A team of researchers in Japan has combined simple agarose with advanced machine learning techniques to study the differentiation of stem cells.

Asian Scientist Newsroom | April 20, 2017 | In the Lab

AsianScientist (Apr. 20, 2017) - Stem cell differentiation can now be seen thanks to a combination of machine learning and microfabrication techniques developed by scientists at the RIKEN Quantitative Biology Center in Japan. The results, published in PLOS ONE, followed the differentiation of human mesenchymal stem cells (MSC) which are easily obtained from adult bone marrow.

MSCs have proven to be important for regenerative medicine and stem cell therapy because they can potentially repair many different types of organ damage. Depending on the way the cells are grown, the results can be quite different, making controlling differentiation is an important goal.

Observing MSC differentiation under different conditions is an essential step in understanding how to control the process. However, this has proved challenging on two fronts. First, the physical space in which the cells are grown has a dramatic impact on the results, causing significant variation in the types of cells into which they differentiate. Studying this effect requires consistent and long lasting spatial confinement. Second, classifying the cell types which have developed through manual observation is time consuming.

Previous studies have confined cell growth with fibronectin on a glass slide. The cells can only adhere and differentiate where the fibronectin is present and are thus chemically confined. However, this procedure requires high technical skill to maintain the confinement for an extended period of time. To overcome this, the first author of the study, Dr. Nobuyuki Tanaka, decided to look for a new way to confine them. Using a simple agarose gel physical confinement system, he found that he could maintain them for up to 15 days.

It was wonderful to be able to do this, because agarose gel is a commonly used material in biology laboratories and can be easily formed into a micro-cast in a PDMS silicone mold, Tanaka said.

The advantage of this system is that once the PDMS molds are obtained the user only needs agarose gel and a vacuum desiccator to create highly reproducible micro-casts.

Tanaka's paper also describes an automated cell type classification system, using machine learning, which reduces the time and labor needed to analyze cells.

Combined together, these tools give us a powerful way to understand how stem cells differentiate in given conditions, he added.

The article can be found at: Tanaka et al. (2017) Simple Agarose Micro-confinement Array and Machine-learning-based Classification for Analyzing the Patterned Differentiation of Mesenchymal Stem Cells.

Source: RIKEN; Photo: Shutterstock. Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

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Automatically Observing Stem Cell Differentiation - Asian Scientist Magazine

Stem cell research begins with scientists, passes on to physicians and ends up with patients.

But those roles arent as separate as they seem, said speakers Thursday at a special meeting held by the California Institute for Regenerative Medicine, the states stem cell agency, and UC San Diego.

The agency is beginning a statewide tour to discuss the progress of its treatments through the lengthy research and clinical trial process. One priority is to make sure all those involved understand each others needs, and how they can help.

Speaker David Higgins has multiple roles built into his life. A San Diegan with Parkinsons disease, Higgins sits on CIRMs governing board.

Patient input is heard throughout CIRM, Higgins said, addressing the audience of more than 100 at the Sanford Consortium for Regenerative Medicine on Torrey Pines Mesa.

Patient advocates sit on reviews for grant funding, Higgins said. Nothing ever goes out the door without it being screened through the eyes of a patient advocate.

Patients can now take a much more active role in managing their illness and advocate for others, Higgins said, because doctors now recognize that treating disease is a partnership.

Now were looking at a two-way relationship, Higgins said. I dont know a single physician that Ive ever talked to who doesnt welcome this, Higgins said.

And in the long run, nobody can escape patienthood, said Dr. Catriona Jamieson, an oncologist-researcher at UCSD Moores Cancer Center.

Were all going to be patients, were all going to be health care users, Jamieson said. I dont see the patient term as in any way stigmatizing, because its part of using our health care system.

Making sure these roles are harmonized is important to CIRM, which has about $800 million left of the $3 billion given by California voters in 2004 in Proposition 71.

And while CIRM cant formally lobby on the issue, those who support the agency recognize they need public support if they want more money from taxpayers.

Jamieson said CIRM has helped her research, her UCSD colleagues and patients by grants and funding alpha stem cell clinics, including one at UCSD. These clinics help translate science into patient care, and help scientists and doctors share ideas and resources.

What we know so far is that great medicine requires great science, said Jamieson, who specializes in blood cancers.

Audience member Adrienne Shapiro was there as a patient advocate for sickle cell disease. Shes a carrier of the trait, and her daughter, Marissa Cors, has the disease. CIRM has funded a program to develop a better bone marrow transplant to treat the disease.

Cors said one of her main issues is dealing with the pain sickle cell disease causes her.

The pain medications are really the key at this particular point in the journey, Cors said, hesitating slightly in discussing the course of her disease.

Cors said shes hopeful that the CIRM program helps others.

Im looking for something effective for the community, Cors said.

bradley.fikes@sduniontribune.com

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News & Observer

UNC researchers ID cell where HIV persists despite treatment, new target for cure research News & Observer But researchers in the Division of Infectious Diseases at the UNC School of Medicine have found that the virus still persists in HIV-infested macrophages large white blood cells found in tissues throughout the body, including the liver, lungs, bone ... and more »

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UNC researchers ID cell where HIV persists despite treatment, new target for cure research - News & Observer

Immune system cells may help your heart keep the beat. These cells, called macrophages, usually protect the body from invading pathogens. But a new study published April 20 in Cell shows that in mice, the immune cells help electricity flow between muscle cells to keep the organ pumping.

Macrophages squeeze in between heart muscle cells, called cardiomyocytes. These muscle cells rhythmically contract in response to electrical signals, pumping blood through the heart. By plugging in to the cardiomyocytes, macrophages help the heart cells receive the signals and stay on beat.

Researchers have known for a couple of years that macrophages live in healthy heart tissue. But their specific functions were still very much a mystery, says Edward Thorp, an immunologist at Northwestern Universitys Feinberg School of Medicine in Chicago. He calls the studys conclusion that macrophages electrically couple with cardiomyocytes paradigm shifting. It highlights the functional diversity and physiologic importance of macrophages, beyond their role in host defense, Thorp says.

Matthias Nahrendorf, a cell biologist at Harvard Medical School, stumbled onto this electrifying find by accident.

Curious about how macrophages impact the heart, he tried to perform a cardiac MRI on a mouse genetically engineered to not have the immune cells. But the rodents heartbeat was too slow and irregular to perform the scan.

Immune cells called macrophages (green) squeeze in between heart cells (red) in an area of the heart called the atrioventricular node, as seen in this reconstruction of a human AV node. This node is a cluster of muscle fibers that electrically connects the upper and lower chambers of the heart.

These symptoms pointed to a problem in the mouses atrioventricular node, a bundle of muscle fibers that electrically connects the upper and lower chambers of the heart. Humans with AV node irregularities may need a pacemaker to keep their heart beating in time. In healthy mice, researchers discovered macrophages concentrated in the AV node, but what the cells were doing there was unknown.

Isolating a heart macrophage and testing it for electrical activity didnt solve the mystery. But when the researchers coupled a macrophage with a cardiomyocyte, the two cells began communicating electrically. Thats important, because the heart muscle cells contract thanks to electrical signals.

Cardiomyocytes have an imbalance of ions. While in the resting state, there are more positive ions outside the cell than inside, but when a cardiomyocyte receives an electrical signal from a neighboring heart cell, that distribution switches. This momentary change causes the cell to contract and send the signal on to the next cardiomyocyte.

Scientists previously thought that cardiomyocytes were capable of this electrical shift, called depolarization, on their own. But Nahrendorf and his team found that macrophages aid in the process. Using a protein, a macrophage hooks up to a cardiomyocyte. This protein directly connects the inside of these cells to each other, allowing macrophages to transfer positive charges, giving cardiomyocytes a boost kind of like with a jumper cable. This makes it easier for the heart cells to depolarize and trigger the heart contraction, Nahrendorf says.

With the help of the macrophages, the conduction system becomes more reliable, and it is able to conduct faster, he says.

Nahrendorf and colleagues found macrophages within the AV node in human hearts as well but dont know if the cells play the same role in people. The next step is to confirm that role and explore whether or not the immune cells could be behind heart problems like arrhythmia, says Nahrendorf.

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Immune cells play surprising role in steady heartbeat - Science News