Drug testing on bioengineered human tissue to fight COVID‐19
Researchers at The University of British Colombia demonstrated inhibition of SARS‐CoV‐2 (COVID‐19) infection and reproduction with human recombinant soluble ACE2 (hrsACE2) in engineered human organoids. Human capillary and renal tubule organoids were synthesized from induced pluripotent stem cells. When the organoids were exposed to a solution of SARS‐CoV‐2 alone vs. SARS‐CoV‐2 with hrsACE2, those exposed to the virus plus hrsACE2 mixture had a significantly reduced viral RNA load than virus alone after 3 days. With a method more closely representative of in vivo observation, the use of engineered human tissues for both studying infectious diseases and investigation into treatments may improve our understanding of the infection process and help us identify effective treatments faster, both of which could accelerate the process of solving the current SARS‐CoV‐2 pandemic and enable us to efficiently prepare for studying the next outbreak.
Penninger JM, Mirazimi A, Montserrat N. Inhibition of SARS‐CoV‐2 infections in engineered human tissues using clinical‐grade soluble human ACE2. Cell. 2020. https://doi.org/10.1016/j.cell.2020.04.004
CytoSorb device approved by FDA for COVID‐19
The previously experimental CytoSorb 300‐mL device for critically ill patients and those undergoing cardiac surgery has been granted emergency authorization by the U.S. Food and Drug Administration (FDA) to fight COVID‐19. The cylindrical device is filled with adsorbent polymer beads designed to bind inflammatory cytokines in the blood when added to the circuit of an external blood pump such as extracorporeal membrane oxygenation (ECMO). By removing circulating inflammatory cytokines responsible for acute respiratory distress syndrome (ARDS) experienced by some COVID‐19 patients, outcomes of those severely affected may improve. By sidestepping their own experimental trial process, the FDA is now allowing to intensive care units in the United States to acquire and use the device to address the need for treatment methods to battle COVID‐19.
https://www.fda.gov/media/136867/download
Patient‐specific stem cells to restore pancreatic endocrine function in diabetes
A team at Washington University in St. Louis successfully treated diabetes induced in mice with patient‐derived, gene‐edited skin cells. Researchers first induced pluripotent stem cells from skin fibroblasts taken from a patient with Wolfram Syndrome, a genetic disease with a mutation in the Wolfram syndrome 1 gene (WFS1) responsible for insulin‐dependent diabetes. Following stem cell isolation, CRISPR‐Cas9 was used to correct the mutant WFS1 gene. Analogous to pancreatic development, the gene‐edited stem cells were exposed to pancreatic‐specific growth factors resulting in successful pancreatic ß cell differentiation. When implanted, the gene‐edited pancreatic ß cells exhibited glucose‐stimulated insulin secretion and reversed streptozotocin‐induced diabetes in mice. While only being shown effective in an animal model, this method of gene correction and transplantation of patient‐specific cells may be the bridge between personalized gene therapy and tissue engineering. Without a doubt, the prospect of combining these potential therapies to restore properties of diseased or non‐functional organs in affected individuals is worth continual investigation.
Maxwell KG, Augsornworawat P, Velazco‐cruz L, et al. Gene‐edited human stem cell‐derived β cells from a patient with monogenic diabetes reverse preexisting diabetes in mice. Sci Transl Med. 2020;12(540). https://doi.org/10.1126/scitranslmed.aax9106
FDA approves 50‐cc temporary total artificial heart
A 50‐cc temporary total artificial heart system (50‐cc TAH‐t), manufactured by SynCardia Systems, LLC has recently received FDA approval for treatment as a bridge to heart transplant for patients who are at imminent risk of death from biventricular failure. This device along with the 70‐cc TAH‐t counterpart are the only 2 dischargeable biventricular support systems that have received approval. The 50‐cc version is approximately 40% smaller than the 70‐cc version and therefore more compatibile with smaller frames (ie, women, adolescents, and elderly patients) with a peak optimal cardiac output of 7.5 L/min vs 9.5 L/min for the 70‐cc device. In the past, only 12% of TAH implantations have been done for women and even less, 5%, have been implanted in pediatric patients, due to concerns with fit of the device. Approval of the 50‐cc system is expected to expand support options to smaller and younger patients in need of biventricular support.
https://syncardia.com/clinicians/our-products/50cc-total-artificial-heart/
Prepared by:
Elizabeth Maynes
Andrew Jordan
Vakhtang Tchantchaleishvili
Thomas Jefferson University, Philadelphia, PA, USA