Implications for treating muscular dystrophy and other muscle wasting diseases

Working with mice, Johns Hopkins researchers have solved a key part of a muscle regeneration mystery plaguing scientists for years, adding strong support to the theory that muscle mass can be built without a complete, fully functional supply of muscle stem cells.

"This is good news for those with muscular dystrophy and other muscle wasting disorders that involve diminished stem cell function," says Se-Jin Lee, M.D., Ph.D., lead author of a report on the research in the August issue of the Proceedings of the National Academy of Sciences and professor of molecular biology and genetics at the Johns Hopkins University School of Medicine.

JoVE Article Shows Steps to Isolate Stem Cells from Brain Tumors

A new video protocol in Journal of Visualized Experiments (JoVE) details an assay to identify brain tumor initiating stem cells from primary brain tumors. Through flow cytometry, scientists separate stem cells from the rest of the tumor, allowing quick and efficient analysis of target cells. This approach has been effectively used to identify similar stem cells in leukemia patients.

"Overall, these tumors are extremely rare, with only around one in 100,000 people being diagnosed with a primary brain cancer," Dr. Sheila Singh, co-author and neurosurgeon from McMaster University, explains. "However, these tumors are the second most common malignancy in the pediatric population, and are behind only leukemia as the cancer with the highest mortality rate."

This publication is significant because it allows scientists to identify, purify, and study brain tumor initiating cells rapidly and without sample loss. Because these stem cells allow scientists to grow films in a petri dish, they serve as an effective model of a tumor expanding in the brain of a patient.

Making it easier to make stem cells

The process researchers use to generate induced pluripotent stem cells (iPSCs)—a special type of stem cell that can be made in the lab from any type of adult cell—is time consuming and inefficient. To speed things up, researchers at Sanford-Burnham turned to kinase inhibitors. These chemical compounds block the activity of kinases, enzymes responsible for many aspects of cellular communication, survival, and growth. As they outline in a paper published September 25 in Nature Communications, the team found several kinase inhibitors that, when added to starter cells, help generate many more iPSCs than the standard method. This new capability will likely speed up research in many fields, better enabling scientists around the world to study human disease and develop new treatments.

The promise of stem cells seems limitless. If they can be coaxed into rebuilding organs, repairing damaged spinal cords and restoring ravaged immune systems, these malleable cells would revolutionize medical treatment. But stem cell research is still in its infancy, as scientists seek to better understand the role of these cells in normal human development and disease.

On Friday, September 14, the Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research at Albert Einstein College of Medicine of Yeshiva University offered the Einstein community and invited guests an opportunity to hear from leading stem cell scientists investigating the dynamic field. The 2012 Einstein Stem Cell Institute Symposium featured speakers from around the globe presenting the latest research on induced pluripotent stem cells (iPS cells), cell reprogramming, as well as cancer and hematopoietic (blood-forming) stem cells.

"This symposium was an important milestone for stem cell research at Einstein and confirms our intent to contribute to advances in stem cell biology," said the event’s host and organizer, Paul Frenette, M.D., director and chair of Einstein’s Stem Cell Institute and professor of medicine and of cell biology.

This is how a heart becomes a heart

A “synchronised dance” of thousands of genes generates a healthy heart, but one faux pas may result in congenital heart defects.

Congenital heart defects (CHD) are one of the most common birth abnormalities in the world. In Australia six babies are born with a heart disease every day and more than 32,000 children under the age of 18 live with a CHD, but a team of researchers at the Gladstone Institutes have found the genetic switches that translate as a functional heart.

Using next-generation DNA sequencing and stem cell technology, the researchers were able to decipher the genomic blueprint (the instruction manual) of a heart. The finding will help understand how certain CHDs such as holes in the heart (septal defects) are formed. “Congenital heart defects are the most common type of birth defects,” said Gladstone Senior Investigator Benoit Bruneau to UCFS news. “But how these defects develop at the genetic level has been difficult to pinpoint because research has focused on a small set of genes. Here, we approach heart formation with a wide-angle lens by looking at the entirety of the genetic material that gives heart cells their unique identity.”

Nanoengineers at the University of California, San Diego have developed a novel technology that can fabricate, in mere seconds, microscale three dimensional (3D) structures out of soft, biocompatible hydrogels. Near term, the technology could lead to better systems for growing and studying cells, including stem cells, in the laboratory. Long-term, the goal is to be able to print biological tissues for regenerative medicine. For example, in the future, doctors may repair the damage caused by heart attack by replacing it with tissue that rolled off of a printer.

The biofabrication technique uses a computer projection system and precisely controlled micromirrors to shine light on a selected area of a solution containing photo-sensitive biopolymers and cells. This photo-induced solidification process forms one layer of solid structure at a time, but in a continuous fashion.

Stem Cells Turn Hearing Back On

Scientists have enabled deaf gerbils to hear again—with the help of transplanted cells that develop into nerves that can transmit auditory information from the ears to the brain. The advance, reported in Nature, could be the basis for a therapy to treat various kinds of hearing loss.

In humans, deafness is most often caused by damage to inner ear hair cells—so named because they sport hairlike cilia that bend when they encounter vibrations from sound waves—or by damage to the neurons that transmit that information to the brain. When the hair cells are damaged, those associated spiral ganglion neurons often begin to degenerate from lack of use. Implants can work in place of the hair cells, but if the sensory neurons are damaged, hearing is still limited.

"Obviously the ultimate aim is to replace both cell types," says Marcelo Rivolta of the University of Sheffield in the United Kingdom, who led the new work. "But we already have cochlear implants to replace hair cells, so we decided the first priority was to start by targeting the neurons."

In the past, scientists have tried to isolate so-called auditory stem cells from embryoid bodie—aggregates of stem cells that have begun to differentiate into different types. But such stem cells can only divide about 25 times, making it impossible to produce them in the quantity needed for a neuron transplant.

Rivolta and his colleagues knew that during embryonic development, a handful of proteins, including fibroblast growth factor (FGF) 3 and 10, are required for ears to form. So they exposed human embryonic stem cells to FGF3 and FGF10. Multiple types of cells formed, including precursor inner-ear hair cells, but they were also able to identify and isolate the cells beginning to differentiate into the desired spiral ganglion neurons. Then, they implanted the neuron precursor cells into the ears of gerbils with damaged ear neurons and followed the animals for 10 weeks. The function of the neurons was restored.

"We’ve only followed the animals for a very limited time," Rivolta says. "We want to follow them long-term now"—both to assess the possibility of increased cancer risk and to observe the long-term function of the new neurons, he adds.

"It’s very exciting," says neuroscientist Mark Maconochie of Sussex University in the United Kingdom, who was not involved in the new work. "In the past, there has been work where someone makes a single hair cell or something that looks like one neuron [from stem cells], and even that gets the field excited. This is a real step change."

The question now, he says, is whether the procedure can be fine-tuned to allow more efficient production of the relay neurons—currently, fewer than 20% of the stem cells treated develop into those ear neurons. By combining growth factors other than FGF3 and FGF10 with the stem cell mix, researchers could harvest even more ear progenitor cells, he hypothesizes.

"The next big challenge will be to do something as effective as this for the hair cells," Maconochie adds.