Cells are dynamic participants within the entire context of their environment, whether in vivo (during development, regeneration, and disease) or in vitro (in engineered tissues). The Laboratory for Stem Cells and Tissue Engineering integrates stem cells, bioreactors and biomaterials to investigate the communication between cells, regulatory molecules, extracellular matrix and physical factors underlying physiological mechanisms. We build controllable, physiologically meaningful bioengineered organs using cells as natural tissue engineers within organ and niche specific tools such as matrix scaffolds and bioreactors. Teams dedicated to various organs and systemic conditions design foundational models that interact, mimicking our bodies in action. Our insights aim to fulfill two translational applications: (i) regenerative medicine, to repair or replace damaged tissue, and (ii) “organs-on-a-chip” platform models of healthy and abnormal physiology.
To maximize our innovative capacity, we collaborate with a diverse team of students, clinicians and investigators at Columbia and around the globe. The extensive resources within the Columbia University Medical Center equip our lab with state-of-the-art technology for basic and translational studies guided by both clinical need and biological principles. As hosts of the NIH Tissue Engineering Resource Center and Center for Dental and Craniofacial Research, our work extends beyond our lab to reach diverse biological applications and nurture the next generation of tissue engineering leaders. Guided by principles of collaboration, clinical translation and human relevance, we hope to advance the field of regenerative medicine for more effective treatment of the world’s most prevalent cardiac, pulmonary and systemic conditions.
BeatProfiler: Multimodal in vitro analysis of cardiac function enables machine learning classification of diseases and drugs
A multi-organ chip with matured tissue niches linked by vascular flow
Xenogeneic cross-circulaton for extracorporeal recovery of injured human lungs
Research Projects
“Organs-on-a-chip” platforms are revolutionary tools for studying human physiology and disease given their capacity to establish a dynamic system of fully human-based components. While cell culture and animal models remain valuable, OOC approaches bridge foundational discoveries to the most relevant clinical context for eventual translation. OOCs connect miniature human tissues into physiological units, capable of mimicking both individual organ functions and collaborative functions that drive disease and repair processes. In our lab, we have extensively developed OOC platforms that incorporate a vascular component, circulating media throughout the platform and allowing communication between organ units to recapitulate the biological complexity of the human system (Ronaldson-Bouchard and Vunjak-Novakovic, Cell Stem Cell, 2018). All tissues can be grown from one iPS cell source to fully capture an individual system and response to disease or damage, and we have successfully integrated heart muscle, innervated skeletal muscle, bone, bone marrow, liver, vasculature, skin, solid tumors and immune components into our platforms. We have shown that tissues can be matured and maintained for long periods of time, while maintaining communication by circulating cells, extracellular vesicles and molecular factors. We are using the “organs on a chip” platforms to investigate systemic pathologies, including off-target effects of drugs, inflammation, and cancer metastasis (to elucidate master regulators and predict drug sensitivity in metastatic cells), however, the applications of OOC platforms are virtually infinite.
Current cardiac interventions fail to meet the demands of the global prevalence and functional damage of heart diseases, with limited ability to repair injured cardiac tissue. Bioengineered cardiac tissues frown from human iPSCs and matured to adult-like phenotypes, developed with monumental findings in mechanistic and biological mechanisms of the heart, have potential to transform the heart disease treatment landscape. Our lab has built upon cardiac tissue engineering by developing models of vascularized human cardiac muscle capable of patient specific study, by allowing us to mimic pivotal mechanisms of healthy, diseased and reparative cardiac physiology from a single cell source. Extensive functional and biological assessment of cardiac tissues in our lab has confirmed their adult-like gene expression profiles, organized ultrastructure, networks of T-tubules, oxidative metabolism, positive force-frequency relationships and calcium handling that demonstrate the level of functional maturity necessary for translational insights (Ronaldson-Bouchard et al., Nature 2018). Cardiac tissue development has allowed us to optimize therapeutic protocols such as extended delivery of exosomes secreted by iPSC-cardiomyocytes, previously shown to protect animal hearts from ischemic injury (Liu et al., Nature Biomed Eng, 2018). Our efforts in developing protocols for mature human heart tissues have granted unprecedented findings to inform therapeutic strategies that effectively repair or replace defective cardiomyocytes. As the sophistication of our model and treatment approach advance, we aim to establish new clinically effective therapeutic regimens to address the disease burden of cardiac injury.
Lung transplantation is the only curative option for nearly 25 million people in the U.S. suffering from end-stage lung disease. Donor lung shortages, long-term rejection, and immunosuppression requirements substantially limit access to transplantation. Lungs are complex organs to study and replicate, with a large spectrum of cell types, hierarchical vasculature and bronchial architecture required for gas exchange and pulmonary functions. Therefore, we focus our lung engineering on finding ways to repair low-quality donor lungs to expand the pool of organs available for transplant. Injured lung regions can be targeted for repair by selective removal of defective cells with complementary preservation of healthy tissue and foundational matrix components. Our lab has led pioneering studies of long-term extracorporeal lung support, extending to 100 hours, and utilizing cross circulation of blood between a living porcine host and a ventilated injured lung for regenerative repair (Hozain et al., J Thor. Cardiovasc Surg., 2020). The cross-circulation platform developed in our lab has demonstrated repair of injured human lungs declined for transplantation, and grants access to routinely monitor, assess and manipulate the ventilated lung to maximize rehabilitation and treatment strategies (Hozain et al., Nature Medicine 2020). At the bench, we have also developed models of pulmonary fibrosis for controlled studies of cell and extracellular matrix roles in initiation and progression of fibrotic disease. Given the complexity of lung architecture and mechanics, our team has also collaborated with multidisciplinary engineers to design image-guided devices for visualization, assessment and delivery of therapeutic components to injured lungs.
