'Body on a chip' used for drug tests

17 September 2013 Last updated at 12:44 ETBy Joe Miller BBC News

The 3D printer that will be used to print miniature organs for the 'body on a chip' system

Miniature human organs developed with a modified 3D printer are being used to test new vaccines in a lab in the US.

The "body on a chip" project replicates human cells to print structures which mimic the functions of the heart, liver, lung and blood vessels.

The organs are then placed on a microchip and connected with a blood substitute, allowing scientists to closely monitor specific treatments.

The US Department of Defense has backed the new technology with $24m (￡15m).

Bioprinting, a form of 3D printing which, in effect, creates human tissue, is not new. Nor is the idea of culturing 3D human tissue on a microchip.

But the tests being carried out at the Wake Forest Institute for Regenerative Medicine in North Carolina are the first to combine several organs on the same device, which then model the human response to chemical toxins or biologic agents.

Printing organs

The modified 3D printers, developed at Wake Forest, print human cells in hydrogel-based scaffolds.

The lab-engineered organs are then placed on a 2in (5cm) chip and linked together with a circulating blood substitute, similar to the type used in trauma surgery.

The blood substitute keeps the cells alive and can be used to introduce chemical or biologic agents, as well as potential therapies, into the system.

Sensors which measure real-time temperature, oxygen levels, pH and other factors feed back information on how the organs react and - crucially - how they interact with each other.

Dr Anthony Atala, institute director at Wake Forest and lead investigator on the project, said the technology would be used both to "predict the effects of chemical and biologic agents and to test the effectiveness of potential treatments".

Miniature tissue samples can be exposed to toxins as well as potential treatments

"You are actually testing human tissue," he explained.

"It works better than testing on animals."

Anti-terrorism

A group of experts from around the US is involved in putting together the technology, which will carry out toxicity testing and identification.

The funding for the project was awarded by the Defense Threat Reduction Agency (DTRA), a division of the US government which combats nuclear, chemical and biological weapons.

The tests being carried out at Wake Forest "would significantly decrease the time and cost needed to develop medical countermeasures" for bioterrorism attacks, said Dr Clint Florence, acting branch chief of vaccines within the Translational Medical Division at DTRA.

Wake Forest said it was able to test for antidotes to sarin gas, recently used against civilians in Syria.

Printed house

Dr Atala, whose field is regenerative medicine, said the bioprinting technology was first used at Wake Forest for building tissues and organs for replacement in patients.

His team had managed to replicate flat organs, such as skin, tubular organs such as blood vessels, and even hollow non-tubular organs like the bladder and the stomach, which have more complex structures and functions.

But building solid organs like the heart and the liver is the hardest challenge yet.

A combination microscope and incubator is used to image tissue over time

It takes about 30 minutes just to print a miniature kidney or heart, which is the size of a small biscuit.

"There are so many cells per centimetre that making a big organ is quite complex," Dr Atala told the BBC.

But the bioprinting of full size solid organs might not be far away.

"We are working on creating solid organ implants," said Dr Atala.

Bioink containing various types of cell is printed into moulds made from agarose gel.

After several days the bioink fuses and the agarose support is removed. The tissue is put into a bioreactor and given low frequency stimulation to mature the muscle fibres.

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New tests to detect drug-resistant malaria

Sep. 10, 2013 — Researchers have developed two tests that can discern within three days whether the malaria parasites in a given patient will be resistant or susceptible to artemisinin, the key drug used to treat malaria. The tests were developed by researchers from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, working with French and Cambodian colleagues in Cambodia. They offer a more rapid, less costly advantage over current drug-responsiveness tests, which require malaria patients to be hospitalized for blood draws every six hours over the course of several days. In both tests, young parasites are briefly exposed to a high dose of artemisinin, mimicking the way parasites are exposed to the drug in people being treated for malaria, and their survival is measured 72 hours later.

The first test is conducted on blood taken from a malaria patient at the same time as the first dose of artemisinin-based combination drug therapy is administered. The test returns results in 72 hours and can predict whether the patient has slow-clearing, drug-resistant parasites. The researchers note that the simple, new test could be used for surveillance studies to monitor and map the emergence or spread of artemisinin-resistant malaria parasites. In the current study, researchers using this test detected artemisinin-resistant parasites at sites in Northern and Eastern Cambodia for the first time.

The second test is conducted on parasites grown in the laboratory. This test requires trained technicians to adapt parasites from a malaria patient to a laboratory culture, synchronize the life-stages of the parasites, and then apply the drug only to those that are three hours old or younger. This test will likely be most useful in future studies designed to elucidate the molecular basis of artemisinin resistance and to screen new malaria drugs.

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Story Source:

The above story is based on materials provided by NIH/National Institute of Allergy and Infectious Diseases, via EurekAlert!, a service of AAAS.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

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Journal Reference:

1. Benoit Witkowski, Chanaki Amaratunga, Nimol Khim Msc A, Sokunthea Sreng, Pheaktra Chim, Saorin Kim, Pharath Lim, Sivanna Mao, Chantha Sopha, Baramey Sam, Jennifer M Anderson, Socheat Duong, Char Meng Chuor, Walter R J Taylor, Seila Suon, Odile Mercereau-Puijalon, Dr Rick M Fairhurst, Didier Menard. Novel phenotypic assays for the detection of artemisinin-resistant Plasmodium falciparum malaria in Cambodia: in-vitro and ex-vivo drug-response studies. The Lancet Infectious Diseases, September 2013

Note: If no author is given, the source is cited instead.

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Smokers' Cell Damage Exists Even If Tests Miss It, Study Says

WEDNESDAY, July 17 (HealthDay News) -- Even if medical tests are normal, smokers whose lungs appear healthy may still have damaged airway cells with characteristics similar to cells found in aggressive lung cancer, a new study indicates.

Researchers analyzed cells that line the airway from healthy nonsmokers and smokers with no detectable lung disease. The smokers' cells showed early signs of changes similar to those found in lung cancer.

"When you smoke a cigarette, some of the genetic programming of your lung cells is lost," senior investigator Dr. Ronald Crystal, chairman and professor of genetic medicine at Weill Cornell Medical College in New York City, said in a college news release.

"Your cells take on the appearance of a more primitive cell. It doesn't necessarily mean you will develop cancer, but that the soil is fertile to develop cancer," he explained.

The results of the study, published July 16 in the journal Stem Cell, show that smoking causes harm even when there is no clinical evidence that anything is wrong.

"The study doesn't say these people have cancer, but that the cells are already starting to lose control and become disordered," Crystal said. "The smoker thinks they are normal, and their doctor's exam is normal, but we know at the biologic level that all cigarette smokers' lungs are abnormal to some degree."

These very early changes can't be detected through physical examinations, lung function tests or X-rays. "The take-home message is: Don't smoke. Smoking is bad, and if you smoke, you're at risk," Crystal said.

Further research is needed to learn why smoking causes these changes. This could help scientists create treatments to prevent lung cancer.

More information

The U.S. National Cancer Institute has more about lung cancer prevention.

SOURCE: Weill Cornell Medical College, news release, July 16, 2013

Copyright c 2013 HealthDay. All rights reserved.

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Blood Tests Might Help Guide Breast Cancer Care

AppId is over the quota
AppId is over the quota

TUESDAY, June 5 (HealthDay News) -- A simple blood test may help gauge prognosis and tailor treatments for women who have been diagnosed with early stage breast cancer.

The test, described in the June 6 online edition of The Lancet Oncology, measures how many tumor cells are circulating in the blood. In the new study, if even one cell was detected in the bloodstream, a woman had a greater chance of her cancer recurring and of dying.

"This may help with prognosis and staging of the cancer and, in the future, with targets for breast cancer treatments," said study lead author Dr. Anthony Lucci, a professor of surgery at the University of Texas MD Anderson Cancer Center, in Houston.

Commenting on the findings, Dr. Stephanie Bernik, chief of surgical oncology at Lenox Hill Hospital in New York City, said, "We are moving into a state where we're looking at a person's individual tumor and this is another way to do that, potentially leading to treatment."

Whether or not cancer has spread to the lymph nodes is currently the best way to predict survival in women with breast cancer. Even so, a substantial number of patients whose cancer has not spread to the lymph nodes will have a recurrence while some of those who do have lymph-node involvement won't relapse.

Blood tests similar to the one investigated in this study have been found to be useful to gauge how well patients who already have metastatic cancer will do.

For this study, researchers counted circulating tumor cells in 302 breast cancer patients who were about to undergo surgery but who hadn't yet received chemotherapy.

Circulating tumor cells were detectable in about one-quarter of the participants, the investigators found. Fifteen percent of these individuals had a relapse and 10 percent died during a five-year follow-up, compared with 3 percent and 2 percent, respectively, of patients who did not have circulating tumor cells.

The more tumor cells a woman had in her bloodstream, the higher the likelihood of relapsing or dying, according to the report.

Although the test may not be far off in terms of clinical practice, "we need additional studies," Lucci said.

One area for study is how well these circulating cells predict recurrence and death in patients who have already had chemotherapy.

Currently, the American Society of Clinical Oncology does not recommend that clinicians measure circulating tumor cells in patients.

And in an accompanying comment article, Justin Stebbing, a professor in the department of surgery and cancer at Imperial College in London, said that "despite increasing evidence supporting the use of [circulating tumor cells] as biomarkers, how this information can be integrated into present practice is uncertain."

According to Bernik, though, "it makes sense that women who have circulating tumor cells would potentially be at higher risk of distant disease at some later date."

The problem is that just having circulating tumor cells may not be enough information to foretell the future, she noted.

"The cells also need to have a propensity to grow elsewhere," she said. "Not every cancer cell becomes a metastatic cancer cell. Hopefully, gaining the ability to tell which cells are more likely to spread potentially could guide therapy," Bernik added.

According to Lucci, circulating tumor cells are also showing promise in predicting melanoma prognosis, so the method may be "effective in several different tumor systems."

More information

The U.S. National Cancer Institute has more on breast cancer.

Copyright c 2012?HealthDay. All rights reserved.