Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Animal studies show stem cells might make biological pacemaker

21.12.2004


In experiments in the lab and with guinea pigs, researchers from Johns Hopkins have found the first evidence that genetically engineered heart cells derived from human embryonic stem (ES) cells might one day be a promising biological alternative to the electronic pacemakers used by hundreds of thousands of people worldwide.



Electronic pacemakers are used in children and adults with certain heart conditions that interfere with a normal heartbeat. However, these life-saving devices can’t react the way the heart’s own pacemaker normally does -- for example, raising the heart rate to help us climb stairs or react to a scary movie.

In the researchers’ experiments, described in the Dec. 20 advance online edition of Circulation, human ES cells were genetically engineered to make a green protein, grown in the lab and then encouraged to become heart cells. The researchers then selected clusters of the cells that beat on their own accord, indicating the presence of pacemaking cells. These clusters triggered the unified beating of heart muscle cells taken from rats, and, when implanted into the hearts of guinea pigs, triggered regular beating of the heart itself.


"These implanted cells also responded appropriately to drugs used to slow or speed the heart rate, which electronic pacemakers can’t do," says study leader Ronald Li, Ph.D., assistant professor of medicine. "But many challenges remain before this technique could be used for patients. We want to bring this to the clinic as fast as possible, but we need to be extremely careful. If this process isn’t done properly, it could jeopardize a very promising field."

The genetic engineering of the ES cells, accomplished by Tian Xue, Ph.D., a postdoctoral fellow at the School of Medicine, inserted a gene (for green fluorescence protein) so that the human cells would be easily distinguished from animal cells in the experiments. Since the engineered cells survived and worked properly, other more clinically important genetic engineering of the cells also will probably not interfere with the cells’ fate, say the researchers.

"To our knowledge, these are the first genetically engineered heart cells derived from human ES cells," notes Xue. "We’re now using genetic engineering to customize the pacing rate of these cells, for example. For any future clinical applications, you want to make sure that the beating rate is what you want it to be."

First isolated at the University of Wisconsin, the human ES cells used by the researchers have the natural ability to become any type of cell found in the human body, and therefore they hold the potential to replace damaged cells. But such applications await proof that the desired type of cells can be obtained, isolated and controlled, because expected risks include primitive cells developing into tumors or implanted cells being rejected.

In the researchers’ experiments, clusters of beating human heart cells derived from ES cells were injected into the heart muscle of six guinea pigs. A few days later, the researchers destroyed each animal’s own pacemaking cells, located near the point of injection, by freezing them. Careful electrical measurements on the hearts revealed a new beat, coordinated by the implanted human cells and slower than the animals’ normal heart rate -- likely reflecting humans’ lower heart rate.

To prove that the human heart cells were controlling the beat of the guinea pigs’ hearts, colleagues Fadi Akar, Ph.D., and Gordon Tomaselli, M.D., conducted careful experiments that showed exactly where the electrical signal originated and followed the signal’s conduction across the heart’s surface. Sure enough, the signal started from the transplanted human cells, easy to locate because of their fluorescence.

"We’ve answered three very important questions," says Xue. "We’ve shown that these human cells survived when we put them into the animals, they were able to combine functionally with the animal’s heart muscle, and they didn’t create tumors for as long as we have watched."

But new questions have come up because of these promising results, notes Li. For instance, the researchers don’t know why the animal’s immune system didn’t attack and kill the human cellular "invaders " -- that was a surprise. One possibility is that the cluster of cells didn’t connect enough with the animal’s circulatory system to trigger an immune response, but more experiments will be necessary to see whether that’s the case and, if so, how that might affect the implanted cells’ long-term survival.

The researchers weren’t too surprised that no tumors formed over the course of a few months of observation, however, since they had selected beating heart cells and left behind any cells that weren’t adequately specialized.

The stem cell approach isn’t the first Hopkins research to create a biological pacemaker, but it is likely to be a better choice if the heart is very damaged. In 2002, Hopkins scientists reported that inserting a particular gene into existing heart muscle cells in a guinea pig allowed the cells to create a pacemaking signal. If heart damage is extensive, however, it might be preferable to introduce new pacemaking cells, rather than to convert existing cells into pacemakers, notes Li.

Joanna Downer | EurekAlert!
Further information:
http://www.jhmi.edu

More articles from Life Sciences:

nachricht Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View
22.06.2018 | University of Sussex

nachricht New cellular pathway helps explain how inflammation leads to artery disease
22.06.2018 | Cedars-Sinai Medical Center

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Temperature-controlled fiber-optic light source with liquid core

In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.

Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Graphene assembled film shows higher thermal conductivity than graphite film

22.06.2018 | Materials Sciences

Fast rising bedrock below West Antarctica reveals an extremely fluid Earth mantle

22.06.2018 | Earth Sciences

Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View

22.06.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>