Skin stem cells produce a human "mini" heart that helps screen drugs

Release date: 2015-07-24

American scientists have genetically recombined pluripotent stem cells extracted from human skin to create a micro-ventricle with human heart cells. This "small heart" can behave like a full-sized heart. Researchers say the "mini" organ can replace animal experiments, screen new drugs or test drugs for infants, and will help scientists reveal more of the secrets of human heart formation and development.

Kevin Healy, a collaborator of the study and a professor of bioengineering at the University of California at Berkeley, said in an interview with the British Daily Mail on July 15th: "We believe this is the first human micro-ventricle that has been cultivated in test tubes. This technology may help us quickly screen for drugs that may cause fetal heart disease."

He and Bruce Conklin, a researcher at the University of California, San Francisco, Gladstone Cardiovascular Institute, used biochemistry and biophysics to promote stem cell differentiation and self-organization into this tiny heart tissue, including the micro-ventricle. Related research is published in the latest issue of Nature Newsletter.

To test the potential of the system as a drug screening tool, the researchers exposed the differentiated cells to the drug thalidomide, which could cause severe birth defects. They found that at normal therapeutic doses, the drug caused abnormalities in the development of the microventricular, including shrinking size, muscle contraction, and decreased heart rate.

Conklin said: "Each year, about 280,000 pregnant women are exposed to drugs that pose a potential risk to the fetus. The most common birth defects include heart disease. The latest system may significantly reduce the chances of pregnant women coming into contact with toxic drugs. And, despite the latest research The main emphasis is on heart tissue, but new technologies have the potential to produce other body organs."

Previously, scientists used cardiomyocytes from experimental mice to study cardiac micro-tissues, but this is not an ideal model for human disease research. The "mini" heart, developed from human stem cells, has revolutionized this practice and will replace animal experiments in the future.

Phoenix Technology News Beijing July 17 news, according to the British Daily Mail reported that researchers use stem cells to create a small beating heart - and that it may revolutionize medicine. This new heart allows new drugs to be tested and provides researchers with new insights into how the heart develops. This small heart even has a micro-chamber that can "pulsate" like a normal-sized heart.

Stem cell culture pulsating artificial heart tissue

Researchers at the University of California, Berkeley, who collaborated with scientists at the Gladstone Institute in the United States, said they have used stem cells to create a new system of pulsating heart tissue templates that can serve as a template for early heart development and drug screening. Check the tools to make pregnancy safer. The Gladstone Institute is an independent non-profit life science research organization affiliated with the University of California, San Francisco.

“We believe this is the first example of a process of cultivating a human heart ventricle in a test tube,” said Kevin Healy, a senior research co-author and professor of bioengineering at the University of California, Berkeley. The senior author is Bruce Conklin, a senior investigator at the Gladstone Institute of Cardiovascular Diseases and a professor of medical genetics and cell and molecular pharmacology at the University of California, San Francisco. “This technology can help us quickly screen for drugs that may cause birth defects and guide decisions about which drugs are likely to be very dangerous during pregnancy.”

The potential for heart defects is the most important issue in determining drug safety during pregnancy.

In a study published in the journal Nature Communications, researchers used biochemical and biophysical cues to promote stem cell differentiation and self-organize to form micron-sized heart tissue, including micro-chambers. To test the potential of this system as a drug screening tool, the researchers exposed different cells to salidol (a sleeping pill, sedative) that is prone to serious birth defects.

They found that at therapeutic doses, the drug caused abnormal development of the microchamber, including volume reduction, muscle contraction problems, and lower heart rate. "We chose drug cardiotoxicity screening to demonstrate clinically relevant applications of cardiac microchambers," Conklin said. “Every year, as many as 280,000 pregnant women are exposed to drugs with potential fetal risks. The most common birth defects involve the heart, and the potential for heart defects is the most important issue in determining drug safety during pregnancy.”

The researchers said that although the study focused on heart tissue, there is great potential for applying this technique to other organ development. "Our focus is on early heart development, but the basic principles of human pluripotent stem cell patterns, and subsequent differentiation, can be extended to a wider range of tissue types to understand embryogenesis and tissue morphogenesis." Healy said. .

This milestone occurred four months after Healy and other Berkeley researchers publicly released a pulsed human heart cell system on the chip that could be used to check drug toxicity. In this new study, scientists mimicked the formation of human tissue, first using stem cells re-encoded from genes extracted from adult skin tissue to form a chamber of pulsating human heart cells. Conklin's laboratory provides these human induced pluripotent stem cells for use in the study.

These undifferentiated stem cells are then placed on a rounded surface that regulates cell differentiation and development. After two weeks, cells growing in a two-dimensional surface environment begin to form a three-dimensional structure that becomes a beating microchamber. In addition, these cells self-organize depending on whether they are located in the perimeter or center of the cell population. Compared to the central cells, the border cells have greater mechanical stress and tension and therefore look more like fibroblasts, which form the connective tissue collagen. In contrast, central cells form heart muscle cells.

"This spatial differentiation occurs naturally in biology, but we did it in test tubes for the first time," said lead research author, Zhen Ma, a postdoctoral fellow in bioengineering at the University of California, Berkeley. “This limited geometry provides biochemical and biophysical clues that directly guide heart differentiation and the formation of a beating microchamber.”

Modeling early heart development in covered petri dishes and cell culture plates is very difficult. This field of research generally involves dissecting animals at different stages of development to study organ formation and what errors can occur in this process. "The fact that we used pluripotent stem cells collected from patients in our research represents a mutation in this field," Healy said. "The previous study of cardiac micro-tissue was mainly the use of mouse cardiomyocytes, but it is an imperfect model of human disease."

Source: Technology Daily

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