Gordana Vunjak-Novakovic

Gordana Vunjak-Novakovic
Columbia University | CU · Biomedical Engineering Ph.D. Program

PhD

About

613
Publications
114,203
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46,501
Citations
Citations since 2017
175 Research Items
17794 Citations
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201720182019202020212022202305001,0001,5002,0002,5003,000
201720182019202020212022202305001,0001,5002,0002,5003,000
201720182019202020212022202305001,0001,5002,0002,5003,000

Publications

Publications (613)
Article
Full-text available
The airway epithelium lining the luminal surface of the respiratory tract creates a protective barrier that ensures maintenance of tissue homeostasis and prevention of respiratory diseases. The airway epithelium, unfortunately, is frequently injured by inhaled toxic materials, trauma, or medical procedures. Substantial or repeated airway epithelial...
Article
Full-text available
Heart failure (HF) is characterized by global alterations in myocardial DNA methylation, yet little is known about epigenetic regulation of the non-coding genome and potential reversibility of DNA methylation with left ventricular assist device (LVAD) therapy. Genome-wide mapping of myocardial DNA methylation in 36 HF patients at LVAD implantation,...
Article
Background Xenogeneic cross-circulation (XC) is an experimental method for ex vivo organ support and recovery that could expand the pool of donor lungs suitable for transplantation. The objective of this study was to establish and validate a standardized, reproducible, and broadly applicable technique for performing xenogeneic XC to support and rec...
Article
Acute leukemias represent the most frequent type of cancer (∼30%) in children and young adults. The lack of robust systems for in vitro culture of primary leukemia samples is a significant barrier for the development of effective genetic and chemical screens for novel therapeutic targets in pediatric leukemia. In vitro systems, including engineered...
Article
Full-text available
Bone grafts can be engineered by differentiating human mesenchymal stromal cells (MSCs) via the endochondral and intramembranous ossification pathways. We evaluated the effects of each pathway on the properties of engineered bone grafts and their capacity to drive bone regeneration. Bone-marrow-derived MSCs were differentiated on silk scaffolds int...
Article
Engineered cardiac tissues derived from human induced pluripotent stem cells offer unique opportunities for patient-specific disease modeling, drug discovery and cardiac repair. Since the first engineered hearts were introduced over two decades ago, human induced pluripotent stem cell-based three-dimensional cardiac organoids and heart-on-a-chip sy...
Article
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Despite over thirty years of intensive research for targeted therapies, treatment of Acute Respiratory Distress Syndrome (ARDS) remains supportive in nature. With mortality upwards of 30%, a high-fidelity pre-clinical model of ARDS on which to test novel therapeutics is critically needed. We aimed to induce a reproducible model of ARDS in human-siz...
Article
Introduction: Mutations in BAG3 result in dilated cardiomyopathy with cardiac fibrosis. Currently, the role of BAG3 in non-myocyte cell types is not known. We tested the hypothesis that BAG3 controls cardiac fibroblast (CF) function and that the loss of fibroblast-specific BAG3 is deleterious, using cells and engineered cardiac tissues (ECT) derive...
Article
Future lunar missions and beyond will require new and innovative approaches to radiation countermeasures. The Translational Research Institute for Space Health (TRISH) is focused on identifying and supporting unique approaches to reduce risks to human health and performance on future missions beyond low Earth orbit. This paper will describe three f...
Article
Full-text available
In the heart, protein kinase A (PKA) is critical for activating calcium handling and sarcomeric proteins in response to beta-adrenergic stimulation leading to increased myocardial contractility and performance. The catalytic activity of PKA is tightly regulated by regulatory subunits that inhibit the catalytic subunit until released by cAMP binding...
Article
Full-text available
Pulmonary air leak is the most common complication of lung surgery, with air leaks that persist longer than 5 days representing a major source of post‐surgery morbidity. Clinical management of air leaks is challenging due to limited methods to precisely locate and assess leaks. Here, we present a sound‐guided methodology that enables rapid quantita...
Article
Background Manifestations of cystic fibrosis, although well-characterized in the proximal airways, are understudied in the distal lung. Characterization of the cystic fibrosis lung ‘matrisome’ (matrix proteome) has not been previously described, and could help identify biomarkers and inform therapeutic strategies. Methods We performed liquid chrom...
Article
Organs-on-chips (OoCs) are systems containing engineered or natural miniature tissues grown inside microfluidic chips. To better mimic human physiology, the chips are designed to control cell microenvironments and maintain tissue-specific functions. Combining advances in tissue engineering and microfabrication, OoCs have gained interest as a next-g...
Article
Many neuromuscular diseases, such as myasthenia gravis (MG), are associated with dysfunction of the neuromuscular junction (NMJ), which is difficult to characterize in animal models due to physiological differences between animals and humans. Tissue engineering offers opportunities to provide in vitro models of functional human NMJs that can be use...
Article
Full-text available
Repeated injury to airway tissue can impair lung function and cause chronic lung disease, such as chronic obstructive pulmonary disease. Advances in regenerative medicine and bioreactor technologies offer opportunities to produce lab-grown functional tissue and organ constructs that can be used to screen drugs, model disease, and engineer tissue re...
Article
Advances in self-organizing cardiac organoids to recapitulate human cardiogenesis have provided a powerful tool for unveiling human cardiac development, studying cardiovascular diseases, testing drugs, and transplantation. Here, we highlight the recent remarkable progress on multicellular cardiac organoids and review the current status for their pr...
Article
Full-text available
Engineered tissues can be used to model human pathophysiology and test the efficacy and safety of drugs. Yet, to model whole-body physiology and systemic diseases, engineered tissues with preserved phenotypes need to physiologically communicate. Here we report the development and applicability of a tissue-chip system in which matured human heart, l...
Article
Full-text available
Engineered human cardiac tissues facilitate progress in regenerative medicine, disease modelling and drug development. In this Perspective, we reflect on the most notable advances in cardiac tissue engineering from the past two decades by analysing pivotal studies and critically examining the most consequential developments. This retrospective anal...
Preprint
Background Human heart failure is characterized by global alterations in the myocardial DNA methylation profile, yet little is known about epigenetic regulation of non-coding transcripts and potential reversibility of DNA methylation with left ventricular assist device (LVAD) support. Method Genome-wide mapping of myocardial DNA methylation was pe...
Article
Major progress in the understanding and treatment of cancer have tremendously improved our knowledge of this complex disease and improved the length and quality of patients’ lives. Still, major challenges remain, in particular with respect to cancer metastasis which still escapes effective treatment and remains responsible for 90% of cancer related...
Article
Full-text available
Recent synergistic advances in organ-on-chip and tissue engineering technologies offer opportunities to create in vitro-grown tissue or organ constructs that can faithfully recapitulate their in vivo counterparts. Such in vitro tissue or organ constructs can be utilized in multiple applications, including rapid drug screening, high-fidelity disease...
Article
Ischemic and non-ischemic cardiomyopathies have distinct etiologies and underlying disease mechanisms, which require in-depth investigation for improved therapeutic interventions. The goal of this study was to use clinically obtained myocardium from healthy and heart failure patients, and characterize the changes in extracellular matrix (ECM) in is...
Article
Osteoarthritis (OA) is the most common joint disease worldwide, yet we continue to lack an understanding of disease etiology and pathology, and effective treatment options. Essential to tissue homeostasis, disease pathogenesis, and therapeutic responses are the stratified organization of cartilage and the crosstalk at the osteochondral junction. An...
Preprint
In the heart, Protein Kinase A (PKA) is critical for activating calcium handling and sarcomeric proteins in response to beta adrenergic stimulation leading to increased myocardial contractility and performance. The catalytic activity of PKA is tightly regulated by regulatory subunits which inhibit the catalytic subunit until released by cAMP bindin...
Article
Full-text available
Injured or diseased airway epithelium due to repeated environmental insults or genetic mutations can lead to a functional decline of the lung and incurable lung diseases. Bioengineered airway tissue constructs can facilitate in vitro investigation of human lung diseases and accelerate the development of effective therapeutics. Here, we report robus...
Preprint
Recent synergistic advances in organ-on-chip and tissue engineering technologies offer opportunities to create in vitro- grown tissue or organ constructs that can faithfully recapitulate their in vivo counterparts. Such in vitro tissue or organ constructs can be utilized in multiple applications, including rapid drug screening, high-fidelity diseas...
Article
Full-text available
Purpose of Review Adult human hematopoiesis resides in the bone marrow (BM), which is comprised of multiple niches capable of supporting hematopoietic stem and progenitor cells (HSPCs), as well as their downstream lineages. In maintaining the blood-forming cells of the body, the BM microenvironment is spatially regulated by a number of stromal supp...
Article
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Functional regeneration of complex large‐scaled defects requires both soft‐ and hard‐tissue grafts. Moreover, bone constructs within these grafts require an extensive vascular supply for survival and metabolism during the engraftment. Soft‐tissue pedicles are often used to vascularize bony constructs. However, extensive autologous tissue‐harvest re...
Article
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Engineered Vascularized Flaps In article number 2008687, Shulamit Levenberg and co‐workers fabricate composite neo‐tissue flaps by combining polymeric matrices and decellularized bone. These are perfused in vivo using hosts via a potent neo‐vascular network. In vivo imaging is utilized to show how composite flaps support long‐term bone repair and v...
Article
The convergence of tissue engineering and patient-specific stem cell biology has enabled the engineering of in vitro tissue models that allow the study of patient-tailored treatment modalities. However, sex-related disparities in health and disease, from systemic hormonal influences to cellular-level differences, are often overlooked in stem cell b...
Article
Extracellular vesicles (EVs) are carriers of biological signals through export and delivery of RNAs and proteins. Of increasing interest is the use of EVs as a platform for delivery of biomolecules. Preclinical studies have effectively used EVs to treat a number of diseases. Uniquely, endogenous machinery within cells can be manipulated in order to...
Article
We explore the utility of bioengineered human tissues-individually or connected into physiological units-for biological research. While much smaller and simpler than their native counterparts, these tissues are complex enough to approximate distinct tissue phenotypes: molecular, structural, and functional. Unlike organoids, which form spontaneously...
Article
Although machine perfusion has gained momentum as an organ preservation technique in liver transplantation, persistent organ shortages and high waitlist mortality highlight unmet needs for improved organ salvage strategies. Beyond preservation, extracorporeal organ support platforms can also aid the development and evaluation of novel therapeutics....
Article
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For decades, fetal bovine serum (FBS) has been used routinely for culturing many cell types, based on its empirically demonstrated effects on cell growth, and the lack of suitable non-xenogeneic alternatives. The FBS-based culture media do not represent the human physiological conditions, and can compromise biomimicry of preclinical models. To reca...
Article
Neuroblastoma (NB) is the most common extracranial pediatric solid cancer originating from undifferentiated neural crest cells. NB cells express EZH2 and GLI1 genes that are known to maintain the undifferentiated phenotype of cancer stem cells (CSC) in NB. Recent studies suggest that tumor-derived extracellular vesicles (EVs) can regulate the trans...
Article
Functional human tissues engineered from patient-specific induced pluripotent stem cells (hiPSCs) hold great promise for investigating the progression, mechanisms, and treatment of musculoskeletal diseases in a controlled and systematic manner. For example, bioengineered models of innervated human skeletal muscle could be used to identify novel the...
Article
Tissue engineering has markedly matured since its early beginnings in the 1980s. In addition to the original goal to regenerate damaged organs, the field has started to explore modeling of human physiology “in a dish.” Induced pluripotent stem cell (iPSC) technologies now enable studies of organ regeneration and disease modeling in a patient-specif...
Article
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In living tissues, mechanical stiffness and biological function are intrinsically linked. Alterations in the stiffness of tissues can induce pathological interactions that affect cellular activity and tissue function. Underlying connections between tissue stiffness and disease highlights the importance of accurate quantitative characterizations of...
Article
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Recent engineering technologies have transformed traditional perspectives of cancer to include the important role of the extracellular matrix (ECM) in recapitulating the malignant behaviors of cancer cells. Novel biomaterials and imaging technologies have advanced our understanding of the role of ECM density, structure, mechanics and remodeling in...
Article
Fibrosis of the knee is a common disorder resulting from an aberrant wound healing response and is characterized by extracellular matrix deposition, joint contraction, and scar tissue formation. The principal regulator of the fibrotic cascade is transforming growth factor beta-1 (TGF-β1), a factor that induces rapid proliferation and differentiatio...
Article
Current interventions fail to recover injured myocardium after infarction and prompt the need for development of cardioprotective strategies. Of increasing interest is the therapeutic use of microRNAs to control gene expression through specific targeting of mRNAs. In this Review, we discuss current microRNA-based therapeutic strategies, describing...
Article
Full-text available
Most cancer deaths are due to tumor metastasis rather than the primary tumor. Metastasis is a highly complex and dynamic process that requires orchestration of signaling between the tumor, its local environment, distant tissue sites, and immune system. Animal models of cancer metastasis provide the necessary systemic environment, but lack control o...
Article
Full-text available
Gastrointestinal disease burden continues to rise in the United States and worldwide. The development of bioengineering strategies to model gut injury or disease and to reestablish functional gut tissue could expand therapeutic options and improve clinical outcomes. Current approaches leverage a rapidly evolving gut bioengineering toolkit aimed at...
Article
Extracellular matrix is known to regulate vascularization by a sequence of multiple factors including mechanical forces. In this issue of Cell Stem Cell, Wei et al. (2020) investigate the roles of matrix biomechanics on early stages of vasculogenesis by using hydrogels with tunable stiffness and stress relaxation.
Conference Paper
Traditional in-vitro models of solid bone tumors used in basic and preclinical research are unable to faithfully recapitulate human physiology. Specifically, monolayer cultures of osteosarcoma fail to recapitulate various features of 3D tumors, and they lack the native bone milieu, where tumor growth, metastasis, and response to therapy are critica...
Article
Joint disorders can be detrimental to quality of life. There is an unmet need for precise functional reconstruction of native-like cartilage and bone tissues in the craniofacial space and particularly for the temporomandibular joint (TMJ). Current surgical methods suffer from lack of precision and comorbidities and frequently involve multiple opera...
Article
Traditional drug screening models are often unable to faithfully recapitulate human physiology in health and disease, motivating the development of microfluidic organs-on-a-chip (OOC) platforms that can mimic many aspects of human physiology and in the process alleviate many of the discrepancies between preclinical studies and clinical trials outco...
Article
Strategies to regenerate cardiac tissue postinjury are limited and heart transplantation remains the only 'cure' for a failing heart. Extracellular vesicles (EVs), membrane-bound cell secretions important in intercellular signaling, have been shown to play a crucial role in regulating heart function. A mechanistic understanding of the role of EVs i...
Article
Full-text available
From microscaled capillaries to millimeter‐sized vessels, human vasculature spans multiple scales and cell types. The convergence of bioengineering, materials science, and stem cell biology has enabled tissue engineers to recreate the structure and function of different hierarchical levels of the vascular tree. Engineering large‐scale vessels aims...
Article
Full-text available
In article number 1910811, Gordana Vunjak‐Novakovic, Sharon Fleischer, and Daniel Naveed Tavakol review approaches to engineering the human vascular tree, ranging from millimeter‐sized arteries to micro‐scaled capillaries. Strategies for engineering vascularized tissues, challenges limiting their translation into clinic, and perspectives on future...
Article
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Patients awaiting lung transplantation face high wait-list mortality, as injury precludes the use of most donor lungs. Although ex vivo lung perfusion (EVLP) is able to recover marginal quality donor lungs, extension of normothermic support beyond 6 h has been challenging. Here we demonstrate that acutely injured human lungs declined for transplant...
Article
Full-text available
The shortage of transplantable donor organs directly affects patients with end-stage lung disease, for which transplantation remains the only definitive treatment. With the current acceptance rate of donor lungs of only 20%, rescuing even one half of the rejected donor lungs would increase the number of transplantable lungs threefold, to 60%. We re...
Article
In this short review, we draw parallels and stress differences between heart regeneration in mice and human, from a bioengineering perspective. As the prevailing dogma that the adult heart is completely post-mitotic is starting to change, there are multiple opportunities for augmenting the limited but definitive turnover of cardiomyocytes, to the e...
Article
The respiratory system, which includes the trachea, airways, and distal alveoli, is a complex multi-cellular organ that intimately links with the cardiovascular system to accomplish gas exchange. In this review and as members of the NIH/NHLBI-supported Progenitor Cell Translational Consortium, we discuss key aspects of lung repair and regeneration....
Article
Full-text available
Articular cartilage injuries are a common source of joint pain and dysfunction. We hypothesized that pulsed electromagnetic fields (PEMFs) would improve growth and healing of tissue engineered cartilage grafts in a time‐ and direction‐dependent manner. PEMF stimulation of engineered cartilage constructs was first evaluated in vitro using passaged a...
Chapter
In the developed world, cardiovascular disease is responsible for the loss of more human lives than all cancer combined. Due to the minimal intrinsic ability of adult heart to regenerate itself following injury, the myocardial infarction results in rapid death of hundreds of millions of cardiomyocytes (CMs), and vigorous inflammatory response. Over...
Chapter
Tissue engineering could generate off-the-shelf organs for transplantation to treat a variety of debilitating ailments such as diabetes or Parkinson’s disease. One of the major barriers to the realization of this enormous potential is the lack of renewable sources of cells for transplantation. Embryonic stem cells (ESCs) and induced pluripotent ste...
Article
Introduction: Neuromuscular Junctions (NMJs) are the synapses between motor neurons and skeletal muscle fibers, and they are responsible for voluntary motor function. NMJs are affected at early stages of numerous neurodegenerative and neuroimmunological diseases. Due to the difficulty of systematically studying and manipulating NMJs in live subject...
Article
Full-text available
Studies of anticancer therapies in traditional cell culture models can demonstrate efficacy of direct-acting compounds, but lack the three-dimensional arrangement of the tumor cells and their tissue-specific microenvironments, both of which are important modulators of treatment effects in vivo. Bone cells reside in complex environments that regulat...
Article
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Objectives: Lung remains the least-utilized solid organ for transplantation. Efforts to recover donor lungs with reversible injuries using ex vivo perfusion systems are limited to <24 hours of support. Here, we demonstrate the feasibility of extending normothermic extracorporeal lung support to 4 days using cross-circulation with conscious swine....
Article
The application of tissue-engineering approaches to human induced pluripotent stem (hiPS) cells enables the development of physiologically relevant human tissue models for in vitro studies of development, regeneration, and disease. However, the immature phenotype of hiPS-derived cardiomyocytes (hiPS-CMs) limits their utility. We have developed a pr...
Article
Full-text available
An Amendment to this paper has been published and can be accessed via a link at the top of the paper.
Article
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The number of available donor organs limits lung transplantation, the only lifesaving therapy for the increasing population of patients with end-stage lung disease. A prevalent etiology of injury that renders lungs unacceptable for transplantation is gastric aspiration, a deleterious insult to the pulmonary epithelium. Currently, severely damaged d...