Stories about: stem cell research

Poised pluripotency: A glimpse of the early embryo just as it’s implanting

poised pluripotency - a newly defined stem cell state
Fawn Gracey illustration (click to enlarge)

Stem cell researchers at Boston Children’s Hospital have, for the first time, profiled a highly elusive kind of stem cell in the early embryo – a cell so fleeting that it makes its entrance and exit within a 12-hour span. They describe this “poised pluripotent” cell in the journal Cell Stem Cell.

In mice, poised cells appear 4.75 to 5.25 days after egg and sperm join to form the embryo, right at the time when the embryo stops floating around and implants itself in the uterine wall.

“People have had a hard time capturing the peri-implantation period because it’s really hard to define,” says Richard Gregory, PhD, who led the research. “It’s a very dynamic stage. Everything happens within a few hours, which is quite remarkable considering the extent of the changes occurring in the properties of the cells.”

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More surprises about blood development — and a possible lead for making lymphocytes

blood development chart
Blood development in the embryo begins with cells that make myeloid and erythroid cells – but not lymphoid cells. Why? A partial answer is in today’s Nature.

Hematopoietic stem cells (HSCs) have long been regarded as the granddaddy of all blood cells. After we’re born, these multipotent cells give rise to all our cell lineages: lymphoid, myeloid and erythroid cells. Hematologists have long focused on capturing HSCs’ emergence in the embryo, hoping to recreate the process in the lab to provide a source of therapeutic blood cells.

But in the embryo, oddly enough, blood development unfolds differently. The first blood cells to show up are already partly differentiated. These so-called “committed progenitors” give rise only to erythroid and myeloid cells — not lymphoid cells like the immune system’s B and T lymphocytes.

Researchers in the lab of George Q. Daley, MD, PhD, part of Boston Children’s Hospital’s Stem Cell Research program, wanted to know why. Does nature deliberately suppress blood cell multipotency in early embryonic development? And could this offer clues about how to reinstate multipotency and more readily generate different blood cell types?

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Science and medicine in 2018: What’s the forecast?

2018 predictions for biomedicine

Vector consulted its many informants to find out which way the wind will blow in 2018. Here are their predictions for what to expect in genetics, stem cell research, immunology and more.

GENETICS

Gene-based therapies mature

We will continue to see successes in 2018 reflecting the maturation of gene therapy as a viable, generalizable platform for curing many rare diseases. Also, we will see exciting new applications of other maturing platforms, like CRISPR/Cas9 gene editing and oligonucleotide therapies for neurologic diseases, building on the success of nusinersen for spinal muscular atrophy.

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News Note: Cell ‘barcodes’ trace the natural development of blood

in situ blood development
(Credit: Stem Cell Program, Boston Children’s Hospital)

Genetic labels, or “barcodes,” are shedding new light on the natural process of blood development and immune-cell production, finds a study published in Nature this week. It was led by Fernando Camargo, PhD, and first author Alejo Rodriguez Fraticelli, PhD, at Boston Children’s Hospital’s Stem Cell Research Program, the Harvard Department of Stem Cell and Regenerative Biology and the Harvard Stem Cell Institute.

Most of what we know about blood production is through observing what happens when blood stem and progenitor cells are transplanted into an animal. To observe what happens “in the wild,” researchers went in and tagged the blood stem and progenitor cells of mice, using genetic elements called transposons. This allowed them to track how the cells differentiated into five kinds of blood cells (above: megakaryocytes, erythroid cells, granulocytes, monocytes and B-cell progenitors).

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2017 pediatric biomedical advances at Boston Children’s Hospital: Our top 10 picks

New tools and technologies fueled biomedicine to great heights in 2017. Here are just a few of our top picks. All are great examples of research informing better care for children (and adults).

1. Gene therapy arrives

(Katherine C. Cohen)

In 2017, gene therapy solidly shed the stigma of Jesse Gelsinger’s 1999 death with the development of safer protocols and delivery vectors. Though each disease must navigate its own technical and regulatory path to gene therapy, the number of clinical trials is mounting worldwide, with seven gene therapy trials now recruiting at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. In August, the first gene therapy won FDA approval: CAR T-cell therapy for pediatric acute lymphoblastic leukemia.

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3D organoids and RNA sequencing reveal the crosstalk driving lung cell formation

lung disease
A healthy lung must maintain two key cell populations: airway cells (left), and alveolar epithelial cells (right). (Joo-Hyeon Lee)

To stay healthy, our lungs have to maintain two key populations of cells: the alveolar epithelial cells, which make up the little sacs where gas exchange takes place, and bronchiolar epithelial cells (also known as airway cells) that are lined with smooth muscle.

“We asked, how does a stem cell know whether it wants to make an airway or an alveolar cell?” says Carla Kim, PhD, of the Stem Cell Research Program at Boston Children’s Hospital.

Figuring this out could help in developing new treatments for such lung disorders as asthma and emphysema, manipulating the natural system for treatment purposes.

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Stem cell workaround cracks open new leads in Diamond Blackfan anemia

Diamond Blackfan anemia iPS cells hematopoietic progenitor cells
Though not bona-fide stem cells, hematopoietic progenitor cells produce red blood cells when exposed to certain chemicals. Could some of these compounds lead to new drugs for Diamond Blackfan anemia?

Diamond Blackfan anemia (DBA) has long been a disease waiting for a cure. First described in 1938 by Louis K. Diamond, MD, of Boston Children’s Hospital and his mentor, Kenneth Blackfan, MD, the rare, severe blood disorder prevents the bone marrow from making enough red blood cells. It’s been linked to mutations affecting a variety of proteins in ribosomes, the cellular organelles that themselves build proteins. The first mutation was reported in 1999.

But scientists have been unable to connect the dots and turn that knowledge into new treatments for DBA. Steroids are still the mainstay of care, and they help only about half of patients. Some people eventually stop responding, and many are forced onto lifelong blood transfusions.

Researchers have tried for years to isolate and study patients’ blood stem cells, hoping to recapture the disease process and gather new therapeutic leads. Some blood stem cells have been isolated, but they’re very rare and can’t be replicated in enough numbers to be useful for research.

Induced pluripotent stem (iPS) cells, first created in 2006 from donor skin cells, seemed to raise new hope. They can theoretically generate virtually any specialized cell, allowing scientists model a patient’s disease in a dish and test potential drugs.

There’s been just one hitch. “People quickly ran into problems with blood,” says hematology researcher Sergei Doulatov, PhD. “iPS cells have been hard to instruct when it comes to making blood cells.”

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Rainbow-hued blood stem cells shed new light on cancer, blood disorders

color-coded blood stem cells
These red blood cells bear color tags made from random combinations of red, green and blue fluorescent proteins. Same-color cells originate from the same blood stem cell (Nature Cell Biology 2016, Henninger et al).

A new color-coding tool is enabling scientists to better track live blood stem cells over time, a key part of understanding how blood disorders and cancers like leukemia arise, report researchers in Boston Children’s Hospital’s Stem Cell Research Program.

In Nature Cell Biology today, they describe the use of their tool in zebrafish to track blood stem cells the fish are born with, the clones (copies) these cells make of themselves and the types of specialized blood cells they give rise to (red cells, white cells and platelets). Leonard Zon, MD, director of the Stem Cell Research Program and a senior author on the paper, believes the tool has many implications for hematology and cancer medicine since zebrafish are surprisingly similar to humans genetically.

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Where science connects with care: A Q&A with Leonard Zon

Leonard Zon in the lab

Leonard Zon, MD, is founder and director of the Stem Cell Research Program at Boston Children’s Hospital and an investigator with the Howard Hughes Medical Institute and the Harvard Stem Cell Institute. His laboratory research focuses on stem cell therapies for patients with cancer and blood disorders, using a high-throughput, automated system for screening potential drugs in zebrafish. Zon was cofounder of Scholar Rock and Fate Therapeutics and founder and past president of the International Society for Stem Cell Research.

Your hospital just received a #1 ranking from U.S. News & World Report. What does this mean relative to your role there?

I’ve been at Boston Children’s Hospital for 25 years, and it’s really satisfying to be at the premier institution for clinical care. And we’re very lucky to have one of the premier stem cell programs in the world. I have a strong sense that my impact on society is as a physician-scientist, bringing basic discoveries to the clinic. We’re able to have a huge impact on finding new diagnoses and new therapies for our children.

What inspires you to do your job every day?

As a hematologist I take care of patients who have devastating diseases – a variety of blood diseases and cancer. When I see these children, I’m always wondering, could there be ways to treating them that haven’t been thought of before? Successfully treating a child gives them an entire lifetime of health.

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Forty years waiting for a cure: ALD gene therapy trial shows early promise

Ethan, who was diagnosed with ALD when he was 9, with his sister Emily
Ethan and me, June 1977

A small piece of notepaper, folded twice, sits tucked in a slot of the secretary desk in the living room. Every so often, I pull it out, read it, then reread.

Addressed to my mom, the paper has a question and two boxes, one “yes” and one “no,” written with the careful precision of a 7-year-old.

I am sad of Ethan. You too?

A check marks the box.

Yes. Yes, I am sad too.

Learning about adrenoleukodystrophy

My brother Ethan Williams was 9 years old in the fall of 1976, when he began to lose his sight. For my parents, that winter brought an endless round of doctor visits, therapists and lab tests.

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