How to Grow New Liver

A new experimental treatment could help treat end-stage liver disease – by growing tiny new livers elsewhere in the patient’s bodies. The technique, pioneered by cell therapy company LyGenesis, is due to begin human clinical trials in the next few weeks. The liver has a powerful regenerative capacity, able to repair itself from the constant damage it sustains as it works to rid the body of toxins. But alcohol intake or an unhealthy diet can impair that ability and lead to liver disease, the end stages of which can require liver transplants.

But the team at LyGenesis has been working on a creative alternative that would be much less invasive. Rather than replacing the liver, the technique would involve growing entirely new ones elsewhere in the bodymini-livers that can perform the same vital functions.

The process involves injecting healthy liver cells, taken from donated organs, into the recipient’s lymph nodes. There, they multiply and grow into functioning mini versions that can support the work of the remaining cells in the original liver. Previous tests in micepigs and dogs showed that the treatment improved their liver function, and can save the lives of many animals that would otherwise succumb to liver failure.

And now LyGenesis is preparing to test the technique in humans for the first time, in a phase 2a clinical trial. Beginning in the next few weeks, 12 adults with end-stage liver disease (ESLD) will receive batches of healthy liver cells. These will be delivered via endoscope and injected directly into the lymph nodes.

The trial participants will be split into three groups of four that receive different doses – either 50 million, 150 million or 250 million cells. It’s thought that for every 50 million cells a patient receives, they will grow one mini liver, meaning the highest dose group could end up with five extra livers. The LyGenesis team will monitor the patients for a year afterwards, assessing the effectiveness and safety of the treatment at the different doses.

Patients will need to receive immune-suppressing drugs to prevent their bodies rejecting the “foreign” mini-livers, much the same as those who currently receive whole organ transplants. However,

Source: https://newatlas.com/

Reprogramming the Brain’s Cleaning Crew to Mop Up Alzheimer’s Disease

The discovery of how to shift damaged brain cells from a diseased state into a healthy one presents a potential new path to treating Alzheimer’s and other forms of dementia, according to a new study from researchers at UC San Francisco (UCSF). The research focuses on microglia, cells that stabilize the brain by clearing out damaged neurons and the protein plaques often associated with dementia and other brain diseases. These cells are understudied, despite the fact that changes in them are known to play a significant role Alzheimer’s and other brain diseases, said Martin Kampmann, PhD, senior author on the study, which appears in Nature Neuroscience.

Microglia (green) derived from human stem cells

Now, using a new CRISPR method we developed, we can uncover how to actually control these microglia, to get them to stop doing toxic things and go back to carrying out their vitally important cleaning jobs,”  Kampmann said. “This capability presents the opportunity for an entirely new type of therapeutic approach.

Most of the genes known to increase the risk for Alzheimer’s disease act through microglial cells. Thus, these cells have a significant impact on how such neurodegenerative diseases play out, said Kampmann. Microglia act as the brain’s immune system. Ordinary immune cells can’t cross the blood-brain barrier, so it’s the task of healthy microglia to clear out waste and toxins, keeping neurons functioning at their best. When microglia start losing their way, the result can be brain inflammation and damage to neurons and the networks they form. Under some conditions, for example, microglia will start removing synapses between neurons. While this is a normal part of brain development in a person’s childhood and adolescent years, it can have disastrous effects in the adult brain.

Over the past five years or so, many studies have observed and profiled these varying microglial states but haven’t been able to characterize the genetics behind them. Kampmann and his team wanted to identify exactly which genes are involved in specific states of microglial activity, and how each of those states are regulated. With that knowledge, they could then flip genes on and off, setting wayward cells back on the right track. Accomplishing that task required surmounting fundamental obstacles that have prevented researchers from controlling gene expression in these cells. For example, microglia are very resistant to the most common CRISPR technique, which involves getting the desired genetic material into the cell by using a virus to deliver it. To overcome this, Kampmann’s team coaxed stem cells donated by human volunteers to become microglia and confirmed that these cells function like their ordinary human counterparts. The team then developed a new platform that combines a form of CRISPR, which enables researchers to turn individual genes on and off – and which Kampmann had a significant hand in developing – with readouts of data that indicate functions and states of individual microglia cells.

Through this analysis, Kampmann and his team pinpointed genes that affect the cell’s ability to survive and proliferate, how actively a cell produces inflammatory substances, and how aggressively a cell prunes synapses. And because the scientists had determined which genes control those activities, they were able to reset the genes and flip the diseased cell to a healthy state.

Source: https://www.ucsf.edu/

How To Intercept Coronavirus Infection

Nanoparticles cloaked in human lung cell membranes and human immune cell membranes can attract and neutralize the SARS-CoV-2 virus in cell culture, causing the virus to lose its ability to hijack host cells and reproduce. The first data describing this new direction for fighting COVID-19 were published on June 17, 2020 in the journal Nano Letters. The “nanosponges” were developed by engineers at the University of California San Diego (UC San Diego) and tested by researchers at Boston University. The UC San Diego researchers call their nano-scale particlesnanosponges” because they soak up harmful pathogens and toxins.

In lab experiments, both the lung cell and immune cell types of nanosponges caused the SARS-CoV-2 virus to lose nearly 90% of its “viral infectivity” in a dose-dependent manner. Viral infectivity is a measure of the ability of the virus to enter the host cell and exploit its resources to replicate and produce additional infectious viral particles.

Instead of targeting the virus itself, these nanosponges are designed to protect the healthy cells the virus invades.

Nanosponges attacking and neutralizing the SARS-COV-2 virus

Traditionally, drug developers for infectious diseases dive deep on the details of the pathogen in order to find druggable targets. Our approach is different. We only need to know what the target cells are. And then we aim to protect the targets by creating biomimetic decoys,” said Liangfang Zhang, a nanoengineering professor at the UC San Diego Jacobs School of Engineering.

His lab first created this biomimetic nanosponge platform more than a decade ago and has been developing it for a wide range of applications ever since. When the novel coronavirus appeared, the idea of using the nanosponge platform to fight it came to Zhang “almost immediately,” he said.

In addition to the encouraging data on neutralizing the virus in cell culture, the researchers note that nanosponges cloaked with fragments of the outer membranes of macrophages could have an added benefit: soaking up inflammatory cytokine proteins, which are implicated in some of the most dangerous aspects of COVID-19 and are driven by immune response to the infection.

Source: https://ucsdnews.ucsd.edu/

Nanorobots Clear Bacteria From Blood

Engineers at the University of California San Diego have developed tiny ultrasound-powered robots that can swim through blood, removing harmful bacteria along with the toxins they produce. These proof-of-concept nanorobots could one day offer a safe and efficient way to detoxify and decontaminate biological fluids.

Researchers built the nanorobots by coating gold nanowires with a hybrid of platelet and red blood cell membranes. This hybrid cell membrane coating allows the nanorobots to perform the tasks of two different cells at once—platelets, which bind pathogens like MRSA bacteria (an antibiotic-resistant strain of Staphylococcus aureus), and red blood cells, which absorb and neutralize the toxins produced by these bacteria. The gold body of the nanorobots responds to ultrasound, which gives them the ability to swim around rapidly without chemical fuel. This mobility helps the nanorobots efficiently mix with their targets (bacteria and toxins) in blood and speed up detoxification.

The work, published May 30 in Science Robotics, combines technologies pioneered by Joseph Wang and Liangfang Zhang, professors in the Department of NanoEngineering at the UC San Diego Jacobs School of Engineering. Wang’s team developed the ultrasound-powered nanorobots, and Zhang’s team invented the technology to coat nanoparticles in natural cell membranes.

SEM image of a MRSA bacterium attached to a hybrid cell membrane coated nanorobot

By integrating natural cell coatings onto synthetic nanomachines, we can impart new capabilities on tiny robots such as removal of pathogens and toxins from the body and from other matrices,” said Wang. “This is a proof-of-concept platform for diverse therapeutic and biodetoxification applications.”

The idea is to create multifunctional nanorobots that can perform as many different tasks at once,” adds co-first author Berta Esteban-Fernández de Ávila, a postdoctoral scholar in Wang’s research group at UC San Diego. “Combining platelet and red blood cell membranes into each nanorobot coating is synergistic—platelets target bacteria, while red blood cells target and neutralize the toxins those bacteria produce.

Source: http://jacobsschool.ucsd.edu/