Innovative approach brings cell-reprograming therapy for heart failure closer to reality

By Ana Maria Rodriguez

Not too long ago the idea of taking, for instance, a skin cell and transforming it into a muscle cell was unthinkable. About 10 years ago, however, revolutionary research showed that it is indeed possible to reprogram differentiated adult cells into other types fully capable of conducting new functions.

Cell reprogramming is a main interest of the lab of Dr. Todd Rosengart, chair, and professor of the Michael E. DeBakey Department of Surgery at Baylor College of Medicine, whose research focuses on finding innovative therapeutic approaches for heart failure.

“Heart failure remains the leading cause of death from heart disease,” said Rosengart, DeBakey-Bard Chair in Surgery and professor of molecular and cellular biology at Baylor. “Nearly 5 million Americans can be expected to develop advanced congestive heart failure, and heart transplant or mechanical circulatory support implantation currently are the only options for patients with end-stage heart disease. However, these options are limited. We need to improve how to treat this devastating condition.”

After a heart attack, the parts of the heart muscle that die do not regenerate into new heart tissue; instead, they are replaced by a scar that does not help the heart to beat. “The idea behind cell reprogramming is to coach the heart to heal itself by inducing the scar tissue, which is made mostly of fibroblasts, to change into functional heart muscle,” said Rosengart, professor of heart and vascular disease at the Texas Heart Institute.

Researchers have succeeded at reprogramming fibroblasts from small animals to become heart muscle, with dramatic improvements in heart function. The challenge has been to apply this technology to human cells — human fibroblasts are more resistant to reprogramming. In this study, published in the journal Scientific Reports, Rosengart and his colleagues explored a novel strategy to enhance the reprogramming efficiency of human fibroblasts.

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New approach using CRISPR can engineer massive quantities of cells for therapeutic applications

Reviewed by Emily Henderson, B.Sc.

A new variation of the CRISPR-Cas9 gene editing system makes it easier to re-engineer massive quantities of cells for therapeutic applications. The approach, developed at Gladstone Institutes and UC San Francisco (UCSF), lets scientists introduce especially long DNA sequences to precise locations in the genomes of cells at remarkably high efficiencies without the viral delivery systems that have traditionally been used to carry DNA into cells.

“One of our goals for many years has been to put lengthy DNA instructions into a targeted site in the genome in a way that doesn’t depend on viral vectors,” says Alex Marson, MD, PhD, director of the Gladstone-UCSF Institute of Genomic Immunology and senior author of the new study. “This is a huge step toward the next generation of safe and effective cell therapies.”

In the new paper published in the journal Nature Biotechnology, Marson and his colleagues not only describe the technology but show how it can be used to generate CAR-T cells with the potential to fight multiple myeloma, a blood cancer, as well as to rewrite gene sequences where mutations can lead to rare inherited immune diseases.

“We showed that we can engineer more than one billion cells in a single run, which is well above the number of cells we need to treat an individual patient,” says first author Brian Shy, MD, PhD, a clinical fellow in Marson’s lab.

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Cornea implant made from pig skin restores vision in landmark pilot trial

A pilot study saw bioengineered implants restore the vision of 14 volunteers who were completely blind before the experimental procedure

By Rich Haridy

A cornea implant made out of collagen gathered from pig skin has restored the vision of 20 volunteers in a landmark pilot study. Pending further testing, the novel bioengineered implant is hoped to improve the vision of millions around the world awaiting difficult and costly cornea transplant surgeries.

More than one million people worldwide are diagnosed blind every year due to damaged or diseased corneas. A person’s vision can be easily disrupted when this thin outer layer of tissue surrounding the eye degenerates.

A person suffering corneal blindness can have their vision restored by receiving a corneal transplant from a human donor. However, a lack of cornea donors means barely one in 70 people with corneal blindness will ever be able to access a transplant. Plus, the surgical procedure can be complex, amplifying the lack of access to this vision-restoring procedure for people in low- and middle-income countries.

This new research first looked to develop cornea implants that didn’t rely on human donor tissue. Over a decade ago the researchers first demonstrated biosynthetic corneas were effective replacements for donor corneas. But those earlier studies still relied on complex lab-grown human collagen, molded into the shape of corneas.

This new study demonstrates the same biosynthetic cornea can be effectively produced using medical-grade collagen sourced from pig skin. Not only is this a cheap and sustainable source of collagen, but improved engineering techniques mean these bioengineered corneas can be safely stored for almost two years, unlike donated human corneas which must be used within two weeks of harvesting.

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Vision in Humans Restored Using Cornea Implants Bioengineered from Pig’s Skin

Cornea implant made of collagen protein from pig’s skin.

By Thor Balkhed

For the estimated 12.7 million people around the world who are blind due to corneal stromal disease, a transplanted cornea from a human donor is the only way of regaining vision. But just one in 70 patients receives a cornea transplant. Now, researchers describe a cell-free engineered corneal tissue implant—made of collagen protein from pig’s skin—and a minimally invasive surgical method for its implantation. In a pilot study, performed in India and Iran (clinicaltrials.gov no. NCT04653922), all 20 patients who received the implants had vision restored.

The study is published in Nature Biotechnology, in the article, “Bioengineered corneal tissue for minimally invasive vision restoration in advanced keratoconus in two clinical cohorts.”

“The results show that it is possible to develop a biomaterial that meets all the criteria for being used as human implants, which can be mass-produced and stored up to two years and thereby reach even more people with vision problems,” said Neil Lagali, PhD, professor at the department of biomedical and clinical sciences at Linköping University (LiU) in Sweden. “This gets us around the problem of shortage of donated corneal tissue and access to other treatments for eye diseases.”

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Artificial Heart: Researchers Use Focused Rotary Jet Spinning Technology for More Advanced Human Transplant

A representation of an artificial heart valve through a 3D Medical Animation

By Marie Morales 

The researchers of Harvard John A. Paulson School of Engineering and Applied Sciences have devised the first-ever biohybrid model of beating cardiac cells aligned helically.

As a Healthclubfinder report specifies, “the future of cardiac medicine involves tissue engineering.” Specifically, it includes the development of a human heart intended for transplant.

The future of cardiac medicine involves tissue engineering. It includes the creation of a human heart for transplant.

This model revealed that the alignment of muscles does, in fact, substantially increase the amount of blood that the ventricle can pump with every contraction.

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DOCTORS GENE-EDIT PATIENT’S LIVER TO MAKE LESS CHOLESTEROL

 BY VICTOR TANGERMANN

THIS COULD BE A GAME CHANGER.

A team of researchers from US biotech company Verve Therapeutics have injected a gene-editing serum into a live patient’s liver with the goal of lowering their cholesterol, a watershed moment in the history of gene editing that could potentially save millions from cardiovascular disease and heart attacks, MIT Technology Review reports.

The clinical trial kicked off with a patient in New Zealand receiving the unusual injection dubbed VERVE-101. Early experiments on monkeys have already yielded hopeful results.

The company claims that these genetic edits will be able to permanently lower levels of “bad” LDL cholesterol, a fatty molecule that at excessive levels can lead to clogged arteries.

And that could be a gamechanger as other interventions such as hard-to-follow diets, exercise, and other prescribed medicine have only been able to make a small dent LDL levels. Many drugs have also remained wildly expensive, with insurers refusing to pay for them, according to MIT Tech.

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Scientists Discover First Effective Drug Treatment Against Hepatitis A

Fluorescence microscopy image of HAV-infected cultured human liver cell. viral RNA targeted by ZCCHC14 appears green, and the virus’s protein red. Credit: Maryna Kapustina, UNC School of Medicine

Scientists Discover Key to Hepatitis A Virus Replication, Show Drug Effectiveness

With no current treatments for hepatitis A, scientists at the University of North Carolina School of Medicine led by Stanley M. Lemon, MD, discovered how a protein and enzymes interact to allow hepatitis A virus to proliferate, and they used a known drug to stop viral replication in an animal model.

The viral replication cycle is essential for a virus to spread inside the body and cause disease. Focusing on that cycle in the hepatitis A virus (HAV), University of North Carolina (UNC) School of Medicine scientists discovered that replication requires particular interactions between the human protein ZCCHC14 and a group of enzymes called TENT4 poly(A) polymerases. They also discovered that the oral compound RG7834 stopped viral replication at a key step, preventing liver cell infection.

These findings are the first to demonstrate an effective drug treatment against HAV in an animal model of the disease. The study was published today (July 4, 2022) in the Proceedings of the National Academy of Sciences.

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This Dissolvable Implant Could Revolutionize Pain Management

Researchers at Northwestern University created an implantable device that attaches to a nerve to deliver pain relief.

By Margaret Osborne

After some success on rats, researchers are hopeful this device could provide humans a more targeted and less addictive alternative to opioids.

Millions of Americans live with pain. While pain can be an important indicator of health, it can also be debilitating, causing fatigue, depression and a decreased quality of life. Researchers from Johns Hopkins University and George Washington University estimated that pain cost the United States $560 billion to $635 billion in 2011.

In the 1990s, pharmaceutical companies claimed they had the answer: opioids. After being assured these drugs were not addictive, doctors prescribed opioids liberally, hoping to relieve their patients’ suffering.

But opioids are highly addictive, and as doctors prescribed more and more, drug abuse escalated. Some patients turned to heroin and synthetic opioids when they couldn’t get ahold of prescription drugs, and between 1999 and 2019, opioid overdoses killed nearly 500,000 people in the U.S. In 2017, the United States Department of Health and Human Services declared the opioid epidemic a public health emergency.

Since discovering the addictive properties of opioids, scientists have been searching for safer alternatives to relieve pain. Biomedical engineer John A. Rogers, of Northwestern University, thinks he may have created one—an implantable, dissolvable device that cools nerves in the body.

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Israeli-developed smart fabric uses electricity to fast-track repair of nerves

Silicone-based invention being tailored for human use after proving itself on rats; it wraps damaged nerves and electrically stimulates them using energy from light shone on skin

By NATHAN JEFFAY

A magnified image of the Israeli-developed material which speeds the repair of damaged nerves using electricity (courtesy of the Technion-Israel Institute of Technology) 

Israeli researchers say they have developed a material that speeds the repair of damaged nerves using electricity.

The ultra-thin material — a high-tech fabric of sorts — can be wrapped around damaged nerves inside the body and then enable electricity derived from light to flow there after the wound is closed up.

Its inventors, from Haifa’s Technion – Israel Institute of Technology, have tested the material on rats and documented its effectiveness in the peer-reviewed journal Nature Materials.

The material speeded up nerve repair in rats by 33 percent, and now heads to development and testing on humans.

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Novel Tissue Model May Help Harness the Liver’s Regenerative Abilities

If up to 70% of the liver is removed, the remaining tissue can regrow a full-sized liver within a couple of months. MIT engineers sought to take advantage of this regenerative ability to help treat chronic liver disease. The team reported that they have created a novel liver tissue model that allows them to trace the steps involved in regeneration more precisely than seen before.

Their findings are published in the journal Proceedings of the National Academy of Sciences(PNAS) in an article titled, “A vascularized model of the human liver mimics regenerative responses.”

“The new model can yield information that couldn’t be gleaned from studies of mice or other animals, whose biology is not identical to that of humans,” explained Sangeeta Bhatia, MD, PhD, the leader of the research team.

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New Technology Can Repair Heart Muscles After an Attack, Say Researchers

In a groundbreaking finding, researchers have developed a technology that can help effectively treat heart diseases in humans. The technology repairs heart muscles in mice after a heart attack and also successfully regenerates them. Researchers, from the University of Houston, have used a synthetic messenger ribonucleic acid (mRNA) to deliver mutated transcription factors to the heart of the mouse. The transcription factors are the proteins that control the conversion of DNA into RNA.

In their study, published in The Journal of Cardiovascular Aging, the team conducted an experiment to show that two mutated transcription factors, Stemin and YAP5SA, work closely to increase the replication of heart muscle cells or cardiomyocytes in mice.

“What we are trying to do is dedifferentiate the cardiomyocyte into a more stem cell-like state so that they can regenerate and proliferate,” said Siyu Xiao, Ph.D graduate and co-author of the study. According to another co-author Dinakar Iyer, Stemin transcription proved to be a game-changer in their experiment. While Stemin triggers stem-like properties in cardiomyocytes, YAP5SA works on organ growth resulting in more replication of the myocytes.

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Could an electronic tattoo revolutionise blood pressure monitoring?

Researchers have developed an electronic tattoo that delivers continuous blood pressure monitoring at high accuracy.

Blood pressure is the most vital indicator of heart health, and although there is a range of monitoring devices, it remains difficult to reliably measure outside of a clinical setting. Researchers at The University of Texas at Austin and Texas A&M University have developed an electronic tattoo that could change the face of blood pressure monitoring forever.

“Blood pressure is the most important vital sign you can measure, but the methods to do it outside of the clinic passively, without a cuff, are very limited,” said Deji Akinwande, a professor in the Department of Electrical and Computer Engineering at UT Austin and one of the co-leaders of the project.

The findings are published in Nature Nanotechnology.

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