Stories about: stem cell research

Regrowing corneas: It’s all about finding the stem cells

A restored cornea grown from human ABCB5-positive limbal stem cells
A restored, clear cornea grown from ABCB5-positive limbal stem cells. (Image courtesy of the researchers)
Severe burns, chemical injury and certain diseases can cause blindness by clouding the eyes’ corneas and killing off a precious population of stem cells that help maintain them. In the past, doctors have tried to regrow corneal tissue by transplanting cells from limbal tissue—found at the border between the cornea and the white of the eye. But they didn’t know whether the tissue contained enough of the active ingredient: limbal stem cells.

How cancer research led to a regenerative treatment for blindness.

Results have therefore been mixed. “Limbal stem cells are very rare, and successful transplants are dependent on these rare cells,” says Bruce Ksander, PhD, of the Massachusetts Eye and Ear/Schepens Eye Research Institute. “If you have a limbal stem cell deficiency and receive a transplant that does not contain stem cells, the cornea will become opaque again.”

Limbal stem cells have been sought for over a decade. That’s where a “tracer” molecule called ABCB5—first studied in the context of cancer—comes in.

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Getting the most of mesenchymal stem cell transplants

Fat cells from mesenchymal stem cell transplant
The fat cells shown in yellow are descended from transplanted human mesenchymal stem cells (green) inside of a mouse after co-transplantation. The red stain shows native mouse fat cells.(Courtesy Juan Melero-Martin)
Joseph Caputo originally wrote this post for the Harvard Stem Cell Institute (HSCI). Vector editor Nancy Fliesler contributed.

Stem cell scientists had what first appeared to be an easy win for regenerative medicine when they discovered mesenchymal stem cells several decades ago. These cells, found in the bone marrow, can give rise to bone, fat and muscle tissue, and have been used in hundreds of clinical trials for tissue repair.

Uses range from tissue protection in heart attack and stroke to immune modification in multiple sclerosis and diabetes. Unfortunately, the results of these trials have been underwhelming. One challenge is that these stem cells don’t stick around in the body long enough to benefit the patient.

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Recapturing the liver’s fountain of youth

fountain of youth stem cellsThis post is condensed from a report from the Harvard Stem Cell Institute.

The liver has been a model of tissue regeneration for decades, and it’s well known that a person’s liver cells can duplicate in response to injury. Even if three-quarters of the liver is surgically removed, duplication alone can return the organ to its normal functioning mass. It’s why people are able to donate part of their liver to someone in need—like this mother to her son who was born with biliary atresia.

But what about people with more chronic liver damage? Researchers led by Fernando Camargo, PhD, of the Harvard Stem Cell Institute and Boston Children’s Hospital’s Stem Cell Program, have new evidence in mice that it may be possible to repair such liver disease by forcing mature liver cells to turn back the clock and revert to a stem cell-like state, able to generate functional liver progenitor cells to replace damaged tissue.

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‘Heart on a chip’ suggests a surprising treatment for a rare genetic disease

heart chip BarthIt was the variability that intrigued pediatric cardiologist William Pu, MD, about his patient with heart failure. The boy suffered from a rare genetic mitochondrial disorder called Barth syndrome. While he ultimately needed a heart transplant, his heart function seemed to vary day-to-day, consistent with reports in the medical literature.

“Often patients present in infancy with severe heart failure, then in childhood it gets much better, and in the teen years, much worse,” says Pu, of the Cardiology Research Center at Boston Children’s Hospital. “This reversibility suggests that this is a disease we should really be able to fix.”

Though it needs much more testing, a potential fix may now be in sight for Barth syndrome, which has no specific treatment and also causes skeletal muscle weakness and low white-blood-cell counts. It’s taken the work of multiple labs collaborating across institutional lines.

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Can blood cells be rebooted into blood stem cells?

Hematopoietic hierarchy blood development stem cells
The classic hematopoietic hierarchy. What if we could turn those arrows around?

Think, for a moment, of a cell as a computer, with its genome as its software, working to give cells particular functions. One set of genetic programs turns a cell into a heart cell, another set creates a neuron, still another a lymphocyte and so on.

The job of controlling which programs get booted up, and when, falls in part to transcription factors—genes that act like molecular switches to turn other genes on and off.

Derrick Rossi, PhD, spends a lot of his time thinking about transcription factors. A stem cell and blood development researcher in Boston Children’s Hospital’s Program in Cellular and Molecular Medicine, Rossi believes that transcription factors hold the power to achieve one of the most sought-after goals in regenerative medicine: producing, from other cell types, transplantable hematopoietic stem cells (HSCs).

“There are about 50,000 HSC transplants every year,” Rossi explains, noting that the success of a transplant is highly dependent on the number of cells a patient receives from her donor. “But HSCs only comprise about one in every 20,000 cells in the bone marrow.

“If we could generate autologous HSCs from a patient’s other cells,” he continues, “it could be transformative for transplant medicine and for our ability to model diseases of blood development.”

As they reported April 24 in Cell, Rossi and his collaborators have taken a significant step toward that goal: Using a cocktail of eight transcription factors, they reprogrammed mature mouse blood cells into what they have dubbed induced HSCs (iHSCs).

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Customized cell therapy for untreatable diseases: Your tax dollars at work

Leonard Zon (top) and Massachusetts Lt. Governor Timothy Murray in the Stem Cell Program's zebrafish facility. (Courtesy MLSC)
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.

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.

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Big things from small places: Modified RNAs eyed as a way to make new drugs

A technology from a small research institute, originally developed as a safer way to make embryonic-like stem cells, just hooked a very large fish. As The New York Times reported yesterday, pharma giant AstraZeneca is betting at least $240 million that this technology could be the source of a variety of new drugs—drugs that spur the body itself to make what it needs.

In 2010, the lab of Derrick Rossi at the Immune Disease Institute, which is now the Program in Cellular and Molecular Medicine at Boston Children’s Hospital, reported that they could reprogram ordinary cells into pluripotent stem cells by simply injecting them with messenger RNAs. The mRNAs reprogrammed the cells up to 100 percent more efficiently than other techniques, and did so without becoming part of the cell’s genome, greatly reducing concerns about cancer associated with other methods.

Key to the discovery were the chemical modifications made to the mRNAs so that cells wouldn’t “see” them as viruses and attack them. This video and this article describe the modified mRNA technique, also described in Cell Stem Cell:

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It’s not the stem cells but what’s inside them that matters for babies with lung disease

The molecular equivalent of a message in a bottle could open up the possibility of stem cell-based therapies for newborn lung disease — but without the cells. (aturkus/Flickr)

Three years ago, Stella Kourembanas, MD, and S. Alex Mitsialis, PhD, thought they had a major breakthrough in treating pulmonary hypertension (PH) — dangerously high blood pressure in the pulmonary artery (the vessel that carries blood from the heart to the lungs) — and bronchopulmonary dysplasia (BPD) — a chronic lung disease that can affect babies born prematurely or who were put on a ventilator.

The two diseases are complex and serious, often occur together and are currently incurable.

The solution for PH and BPD, the two researchers from Boston Children’s Division of Newborn Medicine thought, was to protect the babies’ fragile lungs with a kind of stem cell called mesenchymal stem cells (MCSs), which can develop into lung tissue.

Their preclinical studies were pretty conclusive. If they transplanted MSCs in mouse models of BPD and PH, the mice didn’t develop the lung inflammation that triggers the disease.

But the results were a little confusing.

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On again, off again, on again…Part 2

This two-part series, a response to the recent appeals court decision lifting an injunction on federal funding of human embryonic stem cell research, was co-authored by M. William Lensch, George Q. Daley, and Leonard Zon of the Stem Cell Research Program at Children’s Hospital Boston. (Read Part 1.)

While there is reason for optimism, the April 29 appeals court ruling lifting the injunction on federal funding for human embryonic stem cell (hESC) research will not be the last chapter in the story of such research in the United States. And there are moments in this story that hold cause for greater alarm.

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On again, off again, on again…Part 1

This two-part series, a response to the recent appeals court decision lifting an injunction on federal funding of human embryonic stem cell research, was co-authored by M. William Lensch, George Q. Daley, and Leonard Zon of the Stem Cell Research Program at Children’s Hospital Boston.

It came as a welcome relief when on April 29 the U.S. Court of Appeals vacated a lower court’s injunction against federal funding of human embryonic stem cell (hESC) research. For those of us working on research projects involving hESCs, whether funded through the National Institutes of Health (NIH) or other federal agencies, it meant that we are once again free to continue our work … for now.

The “for now” part relates to the fact that the recent ruling is but one chapter in the ongoing story of hESC research funding. The desultory nature of federal funding for hESC research has been a constant source of uncertainty for scientists and the general public alike, and to understand the full story, we need to look back to the mid 1990s, before the derivation of the first hESC lines.

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