Using a novel 3-D culture method, scientists were able to prod lung (bronchioalveolar) stem cells to produce colonies with the cell type of choice: airway (bronchiolar) epithelial cells, alveolar epithelial cells or both. (Images: Joo-Hyeon Lee)
Someday it may be possible to treat lung diseases like emphysema, pulmonary fibrosis or asthma by prodding the lungs to produce healthy versions of the cells that are damaged.
That’s the hope of researchers Carla Kim, PhD, and Joo-Hyeon Lee, PhD, of the Stem Cell Research Program at Boston Children’s Hospital. In the Jan. 30 issue of Cell, they describe a pathway in the lungs, activated by injury, that directs stem cells to transform into specific kinds of cells—and that can be manipulated to enhance different kinds of repair, at least in a mouse model.
By boosting the pathway, Kim, Lee and colleagues successfully increased production of alveolar epithelial cells, which line the lung’s alveoli—the tiny sacs where gas exchange takes place, and that are irreversibly damaged in diseases like pulmonary fibrosis and emphysema. Full story »
Scaffolds made of silk could give doctors a simple, more effective material for performing bladder augmentation in people with urinary tract defects—to relieve incontinence and prevent kidney damage in children born with small bladders, for example. Rather than using cells to augment the bladder, a complicated process, silk could provide an “off the shelf” option, says Carlos Estrada, MD, a urologist at Boston Children’s Hospital.
Recent research by Estrada and Joshua Mauney, PhD, shows that scaffolds made of fibroin (the protein that makes up raw silk) have worked well in augmenting bladders in animal models—without the need for cells.
Estrada and Mauney built on the work of Anthony Atala, MD, who became head of the Institute for Regenerative Medicine at Wake Forest after undertaking pioneer work in tissue engineering in Boston Children’s Urology Department. Full story »
In a one-two-three punch, a rapid screen in zebrafish can quickly identify a short list of drug candidates to test in mice and in patient-derived cells.
Scientists have had little success in growing skeletal muscle for patients with muscular dystrophy and other disorders that degrade and weaken muscle. Undertaking experiments in zebrafish, mouse and human cells, researchers have identified a way to do that, creating cells that Leonard Zon, MD
, hopes to see tested in patients in the next several years.
But what really excites Zon, director of the Stem Cell research program at Boston Children’s Hospital, is the power of the chemical screening platform he and his colleagues used. Described last week in the journal Cell, it found a cocktail of three compounds that induced human muscle cells to grow—in just a matter of weeks. Zon believes it could fast-track drug discovery for multiple disorders. Full story »
In mice, VEGF-A modRNA visibly improved blood supply to heart muscle (right image) as compared with no treatment.
Heart attacks cause the death of billions of the heart’s muscle cells. If these cardiomyocytes could be made to regenerate after an infarct, the heart could potentially be mended and its function restored.
Researchers have struggled to find the right approach to regeneration. Cell transplants have been tried, but the cells don’t engraft well long term and haven’t shown efficacy. Gene therapy to spur regeneration has been tested in animals, but dosage is hard to control and there’s a risk of genes going where they shouldn’t, causing tumors and other problems. Protein drugs have been tried, but they have short half-lives, being degraded or eliminated by the body before they can do much good. They are also hard to target to the heart.
A more recent approach to cardiac regeneration is to stimulate the body itself—and, specifically, progenitor cells— to repair the heart from within. Full story »
In this mouse adrenal gland, the green stripes radiating from the outer region containing the zona glomerulosa (zG) to the inner region containing the zona fasiculata (zF) provide evidence for direct lineage conversion of these two cell types.
In 2006, Shinya Yamanaka, MD, PhD, discovered a way to reprogram mature skin cells back to a stem cell state so they can be converted into any cell type a scientist is interested in studying. That work earned him last year’s Nobel Prize in Physiology or Medicine.
Yamanaka’s discovery raised the tantalizing question of whether similar reprogramming ever occurs in nature. In fact, it does, discovered David Breault, MD, PhD, an endocrinologist at Boston Children’s Hospital and a member of the Harvard Stem Cell Institute. In the journal Developmental Cell, Breault recently showed that the adrenal gland uses cellular reprogramming (called lineage conversion) for daily maintenance and to repair itself after injury.
“This is going to be important for how we think of tissue maintenance and regeneration,” Breault says. Full story »
Although stem cells have the potential to differentiate into any type, they often prefer a particular route. Could scientists take advantage of that? (Flickr/Jonathan Billinger)
Some people are born football players, others are made for basketball: Yi Zhang, PhD
, reaches often for this metaphor as he explains his research with stem cell differentiation, recently published in Stem Cell Reports
Stem cells are well-known for their ability to differentiate, or transform, into different types of cells. Two types of stem cells—embryonic stem cells and induced pluripotent stem cells—are able to ultimately change into any human cell. But that doesn’t mean all stem cells in these groups are equal: They have certain molecular features that bias them toward transforming into particular cell types. The ability to predict a stem cell’s differentiation bias would enable scientists to select a specific embryonic or induced pluripotent cell line to create cells for different applications—like grooming some youth athletes for football, others for basketball.
Zhang’s lab has identified a gene that acts as a powerful biomarker—physical or chemical characteristic whose appearance heralds a particular process—predicting a pluripotent stem cell’s tendency to differentiate into endoderm, cells on the inner layer of an embryo that become lung, digestive tract, pancreas and liver cells. It could be the first of a family of genetic biomarkers that guide scientists trying to create different cells and tissues for regenerative medicine. Full story »
Lin28, a known player in cancer, is hard to suppress with drugs. But two related enzymes present highly druggable targets. (Emw/Wikimedia Commons)
Two fundamental processes in biology—stem cell generation and carcinogenesis—are turning out to be closely intertwined. The lab of Richard Gregory, PhD
, has been teasing out this relationship at the molecular level.
In 2008, Gregory and his colleagues showed how a factor called Lin28, which is associated with numerous cancers, makes a cell more prone to revert to a less specialized, stem-like state.
Lin28 acts by preventing maturation of Let-7—an ancient family of microRNAs found in creatures from humans to worms. Let-7 is the yin to Lin28’s yang: it causes stem cells to differentiate (embryonic stem cells, which are completely unspecialized, have very low levels of it). If a cell’s Let-7 can’t mature, it can’t differentiate; instead, it remains stem-like and can potentially become cancerous.
Suppressing Lin28 with RNA interference (RNAi) has been shown to suppress tumor growth. But Lin28 is difficult to target with drugs. Full story »
In mice, boosting amounts of a microRNA family called miR-17-92 led to dramatic enlargements of embryonic and postnatal hearts, with thicker ventricle walls.
Challenging accepted wisdom about the heart, Boston Children’s Hospital cardiologist Bernhard Kühn, MD
, recently showed that infants, children and adolescents are capable of generating new heart muscle cells
, or cardiomyocytes. That work raised the possibility that scientists could stimulate regeneration to repair injured hearts.
Now, we have a potential therapeutic target to accomplish this: a family of microRNAs called miR-17-92 that regulates cardiomyocyte proliferation. In Circulation Research earlier this month, a team led by Kühn’s research colleague Da-Zhi Wang, PhD, demonstrates its potential. Full story »
Ed. Note: Leonard Zon, MD, is founder and director of the Boston Children’s Hospital Stem Cell Program, which yesterday was awarded $4 million by the Massachusetts Life Sciences Center to build the Children’s Center for Cell Therapy.
Leonard Zon (top) and Massachusetts Lt. Governor Timothy Murray in the Stem Cell Program's zebrafish facility. (Courtesy MLSC)
As a hematologist, I see all too many children battling blood disorders that are essentially untreatable. Babies with immune deficiencies living life in a virtual bubble, hospitalized again and again for infections their bodies can’t fight. Children disabled by strokes caused by sickle cell disease, or suffering through sickle cell crises that drug treatments can’t completely prevent. Children whose only recourse is to risk a bone marrow transplant—if a suitably matched donor can even be found.
Over the past 20 years, my lab and that of George Daley, MD, PhD, at Boston Children’s Hospital have worked hard to give these children a one-time, potentially curative option—a treatment that begins with patients’ own cells and doesn’t require finding a match. Full story »
Face models made through 3D printing (S zillayali/Wikimedia Commons)
Thorsten Schlaeger, PhD, heads the Human Embryonic Stem Cell Core of the Boston Children’s Hospital Stem Cell Program.
I recently took my 6-year-old son to a Family Science Day, hosted by the 2013 American Association for the Advancement of Science (AAAS) Annual Meeting in Boston. He was most excited by a model airplane made out of parts that had been generated with a 3D printer. The scientist, from MIT, explained to us how this technology works: Instead of generating 2D printouts by spraying ink onto paper, 3D printing technologies assemble 3D objects layer by layer from a digital model, generally using molten plastics or metals.
3D printing is quickly being adopted by many professions, from architects and jewelers who want to build mock-ups for clients, to manufacturers of products like bikes, cars or airplanes. Soon we might all have 3D printers in our homes: The kids could design and print their own toys, while the grownups might use the technology to generate replacement parts for minor home improvement jobs (our broken shower faucet knob comes to mind). Full story »