissue structure, and flow hemodynamics during embryonic stages. The potential onset of HLHS can be traced back to the linear heart tube stage when the human heart begins pumping blood (days 21-22), introducing hemodynamic and biomechanical stimulations to the developing organ. The prevalent “no flow, no grow” theory suggests that decreased blood flow passing through the developing heart causes HLHS via abnormal cardiac growth and remodeling. However, due to suboptimal experimental models, the underlying mechanisms of genetics, dynamic cell-microenvironment interactions, and their critical roles in HLHS pathogenesis remain elusive. Advances in 3D bioprinting and stem cell technologies have enabled the fabrication of cardiac tissues with complex structural, cellular, molecular, and extracellular matrix components. This thesis aimed to study the roles of intrinsic genetics and extrinsic hemodynamics in human heart development and HLHS using a novel 3D bioprinted model of the human embryonic heart tube (eHT) composed of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and endocardial cells (ECs). In Aim 1, a perfusable 3D in vitro model of the human eHT was established using 3D bioprinting, hiPSC differentiation, and perfusion bioreactor technologies. In Aim 2, the roles of intrinsic genetics and extrinsic flow hemodynamics in HLHS pathogenesis were examined by incorporating patient-specific HLHS cells and flow alterations into the eHT model. Collectively, multidimensional flow hemodynamics, transcriptomics, and immunohistochemical analyses demonstrated that genetics and dynamic flow function as critical cues for cardiac maturation and cell lineage commitment, potentially driving the pathogenesis of HLHS. This study offered a robust 3D in vitro platform for modeling human heart development and understanding cellular mechanisms underlying HLHS pathogenesis, highlighting potential therapeutic approaches for the prenatal intervention of HLHS.