Dr. Zhu is a general cardiologist with specialized clinical and research training in cardio-oncology and cardio-immunology. She focuses on the cardiovascular care of patients undergoing therapies for cancer, with a particular focus on the effects of immunotherapies on the heart. She completed clinical cardiology fellowship and internal medicine residency training at Stanford University School of Medicine. During her post-doctoral training, Dr. Zhu’s research focuses on myocarditis, cardiac inflammation, and the effects of cancer therapeutics on the cardiovascular system. Her current research employs clinical data, bio-banked samples, and animal models to study T-cell toxicities in the heart. Dr. Zhu's clinic sees cardio-oncology and cardio-immunology patients and focuses on devising new methods for minimizing cardiovascular complications in the cancer patient population.
- Cardiovascular Disease
Honors & Awards
Melvin L. Marcus Early Career Investigator Award Finalist, American Heart Association (AHA) - Basic Cardiovascular Sciences (BCVS) (2021)
Gerald Reaven Basic Science Research Award, Stanford University (2020)
Sarnoff Scholar Career Development Award, Sarnoff Cardiovascular Foundation (2020)
Sanofi Innovation Awards (iAwards), Sanofi (2019-2021)
NIH F32 Ruth Kirschstein National Research Service Award Grant, National Institute of Health (NIH) (2019)
Stanford Cancer Institute (SCI) Innovation Award, Stanford Cancer Institute (SCI) (2019)
Alpha Omega Alpha (AOA) Member, Alpha Omega Alpha (AOA) (2014)
Myron F. Kanter and Lawrence J. Kanter Endowment Fund Award, Myron F. Kanter and Lawrence J. Kanter Foundation (2014)
Sarnoff Cardiovascular Research Foundation Fellowship, Sarnoff Cardiovascular Foundation (2012-2013)
Irwin H. Lepow Research Award, Irwin H. Lepow Research Foundation (2011)
American Federation of Aging Research (AFAR) Grant Recipient, American Federation of Aging Research (AFAR) (2010)
Boards, Advisory Committees, Professional Organizations
Assistant Editor, JACC: CardioOncology (2020 - Present)
Committee Member, AHA Statement on Preclinical Models in Cardio-Oncology Writing Group (2020 - Present)
Cardio-Oncology Subcommittee Member, American Heart Association (AHA) (2019 - Present)
Committee Member, American College of Cardiology Cardio-Oncology - California Chapter (2020 - Present)
Member, Society of Cardiovascular Computed Tomography (SCCT) (2019 - Present)
Member, American Society of Echocardiography (2019 - Present)
Board Certification: American Board of Internal Medicine, Cardiovascular Disease (2020)
Board Certification, American College of Cardiology/ABIM, Cardiovascular Disease (2020)
Fellowship: Stanford University Cardiovascular Medicine Fellowship (2020) CA
Board Certification, Society of Cardiovascular Computer Tomography (SCCT), Cardiac CT (2019)
Board Certification: National Board of Echocardiography, Adult Comprehensive Echocardiography (2019)
Board Certification: American Board of Internal Medicine, Internal Medicine (2017)
Residency: Stanford University Internal Medicine Residency (2017) CA
Medical Education: Case Western Reserve School of Medicine (2014) OH
Residency, Stanford University, Internal Medicine (2017)
Doctor of Medicine, Case Western Reserve University School of Medicine, Medicine (2014)
Bachelor of Science, Massachusetts Institute of Technology (MIT), Biological Engineering (2009)
Pilot Study for Optimizing Mental Wellbeing & Heart Health for Black Patients w/ Prostate Cancer
Pilot study to determine the feasibility of providing psychosocial and cardiac rehabilitation services to address socioeconomic health disparities and improve wellbeing for black men with prostate cancer.
- Myocarditis Surveillance with High-Sensitivity Troponin I During Cancer Treatment with Immune Checkpoint Inhibitors. JACC. CardioOncology 2021; 3 (1): 137–39
Preclinical Models of Cancer Therapy-Associated Cardiovascular Toxicity: A Scientific Statement From the American Heart Association.
Although cardiovascular toxicity from traditional chemotherapies has been well recognized for decades, the recent explosion of effective novel targeted cancer therapies with cardiovascular sequelae has driven the emergence of cardio-oncology as a new clinical and research field. Cardiovascular toxicity associated with cancer therapy can manifest as a broad range of potentially life-threatening complications, including heart failure, arrhythmia, myocarditis, and vascular events. Beyond toxicology, the intersection of cancer and heart disease has blossomed to include discovery of genetic and environmental risk factors that predispose to both. There is a pressing need to understand the underlying molecular mechanisms of cardiovascular toxicity to improve outcomes in patients with cancer. Preclinical cardiovascular models, ranging from cellular assays to large animals, serve as the foundation for mechanistic studies, with the ultimate goal of identifying biologically sound biomarkers and cardioprotective therapies that allow the optimal use of cancer treatments while minimizing toxicities. Given that novel cancer therapies target specific pathways integral to normal cardiovascular homeostasis, a better mechanistic understanding of toxicity may provide insights into fundamental pathways that lead to cardiovascular disease when dysregulated. The goal of this scientific statement is to summarize the strengths and weaknesses of preclinical models of cancer therapy-associated cardiovascular toxicity, to highlight overlapping mechanisms driving cancer and cardiovascular disease, and to discuss opportunities to leverage cardio-oncology models to address important mechanistic questions relevant to all patients with cardiovascular disease, including those with and without cancer.
View details for DOI 10.1161/RES.0000000000000473
View details for PubMedID 33934611
Immune checkpoint inhibitor cardiotoxicity: Breaking barriers in the cardiovascular immune landscape.
Journal of molecular and cellular cardiology
Immune checkpoint inhibitors (ICI) have changed the landscape of cancer therapy, but their use carries a high risk of cardiac immune related adverse events (iRAEs). With the expanding utilization of ICI therapy, there is a growing need to understand the underlying mechanisms behind their anti-tumor activity as well as their immune-mediated toxicities. In this review, we will focus on clinical characteristics and immune pathways of ICI cardiotoxicity, with an emphasis on single-cell technologies used to gain insights in this field. We will focus on three key areas of ICI-mediated immune pathways, including the anti-tumor immune response, the augmentation of the immune response by ICIs, and the pathologic "autoimmune" response in some individuals leading to immune-mediated toxicity, as well as local factors in the myocardial immune environment predisposing to autoimmunity. Discerning the underlying mechanisms of these immune pathways is necessary to inform the development of targeted therapies for ICI cardiotoxicities and reduce treatment related morbidity and mortality.
View details for DOI 10.1016/j.yjmcc.2021.07.006
View details for PubMedID 34303670
Immune Checkpoint Inhibitor Cardiotoxicity: Understanding Basic Mechanisms and Clinical Characteristics and Finding a Cure.
Annual review of pharmacology and toxicology
Immune checkpoint inhibitors (ICIs) attenuate mechanisms of self-tolerance in the immune system, enabling T cell responses to cancerous tissues and revolutionizing care for cancer patients. However, by lowering barriers against self-reactivity, ICIs often result in varying degrees of autoimmunity. Cardiovascular complications, particularly myocarditis but also arrhythmias, pericarditis, and vasculitis, have emerged as significant complications associated with ICIs. In this review, we examine the clinical aspects and basic science principles that underlie ICI-associated myocarditis and other cardiovascular toxicities. In addition, we discuss current therapeutic approaches. We believe a better mechanistic understanding of ICI-associated toxicities can lead to improved patient outcomes by reducing treatment-related morbidity. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 61 is January 8, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
View details for DOI 10.1146/annurev-pharmtox-010919-023451
View details for PubMedID 32776859
Mono- and Biallelic Protein-Truncating Variants in Alpha-Actinin 2 Cause Cardiomyopathy Through Distinct Mechanisms.
Circulation. Genomic and precision medicine
BACKGROUND: ACTN2 (alpha-actinin 2) anchors actin within cardiac sarcomeres. The mechanisms linking ACTN2 mutations to myocardial disease phenotypes are unknown. Here, we characterize patients with novel ACTN2 mutations to reveal insights into the physiological function of ACTN2.METHODS: Patients harboring ACTN2 protein-truncating variants were identified using a custom mutation pipeline. In patient-derived iPSC-cardiomyocytes, we investigated transcriptional profiles using RNA sequencing, contractile properties using video-based edge detection, and cellular hypertrophy using immunohistochemistry. Structural changes were analyzed through electron microscopy. For mechanistic studies, we used coimmunoprecipitation for ACTN2, followed by mass-spectrometry to investigate protein-protein interaction, and protein tagging followed by confocal microscopy to investigate introduction of truncated ACTN2 into the sarcomeres.RESULTS: Patient-derived iPSC-cardiomyocytes were hypertrophic, displayed sarcomeric structural disarray, impaired contractility, and aberrant Ca2+-signaling. In heterozygous indel cells, the truncated protein incorporates into cardiac sarcomeres, leading to aberrant Z-disc ultrastructure. In homozygous stop-gain cells, affinity-purification mass-spectrometry reveals an intricate ACTN2 interactome with sarcomere and sarcolemma-associated proteins. Loss of the C-terminus of ACTN2 disrupts interaction with ACTN1 and GJA1, 2 sarcolemma-associated proteins, which may contribute to the clinical arrhythmic and relaxation defects. The causality of the stop-gain mutation was verified using CRISPR-Cas9 gene editing.CONCLUSIONS: Together, these data advance our understanding of the role of ACTN2 in the human heart and establish recessive inheritance of ACTN2 truncation as causative of disease.
View details for DOI 10.1161/CIRCGEN.121.003419
View details for PubMedID 34802252
Pharmacovigilance analysis of cardiac toxicities associated with targeted therapies for metastatic non-small cell lung carcinoma.
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
INTRODUCTION: Targeted therapies have transformed treatment of driver-mutated metastatic non-small cell lung carcinoma (NSCLC). We compared cardiovascular adverse events between and within targeted therapy classes.METHODS: We used WHO pharmacovigilance database VigiBase to compare odds of heart failure, conduction disease, QT prolongation, supraventricular tachycardia (SVT), and ventricular arrhythmias between inhibitors of EGFR (erlotinib, gefitinib, afatinib, osimertinib), BRAF (dabrafenib), MEK (trametinib), and ALK ± ROS1 (alectinib, brigatinib, ceritinib, crizotinib, lorlatinib).RESULTS: Of 98,765 adverse reactions reported with NSCLC targeted therapies, 1,783 (1.8%) were arrhythmias and 1,146 (1.2%) were heart failure. ALK/ROS1 inhibitors were associated with increased odds of conduction disease (reporting odds ratio [ROR] 12.95, 99% CI: 10.14-16.55) and QT prolongation (ROR 5.16, 99% CI: 3.92-6.81) relative to BRAF and EGFR inhibitors. Among ALK/ROS1 inhibitors, crizotinib had highest odds of conduction disease (ROR 1.75, 99% CI: 1.30-2.36) and QT prolongation (ROR 1.91, 99% CI: 1.22-3.00). Dabrafenib (ROR 2.24, 99% CI: 1.86-2.70) and trametinib (ROR 2.44, 99% CI: 2.03-2.92) had higher odds of heart failure than other targeted therapies. Osimertinib was strongly associated with QT prolongation (ROR 6.13, 99% CI: 4.43-8.48), heart failure (ROR 3.64, 99% CI: 2.94-4.50), and SVT (ROR 1.90, 99% CI: 1.26-2.86) relative to other targeted therapies.CONCLUSIONS: ALK/ROS1 inhibitors are associated with higher odds of conduction disease and QT prolongation than other targeted therapies. Osimertinib is strongly associated with QT prolongation, SVT, and heart failure relative to other EGFR inhibitors and targeted therapies. Monitoring for heart failure and arrhythmias should be considered with NSCLC targeted therapies, especially osimertinib.
View details for DOI 10.1016/j.jtho.2021.07.030
View details for PubMedID 34418561
- Immune Profiling and Causal Antigen Discovery in Mouse and Human Models of Immune Checkpoint Inhibitor-induced Myocarditis LIPPINCOTT WILLIAMS & WILKINS. 2020
- Correction to: Cardiovascular Complications in Patients with COVID-19: Consequences of Viral Toxicities and Host Immune Response. Current cardiology reports 2020; 22 (5): 36
Cardiovascular Complications in Patients with COVID-19: Consequences of Viral Toxicities and Host Immune Response
Curr Cardiol Rep
2020; 22 (5)
View details for DOI 10.1007/s11886-020-01292-3
Cardiovascular Risks in Patients with COVID-19: Potential Mechanisms and Areas of Uncertainty.
Current cardiology reports
2020; 22 (5): 34
COronaVirus Disease 2019 (COVID-19) has spread at unprecedented speed and scale into a global pandemic with cardiovascular risk factors and complications emerging as important disease modifiers. We aim to review available clinical and biomedical literature on cardiovascular risks of COVID-19.SARS-CoV2, the virus responsible for COVID-19, enters the cell via ACE2 expressed in select organs. Emerging epidemiological evidence suggest cardiovascular risk factors are associated with increased disease severity and mortality in COVID-19 patients. Patients with a more severe form of COVID-19 are also more likely to develop cardiac complications such as myocardial injury and arrhythmia. The true incidence of and mechanism underlying these events remain elusive. Cardiovascular diseases appear intricately linked with COVID-19, with cardiac complications contributing to the elevated morbidity/mortality of COVID-19. Robust epidemiologic and biologic studies are urgently needed to better understand the mechanism underlying these associations to develop better therapies.
View details for DOI 10.1007/s11886-020-01293-2
View details for PubMedID 32350632
Low Wall Shear Stress Is Associated with Saphenous Vein Graft Stenosis in Patients with Coronary Artery Bypass Grafting.
Journal of cardiovascular translational research
Biomechanical forces may play a key role in saphenous vein graft (SVG) disease after coronary artery bypass graft (CABG) surgery. Computed tomography angiography (CTA) of 430 post-CABG patients were evaluated and 15 patients were identified with both stenosed and healthy SVGs for paired analysis. The stenosis was virtually removed, and detailed 3D models were reconstructed to perform patient-specific computational fluid dynamic (CFD) simulations. Models were processed to compute anatomic parameters, and hemodynamic parameters such as local and vessel-averaged wall shear stress (WSS), normalized WSS (WSS*), low shear area (LSA), oscillatory shear index (OSI), and flow rate. WSS* was significantly lower in pre-diseased SVG segments compared to corresponding control segments without disease (1.22 vs. 1.73, p = 0.012) and the area under the ROC curve was 0.71. No differences were observed in vessel-averaged anatomic or hemodynamic parameters between pre-stenosed and control whole SVGs. There are currently no clinically available tools to predict SVG failure post-CABG. CFD modeling has the potential to identify high-risk CABG patients who may benefit from more aggressive medical therapy and closer surveillance. Graphical Abstract.
View details for DOI 10.1007/s12265-020-09982-7
View details for PubMedID 32240496
- A Case of Early Immune Checkpoint Inhibitor Myocarditis Detected on Routine Troponin Monitoring Advancing the Cardiovascular Care of the Oncology Patient 2020
- Immune Profiling and Causal Antigen Discovery in Mouse and Human Models of Immune Checkpoint Inhibitor-induced Myocarditis Basic Cardiovascular Sciences (BCVS) Scientific Sessions 2020
NOVEL ALPHA-ACTININ 2 MUTATIONS ARE ASSOCIATED WITH CARDIOMYOPATHY AND HYPERTROPHY IN HUMAN CARDIAC TISSUE AND IPSC-DERIVED CARDIOMYOCYTES
ELSEVIER SCIENCE INC. 2019: 1027
View details for Web of Science ID 000460565901040
Computational Fluid Dynamics (BypassCFD) Trumps Anatomic Predictors of Saphenous Vein Graft Failure in CABG Patients
LIPPINCOTT WILLIAMS & WILKINS. 2018
View details for Web of Science ID 000528619404279
- Computational Fluid Dynamics (BypassCFD) Trumps Anatomic Predictors of Saphenous Vein Graft Failure in CABG Patients American Heart Association 2018
Sinoatrial node toxicity after stereotactic ablative radiation therapy to lung tumors.
Practical radiation oncology
Stereotactic ablative radiation therapy (SABR) is an established treatment for selected lung tumors. Sinoatrial node (SAN) toxicity after thoracic SABR has not been reported in the literature. We sought to understand the risk of SAN toxicity owing to incidental dose to the SAN from SABR.We conducted a retrospective review of patients with early-stage lung cancer or limited pulmonary metastases who underwent thoracic SABR to a right-sided central lung tumor (within 2 cm of the mainstem bronchus or other mediastinal structures) between January 2008 and December 2014, analyzed a subset whose treatment imparted dose to the SAN exceeding 10% of the prescription dose, and examined patient and treatment dosimetric characteristics. Mean follow-up interval was 28 months. Time to toxicity was defined from start of SABR.Of 47 patients with central tumors in the right lung treated with SABR reviewed, 13 met our study criteria. A contouring atlas of regional cardiac anatomy was created. One patient treated with SABR for non-small cell lung cancer at the right hilum developed symptomatic sick sinus syndrome, requiring pacemaker placement 6 months after treatment. Her acute presentation and short interval between SABR and onset of symptoms suggest that SAN toxicity was likely due to radiation-induced injury. Both her age and mean dose to her SAN were the third highest in our cohort. She remained free from cancer progression at 24 months' follow-up. Twelve additional patients who received significant dose to the SAN from SABR did not develop toxicity.While uncommon, SAN toxicity from SABR to right-sided central thoracic tumors should be recognized and followed in future studies.
View details for PubMedID 28669706
ACTN2 Mutations Are Associated With Cardiomyopathy and Cardiomyocyte Hypertrophy
LIPPINCOTT WILLIAMS & WILKINS. 2016
View details for Web of Science ID 000396815606012
Glucocorticoids enhance muscle endurance and ameliorate Duchenne muscular dystrophy through a defined metabolic program.
Proceedings of the National Academy of Sciences of the United States of America
2015; 112 (49): E6780–9
Classic physiology studies dating to the 1930s demonstrate that moderate or transient glucocorticoid (GC) exposure improves muscle performance. The ergogenic properties of GCs are further evidenced by their surreptitious use as doping agents by endurance athletes and poorly understood efficacy in Duchenne muscular dystrophy (DMD), a genetic muscle-wasting disease. A defined molecular basis underlying these performance-enhancing properties of GCs in skeletal muscle remains obscure. Here, we demonstrate that ergogenic effects of GCs are mediated by direct induction of the metabolic transcription factor KLF15, defining a downstream pathway distinct from that resulting in GC-related muscle atrophy. Furthermore, we establish that KLF15 deficiency exacerbates dystrophic severity and muscle GC-KLF15 signaling mediates salutary therapeutic effects in the mdx mouse model of DMD. Thus, although glucocorticoid receptor (GR)-mediated transactivation is often associated with muscle atrophy and other adverse effects of pharmacologic GC administration, our data define a distinct GR-induced gene regulatory pathway that contributes to therapeutic effects of GCs in DMD through proergogenic metabolic programming.
View details for DOI 10.1073/pnas.1512968112
View details for PubMedID 26598680
View details for PubMedCentralID PMC4679037
miR-222 is necessary for exercise-induced cardiac growth and protects against pathological cardiac remodeling.
2015; 21 (4): 584–95
Exercise induces physiological cardiac growth and protects the heart against pathological remodeling. Recent work suggests exercise also enhances the heart's capacity for repair, which could be important for regenerative therapies. While microRNAs are important in certain cardiac pathologies, less is known about their functional roles in exercise-induced cardiac phenotypes. We profiled cardiac microRNA expression in two distinct models of exercise and found microRNA-222 (miR-222) was upregulated in both. Downstream miR-222 targets modulating cardiomyocyte phenotypes were identified, including HIPK1 and HMBOX1. Inhibition of miR-222 in vivo completely blocked cardiac and cardiomyocyte growth in response to exercise while reducing markers of cardiomyocyte proliferation. Importantly, mice with inducible cardiomyocyte miR-222 expression were resistant to adverse cardiac remodeling and dysfunction after ischemic injury. These studies implicate miR-222 as necessary for exercise-induced cardiomyocyte growth and proliferation in the adult mammalian heart and show that it is sufficient to protect the heart against adverse remodeling.
View details for DOI 10.1016/j.cmet.2015.02.014
View details for PubMedID 25863248
View details for PubMedCentralID PMC4393846
Kruppel-like factor 15 is a critical regulator of cardiac lipid metabolism.
The Journal of biological chemistry
2014; 289 (9): 5914–24
The mammalian heart, the body's largest energy consumer, has evolved robust mechanisms to tightly couple fuel supply with energy demand across a wide range of physiologic and pathophysiologic states, yet, when compared with other organs, relatively little is known about the molecular machinery that directly governs metabolic plasticity in the heart. Although previous studies have defined Kruppel-like factor 15 (KLF15) as a transcriptional repressor of pathologic cardiac hypertrophy, a direct role for the KLF family in cardiac metabolism has not been previously established. We show in human heart samples that KLF15 is induced after birth and reduced in heart failure, a myocardial expression pattern that parallels reliance on lipid oxidation. Isolated working heart studies and unbiased transcriptomic profiling in Klf15-deficient hearts demonstrate that KLF15 is an essential regulator of lipid flux and metabolic homeostasis in the adult myocardium. An important mechanism by which KLF15 regulates its direct transcriptional targets is via interaction with p300 and recruitment of this critical co-activator to promoters. This study establishes KLF15 as a key regulator of myocardial lipid utilization and is the first to implicate the KLF transcription factor family in cardiac metabolism.
View details for DOI 10.1074/jbc.M113.531384
View details for PubMedID 24407292
View details for PubMedCentralID PMC3937660
Kruppel-like factor 15 regulates skeletal muscle lipid flux and exercise adaptation.
Proceedings of the National Academy of Sciences of the United States of America
2012; 109 (17): 6739–44
The ability of skeletal muscle to enhance lipid utilization during exercise is a form of metabolic plasticity essential for survival. Conversely, metabolic inflexibility in muscle can cause organ dysfunction and disease. Although the transcription factor Kruppel-like factor 15 (KLF15) is an important regulator of glucose and amino acid metabolism, its endogenous role in lipid homeostasis and muscle physiology is unknown. Here we demonstrate that KLF15 is essential for skeletal muscle lipid utilization and physiologic performance. KLF15 directly regulates a broad transcriptional program spanning all major segments of the lipid-flux pathway in muscle. Consequently, Klf15-deficient mice have abnormal lipid and energy flux, excessive reliance on carbohydrate fuels, exaggerated muscle fatigue, and impaired endurance exercise capacity. Elucidation of this heretofore unrecognized role for KLF15 now implicates this factor as a central component of the transcriptional circuitry that coordinates physiologic flux of all three basic cellular nutrients: glucose, amino acids, and lipids.
View details for DOI 10.1073/pnas.1121060109
View details for PubMedID 22493257
View details for PubMedCentralID PMC3340075
Elevated fibroblast growth factor-2 increases tumor necrosis factor-alpha induced endothelial cell death in high glucose.
Journal of cellular physiology
2008; 217 (1): 86–92
Glucose and tumor necrosis factor-alpha (TNFalpha) concentrations are elevated in diabetes. Both of these factors correlate with diabetic vasculopathy and endothelial cell apoptosis, yet their combined effects have not been measured. We have previously shown that the angiogenic growth factor fibroblast growth factor-2 (FGF-2), which is generally protective against endothelial cell death, is similarly elevated in high glucose conditions. We therefore investigated the effect of TNFalpha on endothelial cell death under normal and elevated glucose conditions, with a particular focus on FGF-2. Porcine aortic endothelial cells were cultured in 5 and 30 mM glucose and stimulated with TNFalpha, together with FGF-2 or a neutralizing FGF-2 antibody. Cell death was measured via cell counts or an annexin apoptotic assay, and cell cycle phase was determined by propidium iodide labeling. TNFalpha-induced endothelial cell death increased for cells in high glucose, and cell death was enhanced with increasing FGF-2 exposure and negated by a neutralizing FGF-2 antibody. Endothelial cells were most susceptible to TNFalpha-induced cell death when stimulated with FGF-2 18 h prior to TNFalpha, corresponding to cell entry into S phase of the proliferative cycle. The FGF-2 associated increase in TNFalpha-induced cell death was negated by blocking cell entry into S phase. Endothelial cell release of FGF-2 in high glucose leads to cell cycle progression, which makes cells more susceptible to TNFalpha-induced cell death. These data suggest that growth factor outcomes in high glucose depend on secondary mediators such as cytokines and stimulation cell cycle timing.
View details for DOI 10.1002/jcp.21476
View details for PubMedID 18446810
View details for PubMedCentralID PMC2838244
A porous photocurable elastomer for cell encapsulation and culture.
2007; 28 (32): 4826–35
Encapsulating cells within a polymer matrix creates a three-dimensional (3D) scaffold that may more accurately represent the native microenvironment and cell organization. Here we report a porous scaffold prepared from a photocurable elastomer, poly(glycerolco-sebacate)-acrylate (PGSA). The scaffold porosity, swelling, mass loss, toxicity and mechanical properties, suggest that porous PGSA could be used to support the growth and differentiation of encapsulated cells. Neuroblastoma (NB) and human embryonic stem cells (hESCs) were encapsulated into the matrix and found to adhere to the material and interact with each other within 24h. After 7 days, encapsulated NB cells were found to grow, and form matrix fibrils and tissue. Undifferentiated hESCs proliferated and differentiated in the PGSA scaffold. In vivo experiments showed that both porous scaffolds have similar biocompatibility profiles as non-porous PGSA, but porous PGSA promotes tissue ingrowth, as compared to non-porous PGSA. We therefore propose that porous PGSA scaffolds can provide a logistical template for 3D growth of cells and tissue engineering.
View details for DOI 10.1016/j.biomaterials.2007.07.039
View details for PubMedID 17692371