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Newswise ANN ARBOR, Mich. Scientists have coaxed stem cells to grow the first three-dimensional mini lungs.

Previous research has focused on deriving lung tissue from flat cell systems or growing cells onto scaffolds made from donated organs. In a study published in the online journal eLife the multi-institution team defined the system for generating the self-organizing human lung organoids, 3D structures that mimic the structure and complexity of human lungs.

These mini lungs can mimic the responses of real tissues and will be a good model to study how organs form, change with disease, and how they might respond to new drugs, says senior study author Jason R. Spence, Ph.D., assistant professor of internal medicine and cell and developmental biology at the University of Michigan Medical School.

The scientists succeeded in growing structures resembling both the large airways known as bronchi and small lung sacs called alveoli.

Since the mini lung structures were developed in a dish, they lack several components of the human lung, including blood vessels, which are a critical component of gas exchange during breathing.

Still, the organoids may serve as a discovery tool for researchers as they churn basic science ideas into clinical innovations. A practical solution lies in using the 3-D structures as a next step from, or complement to, animal research.

Cell behavior has traditionally been studied in the lab in 2-D situations where cells are grown in thin layers on cell-culture dishes. But most cells in the body exist in a three-dimensional environment as part of complex tissues and organs.

Researchers have been attempting to re-create these environments in the lab, successfully generating organoids that serve as models of the stomach, brain, liver and human intestine.

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Scientists Coax Stem Cells to Form 3D Mini Lungs

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IMAGE:Karsten Sauer, Ph.D., is an associate professor at The Scripps Research Institute. view more

Credit: Photo courtesy of The Scripps Research Institute.

LA JOLLA, CA - March 23, 2015 - Stem cells can generate any type of cell in the body, but they are inactive most of the time--and for good reason. When stem cells become too active and divide too often, they risk acquiring cell damage and mutations. In the case of blood stem cells (also called hematopoietic stem cells or HSCs), this can lead to blood cancers, a loss of blood cells and an impaired ability to fight disease.

Now scientists at The Scripps Research Institute (TSRI) have found that a particular enzyme in HSCs is key to maintaining healthy periods of inactivity. Their findings, published recently in the journal Blood, show that animal models without this enzyme experience dangerous HSC activation and ultimately succumb to lethal anemia.

"These HSCs remain active too long and then disappear," said TSRI Associate Professor Karsten Sauer, senior author of the new study. "As a consequence, the mice lose their red blood cells and die."

With this new understanding of the enzyme, called Inositol trisphosphate 3-kinase B (ItpkB), scientists are closer to improving therapies for diseases such as bone marrow failure syndrome, anemia, leukemia, lymphoma and immunodeficiencies.

Stem Cells Need Rest

HSCs are a type of adult stem cell that lives in little niches in the bone marrow. They are normally inactive, or "quiescent," and only divide to self-renew about every two months.

However, when mature blood cells are lost, for example through severe bleeding or during infections, HSCs become activated to generate new "progenitor" cells--the cells that replenish the blood supply and produce immune cells to fight disease. Once the blood cells have been replenished, the HSC become quiescent again.

The balance between inactivity and activity is important because HSC activation generates side products that harm HSC. In addition, every division introduces a risk of mutation, sometimes leading to cancer. "It's like a car wearing down its own engine while it is doing its work," said Sauer. "Like people, HSCs need long periods of rest to remain healthy and work well."

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TSRI team discovers enzyme that keeps blood stem cells functional to prevent anemia

In a first of its kind effort, students of a city-based college have donated their stem cells and created a registry. Nearly 1,000 students of Meenakshi College for Women in Kodambakkam have registered as potential stem cell donors with Datri Blood Stem Cell Donors Registry. Another 500 students are expected to register on March 30.

The unique initiative was the brainchild of college principal K.S. Lakshmi. It all began after a casual visit to the Cancer Institute, Adyar. I had undergone two surgeries for a tumour in the throat which turned out to be benign.

During one of my visits to the hospital I noticed the hopelessness of the cancer patients. I wanted to donate only money but I was told that more than money the hospital wanted donations for a registry of stem cells, she said.

She took it up with the students in her college during the prayer assembly sessions. The students were encouraged to discuss the issue and soon through the colleges various student clubs it gathered momentum.

Only students above 18 years are allowed to donate. The student-donors had to get a consent letter from their parents. Encouragingly, only one parent refused to allow his daughter to participate, the principal said.

Datri provided a donation kit to each donor and also explained what the students had to do. The students were registered by providing their names with the college ID. They may change their mind at a later date but their donations could be used for research purposes at least, Ms. Lakshmi said.

To safeguard the interest of the donors the college took an undertaking from Datri that the donor stem cells would not be misused.

Datris co-founder Raghu Rajagopal said it was phenomenal that so many women had registered as potential donors. The donation drives help as the probability of finding a match (of stem cells) in ones own family is less than 25 per cent. I may get 15 requests for stem cells today but only one might be the right match, he says.

Of the 80,000 donors registered with Datri more than 11,000 are based in Tamil Nadu. So far the organisation has facilitated 92 transplants, six of them for patients living abroad.

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Students donate stem cells

16 hours ago by Denis Paiste MIT biological engineering graduate student Frances Liu works with a spiral-shaped inertial microfluidic separation device for separating stem cell populations in the Laboratory for Material Chemomechanics at MIT. This device was adapted from previous designs to separate cells as a function of diameter. Liu also grows bone marrow-derived stem cells and studies how those stem cells release certain chemicals in response to mechanical interactions with materials in the surrounding environment. Credit: Denis Paiste/Materials Processing Center

Researchers in MIT Associate Professor Krystyn J. Van Vliet's group last year showed that three biomechanical and biophysical markers could accurately identify the most desirable stem cells from a mixed group of bone marrow-derived cells. Now, MIT biological engineering graduate student Frances Liu is trying to advance that work by understanding how to alter the stem cells' physical environment to get them to produce the most desirable chemical output.

The bone marrow cells secrete special chemicals called cytokines that are needed in the body to repair bone tissue, fat tissue, and connective tissue like cartilage. "These so-called factors that the cells produce are associated with those tissue growth functions and tissue repair functions," Van Vliet says.

Liu grows bone marrow-derived stem cells and studies how those stem cells release certain chemicals in response to mechanical interactions with materials in their surrounding environment. "I would like to manipulate the cells, using cell-material interactions, or synthetic materials, to produce certain chemicals beneficial to tissue repair," Liu explains in the Laboratory for Material Chemomechanics at MIT. "Right now we are in the characterization phase, quantifying which and how much of different cytokines the cells secrete in response to different chemical and mechanical cues that we provide. Down the line, we aim to engineer those cytokine profiles using cell-material interactions." Liu, 24, is a third-year PhD student and expects to complete her doctorate in 2017. She received her bachelor of science degree in biomedical engineering from Brown University.

Liu is examining how various groups of stem cells differ in response to lab-controlled changes in their environment in ways that might be important for tissue repair in the body. "Frances is determining the correlations between the mechanical properties of the materials the cells interact with and the chemical factors that they produce in response to that chemomechanical coupling," Van Vliet says.

Heterogeneous cellular factories

"You can think of the cells as factories; they're factories of chemicals," Van Vliet explains. "One of the main ways you change the way that factory operates is you change the material properties of its environment. How stiff that environment is, how acidic that environment is, how rough that environment is, all of those characteristics of the cell's outside world can directly correlate with the chemicals that that cell produces. We don't really understand all of why that happens yet, but part of Frances' thesis is to understand these particular stem cells and the subpopulations within them."

While other researchers previously studied mechanical factors such as stiffness on the function of these mesenchymal (bone marrow-derived) stem cells, it wasn't widely recognized that they were examining a mixed population of cells, not a single well-defined cell population. "Some of them were stem cells, but some were not," Van Vliet says.

One way that Liu sorts her stem cells into groups is using an inertial microfluidic separation device that separates cells of large diameter cells from those of small diameter. This device was adapted from previous designs of their collaborator, MIT Professor Jongyoon Han, as part of the interdisciplinary team that Van Vliet leads within the Singapore-MIT Alliance for Research and Technology (SMART). The group showed in a 2014 paper that three markerssize, mechanical stiffness, and how much the nucleus inside the cell moves aroundare sufficient to identify stem cells in a heterogeneous population of chemically similar but non-stem cells. "We measured those three properties as well as several other properties, but only those three properties together, that triplet of properties, distinguished a stem cell from a non-stem cell," Van Vliet says.

By using the microfluidic device, we can better understand the differences between the subpopulations of these heterogeneous bone marrow cells and which cytokines each subpopulation may be secreting, both in the body and in the lab.

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Altering mechanical properties of cell environments to produce desired chemical outputs

FREDERICK, Md., March 23, 2015 /PRNewswire-USNewswire/ --Recent studies employing adult stem cells obtained from bone marrow and fat have been used in patients suffering from osteoarthritis of the knee. Results have indicated not only symptomatic improvement but also suggest that cartilage healing and regeneration may be taking place.

According to Director, Dr. Nathan Wei of the Arthritis Treatment Center, "Osteoarthritis options in the past have been limited to symptom relief. We are now entering an era where we have therapies that may also rebuild lost cartilage."

Osteoarthritis (OA) of the knee affects more than 20 million Americans. It is a disease due to loss of cartilage, the gristle that caps the ends of long bones and provides cushioning and shock absorption.

He goes on to say, "by administering adult stem cells, in a certain fashion, we may be able to restore lost cartilage. While this action has been demonstrated in multiple animal models, it has only been described in anecdotal reports in humans. Fortunately, we are now conducting clinical studies that are much better controlled and more scientifically valid."

Dr. Wei adds, "The positive effect on arthritis is not only due to multiplication, division, and transformation of the stem cell into cartilage, but it is also due to the fact the stem cell releases proteins that attract other reparative cells to the area. This is called the 'paracrine' effect."

"We are excited about the early results of our investigation and hope the results will continue to be positive. If so, I hope that knee replacement surgery might become a thing of the past," he concludes.

Dr. Wei is a board-certified rheumatologist and regenerative medicine expert. He is director of the Arthritis Treatment Center located in Frederick, Maryland.

SOURCE Arthritis Treatment Center

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Stem cell treatment for knee arthritis shows promising results