Sarah J Rockwood1, Madelyn Arzt2,3,4,5, Arun Sharma6,7,8,9. 1. Stanford University Medical Scientist Training Program, 1600 Sand Hill Road, Palo Alto, CA, 94304, USA. 2. Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA, USA, 90048. 3. Smidt Heart Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA, USA, 90048. 4. Department of Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA, USA, 90048. 5. Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA, USA, 90048. 6. Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA, USA, 90048. arun.sharma@cshs.org. 7. Smidt Heart Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA, USA, 90048. arun.sharma@cshs.org. 8. Department of Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA, USA, 90048. arun.sharma@cshs.org. 9. Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA, USA, 90048. arun.sharma@cshs.org.
Abstract
Although SARS-CoV-2, the causative virus of the global COVID-19 pandemic, primarily affects the respiratory tract, it is now recognized to have broad multi-organ tropism and systemic effects. Early reports indicated that SARS-CoV-2 infection could lead to cardiac damage, suggesting the virus may directly impact the heart. Cardiac cell types derived from human pluripotent stem cells (hPSCs) enable mechanistic interrogation of SARS-CoV-2 infection in human cardiac tissue. PURPOSE OF REVIEW: To review the studies published since the emergence of the COVID-19 pandemic which utilize hPSCs and their cardiovascular derivative cell types to interrogate the tropism and effects of SARS-CoV-2 infection in the heart, as well as explore potential therapies. RECENT FINDINGS: Recent studies reveal that SARS-CoV-2 is capable of infecting and replicating within hPSC-derived cardiomyocytes and sinoatrial nodal cells, but not as extensively in their non-parenchymal counterparts. Additionally, they show striking viral effects on cardiomyocyte structure, transcriptional activity, and survival, along with potential mechanisms and therapeutic targets. Cardiac models derived from hPSCs are a viable platform to study the impact of SARS-CoV-2 on cardiac tissue and may lead to novel mechanistic insight as well as therapeutic interventions.
Although SARS-CoV-2, the causative virus of the global COVID-19 pandemic, primarily affects the respiratory tract, it is now recognized to have broad multi-organ tropism and systemic effects. Early reports indicated that SARS-CoV-2 infection could lead to cardiac damage, suggesting the virus may directly impact the heart. Cardiac cell types derived from human pluripotent stem cells (hPSCs) enable mechanistic interrogation of SARS-CoV-2 infection in human cardiac tissue. PURPOSE OF REVIEW: To review the studies published since the emergence of the COVID-19 pandemic which utilize hPSCs and their cardiovascular derivative cell types to interrogate the tropism and effects of SARS-CoV-2 infection in the heart, as well as explore potential therapies. RECENT FINDINGS: Recent studies reveal that SARS-CoV-2 is capable of infecting and replicating within hPSC-derived cardiomyocytes and sinoatrial nodal cells, but not as extensively in their non-parenchymal counterparts. Additionally, they show striking viral effects on cardiomyocyte structure, transcriptional activity, and survival, along with potential mechanisms and therapeutic targets. Cardiac models derived from hPSCs are a viable platform to study the impact of SARS-CoV-2 on cardiac tissue and may lead to novel mechanistic insight as well as therapeutic interventions.
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