­

The Stem-Cell Revolution Is Coming — Slowly

By WALLACE RAVVEN JAN. 16, 2017 The New York Times In 2001, President George W. Bush issued an executive order banning federal funding for new sources of stem cells developed from preimplantation human embryos. The action stalled research and discouraged scientists. Five years later, a Kyoto University scientist, Shinya Yamanaka, and his graduate student, Kazutoshi Takahashi, re-energized the field by devising a technique to “reprogram” any adult cell, such as a skin cell, and coax it back to its earliest “pluripotent” stage. From there it can become any type of cell, from a heart muscle cell to a neuron. The breakthrough sidestepped the embryo controversy, offering researchers an unlimited supply of stem cells. Dr. Yamanaka shared the 2012 Nobel Prize in Physiology or Medicine for reprogramming mature cells into what are now called induced pluripotent stem cells, or iPS cells. Still, the march toward new treatments has been halting. Dr. Yamanaka directs Kyoto University’s Center for iPS Cell Research and Application. He also leads a small research lab at the Gladstone Institutes, affiliated with the University of California, San Francisco, where his group studies the molecular mechanisms that underlie pluripotency and the factors that induce reprogramming. I interviewed him recently in San Francisco. Our conversation has been edited for length and clarity. Q. There has been great enthusiasm and confidence for nearly 20 years that the use of stem cells will lead to powerful new treatments for a range of diseases. Now, 10 years after your discovery, what treatments have been developed? A. We are still in the early stages. In 2014, Dr. Masayo Takahashi and her colleagues at the Riken Center for Developmental Biology had great success using iPS cells to treat macular degeneration. [...]

Stem cell therapy trial at Sanford first of its kind in U.S. for shoulder injuries

FDA-approved study explores utility of fat-derived stem cells SIOUX FALLS, S.D. – The first FDA-approved clinical trial of its kind in the United States using a person’s own fat-derived adult stem cells to treat shoulder injuries is available at Sanford Health. The trial opened in December and explores if adipose stem cells, which are taken from a participant’s own abdominal fat, can safely repair small and partial thickness tears in the rotator cuff by activating the body’s natural healing processes when injected into the injury area. The cell therapy technique may accelerate healing or regenerate tissue. According to clinicaltrials.gov, it’s the only trial the FDA has approved that uses adipose stems cells for this type of injury. Sanford’s Jason Hurd, M.D., who is based in Sioux Falls, and Mark Lundeen, M.D., of Fargo are the study’s principal investigators. Both are orthopedic surgeons. “Sanford Health physicians and scientists are the first in the country to work with the FDA on a trial using adipose stem cells in rotator cuff tears, which are quite common,” said Kelby Krabbenhoft, president and CEO of Sanford Health. “We’ve been monitoring the potential of these types of stem cells for quite some time. In Europe, adipose stem cells have been used as a therapy option for damaged tissues and are approved to carry the CE mark, which signifies that a product has been assessed by and meets certain safety, health and environmental protection requirements in the European Union.” Cell therapy, according to Sanford experts, uses the body’s own cells as therapy. Stem cells, in particular, have the ability to repair or regenerate cells that are damaged or killed as the result of injury or disease. Sanford’s cell therapy techniques focus on [...]

Using Fat to Help Wounds Heal Without Scars

Penn researchers help break ground on method to transform cells January 05, 2017 PHILADELPHIA – Doctors have found a way to manipulate wounds to heal as regenerated skin rather than scar tissue. The method involves transforming the most common type of cells found in wounds into fat cells – something that was previously thought to be impossible in humans. Researchers began this work at the Perelman School of Medicine at the University of Pennsylvania, which led to a large-scale, multi-year study in connection with the Plikus Laboratory for Developmental and Regenerative Biology at the University of California, Irvine. They published their findings online in the journal Science on Thursday, January 5th, 2017.Fat cells called adipocytes are normally found in the skin, but they’re lost when wounds heal as scars. The most common cells found in healing wounds are myofibroblasts, which were thought to only form a scar. Scar tissue also does not have any hair follicles associated with it, which is another factor that gives it an abnormal appearance from the rest of the skin. Researchers used these characteristics as the basis for their work – changing the already present myofibroblasts into fat cells that do not cause scarring. “Essentially, we can manipulate wound healing so that it leads to skin regeneration rather than scarring,” said George Cotsarelis, MD, the chair of the Department of Dermatology and the Milton Bixler Hartzell Professor of Dermatology at Penn, and the principal investigator of the project. “The secret is to regenerate hair follicles first. After that, the fat will regenerate in response to the signals from those follicles.” The study showed hair and fat develop separately but not independently. Hair follicles form first, and the Cotsarelis lab previously [...]

Researchers Develop Novel Wound-Healing Technology

Tue, 11/29/2016 - 2:10pm by Washington State University A WSU research team has successfully used a mild electric current to take on and beat drug-resistant bacterial infections, a technology that may eventually be used to treat chronic wound infections. The researchers report on their work in the online edition of npj Biofilms and Microbiomes. Led by Haluk Beyenal, Paul Hohenschuh Distinguished Professor in the Gene and Linda Voiland School of Chemical Engineering and Bioengineering, the research team used an antibiotic in combination with the electric current to kill all of the highly persistent Pseudomonas aeruginosa PAO1 bacteria in their samples. The bacteria is responsible for chronic and serious infections in people with lung diseases, such as cystic fibrosis, and in chronic wounds. It also often causes pneumonia for people who are on ventilators and infections in burn victims. "I didn't believe it. Killing most of the persister cells was unexpected," said Beyenal, when he first saw the results. "Then we replicated it many, many times." Bacterial resistance is a growing problem around the world. While antibiotics were a miracle drug of the 20th century, their widespread use has led to drug-resistant strains. In the U.S. at least two million infections and 23,000 deaths are now attributable to antibiotic-resistant bacteria each year, according to the Centers for Disease Control. When doctors use antibiotics to treat a bacterial infection, many of the bacteria die. Bacteria that form a slime layer (called a biofilm), however, are more difficult to kill because antibiotics only partially penetrate this protective layer. Subpopulations of "persister" cells survive treatment and are able to grow and multiply, resulting in chronic infections. In the new study, the researchers used an "e-scaffold," a sort of electronic band-aid made out of conductive carbon fabric, along [...]

Changing cell behavior could boost biofuels, medicine

By Beth Miller November 7, 2016 An engineer at Washington University in St. Louis developed an algorithm that suggests gene to remove from certain cells, such as yeast, to get them to perform a normal activity in a different environment or situation. A computer scientist at Washington University in St. Louis has developed a way to coax cells to do natural things under unnatural circumstances, which could be useful for stem cell research, gene therapy and biofuel production. Brent Michael Brent, the Henry Edwin Sever Professor of Engineering in the School of Engineering & Applied Science, has designed an algorithm, called NetSurgeon, that recommends genes to surgically remove from a cell’s genome to force it to perform a normal activity in a different environment or circumstance. For example, ordinary baker’s yeast cells normally produce a lot of alcohol, a biofuel, when fed sugar extracted from the edible kernels of corn plants. NetSurgeon designed genetic surgeries that convinced the cells to make more alcohol when fed a type of sugar found in the inedible leaves and stalks. The research is published in PNAS Early Edition Oct. 31. “Yeast have been engineered to make alcohol out of xylose, a type of sugar found in the woody parts of plants, but they don’t do it very well,” Brent said. “We think the problem is not that they can’t do it, but that they don’t want to. So we have to convince them by making them use the same set of genes they use when they’re fed sugar from corn kernels. We sometimes think about this as causing the yeast to ‘hallucinate’ that they are in a sugar they like to turn into alcohol. “Ultimately, what we want to [...]

Lab-Grown Human ‘Mini Lungs’ Successfully Engraft in Mice, a Respiratory Research Breakthrough

Shantell M. Kirkendoll November 07, 2016 6:00 AM Scientists can now grow 3-D models of various organs from stem cells, creating new ways to study disease. More than a year ago, scientists made studying lung cells in a petri dish appear old-fashioned. A team led by University of Michigan Medical School researchers coaxed stem cells to grow into three-dimensional miniature lungs, which mimic several aspects of the structure and complexity of human lungs. Now, the researchers have transplanted the 3-D mini lungs into immunosuppressed mice and have shown that the mini lungs can survive, grow and mature. The milestone is published in the Nov. 1 issue of eLife. “In many ways, the transplanted mini lungs were indistinguishable from human adult tissue,” says senior study author Jason Spence, Ph.D., associate professor in the Department of Internal Medicine and the Department of Cell and Developmental Biology at the U-M Medical School. Respiratory diseases account for nearly 1 in 5 deaths worldwide, and lung cancer survival rates remain poor despite numerous therapeutic advances during the past 30 years. These numbers highlight the need for new, physiologically relevant models for translational lung research. Lab-grown lungs can help because they provide a human model to screen drugs, understand gene function, generate transplantable tissue and study complex human diseases, such as asthma. And they’re not the only tissues in development. As a developmental biologist, Spence has been tinkering with creating other tissues from stem cells, termed “organoids.” Researchers in the Spence Lab have had remarkable success with what some have called “intestines in a dish,” for example, which may help with the study of inflammatory bowel disease. "In just eight weeks, the resulting transplanted tissue had impressive tube-shaped airway structures similar to [...]

UTHealth research: Stem cell therapy appears to have TBI treatment effect

HOUSTON – (Nov. 2, 2016) – Results of a cellular therapy clinical trial for traumatic brain injury (TBI) using a patient’s own stem cells showed that the therapy appears to dampen the body’s neuroinflammatory response to trauma and preserve brain tissue, according to researchers at The University of Texas Health Science Center at Houston (UTHealth). The results, which also confirmed safety and feasibility as cited in earlier studies, were published yesterday online in the journal STEM CELLS. “The data derived from this trial moves beyond just testing safety of this approach,” said Charles S. Cox, Jr., M.D., principal investigator, the George and Cynthia Mitchell Distinguished Chair in Neurosciences at UTHealth, professor in the Department of Pediatric Surgery and co-director of the Memorial Hermann Red Duke Trauma Institute. “We now have a hint of a treatment effect that mirrors our pre-clinical work, and we are now pursuing this approach in a Phase 2b clinical trial sponsored by the Joint Warfighter Program within the U.S. Army Medical Research Acquisition Activity, as well as our ongoing Phase 2b pediatric severe TBI clinical trial – both using the same autologous cell therapy.” Cox was recently awarded $6.8 million in funding from the U.S. Department of Defense (DOD) for the Phase 2b study to assess the safety and efficacy – including whether there are structural improvements in the brain – of autologous stem cell therapy in adults with emergent traumatic brain injury. Memorial Hermann-Texas Medical Center is the site for the study. According to the Centers for Disease Control, 1.7 million Americans sustain a traumatic brain injury annually. Of those, 275,000 are hospitalized and 52,000 die. TBI is a contributing factor to a third of all injury-related deaths in the [...]

Sickle Cell Disease: Gene-Editing Tools Point to Possible Ultimate Cure

Posted on October 25, 2016 by Dr. Francis Collins Caption: An electron micrograph showing two red blood cells, one normal (right) and the other (left) deformed by crystalline hemoglobin into the “sickle” shape characteristic of patients with sickle cell disease. Credit: Frans Kuypers: RBClab.com, UCSF Benioff Children’s Hospital Oakland Scientists first described the sickle-shaped red blood cells that give sickle cell disease its name more than a century ago. By the 1950s, the precise molecular and genetic underpinnings of this painful and debilitating condition had become clear, making sickle cell the first “molecular disease” ever characterized. The cause is a single letter “typo” in the gene encoding oxygen-carrying hemoglobin. Red blood cells containing the defective hemoglobin become stiff, deformed, and prone to clumping. Individuals carrying one copy of the sickle mutation have sickle trait, and are generally fine. Those with two copies have sickle cell disease and face major medical challenges. Yet, despite all this progress in scientific understanding, nearly 70 years later, we still have no safe and reliable means for a cure. Recent advances in CRISPR/Cas9 gene-editing tools, which the blog has highlighted in the past, have renewed hope that it might be possible to cure sickle cell disease by correcting DNA typos in just the right set of cells. Now, in a study published in Science Translational Medicine, an NIH-funded research team has taken an encouraging step toward this goal [1]. For the first time, the scientists showed that it’s possible to correct the hemoglobin mutation in blood-forming human stem cells, taken directly from donors, at a frequency that might be sufficient to help patients. In addition, their gene-edited human stem cells persisted for 16 weeks when transplanted into mice, suggesting that [...]

Research on Rare Genetic Disease Reveals New Stem Cell Pathway

Scientists enhance efficiency of stem cell reprogramming with gene mutation that causes “stone man syndrome” Gladstone Press Release / October 21, 2016 SAN FRANCISCO, CA—How do you improve a Nobel Prize-winning discovery? Add a debilitating disease-causing gene mutation. In a study published in the journal Proceedings of the National Academy of Sciences, Shinya Yamanaka, MD, PhD, who first created induced pluripotent stem cells (iPSCs), and his colleagues at the Gladstone Institutes found a way to increase the efficiency of stem cell reprogramming through research on a rare genetic disease. iPSCs—stem cells created from skin cells that can be transformed into any type of cell in the body—revolutionized biomedical science. They have contributed to breakthroughs in regenerative medicine and drug discovery, surpassing what researchers once thought possible. But like any new technology, there is room for improvement. For example, using existing techniques, fewer than one percent of adult skin cells are reprogrammed into iPSCs. “Inefficiency in creating iPSCs is a major roadblock toward applying this technology to biomedicine,” said Yamanaka, a senior investigator at Gladstone and director of the Center for iPSC Research and Application (CiRA) in Japan. “Our study identified a surprising way to increase the number of iPSCs that we can generate.” The scientists started with a very different goal: to create a cellular model to study fibrodysplasia ossificans progressiva (FOP). This extremely rare genetic disease causes muscle, tendons, and ligaments to turn into bone, earning it the nickname “stone man syndrome.” It is caused by a mutation in the ACVR1 gene, which over-activates a cellular signaling process that is important for embryo development and involves a protein called BMP. Surprisingly, the scientists discovered that they could create more iPSCs from cells taken from [...]

St. Louis Character: Dena Ladd keeps the state’s medical research climate comfortable

Oct 13, 2016, 2:30pm CDT St. Louis Business Journal As executive director for Missouri Cures, a medical research advocacy organization, Dena Ladd works with leading medical researchers throughout the United States. It’s not what she had in mind when she started her career in the fashion industry creating training programs for Christian Dior and traveling between New York and Paris. The transition began when Ladd wanted to supplement her “glamour job” at Christian Dior with volunteering in the community. She found that her true passion rested community organizations, so she went back to school to study public policy. That decision and subsequent requests from Dr. William Danforth, Sen. Betty Simms and Rep. Emmy McClelland led her to a career in advocating and creating communication networks for medical researchers and patients in Missouri and across the United States. Ladd has earned the respect of leaders throughout the region for her work, including Danforth who characterized her as, “Very good on the issues and understanding how things work. She is efficient at running a state-wide organization and works well with people. Everyone enjoys working with her.” Bob O’Loughlin, chairman and CEO of Lodging Hospitality Management, said, “Dena is a smart, compassionate person who cares about saving lives through research with Missouri Cures. I’ve known Dena to be well connected and someone who is well respected in the state of Missouri. I have and will continue to support her in the causes she gets involved with in Missouri.” Missouri Cures, the 501(c)(4), and the Missouri Cures Education Foundation, the 501(c)(3), have a combined budget of about $800,000. Ladd and Outreach Director Margaret Tollerton are the only employees of the group. What attracted you to public policy? As I volunteered with various organizations and sat on boards, it seemed like [...]