Category Archives: Cell Medicine

INTERNATIONAL REGENERATIVE MEDICINE COMMUNITY TO CONVENE FOR 13TH WORLD STEM CELL SUMMIT IN MIAMI, JANUARY 2018

The 13ththWorld Stem Cell Summit http://www.worldstemcellsummit.com is taking place January 23-26, 2018 at the Hyatt Regency Miami. Produced by the nonprofit Regenerative Medicine Foundation (RMF), the event is the global ecosystem meeting for advanced therapies; fostering public understanding, promoting positive policy initiatives and collaborations.

The World Stem Cell Summit will be co-located with the fields premier industry partnering event, Phacilitate Leaders Forum, Cell & Gene Therapy World and Immunotherapy World.

In addition to compelling keynotes, plenary and focus sessions, thediverse four-day program includesexpert lunch roundtables; a centrally located Expo packed with innovators in industry, academia and government; a poster forum showcasing science and policy research; the galaStem Cell Action Awards Dinnerhttp://regmedfoundation.org/awards/; as well as many exclusive networking and partnering opportunities.

RMF Executive Director Bernard Siegel, founder and co-chair of the Summit said, We are proud to select Miami to be our host for the next World Stem Cell Summit. Miami is often referred to as the 'City of the Future' and in 2018 it will be the center of the stem cell universe. Its the perfect venue for Summit attendees to gain knowledge, network and collect opportunities to advance their goals, in a superlative, cosmopolitan setting.

ABOUT RMFRegenerative Medicine Foundation is dedicated to accelerating regenerative medicine to improve health and deliver cures. RMF pursues its mission by producing its flagship World Stem Cell Summit, honoring leaders through the Stem Cell Action Awards http://worldstemcellsummit.com/stem-cell-action-awards/, publishing the World Stem Cell Report and RegMed Newsletter, organizing educational initiatives such as the upcoming Regenerative Medicine Essentials Course http://www.wakehealth.edu/Research/WFIRM/RMEssentials/Regenerative-Medicine-Essentials.htm and fostering strategic collaborations.

For more information about RMF, visitwww.regmedfoundation.orgor contact Bernard Siegel directly at Bernard@regmedfoundation.org.

Attachments:

A photo accompanying this announcement is available at http://www.globenewswire.com/NewsRoom/AttachmentNg/64ef8cd8-84a3-4130-8a8f-f1e020eaeba3

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INTERNATIONAL REGENERATIVE MEDICINE COMMUNITY TO ... - EconoTimes

To Dr. Mark Gomelsky, a professor at the University of Wyoming, genetically engineered therapeutic cells are like troops on a mission.

The first act is training. Using genetic editing tools such as CRISPR, scientists can train a patients own cells to specifically recognize and attack a variety of enemies, including rogue tumor soldiers and HIV terrorists.

Then comes the incursion. Engineered cells are surgically implanted to the target site, where theyre left to immediately carry out the mission. The problem, says Gomelsky, is adding a command center that could coordinate their activities in real time according to the developing situation, such as telling cells when to activate and when to stop.

The problem has been figuring out a way to bundle a command system with the cellular implants, so that control signals come from within the body. Now, thanks to a new study published in Science Translational Medicine, were one step closer to smart cell therapies, where the command center forms a single closed-loop unit with the engineered soldiers.

In an elegant feat of synthetic biology, a team of Chinese scientists married optogenetics with cellular engineering, generating live cells that can release insulin when bathed under red light.

The cells were then embedded with tiny LED lights inside a hydrogel and transplanted under the skin of diabetic mice. Andget thisthe entire system was controlled with a custom Android app, which remotely turns on the implanted LEDs and activates insulin-producing cells based on the level of circulating blood sugar levels.

After about four hours of light each day, the diabetic mice showed stabilized blood sugar and normal insulin production for over two weeks.

According to lead author Dr. Haifeng Ye at East China Normal University in Shanghai, the goal is to engineer a smart circuit that can sense, monitor and profile insulin levels in the bloodstream, 24 hours a day, using only a smartphone.

And thats just the beginning. These remote-controlled cells offer proof-of-concept evidence that cell-based semiautomatic therapies are possible. This could pave the way for a new era of personalized, digitized and globalized precision medicine, the authors say.

Controlling a cells activity is hard. Drugs are a common method, but as anyone whos ever taken an Advil for a blaring headache can attest to, drugs have a significant onset time lag.

So when scientists discovered that they could precisely control the activity of mammalian cells with light, the field of optogenetics took off like a rocket launcher.

Heres how it works: most of our cells dont usually respond to light, but those in algae do. Algae have several types of light-activated proteins that sit on their membranes, and in response to certain wavelengths of light, these proteins open up like a canal, allowing ions and molecules from outside the cell to flow in. Depending on what those molecules are, this either activates or inhibits the cell.

About a decade ago, scientists realized they could pluck these light-responsive proteins channelrhodopsins from algae, and insert them into mammalian cells. The result? Depending on the cell type, optogenetics can reverse blindness, restore heart rhythms, incept memories into nave mice, drive satiated mice to binge eat or turn on their predatory instincts.

Without doubt, optogenetics is powerful. But because scientists need to use gene therapy to insert channelrhodopsin into cells, translating the method to humans has been tough (although clinical trials are in the works).

This is where cell therapy comes in. Rather than trying to insert a gene into cells inside the body, its much easier to tweak a cells wiring in the lab before transplanting them. Thats the approach that Ye and team took for their smart insulin-pumping cells.

The team first engineered a multi-modular protein, so that it responded to far-red light by activating the genes that produce insulin. Unlike previous generations of light-sensing proteins that were leaky, this new construct had very low background activity in the dark.

To see if the circuit worked, the scientist embedded the cells with tiny biocompatible LED lights into a hydrogel and implanted them under the skin of diabetic mice. Then, he used an external transmitting coil to turn on LEDs through electromagnetic induction and voilainsulin in the bloodstream.

Once the basic system worked, the team went on to engineer a command center. Ye credited his inspiration to the SmartHome project, which seeks to create wireless homes furnished with smartphone-regulated electrical appliances like the Nest thermometer.

At the heart of their SmartController system is a home server box that contains a microprocessor unit chip and a WiFi-powered data receiver unit. To measure blood sugar levels, the team designed a custom digital glucometer that can transmit data to an Android app using Bluetooth. The app relays the glucose measurements to the control box, where it gets analyzed in real-time to control the magnetic transmitting coil.

If blood sugar levels are abnormally high, for example, the controller activates the electromagnetic field generator, which in turn switches on the implanted LED lights.

This triggers cells to release just enough insulin to revert blood sugar levels back to normal without causing low blood sugar symptoms.

We programmed the microcontroller chip to automatically translate blood sugar thresholds into different LED illumination strengths, which allows fully self-sufficient activation of antidiabetic cells based on blood sugar levels, the authors say.

The entire process can be tracked through the app interface, so that doctors could easily intervene in case of unforeseeable errors.

The whole process takes about two hours for sky-high blood sugar levels to return to non-diabetic levels. Once there, the system steadily maintained normal blood sugar levels for 15 days with no observable side effects, all without outside intervention.

This exciting accomplishment is a tribute to an ambitious but careful system design, rigorous optimization and meticulous testing, says Gomelsky, who was not involved in the study.

The current rendition of SmartController is only semiautomatic, in that the team has to manually draw blood from the diabetic mice to feed to the glucometer.

This is easy to tacklescientists just have to replace the glucometer with a continuous glucose monitor, implanted inside the body to provide continuous data to the smartphone app around the clock.

A tad trickier is the power problem. For the transmitting coils to reliably activate the implanted LED lights, the animals had to be within a certain distance from the coil, which limits movement. The team is now looking into replacing electromagnetic induction with biocompatible batteries to power the lights, and also avoiding exposure to electromagnetic radiation.

As with all cell therapies, the system will have to work in patient-derived cells or other cell types that wont generate an immune response after implantation.

With the FDA approving the first closed-circuit automatic insulin pump last year, Yes optogentics-meets-cell-therapy system may not ever hit the market. But thats not the point.

How soon should we expect to see people on the street wearing fashionable LED wristbands that irradiate implanted cells engineered to produce genetically encoded drugs under the control of a smartphone? asks Gomesky rhetorically.

Not just yet, he answers, but this study offers an exciting glimpse into the promising future of smart-cell therapies and what may soon be possible.

Image Credit: Shutterstock

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These Cells Are Engineered to Be Controlled by a Smartphone - Singularity Hub

Iran is expanding investment in stem cell research and its application in various therapies, particularly for hard-to-treat diseases, through the Office of the Vice- Presidency for Science and Technology. As a result of the increase in the number of companies active in the domain of stem cells in the past three years, more than 400 products are processed in the country, indicating a multifold growth compared with the eight-year tenure of previous administration when there were fewer than 50 knowledge-based firms in total.

There are over 40 knowledgebased firms in the field of stem cell and regenerative medicine alone in Iran today, said Amir Ali Hamidiyeh, secretary of the Headquarters for Development of Stem Cell Science and Technology (HDSCST). He made the statement at a press briefing for the second National Festival and International Congress on Stem Cell Sciences and Technologies and Regenerative Medicine to be held July 13- 15 in Tehran, Mehr News Agency reports. According to the conference secretariat, 1,444 people have signed up to attend the event from across the world, including from Iraq, India, Pakistan, Jordan, Russia, Australia, Germany, China, Britain and South Korea. They all are among their countrys respected figures in centers with high academic standing.

The congress is co-sponsored by the Vice-Presidency for Science and Technology and Council on Development of Stem Cell Sciences and Technology. So far, eight stem-cell therapy products for use in hospitals have been produced at the HDSCST laboratories. Manufacturinglicenses have been granted for anadditional number, while others are on thewait list.

Prior to 2014, only 25 knowledgebased companies had applied to operate in this field, of which only one was actively producing quality stem cell products, Hamidiyeh pointed out.

But since then, over 25 workgroups have been formed in cooperation with experts in the specific sciences. Stem cells are cells that have the ability to divide and develop into many different cell types in the body during early life and growth. Stem-cell therapy is the use of stem cells to treat or prevent a disease or condition. Bone marrow transplant is the most widely used stem-cell therapy, but some therapies derived from umbilical cord blood are also in use.

Future of Medicine in Stem

Cells The future of medicine is interrelated with stem cell therapy and the treatment ofrefractory and incurable diseases is in this field of medicine, according to Dr. Ahmad Vosouq Dizaj, the clinical deputy of Royan Institute. Having access to engineering sciences as well as the combination of biology and medicine can play a crucial role in redressing health problems, he said. Stem cells have the ability to replace damaged cells and treat disease. They can also be used to study diseases and provide a resource for testing new medical treatments. The use of stem cells reduces the risk of viral diseases transmission and incidence of Graft Versus Host Disease (GVHD). The ability to perform organ transplants is among the benefits ofumbilical cord blood transfusion.Using stems cells is also one of thebest ways to treat blood diseases sincethe method has a success rate of 70%worldwide.

Storage of stem cells is a valuable investment. So far, 27 cord blood banks have been launched across the country. There are two types: public and private banks for stem cell storage. The former does not charge a fee for storage. But in the latter, the cost of collection and genetictesting is about $645 and the annualcharge for storage is $33, according toISNA.Iran is a leading country in biomedicalresearch. Researchers and physicians have been successfully performing bone marrow transplants during the past fewyears.Irans stem cell research is centeredat the Royan Institute for ReproductiveBiomedicine, Stem Cell Biology andTechnology, located in northern Tehran.

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Growth in Stem Cell Research - Financial Tribune

White Papers are used often by Biotech companies as a tool to secure financing and US Stem Cell Inc (OTCMKTS:USRM)utilized a White Paper Series to open the eyes of investors as to how significant the results were. Normally this prompts those who take the time to read them and creates an Ah Ha, moment where the light goes on for the investor.

If you look at the timing of the White Paper released by Kristen Comella in late January you can see how the market reacted to this information. The stock went from triple zero sub penny to near .13 cents, which is a very large move. USRM went on to secure financing and has funding for operations for years to come, it is good to see stocks where this process works with fluidity, more microcap stocks should be looking at employing this White Paper marketing strategy to secure investors.

US Stem Cell Inc (OTCMKTS:USRM)is a Florida corporation and leader in novel regenerative medicine solutions and physician-based stem cell therapies to human and animal patients.Effects of the intradiscal implantation of stromal vascular fraction plus platelet rich plasma in patients with degenerative disc disease was published in the January volume of theJournal of Translational Medicine. The study focused on the implantation of stromal vascular fraction (SVF) in patients suffering from degenerative disc disease. Patients underwent a local tumescent liposuction procedure to remove approximately 60 ml of fat tissue from the abdomen. The fat was separated to isolate the SVF and the cells were delivered directly into the damaged discs. Patients were monitored for a period of 6 months post-treatment, noting considerable decreases in pain and increases in flexion.

Ms. Comellas previous paper, Effects of the intramyocardial implantation of stromal vascular fraction in patients with chronic ischemic cardiomyopathy, was released in theJournal of Translational Medicines June 2016 edition. Using the same procedure, chronic ischemic cardiomyopathy patients were evaluated after SVF injection and able to walk more than 80 additional meters 3 to 6 months after treatment.

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U.S. Stem Cell, Inc., is committed to new technological advancements and therapies that give a renewed sense of hope to patients with degenerative diseases. SVF is the latest therapy in a long line of successful treatments the company pioneered. Ms. Comella plans to continue her work with SVF, which has consistently repeated its strong safety profile and success in treating patients.

The second piece of the puzzle was raising capital and the company recently secured a commitment to invest up to $5,000,000 from private equity firm General American Capital Partners LLC (GACP) in exchange for up to 63,873,275 shares of common stock.

We see exponential growth in the stem cell industry, estimated to grow to $170 billion by 2020, said Joseph DaGrosa, Jr., a Principal with General American Capital Partners. We are very pleased to join forces with U.S. Stem Cell, Inc., a leader in regenerative medicine solutions, to help expand our role in this important market.

The 21st Century Cures Act, signed into effect in December of 2016, builds on the FDAs ongoing efforts to advance medical product innovation and ensure that patients get access to treatments as quickly as possible, with continued assurance from high quality evidence that they are safe and effective.

Patient demand for regenerative medicine procedures as a viable alternative to surgery, as well as the transformative capacity of stem cell therapies, are leading the way to increased acceptance by both the medical and regulatory communities, said Mike Tomas, President and CEO of U.S. Stem Cell, Inc.

Few know that as recently as December 2015 these shares were near $2.00 as stem cell was a sector in biotech that had big multiples and a larger hope for the future. U.S. Stem Cell, Inc. (OTCMKTS:USRM) has renewed this hope for many shareholders who have stayed with the stock. Through consolidation and internal organizational changes the company has combined operating divisions (US Stem Cell Training, Vetbiologics, and US Stem Cell Clinic)which include the development of proprietary cell therapy products. They also generate physician and patient based regenerative medicine and cell collection and cell storage services, the sale of cell collection and treatment kits for humans and animals, and the operation of a cell therapy clinic.

The White Papers take the time to explain how the science works, and all this company needed was one yes answer from a larger investor to secure financing to jump start operations and ultimately the stock price. USRM is one of the most exciting stories on the OTC stay tuned we will update the story soon.For more news on $USRM and other fast-moving penny stocks, please subscribe to OracleDispatch.com below.

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US Stem Cell Inc (OTCMKTS:USRM) Starting to Open Eyes - The Oracle Dispatch

LUCKNOW: In what may come as a relief to over 1 lakh patients of thalassemia in India, a public sector stem cell bank is set to come up at UP's King George's Medical University here. A project of the university's transfusion medicine department, the stem cell bank would roll out stem cell therapy to patients of thalassemia and sickle cell anaemia. The proposal is awaiting clearance from state department of medical education.

Stem cells are omnipotent and can take shape of any cell inside the body. If infused in the pancreas, stem cells will become pancreatic while in the liver, they will become liver cells.

These are found in human bone marrow and can be derived from the umbilical cord which contains blood vessels that connect baby in the womb to the mother to ingest nutrition required for development.

Research on the therapeutic use of stem cells is underway in US, Europe, China, South East Asia besides India. In UP, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS) and KGMU are both trying to explore the potential of stem cells to treat various health problems. SGPGI has, so far, restricted itself to use of allogenic (stem cells derived from bone marrow of a person), while KGMU has used stem cells derived from the umbilical cord.

Head of transfusion medicine department of KGMU, Prof Tulika Chandra said, "Several private sector stem cell banks like Life Cell and Cord Life India are operating in India but they serve only those who have deposited the baby's cord, while our bank will help everyone."

KGMU has sustained access to umbilical cord because of a very developed obstetrics and gynaecology department. The cord is gathered from the placenta in the uterus of pregnant women which nourishes and maintains the baby through the umbilical cord.

Sources in medical education department said the proposal is worth Rs 9 crore including infrastructure cost. "Stem cell bank promises to become financially self-sustaining within 2-3 years of inception," said a directorate officer.

Talking about why children with thalassemia and sickle cell anaemia were chosen, Chandra said, "Global literature shows umbilical cord stem cells can induce extraordinary results on such children. In fact, success rate is around 70-75% and higher score can be achieved if therapy is provided at an earlier age."

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First public sector stem cell bank to come up at KGMU - Times of India

DUBLIN--(BUSINESS WIRE)--Research and Markets has announced the addition of the "FDA's Regulation of Regenerative Medicine including Stem Cell Treatments, Tissue Engineering & Gene Therapies: 2-Day In-person Seminar" conference to their offering.

Stem cells harness the power to differentiate into numerous cells upon stimulation. This has led to their wide exploration across all of medicine, including high risk diseases. Of course, significant scientific breakthroughs in the use of stem cells to prevent, diagnose, and treat numerous diseases has caused numerous start-up companies to form. Despite, such promise, the FDA has yet to approve stem cell therapies for a wide range of diseases, except cord blood-derived hematopoietic progenitor cells for certain indications.

This tutorial will provide an historical context for the use of stem cells in medicine, where the field has been and where it is going. It will also provide the few examples of FDA approved use of stem cells in medicine and what is needed for the field to progress. For example, in 2006, the U.S. FDA implemented regulations governing the use of human cells, tissues, and cellular and tissue-based products in humans including bone, ligament, skin, dura mater, stem cells, cartilage cells, and various other cellular and tissue-based products. Currently, there is an ongoing debate in industry on how such therapies should be regulated, in particular by the FDA or under the practice of medicine, under federal law or state law, and as drugs or simply biologics.

Learning Objectives:

Fundamentals of stem cells

- What is all the excitement about

- How to control stem cell differentiation

- Sources of stem cells

- Incorporating stem cells into biomaterials

- Avoiding immune system clearance of stem cells

FDA regulatory approvals for the use of stem cells in medicine

- Currently approved use of stem cells in medicine

- FDA guidance documents for stem cell technologies

- Global approval of stem cell technologies

- How the FDA regulates regenerative treatments and therapies

- The use of human cells, tissues, and cellular and tissue-based product criteria and Minimal Manipulation Standard

- The drug and biological approval process

- Regenerative products as medical devices

- How to design appropriate clinical trials

- Applicable good manufacturing and good laboratory practices

- Product labeling, marketing and advertising

- FDA and other federal agency enforcement action

Future thoughts on approaches for regulatory approval of stem cell technologies

- Remaining hurdles

- Outlook for new technologies

For more information about this conference visit http://www.researchandmarkets.com/research/ljt255/fdas_regulation

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Two Day FDA's Regulation of Regenerative Medicine Seminar ... - Business Wire (press release)

In a recent study published in Circulation, researchers managed to convert de-differentiated human fibroblasts, support cells key in healing, to red blood cells or cells that line the interiors of blood vessels via manipulation of the SOX17 transcription factor. The de-differentiated fibroblasts can improve heart function after a heart attack and provide patient-specific cells that do not suffer from premature aging.

Fibroblasts, a support cell key in healing, are commonly used for de-differentiation. De-differentiated cells are similar to stem cells; depending on the environment they are in and what genes are active, they become different cells. De-differentiated cells have many medical uses; as many as the number of cells that they can become. In a recent study published in Circulation, researchers from the University of Illinois College of Medicine and the Indiana University School of Medicine managed to convert de-differentiated human fibroblasts to endothelial cells and erythroblasts. Endothelial cells are the cells that make up the lining of the interior of blood vessels. Erythroblasts are commonly known as red blood cells.

The researchers first de-differentiated the fibroblasts by overexpression of the proteins that transcribe DNA into RNA, specifically, pluripotency transcription factors. The de-differentiated cells were then placed into different media to transform them into endothelial cells and erythroblasts. The researchers observed that a specific transcriptional regulator, SOX17, and its respective activity corresponded to which cell the de-differentiated fibroblasts became. The researchers also experimented on rats that had suffered heart attacks. They implanted the de-differentiated fibroblasts into the rats and found that they improved heart function after a heart attack. Finally, the researchers observed that the cells generated from the de-differentiated fibroblast had increased production of telomerase. Telomerase is a transcription factor that produces telomeres, which are at the ends of chromosomes. The length of telomeres corresponds to the age of a cell, with longer being younger.

All this research shows the power of de-differentiated cells. De-differentiated fibroblasts can make patient-specific cells. These cells may avoid premature aging because of the increased production of telomerase: Helpful for enabling older patients to have personalized cells. Though only shown in mice, the de-differentiated fibroblasts did improve cardiac function after their heart attacks and may benefit humans as well. Pinpointing SOX17 as the switch for making endothelial cells or erythroblasts will optimize their generation, which will prove valuable for tissue regeneration and disease modeling.

Written By:Brian Jones

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Reprogrammed Cells Improve Heart Function After a Heart Attack - Medical News Bulletin

May 8, 2017 by Carol Marie Cropper Strand of human hair at 200x magnification. Credit: Jan Homann/Wikipedia

UT Southwestern Medical Center researchers have identified the cells that directly give rise to hair as well as the mechanism that causes hair to turn gray findings that could one day help identify possible treatments for balding and hair graying.

"Although this project was started in an effort to understand how certain kinds of tumors form, we ended up learning why hair turns gray and discovering the identity of the cell that directly gives rise to hair," said Dr. Lu Le, Associate Professor of Dermatology with the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. "With this knowledge, we hope in the future to create a topical compound or to safely deliver the necessary gene to hair follicles to correct these cosmetic problems."

The researchers found that a protein called KROX20, more commonly associated with nerve development, in this case turns on in skin cells that become the hair shaft. These hair precursor, or progenitor, cells then produce a protein called stem cell factor (SCF) that the researchers showed is essential for hair pigmentation.

When they deleted the SCF gene in the hair progenitor cells in mouse models, the animal's hair turned white. When they deleted the KROX20-producing cells, no hair grew and the mice became bald, according to the study.

The findings are published online in Genes & Development.

Dr. Le, who holds the Thomas L. Shields, M.D. Professorship in Dermatology, said he and his researchers serendipitously uncovered this explanation for balding and hair graying while studying a disorder called Neurofibromatosis Type 1, a rare genetic disease that causes tumors to grow on nerves.

Scientists already knew that stem cells contained in a bulge area of hair follicles are involved in making hair and that SCF is important for pigmented cells, said Dr. Le, a member of the Hamon Center for Regenerative Science and Medicine.

What they did not know in detail is what happens after those stem cells move down to the base, or bulb, of hair follicles and which cells in the hair follicles produce SCF or that cells involved in hair shaft creation make the KROX20 protein, he said.

If cells with functioning KROX20 and SCF are present, they move up from the bulb, interact with pigment-producing melanocyte cells, and grow into pigmented hairs.

But without SCF, the hair in mouse models was gray, and then turned white with age, according to the study. Without KROX20-producing cells, no hair grew, the study said.

UT Southwestern researchers will now try to find out if the KROX20 in cells and the SCF gene stop working properly as people age, leading to the graying and hair thinning seen in older people as well as in male pattern baldness, Dr. Le said.

The research also could provide answers about why we age in general as hair graying and hair loss are among the first signs of aging.

Explore further: New research provides clues on why hair turns gray

More information: Chung-Ping Liao et al. Identification of hair shaft progenitors that create a niche for hair pigmentation, Genes & Development (2017). DOI: 10.1101/gad.298703.117

UT Southwestern Medical Center researchers have identified the cells that directly give rise to hair as well as the mechanism that causes hair to turn gray findings that could one day help identify possible treatments ...

Men and women differ in obvious and less obvious waysfor example, in the prevalence of certain diseases or reactions to drugs. How are these connected to one's sex? Weizmann Institute of Science researchers recently uncovered ...

Salk Institute scientists have developed a novel technology to correct disease-causing aberrations in the chemical tags on DNA that affect how genes are expressed. These types of chemical modifications, collectively referred ...

Scientists are closer to understanding the genetic causes of type 2 diabetes by identifying 111 new chromosome locations ('loci') on the human genome that indicate susceptibility to the disease, according to a UCL-led study ...

A worldwide consensus co-authored by more than 40 scientists sets out ways to address research bottlenecks as the international community strives to diagnose most rare genetic diseases by 2020.

Researchers have undertaken the world's largest genetic study of childhood overgrowth syndromes - providing new insights into their causes, and new recommendations for genetic testing.

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Scientists find skin cells at the root of balding, gray hair - Medical Xpress

Human lungs, like all organs, begin their existence as clumps of undifferentiated stem cells. But in a matter of months, the cells get organized. They gather together, branch and bud, some forming airways and others alveoli, the delicate sacs where our bodies exchange oxygen for carbon dioxide. The end result, ideally: two healthy, breathing lungs.

For years, scientists who study lung diseases like cystic fibrosis have tried to track this process in detail, from start to finish, in the hope that understanding how lungs form normally may help explain how things go wrong. Now, scientists at Boston University's Center for Regenerative Medicine (CReM) have announced two major findings that further our understanding of this process: the ability to grow and purify the earliest lung progenitors that emerge from human stem cells, and the ability to differentiate these cells into tiny "bronchospheres" that model cystic fibrosis. Researchers hope that the results, published separately in the Journal of Clinical Investigation and Cell Stem Cell, will lead to new, "personalized medicine" approaches to treating lung disease.

"Sorting these cells to purity is really difficult and important," says Darrell Kotton, director of CReM and co-senior author of both papers, with Brian Davis of UTHealth at the University of Texas. "It's the first step in trying to predict how an individual might respond to existing treatments or new drugs."

"There's a long list of lung diseases for which there are no treatments other than a lung transplant," added Kotton, whose work is funded by the National Institutes of Health (NIH), the Cystic Fibrosis Foundation, and the Massachusetts Life Sciences Center. "It's critically important to develop new tools for understanding these diseases."

CReM scientists work with induced pluripotent stem cells, or iPSCs, which were discovered by Shinya Yamanaka in 2006. Yamanaka figured out how to take an adult cell in the human body -- like a blood cell or skin cell -- and "reprogram" it into a stem cell with the ability to grow into any organ. In recent years, several groups of scientists have grown lung cells from human iPSCs, but the recipes aren't perfect -- the resulting lung cells grow amidst a jumble of liver cells, intestinal cells, and other tissues.

"That's a big issue," says Finn Hawkins, a BU School of Medicine (MED) assistant professor of medicine and part of the CReM team. Hawkins is co-first author on the Journal of Clinical Investigation paper, along with Philipp Kramer, formerly of UTHealth. "If you want to use these cells to study the lung, you need to get rid of those others."

First, Hawkins needed a way to identify the lung cells. Previous work by Kotton and other CReM scientists demonstrated that mouse stem cells express a gene called Nkx2-1 at the "fate decision" -- the moment they turn into lung cells. "That's the first gene that comes on that says, 'I'm a lung cell,'" says Hawkins. Kotton built a reporter gene that glowed green when the stem cells first expressed Nkx2-1, and Hawkins engineered the same gene into human cells. Now, he could easily spot and purify the glowing green lung cells.

Using a flow cytometer, Hawkins and his colleagues separated the green cells out from the mix, then grew them in a matrix. The result: tiny green spheres about half a millimeter across, "a population of pure, early lung cells," says Hawkins. The team calls the tiny spheres "organoids," simplified and miniaturized versions of an organ, containing key types of lung cells. The organoids are tools, and they serve at least two important purposes. First, they allow scientists to study, in detail, a critical juncture in human lung development about which very little is known. "We discovered that many of the genes that control lung development in other species, such as mice, are also expressed in these human cells," says Hawkins.

The organoids serve another purpose, as well: scientists can grow them into more mature, specific cell types -- like airway cells or alveolar cells -- that are critical for lung function. "Now we can actually start looking at disease," says Hawkins. That's where Katherine McCauley (MED'17), a fifth-year PhD candidate at CReM, enters the picture.

McCauley's interest is cystic fibrosis, a disease caused by mutations in a single gene, CFTR. The mutation causes a person's lungs to produce a thick, viscous mucus that leads to infection, inflammation, and, eventually, lung failure. For many patients, there is no cure.

McCauley, looking at the earliest stages of the disease, wanted to take Hawkins' purified lung cells to the next step and figure out how they became airway cells. Through many painstaking experiments, she zeroed in on a signaling pathway called Wnt, known to be important in mouse lung development. By turning the pathway off, she guided the immature lung cells into becoming airway cells. Then, she grew them into tiny balls of cells, which she called "bronchospheres."

Like Hawkins' organoids, the bronchospheres don't act like a bronchus; they are simply a collection of specific cells. But their specificity makes them exquisitely useful. "We wanted to see if we could use these to study airway diseases," says McCauley. "That's one of the big goals: to engineer these cells from patients and then use them to study those patients' diseases."

As a proof of concept, McCauley obtained two cell lines from a patient with cystic fibrosis, one in which the CFTR mutation that caused the disease had been corrected, and one in which it hadn't, and grew them into bronchospheres. To see if her recipe worked, she ran a test, applying a drug that should cause spheres made of normal, functioning cells to fill with fluid. It worked: the "fixed" bronchospheres began to swell, while the cystic fibrosis spheres didn't react. "The cool part is that we measured this using high-throughput microscopy, and then we calculated the change in area with time," says McCauley, who published these results in Cell Stem Cell and is lead author on the study. "So now we can evaluate CFTR function in a quantitative way."

The next step, says McCauley, is to improve the test, and scale it up, and create similar tests for other lung diseases. "The end goal is to take cells from a patient, and then screen different combinations of drugs," she says. "The idea that we could take a patient's cells and test not twenty, but hundreds or thousands of drugs, and actually understand how the patient was going to respond before we even give them the treatment, is just an incredible idea."

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Scientists turn human induced pluripotent stem cells into lung cells - Science Daily

Newswise BIRMINGHAM, Ala. The third annual Cardiovascular Tissue Engineering Symposium met at the University of Alabama at Birmingham last month, a gathering of noted physicians and scientists who share the goal of creating new tissues and new knowledge that can prevent or repair heart disease and heart attacks.

Talks ranged from the cutting-edge translational work of Phillippe Menasche, M.D., Ph.D., professor of thoracic and cardiovascular surgery, Paris Descartes University, to the basic biology research of Sean Wu, M.D., Ph.D., an associate professor of medicine, Stanford University School of Medicine. Menasches work pioneers human treatment with engineered heart tissue. Wus work opens the door to generating heart chamber-specific cardiomyocytes from human induced pluripotent stem cells, which act similarly to embryonic stem cells, having the potential to differentiate into any type of cell.

Menasche has placed engineered heart tissue derived from embryonic stem cell-derived cardiac cells onto the hearts of six heart attack patients in France in an initial safety study for this engineered tissue approach. Wu has used single-cell RNA sequencing to show 18 categories of cardiomyocytes in the heart, differing by cell type and anatomical location, even though they all derived from the same lineage.

We are creating a new community of engineer-scientists, said Jay Zhang, M.D., Ph.D., chair and professor of the UAB Department of Biomedical Engineering. In their welcoming remarks, both Selwyn Vickers, M.D., dean of the UAB School of Medicine, and Victor Dzau, M.D., professor of medicine at Duke University School of Medicine and president of the National Academy of Medicine, spoke of the growing convergence between scientists and physicians that is leading to tremendous possibilities to improve patient care.

The tissue engineering field is moving fast.

Cardiac progenitor cells that can contribute to growth or repair injury in the heart were only discovered in 2003, says symposium presenter Michael Davis, Ph.D., associate professor of Medicine, Department of Biomedical Engineering, Georgia Tech College of Engineering and Emory University School of Medicine. In 2006, the Japanese scientist Shinya Yamanaka first showed how to transform adult cells into induced pluripotent stem cells. This potentially provides feedstock for tissue engineering using either pluripotent cells or specific progenitor cells for certain tissue lineages.

One example of the pace of change was given by Bjorn Knollman, M.D., Ph.D., professor of medicine and pharmacology at Vanderbilt University School of Medicine. Knollman noted an ugly truth that everyone recognized in 2013 that cardiomyocytes derived from induced pluripotent stem cells were nothing like normal adult cardiomyocytes in shape, size and function.

He described the improved steps like culturing the derived cardiomyocytes in a Matrigel mattress and giving them a 14-day hormone treatment that have led to derived cardiomyocytes with greatly improved cell volume, morphology and function. His take-home message: In just four years, from 2013 to 2017, researchers were able to remove the differences between induced pluripotent stem cell-derived cardiomyocytes and normal adult cardiomyocytes.

In other highlights of the symposium, Joo Soares, Ph.D., a research scientist for the Center for Cardiovascular Simulation, University of Texas at Austin, explained how subjecting engineered heart valve tissue to cyclic flexure as it is grown in a bioreactor leads to improved quantity, quality and distribution of collagen, as opposed to tissue that is not mechanically stressed.

Sumanth Prabhu, M.D., professor and chair of the Division of Cardiovascular Disease, UAB School of Medicine, talked about the role of immune cells in cardiac remodeling and heart failure. He noted the distinct phases after a heart attack acute inflammation and dead tissue degradation, zero to four days; the healing phase of resolution and repair, four to 14 days; and the chronic ischemic heart failure that can occur weeks to months later. Prabhu described experiments to show how specialized spleen macrophages specifically marginal-zone metallophilic macrophages migrate to the heart after a heart attack and are required for heart repair to commence.

Nenad Bursac, Ph.D., professor of Biomedical Engineering, Duke University School of Medicine, described his advances in engineering vascularized heart tissue for repair after a heart attack. Bursac said a better understanding of how to grow the tissue from heart tissue progenitor cells has allowed formation of mature giga patches up to 4 centimeters square that have good propagation of heartbeat contractions and spontaneous formation of capillaries from derived-vascular endothelial and smooth muscle cells. These patches are being tested in pigs.

Duke Universitys Victor Dzau gave a perspective of the paracrine hypothesis over the past 15 years. In 2003, researchers had seen that applying mesenchymal stem cells to a heart attack area led to improved heart function, with beneficial effects seen as early as 72 hours. However, there was little engraftment and survival of the stem cells. Thus was born the hypothesis, which has been worked out in detail since then that stem cells do their work by release of biologically active factors that act on other cells, similar to the way that paracrine hormones have their effect only in the vicinity of the gland secreting it.

Joseph Wu, M.D., Ph.D., professor of radiology, Stanford University School of Medicine, showed how heart cells derived from induced pluripotent stem cells could be used to develop personalized medicine approaches for cancer patients. The problem, he explained, is that some cancer patients are susceptible to a deadly cardiotoxicity when treated with the potent drug doxorubicin. Hence, the drug has a black box warning, the strictest warning mandated by the Food and Drug Administration. Wu was able to use a library of induced pluripotent stem cell-derived cardiomyocytes to associate certain genotypes and phenotypes with doxorubicin sensitivity, in what he called a clinical trial in a dish. From this knowledge, it will be possible to look at the transcriptome profile in patient-specific cardiomyocytes derived from induced pluripotent stem cells to predict patient-specific drug safety and efficacy, thus fulfilling the definition of precision medicine the right treatment at the right time to the right person.

In all, UABs Cardiovascular Tissue Engineering Symposium included more than 30 presentations. The entire symposium will be summarized in a paper for the journal Circulation Research, expected to be published shortly, Zhang says.

Presentations of the 2015 Cardiovascular Tissue Engineering Symposium were published in the journal Science Translational Medicine, and the presentations of the 2016 Cardiovascular Tissue Engineering Symposium were published in the journal Circulation Research.

At UAB, Zhang holds the T. Michael and Gillian Goodrich Endowed Chair of Engineering Leadership, Vickers holds the James C. Lee Jr. Endowed Chair for the Dean of the School of Medicine, and Prabhu holds the Mary Gertrude Waters Chair of Cardiovascular Medicine.

Excerpt from:
Fixing Broken Hearts Through Tissue Engineering - Newswise (press release)