Category Archives: Stem Cell Medical Center


To fight nasty digestive bugs, scientists set out to build a better gut — using stem cells

New $6.4M federal grant support will fuel the development of 'guts in a dish' to study interaction between cells & microbes in both health and disease

IMAGE:These HIO structures, each about the size of a BB and grown from stem cells, allow scientists to study the interaction between the cells of the gut lining and microbes... view more

Credit: University of Michigan Medical School

ANN ARBOR, Mich. -- If you got hit with any of the 'intestinal bugs' that went around this winter, you've felt the effects of infectious microbes on your digestive system.

But scientists don't fully understand what's going on in gut infections like that - or in far more serious ones that can kill. Many mysteries remain in the complex interaction between our own cells, the helpful bacteria that live inside us, and tiny invaders.

Now, a team of University of Michigan scientists will tackle that issue in a new way. Using human stem cells, they'll grow tiny "guts in a dish" in the laboratory and study how disease-causing bacteria and viruses affect the microbial ecosystem in our guts. The approach could lead to new treatments, and aid research on a wide range of diseases.

This work was started as part of the U-M Medical School's self-funded Host Microbiome Initiative and Center for Organogenesis, and the U-M Center for Gastrointestinal Research, funded by the National Institutes of Health. It also received funding from the U-M's MCubed initiative for interdisciplinary work.

Now, the project has received a $6.4 million boost with a new five-year NIH grant.

It will allow the U-M team to expand their effort to grow human intestinal organoids, or HIOs - tiny hollow spheres of cells into which they can inject a mix of bacteria. They'll work with researchers at other institutions, as part of the Novel, Alternative Model Systems for Enteric Diseases, or NAMSED, initiative sponsored by the NIH's National Institute of Allergy and Infectious Diseases.

Balls of cells become mini-guts

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To fight nasty digestive bugs, scientists set out to build a better gut -- using stem cells

Researchers identify drug target for ATRA, the first precision cancer therapy

Targeted cancer therapies work by blocking a single oncogenic pathway to halt tumor growth. But because cancerous tumors have the unique ability to activate alternative pathways, they are often able to evade these therapies -- and regrow. Moreover, tumors contain a small portion of cancer stem cells that are believed to be responsible for tumor initiation, metastasis and drug resistance. Thus, eradicating cancer stem cells may be critical for achieving long-lasting remission, but there are no drugs available that specifically attack cancer stem cells.

Now a research team led by investigators in the Cancer Research Institute at Beth Israel Deaconess Medical Center (BIDMC), has identified an inhibitor of the Pin1 enzyme that can address both of these challenges in acute promyelocytic leukemia (APL) and triple negative breast cancer.

Their surprising discovery demonstrates that the vitamin A derivative ATRA (all-trans retinoic acid), a treatment for APL that is considered to be the first example of modern targeted cancer therapy, can block multiple cancer-driving pathways and, at the same time, eliminate cancer stem cells by degrading the Pin1 enzyme. Reported online in Nature Medicine, these novel findings suggest a promising new way to fight cancer -- particularly cancers that are aggressive or drug resistant.

"Pin1 changes protein shape through proline-directed phosphorylation, which is a major control mechanism for disease," explains co-senior author Kun Ping Lu, MD, PhD, Director of Translational Therapeutics in the Cancer Research Institute at BIDMC and Professor of Medicine at Harvard Medical School who co-discovered the enzyme in 1996. "Pin1 is a common key regulator in many types of cancer, and as a result, can control over 50 oncogenes and tumor suppressors, many of which are known to also control cancer stem cells."

Until now, agents that inhibit Pin1 have been developed mainly through rational drug design. Although these inhibitors have proven to be active against Pin1 in the test tube, when they are tested in vitro in a cell model or in vivo in a living animal they are unable to efficiently enter cells to successfully inhibit Pin1 function.

In this new work, co-senior author Xiao Zhen Zhou, MD, an investigator in BIDMC's Division of Translational Therapeutics and Assistant Professor at Harvard Medical School, decided to take a different approach to identify Pin1 inhibitors: She developed a mechanism-based high throughput screen to identify compounds that were targeting active Pin1.

"We had previously identified Pin1 substrate-mimicking peptide inhibitors," explains Zhou. "We therefore used these as a probe in a competition binding assay and screened approximately 8,200 chemical compounds, including both approved drugs and other known bioactive compounds." To increase screening success, Zhou chose a probe that specifically binds to the Pin1 enzyme active site very tightly, an approach that is not commonly used for this kind of screen.

"Initially, it appeared that the screening results had no positive hits, so we had to manually sift through them looking for the one that would bind to Pin1. We eventually spotted cis retinoic acid, which has the same chemical formula as all-trans retinoic acid [ATRA], but with a different chemical structure." It turned out, Zhou explains, that Pin1 prefers binding to ATRA and cis retinoic acid needs to convert ATRA in order to bind Pin1.

ATRA was first discovered for the treatment of acute promyelocytic leukemia (APL) in 1987. "Before tamoxifen or other targeted drugs, there was ATRA," says Lu. It was originally thought that ATRA was successfully treating APL by inducing cell differentiation, causing cancer cells to change into normal cells by activating the cellular retinoic acid receptors. But as these new findings reveal, although this differentiation activity is obvious, it is not the mechanism that is actually behind ATRA's successful outcomes in treating APL.

"While it has been previously shown that ATRA's ability to degrade the leukemia-causing fusion oncogene PML-RAR causes ATRA to stop the leukemia stem cells that drive APL, the underlying mechanism has remained elusive," says Lu. "Our new high throughput drug screening has revealed the ATRA drug target, unexpectedly showing that ATRA directly binds, inhibits and ultimately degrades active Pin1 selectively in cancer cells. The Pin1-ATRA complex structure suggests that ATRA is trapped in the Pin1 active site by mimicking an unreleasable enzyme substrate. Importantly, ATRA-induced Pin1 ablation degrades the fusion oncogene PML-RAR and treats APL in cell and animal models as well as in human patients.

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Researchers identify drug target for ATRA, the first precision cancer therapy

Stem Cells, Fecal Transplants Show Promise for Crohn's Disease

By Amy Norton HealthDay Reporter

FRIDAY, April 10, 2015 (HealthDay News) -- Two experimental therapies might help manage the inflammatory bowel disorder Crohn's disease, if this early research pans out.

In one study, researchers found that a fecal transplant -- stool samples taken from a healthy donor -- seemed to send Crohn's symptoms into remission in seven of nine children treated.

In another, a separate research team showed that stem cells can have lasting benefits for a serious Crohn's complication called fistula.

According to the Crohn's & Colitis Foundation, up to 700,000 Americans have Crohn's -- a chronic inflammatory disease that causes abdominal cramps, diarrhea, constipation and rectal bleeding. It arises when the immune system mistakenly attacks the lining of the digestive tract.

A number of drugs are available to treat Crohn's, including drugs called biologics, which block certain immune-system proteins.

But fecal transplants take a different approach, explained Dr. David Suskind, a gastroenterologist at Seattle Children's Hospital who led the new study.

Instead of suppressing the immune system, he said, the transplants alter the environment that the immune system is reacting against: the "microbiome," which refers to the trillions of bacteria that dwell in the gut.

Like the name implies, a fecal transplant involves transferring stool from a donor into a Crohn's patient's digestive tract. The idea is to change the bacterial composition of the gut, and hopefully quiet the inflammation that causes symptoms.

And for most kids in the new study, it seemed to work. Within two weeks, seven of nine children were showing few to no Crohn's symptoms. Five were still in remission after 12 weeks, with no additional therapy, the researchers reported in a recent issue of the journal Inflammatory Bowel Diseases.

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Stem Cells, Fecal Transplants Show Promise for Crohn's Disease

iPSC model helps to better understand genetic lung/liver disease

Using patient-derived stem cells known as induced pluripotent stem cells (iPSC) to study the genetic lung/liver disease called alpha-1 antitrypsin (AAT) deficiency, researchers have for the first time created a disease signature that may help explain how abnormal protein leads to liver disease.

The study, which appears in Stem Cell Reports, also found that liver cells derived from AAT deficient iPSCs are more sensitive to drugs that cause liver toxicity than liver cells derived from normal iPSCs. This finding may ultimately lead to new treatments for the condition.

IPSC's are derived from the donated skin or blood cells of adults and, with the reactivation of four genes, are reprogrammed back to an embryonic stem cell-like state. Like embryonic stem cells, iPSC can be differentiated toward any cell type in the body, but they do not require the use of embryos. Alpha-1 antitrypsin deficiency is a common genetic cause of both liver and lung disease affecting an estimated 3.4 million people worldwide.

Researchers from the Center for Regenerative Medicine (CReM) at Boston University and Boston Medical Center (BMC) worked for several years in collaboration with Dr. Paul Gadue and his group from Children's Hospital of Philadelphia to create iPSC from patients with and without AAT deficiency. They then exposed these cells to certain growth factors in-vitro to cause them to turn into liver-like cells, in a process that mimics embryonic development. Then the researchers studied these "iPSC-hepatic cells" and found the diseased cells secrete AAT protein more slowly than normal cells. This finding demonstrated that the iPSC model recapitulates a critical aspect of the disease as it occurs in patients. AAT deficiency is caused by a mutation of a single DNA base. Correcting this single base back to the normal sequence fixed the abnormal secretion.

"We found that these corrected cells had a normal secretion kinetic when compared with their diseased, parental cells that are otherwise genetically identical except for this single DNA base," explained lead author Andrew A. Wilson, MD, assistant professor of medicine at Boston University School of Medicine and Director of the Alpha-1 Center at Bu and BMC.

They also found the diseased (AAT deficient) iPSC-liver cells were more sensitive to certain drugs (experience increased toxicity) than those from normal individuals. "This is important because it suggests that the livers of actual patients with this disease might be more sensitive in the same way," said Wilson, who is also a physician in pulmonary, critical care and allergy medicine at BMC.

According to Wilson, while some patients are often advised by their physicians to avoid these types of drugs, these recommendations are not based on solid scientific evidence. "This approach might now be used to generate that sort of evidence to guide clinical decisions," he added.

The researchers believe that studies using patient-derived stem cells will allow them to better understand how patients with AAT deficiency develop liver disease. "We hope that the insights we gain from these studies will result in the discovery of new potential treatments for affected patients in the near future," said Wilson.

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The above story is based on materials provided by Boston University Medical Center. Note: Materials may be edited for content and length.

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iPSC model helps to better understand genetic lung/liver disease

Key Mechanism Identified in Pediatric Bone Cancers That Allows Proliferation of Tumor-Forming Stem Cells

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Newswise A particular molecular pathway permits stem cells in pediatric bone cancers to grow rapidly and aggressively, according to researchers at NYU Langone Medical Center and its Laura and Isaac Perlmutter Cancer Center.

In normal cell growth, the Hippo pathway, which controls organ size in animals, works as a dam, regulating cell proliferation. What the researchers found is that the transcription factor of a DNA binding protein called sex determining region Y box 2, or Sox2 for short, which normally maintains cell self-renewal, actually releases the floodgates in the Hippo pathway in osteosarcomas and other cancers, permitting the growth of highly aggressive, tumor-forming stem cells.

Results from the study are to be published in the journal Nature Communications online April 2.

This study is one of the first to identify the mechanisms that underlie how an osteosarcoma cancer stem cell maintains its tumor-initiating properties, says senior study investigator Claudio Basilico, MD, the Jan T. Vilcek Professor of Molecular Pathogenesis at NYU Langone and a member of its Perlmutter Cancer Center.

In the study, the investigators used human and mouse osteosarcomas to pinpoint the molecular mechanisms that inhibit the tumor-suppressive Hippo pathway. The researchers concluded that Sox2 represses the functioning of the Hippo pathway, which, in turn, leads to an increase of the potent growth stimulator Yes Associated Protein, known as YAP, permitting cancer cell proliferation.

Our research is an important step forward in developing novel targeted therapies for these highly aggressive cancers, says study co-investigator Alka Mansukhani, PhD, an associate professor at NYU Langone and also a member of the Perlmutter Cancer Center. One possibility is to develop a small molecule that could knock out the Sox2 transcription factor and free the Hippo pathway to re-exert tumor suppression.

Mansukhani adds that the research suggests that drugs such as verteporfin, which interfere with cancer-promoting YAP function, might prove useful in Sox2-dependent tumors.

The study expands on previous work in Basilicos and Mansukhanis molecular oncology laboratories at NYU Langone and on earlier work by Upal Basu Roy, PhD, MPH, the lead study investigator, who found that Sox2 was an essential transcription factor for the maintenance of osteosarcoma stem cells.

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Key Mechanism Identified in Pediatric Bone Cancers That Allows Proliferation of Tumor-Forming Stem Cells

Researchers produce iPSC model to better understand genetic lung/liver disease

(Boston)--Using patient-derived stem cells known as induced pluripotent stem cells (iPSC) to study the genetic lung/liver disease called alpha-1 antitrypsin (AAT) deficiency, researchers have for the first time created a disease signature that may help explain how abnormal protein leads to liver disease.

The study, which appears in Stem Cell Reports, also found that liver cells derived from AAT deficient iPSCs are more sensitive to drugs that cause liver toxicity than liver cells derived from normal iPSCs. This finding may ultimately lead to new treatments for the condition.

IPSC's are derived from the donated skin or blood cells of adults and, with the reactivation of four genes, are reprogrammed back to an embryonic stem cell-like state. Like embryonic stem cells, iPSC can be differentiated toward any cell type in the body, but they do not require the use of embryos. Alpha-1 antitrypsin deficiency is a common genetic cause of both liver and lung disease affecting an estimated 3.4 million people worldwide.

Researchers from the Center for Regenerative Medicine (CReM) at Boston University and Boston Medical Center (BMC) worked for several years in collaboration with Dr. Paul Gadue and his group from Children's Hospital of Philadelphia to create iPSC from patients with and without AAT deficiency. They then exposed these cells to certain growth factors in-vitro to cause them to turn into liver-like cells, in a process that mimics embryonic development. Then the researchers studied these "iPSC-hepatic cells" and found the diseased cells secrete AAT protein more slowly than normal cells. This finding demonstrated that the iPSC model recapitulates a critical aspect of the disease as it occurs in patients. AAT deficiency is caused by a mutation of a single DNA base. Correcting this single base back to the normal sequence fixed the abnormal secretion.

"We found that these corrected cells had a normal secretion kinetic when compared with their diseased, parental cells that are otherwise genetically identical except for this single DNA base," explained lead author Andrew A. Wilson, MD, assistant professor of medicine at Boston University School of Medicine and Director of the Alpha-1 Center at Bu and BMC.

They also found the diseased (AAT deficient) iPSC-liver cells were more sensitive to certain drugs (experience increased toxicity) than those from normal individuals. "This is important because it suggests that the livers of actual patients with this disease might be more sensitive in the same way," said Wilson, who is also a physician in pulmonary, critical care and allergy medicine at BMC.

According to Wilson, while some patients are often advised by their physicians to avoid these types of drugs, these recommendations are not based on solid scientific evidence. "This approach might now be used to generate that sort of evidence to guide clinical decisions," he added.

The researchers believe that studies using patient-derived stem cells will allow them to better understand how patients with AAT deficiency develop liver disease. "We hope that the insights we gain from these studies will result in the discovery of new potential treatments for affected patients in the near future," said Wilson.

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Funding was provided by an ARRA stimulus grant (1RC2HL101535-01) awarded by the National Institutes of Health (NIH) to Boston University School of Medicine, Boston Medical Center and the Children's Hospital of Philadelphia. Additional funding was provided by K08 HL103771, FAMRI 062572_YCSA, an Alpha-1 Foundation Research Grant and a Boston University Department of Medicine Career Investment Award. Additional grants from NIH 1R01HL095993 and 1R01HL108678 and an ARC award from the Evans Center for Interdisciplinary Research at Boston University supported this work.

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Researchers produce iPSC model to better understand genetic lung/liver disease

Cellular Dynamics Webinar Spotlights Diabetic Cardiomyopathy-in-a-dish Model that May Elucidate Mechanisms for Repair …

Yorba Linda, CA (PRWEB) March 30, 2015

Developing new treatments for Diabetes Type 2 complications is challenging due to the use of cellular models that recapitulate only some subset of the specific features, but not the entirety of the disease.

A company that specializes in developing and manufacturing fully functioning human cells to precise specifications has created iPSC-derived cardiomyocytes (heart muscle cells), which have been used to develop environmentally and genetically driven in vitro models of Diabetes Type 2. The development process involves mimicking diabetic clinical chemistry to induce a phenotypic surrogate of diabetic cardiomyopathy, observing structural and functional disarray.

Cellular Dynamics International (CDI) is sponsoring a new educational webinar, Diabetic Cardiomyopathy Modeling & Screening with iPSC-derived Cardiomyocytes, to present the first patient-specific iPSC model of a complex metabolic condition, demonstrating the power of this model for discovery and testing of new therapeutic strategies. The webinar concludes with the presentation of a new approach using chemical biology to ultimately elucidate novel mechanisms activating the repair and regeneration of cardiomyocytes. Webinar speakers are Roberto Iacone, PhD and Brad Swanson, PhD.

Dr. Iacone, Senior Principal Scientist at Roche, pharma and research development (pRED), Basel, Switzerland, established the Stem Cell Group in the Cardiovascular and Metabolic Discovery at the company. Research in his group has focused on understanding the pathophysiological mechanisms and development complications in the heart using patient-specific iPSCs: the patient in a dish paradigm. The group is establishing in vitro disease modeling to identify new drugs for the retina remodeling linked to age-related macular degeneration. His research interest includes the identification and characterization of genes that regulate tissue repair and regeneration, aiming to develop regenerative medicines activating endogenous tissue progenitors.

Dr. Swanson is Senior Director of Cell Biology Research and Development, Cellular Dynamics International, Madison, Wisconsin, where he led the effort to develop the first commercially available human iPSC-derived cell product, iCell Cardiomyocytes, and several other iPSC models. Previously, he was a Senior Scientist at Roche NimbleGen, where he established the industrys first sequence capture product for targeted next generation sequencing workflows. Swanson received his PhD in Cellular and Molecular Biology (cardiac differentiation) from UW-Madison, undertook postdoctoral research in T cell behavior at the National Jewish Medical Center-HHMI in Denver, Colorado, and joined Columbus Childrens Research Institute/Ohio State University Center for Vaccines and Immunity as an Assistant Professor.

The free webinar, hosted by LabRoots, will be presented on April 7, 2015, at 8:30 am PST/11:30 am EST/5:30 pm CET.

For full details and free registration, click here.

About Cellular Dynamics International, Inc. Cellular Dynamics International, Inc. is a leading developer and producer of fully functioning human cells in industrial quantities to precise specifications. CDI's proprietary products include true human cells in multiple cell types (iCell products), human induced pluripotent stem cells (iPSCs) and custom iPSCs and iCell products (MyCell Products). CDI's products provide standardized, easy-to-use, cost-effective access to the human cell, the smallest fully functioning operating unit of human biology. Customers use our products, among other purposes, for drug discovery and screening; to test the safety and efficacy of their small molecule and biologic drug candidates; for stem cell banking; and in the research and development of cellular therapeutics. CDI was founded in 2004 by Dr. James Thomson, a pioneer in human pluripotent stem cell research at the University of Wisconsin-Madison. CDI's facilities are located in Madison, Wisconsin, with a second facility in Novato, California. See http://www.cellulardynamics.com.

About LabRoots: LabRoots is the leading scientific social networking website and producer of online educational events and webinars. And we are a powerful advocate in amplifying global networks and communities, and contributing to the advancement of science through content sharing capabilities and encouraging group interactions.

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Cellular Dynamics Webinar Spotlights Diabetic Cardiomyopathy-in-a-dish Model that May Elucidate Mechanisms for Repair ...

Researchers discover genetic origins of myelodysplastic syndrome using stem cells

(New York - March 25, 2015) Induced pluripotent stem cells (iPSCs) -- adult cells reprogrammed back to an embryonic stem cell-like state--may better model the genetic contributions to each patient's particular disease. In a process called cellular reprogramming, researchers at Icahn School of Medicine at Mount Sinai have taken mature blood cells from patients with myelodysplastic syndrome (MDS) and reprogrammed them back into iPSCs to study the genetic origins of this rare blood cancer. The results appear in an upcoming issue of Nature Biotechnology.

In MDS, genetic mutations in the bone marrow stem cell cause the number and quality of blood-forming cells to decline irreversibly, further impairing blood production. Patients with MDS can develop severe anemia and in some cases leukemia also known as AML. But which genetic mutations are the critical ones causing this disease?

In this study, researchers took cells from patients with blood cancer MDS and turned them into stem cells to study the deletions of human chromosome 7 often associated with this disease.

"With this approach, we were able to pinpoint a region on chromosome 7 that is critical and were able to identify candidate genes residing there that may cause this disease," said lead researcher Eirini Papapetrou, MD, PhD, Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai.

Chromosomal deletions are difficult to study with existing tools because they contain a large number of genes, making it hard to pinpoint the critical ones causing cancer. Chromosome 7 deletion is a characteristic cellular abnormality in MDS and is well-recognized for decades as a marker of unfavorable prognosis. However, the role of this deletion in the development of the disease remained unclear going into this study.

Understanding the role of specific chromosomal deletions in cancers requires determining if a deletion has observable consequences as well as identifying which specific genetic elements are critically lost. Researchers used cellular reprogramming and genome engineering to dissect the loss of chromosome 7. The methods used in this study for engineering deletions can enable studies of the consequences of alterations in genes in human cells.

"Genetic engineering of human stem cells has not been used for disease-associated genomic deletions," said Dr. Papapetrou. "This work sheds new light on how blood cancer develops and also provides a new approach that can be used to study chromosomal deletions associated with a variety of human cancers, neurological and developmental diseases."

Reprogramming MDS cells could provide a powerful tool to dissect the architecture and evolution of this disease and to link the genetic make-up of MDS cells to characteristics and traits of these cells. Further dissecting the MDS stem cells at the molecular level could provide insights into the origins and development of MDS and other blood cancers. Moreover, this work could provide a platform to test and discover new treatments for these diseases.

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This study was supported by grants from the National Institutes of Health, the American Society of Hematology, the Sidney Kimmel Foundation for Cancer Research, the Aplastic Anemia & MDS International Foundation, the Ellison Medical Foundation, the Damon Runyon Cancer Research Foundation, the University of Washington Royalty Research Fund, and a John H. Tietze Stem Cell Scientist Award.

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Researchers discover genetic origins of myelodysplastic syndrome using stem cells

Stem cells make similar decisions to humans

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Scientists at the University of Copenhagen have captured thousands of progenitor cells of the pancreas on video as they made decisions to divide and expand the organ or to specialize into the endocrine cells that regulate our blood sugar levels.

The study reveals that stem cells behave as people in a society, making individual choices but with enough interactions to bring them to their end-goal. The results could eventually lead to a better control over the production of insulin-producing endocrine cells for diabetes therapy.

The research is published in the scientific journal PLOS Biology.

Why one cell matters

In a joint collaboration between the University of Copenhagen and University of Cambridge, Professor Anne Grapin- Botton and a team of researchers including Assistant Professor Yung Hae Kim from DanStem Center focused on marking the progenitor cells of the embryonic pancreas, commonly referred to as 'mothers', and their 'daughters' in different fluorescent colours and then captured them on video to analyse how they make decisions.

Prior to this work, there were methods to predict how specific types of pancreas cells would evolve as the embryo develops. However, by looking at individual cells, the scientists found that even within one group of cells presumed to be of the same type, some will divide many times to make the organ bigger while others will become specialized and will stop dividing.

The scientists witnessed interesting occurrences where the 'mother' of two 'daughters' made a decision and passed it on to the two 'daughters' who then acquired their specialization in synchrony. By observing enough cells, they were able to extract logic rules of decision-making, and with the help of Pau Ru, a mathematician from the University of Cambridge, they developed a mathematical model to make long-term predictions over multiple generations of cells.

Stem cell movies

'It is the first time we have made movies of a quality that is high enough to follow thousands of individual cells in this organ, for periods of time that are long enough for us to follow the slow decision process. The task seemed daunting and technically challenging, but fascinating", says Professor Grapin-Botton.

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Stem cells make similar decisions to humans

Growing 3D miniature lungs from stem cells

Chuck Bednar for redOrbit.com @BednarChuck

Researchers from the University of Michigan have cooked-up the perfect recipe for growing miniature, three-dimensional human lungs from stem cells, but you wont find this recipe in a cookbook it appears in the latest edition of the journal eLife.

Lead author Dr. Jason Spence, a professor at the UM Medical School in Ann Arbor, and colleagues from the Cincinnati Childrens Hospital Medical Center, the University of California, San Francisco (UCSF), Seattle Childrens Hospital and the University of Washington reported in their paper how they converted human pluripotent stem cells (hPSCs) into mini lungs.

Their work compliments with other recent research in the field (including building lung tissue from the scaffold of donated organs), the publishers of eLife said, and their method produces an organ that is more similar to the human lung than previous efforts because it can grow structures that closely resemble both the large proximal airways and the small distal airways.

The process

They took hPSCs (both embryonic and induced) and added a protein known as ActivinA, which is involved in lung development. They left the stem cells for four days, and during this period, a type of tissue known as endoderm formed. Found in early embryos, forms several internal organ types, including the lung and the liver.

[STORY: Testing astronauts' lungs in the ISS airlock]

Next, they added a second protein a growth factor called Noggin and again left the growing tissues for four days. The endoderm was then induced to form 3D spherical structures known as the foregut spheroids. At this point, the scientists worked to make these structures expand and form into lung tissue by exposing the cells to proteins involved in lung development.

Once the spheroids were transferred into the protein mixture, they were allowed to incubate at room temperature for 10 minutes until the mixture solidified. They were treated with additional proteins every four days and transferred into a new protein mixture every 10 to 15 days.

The process is used to create lung organoids that should survive in culture for over 100 days and develop into well-organized structures containing cell types found in the lung, the study authors explained. The mini-lungs are essentially self-organizing, and once they are formed, they require no additional manipulation to generate three-dimensional tissues, they added.

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Growing 3D miniature lungs from stem cells