Developing kidney organoids to reveal how the coronavirus ravages the body

Núria Montserrat – Institut de Bioenginyeria de Catalunya (IBEC)

Quantum entanglement is a process by which microscopic objects like electrons or atoms lose their individuality to become better coordinated with each other. Entanglement is at the heart of quantum technologies that promise large advances in computing, communications and sensing, for example detecting gravitational waves. Entanglement is also thought to play an important role in macroscopic quantum phenomena such as superconductivity.

Entangled states are famously fragile: in most cases even a tiny disturbance will undo the entanglement. For this reason, current quantum technologies take great pains to isolate the microscopic systems they work with, and typically operate at temperatures close to absolute zero. Here, in contrast, we heated a collection of atoms to 450 Kelvin, millions of times hotter than most atoms used for quantum technology. Moreover, the individual atoms were anything but isolated; they collided with each other every few microseconds, and each collision set their electrons spinning in random directions.

We then used a laser to monitor the magnetization of this hot, chaotic gas. The magnetization is caused by the spinning electrons in the atoms, and provides a way to study the effect of the collisions and to detect entanglement. What we observed was an enormous number of entangled atoms – about 100 times more than ever before observed. We also saw that the entanglement is non-local – it involves atoms that are not close to each other. Between any two entangled atoms there are thousands of other atoms, many of which are entangled with still other atoms, in a giant, hot and messy entangled state.

Reference
Monteil V, Kwon H, Prado P, Hagelkrüys A, Wimmer RA, Stahl M, Leopoldi A, Garreta E, Hurtado Del Pozo C, Prosper F, Romero JP, Wirnsberger G, Zhang H, Slutsky AS, Conder R, Montserrat N, Mirazimi A, Penninger JM 2020, ‘Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2’. Cell, 181(4):905-913.e7.

Confocal image of a kidney organoid that has been generated in vitro by hPSC differentiation using specific renal inductive signals, a methodology that lasts 20 days. Proximal tubule-like structures are detected by LTL staining (in green) and podocyte-like cells are characterized by the co-expression of WT1 (in red) and podocalyxin [PODXL] (in yellow). Nuclei are detected by DAPI staining (in blue).

SARS-CoV-2 enters into human cells using ACE2 which is expressed different tissues, including kidney and blood vessels. Since ACE2 exists both in membrane-bound and soluble circulating forms, one proposed therapy for COVID19 disease would be administering soluble recombinant form of ACE2 (sACE2). In this manner sACE2 would act as a decoy to interfere with the binding of SARSCoV- 2 to the full-length ACE2 that is membrane bound. Here we exploit organoid technology to explore these questions validating on the efficacy of sACE2 to reduce viral load in vitro.