Stories about: stem cells

Rescuing intestinal stem cells from attack in diabetes

diabetic enteropathy and colonic stem cells
Blood levels of the hormone IGFBP3 (enterostaminine), shown here in green, are markedly elevated in people with longstanding type 1 diabetes and launch a lethal attack on intestinal stem cells. Adding a protein that soaks up the excess hormone restores normal stem cell function and could help prevent or treat diabetic enteropathy. (All images by Riseon)

Up to 80 percent of people with long-standing type 1 diabetes develop gastrointestinal symptoms—abdominal pain, bloating, nausea, vomiting, diarrhea, constipation and fecal incontinence—that severely diminish quality of life. Recent evidence suggests that this condition, known as diabetic enteropathy, results from damage to the intestinal lining, but the details beyond that have been unclear.

A study in this week’s Cell Stem Cell, led by Paolo Fiorina, MD, PhD, now provides some answers. It demonstrates how diabetes can lead to destruction of the stem cells that maintain the intestinal lining, and identifies a potential drug that could protect these stem cells and prevent or treat diabetic enteropathy.

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Stress-induced stem cells debunked: The final word on STAP

In early 2014, controversy erupted when two papers in Nature indicated that exposing ordinary cells to stress—an acid bath or mechanical stress—could quickly and efficiently turn them into pluripotent stem cells, capable of developing into virtually all the tissues in the body.

The technique, called “stimulus-triggered acquisition of pluripotency,” or STAP, was lauded for its simplicity compared to other methods like nuclear transfer into egg cells or cellular reprogramming with a set of transcription factors.

Not so fast.

Six months later, the papers were retracted. And this week in Nature, a team led by George Q. Daley, MD, PhD, director of the Stem Cell Transplantation Program at Boston Children’s Hospital, and Peter Park, PhD, head of the Computational Genomics Group at Harvard Medical School (HMS) details what went wrong. In a companion paper, the Daley Lab provides a roadmap for verifying a cell’s pluripotent status.

Read the full story on the HMS website.

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Gene therapy to germline editing: Promises, challenges, ethics

A report this April rocked the scientific world: scientists in China reported editing the genomes of human embryos using CRISPR/Cas9 technology. It was a limited success: of 86 embryos injected with CRISPR/Cas9, only 71 survived and only 4 had their target gene successfully edited. The edits didn’t take in every cell, creating a mosaic pattern, and worse, unwanted DNA mutations were introduced.

“Their study should give pause to any practitioner who thinks the technology is ready for testing to eradicate disease genes during [in vitro fertilization],” George Q. Daley, MD, PhD, director of the Stem Cell Transplantation Program at Boston Children’s Hospital, told The New York Times. “This is an unsafe procedure and should not be practiced at this time, and perhaps never.”

As Daley detailed last week in his excellent presentation at Harvard Medical School’s Talks@12 series, the report reignited an ethical debate around tampering with life that’s hummed around genetic and stem cell research for decades. What the Chinese report adds is the theoretical capability of not just changing your genetic makeup, but changing the DNA you pass on to your children.

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Souped-up fish facility boosts drug discovery and testing

closeup of zebrafish-20150526_ZebraFishCeremony-60The care and feeding of more than 250,000 zebrafish just got better, thanks to a $4 million grant from the Massachusetts Life Sciences Center to upgrade Boston Children’s Hospital’s Karp Aquatics Facility. Aside from the fish, patients with cancer, blood diseases and more stand to benefit.

From a new crop of Boston-Children’s-patented spawning tanks to a robotic feeding system, the upgrade will help raise the large numbers of the striped tropical fish needed to rapidly identify and screen potential new therapeutics. It’s all part of the Children’s Center for Cell Therapy, established in 2013. We put on shoe covers and took a look behind the scenes. (Photos: Katherine Cohen)

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New Human Neuron Core to analyze ‘disease in a dish’

Human Neuron CoreLast week was a good week for neuroscience. Boston Children’s Hospital received nearly $2.2 million from the Massachusetts Life Sciences Center (MLSC) to create a Human Neuron Core. The facility will allow researchers at Boston Children’s and beyond to study neurodevelopmental, psychiatric and neurological disorders directly in living, functioning neurons made from patients with these disorders.

“Nobody’s tried to make human neurons available in a core facility like this before,” says Robin Kleiman, PhD, Director of Preclinical Research for Boston Children’s Translational Neuroscience Center (TNC), who will oversee the Core along with neurologist and TNC director Mustafa Sahin, MD, PhD, and Clifford Woolf, PhD, of Boston Children’s F.M. Kirby Neurobiology Center. “Neurons are really complicated, and there are many different subtypes. Coming up with standard operating procedures for making each type of neuron reproducibly is labor-intensive and expensive.”

Patient-derived neurons are ideal for modeling disease and for preclinical screening of potential drug candidates, including existing, FDA-approved drugs. Created from induced pluripotent stem cells (iPSCs) made from a small skin sample, the lab-created human neurons capture disease physiology at the cellular level in a way that neurons from rats or mice cannot.

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15 health care predictions for 2015

healthcare predictions
2014 continued to see massive evolution in health care—from digital health innovations to the maturation of technologies in genomics, genome editing and regenerative medicine to the configuration of the health care system itself. We asked leaders from the clinical, research and business corners of Boston Children’s Hospital to weigh in with their forecasts for 2015. Click “Full story” for them all, or jump to:
The consumer movement in health care
Evolving care models
Genomics in medicine
Stem cell therapeutics
Therapeutic development
New technology
Biomedical research

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Biological ‘programmers’ crack new code in stem cells

Stem cell colony Wyss Institute James Collins George Daley complexity
Researchers discovered many small nuances in pluripotency states of stem cells by subjecting the cells to various perturbations and then analyzing each individual cell to observe all the different reactions to developmental cues within a stem cell colony. (Credit: Wyss Institute at Harvard University)

Stem cells offer great potential in biomedical engineering because they’re pluripotent—meaning they can multiply indefinitely and develop into any of the hundreds of different kinds of cells and tissues in the body. But in trying to tap these cells’ creative potential, it has so far been hard to pinpoint the precise biological mechanisms and genetic makeups that dictate how stem cells diverge on the path to development.

Part of the challenge, according to James Collins, PhD, a core faculty member at the Wyss Institute for Biologically Inspired Engineering, is that not all stem cells are created the same. “Stem cell colonies contain much variability between individual cells. This has been considered somewhat problematic for developing predictive approaches in stem cell engineering,” he says.

But now, Collins and Boston Children’s Hospital’s George Q. Daley, MD, PhD, have used a new, very sensitive single-cell genetic profiling method to reveal how the variability in pluripotent stem cells runs way deeper than we thought.

While at first glimmer, it could appear this would make predictive stem cell engineering more difficult, it might actually present an opportunity to exert even more programmable control over stem cell differentiation and development than was originally envisioned. “What was previously considered problematic variability could actually be beneficial to our ability to precisely control stem cells,” says Collins.

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Modeling pain in a dish: Nociceptors made from skin recreate pain physiology

Pain in a dish nociceptors

Chronic pain, affecting tens of millions of Americans alone, is debilitating and demoralizing. It has many causes, and in the worst cases, people become “hypersensitized”—their nervous systems fire off pain signals in response to very minor triggers.

There are no good medications to calm these signals, in part because the subjectivity of pain makes it difficult to study, and in part because there haven’t been good research models. Drugs have been tested in animal models and “off the shelf” cell lines, some of them engineered to carry target molecules (such as the ion channels that trigger pain signals). Drug candidates emerging from these studies initially looked promising but haven’t panned out in clinical testing.

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Hearing restoration has a sound future

Ear-engraved styleThis post is adapted from a commentary in this week’s edition of Science by Jeffrey R. Holt, PhD, and Gwenaelle S. G. Géléoc, PhD, of the Department of Otolaryngology and F.M. Kirby Neurobiology Center at Boston Children’s Hospital.

Hearing loss affects more than 300 million people worldwide, making it the most common sensory disorder. While there are no cures, recent efforts to develop biological treatments for hearing loss provide reason for cautious optimism. Three strategies—gene therapy, stem cells and drugs—have shown encouraging results in animal models, poising them for translation into potential therapies for humans.

Hearing loss can arise from many different causes, so it is unlikely that a single “magic bullet” will be developed to treat all forms of deafness. Rather, each individual cause may require a tailored and specific treatment strategy.

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Reversing lung disease in mice by coaxing production of healthy cells

Using a novel 3-D culture method, scientists were able to prod lung (bronchioalveolar) stem cells to produce colonies containing the cell type of choice: airway (bronchiolar) epithelial cells, alveolar epithelial cells or both. (Images: Joo-Hyeon Lee)
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.

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