At TEDx Longwood this spring, Leonard Zon, MD, founder and director of the Stem Cell Program at Boston Children’s Hospital, took the stage. In his enthusiastic yet humble style, he took the audience on a journey that included time-lapse video of zebrafish embryos developing, a riff by Jay Leno and a comparison of stem cell “engraftment” to a college kid coming home after finals: “You sleep for three days, and on day 4, you wake up and you’re in your own bed.” Three takeaways:

1)   Stem cells made from our own skin cells can help find new therapeutics. With the right handling, they themselves can be therapeutics, producing healthy muscle, insulin-secreting cells, pretty much anything we need. (So far, this has just been done in mice.)

2)   Zebrafish, especially when they’re see-through, can teach us how stem cells work and can be used for mass screening of potential drugs. The Zon Lab boasts 300,000 of these aquarium fish, and can mount robust “clinical trials” with 100 fish per group.

3)   Drugs discovered via zebrafish are in human clinical trials right now: A drug to enhance cord blood transplants for leukemia or lymphoma, and an anti-melanoma drug originally used to treat arthritis.

Zon, who co-founded the biopharm company Fate Therapeutics, will be part of a judging panel of clinicians and venture capitalists for the Innovation Tank at Boston Children’s Global Pediatric Innovation Summit + Awards (Oct. 30-31). Don’t miss it!

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Clinical excellence is the foundation of patient care. But at a recent TEDx Longwood event, Elaine C. Meyer, PhD, RN, co-founder and director of the Institute for Professionalism and Ethical Practice at Boston Children’s Hospital and an Associate Professor of Psychology at Harvard Medical School, offered insight on the other half of the health care equation: the human connection and the power of conversation.

Meyer’s moving presentation makes clear how communication—listening and sharing words of comfort—profoundly impacts patient experiences, as does its absence. Through heartfelt stories, including her own experience as a patient, her talk empowers physicians, nurses, social workers, psychologists and other medical staff to “be present” and communicate with patients and families compassionately.

“Dig deep, find your inspiration to have conversations,” Meyer says, because patients remember the words spoken to them and how those words made them feel.

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ADHD long term drug safety rare adverse events FDA approval Kenneth Mandl Florence BourgeoisYou’d think drugs meant to be taken by children for years would be studied in children for a long time to measure their long-term safety.

You’d think drugs for a condition affecting millions of children would be tested in many, many children to catch any rare side effects.

You’d think all this would happen before the Food and Drug Administration, an agency known for its strict criteria, approved them for marketing.

But if a new PLoS ONE paper by Boston Children’s Hospital’s Florence Bourgeois, MD, MPH, and Kenneth Mandl, MD, MPH, is any indication, you’d be wrong.

In it, the pair reports that the FDA approved 20 attention deficit hyperactivity disorder (ADHD) drugs over the last 60 years without what would be considered sufficient long-term safety and rare adverse event data.

Their findings, they say, point to larger issues in how the FDA’s approval process addresses the long-term safety of drugs intended for chronic use in children. Full story »

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Drug-eluting contact lens

(Credit: John Earle Photography)

Growing up, my grandmother’s eyes were always a problem. For years, she was losing her central vision to glaucoma, and numerous surgeries and treatments did not seem to help. Later in life, she could not see my face but could always tell who I was when I was close.

Glaucoma is the leading cause of irreversible blindness worldwide. While FDA-approved medications such as latanoprost can prevent vision loss by reducing pressure in the eye, their beneficial effects are limited by poor patient compliance: At six months of treatment, compliance is estimated to be little more than 50 percent.

Why? First, the medications are typically delivered as eye drops, and the drops themselves can cause stinging and burning. The drops also contain preservatives that can cause ocular surface disease.

Perhaps most importantly, latanoprost and other glaucoma drugs halt the disease’s progression but do not reverse it. Taking the drugs does not provide positive feedback that will motivate patients, such as relieving pain. Full story »

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Wong-Baker pain faces subjective objective pain assessment systems neuroscience David Borsook

Subjective measures of pain, like the Wong-Baker face scale (above), are useful in assessing patients' pain, but objective measures would be far better.

“How much pain are you in?” It’s a harder question than you think. Tools for assessing patients’ pain—be they children or adults—rely on their perception: a subjective measure that eludes quantification and can change in response to any number of emotional, psychological or physiological factors.

Being able to objectively quantify pain could open the door to better pain management (especially for patients with chronic or neuropathic pain), better anesthetic dosing during surgical procedures, better understanding of addiction (and how to avoid it) and more.

To do so, we need measurable markers: physiologic parameters that reliably and quantitatively change during the experience of pain. But according to pain researcher David Borsook, MD, PhD—of Boston Children’s Hospital’s departments of Anesthesiology, Perioperative and Pain Medicine and Radiology—discovering such markers requires a better understanding of the larger context and of events that trigger pain, a perspective he refers to as “systems neuroscience.” Full story »

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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. Full story »

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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. Full story »

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Old car aging blood cell hematopoietic stem cell blood disorder Derrick Rossi

Like an old, unused car, our aging blood stem cells can accumulate damage over time that they can't fully repair.

My first car was my grandfather’s 1980 Chevrolet Malibu. For about two years before my family gave it to me, it sat unused in Grandpa’s garage—just enough time for all of the belts and hoses to rot and the battery to trickle down to nothing.

Why am I telling this story? Because it’s much like what happens to the DNA in our blood-forming stem cells as we age.

Hematopoietic stem cells (HSCs) spend very little of their lives in an active, cycling state. Much of the time they’re quiescent or dormant, keeping their molecular and metabolic processes dialed down. These quiet periods allow the cells to conserve resources, but also give time an opportunity to wear away at their genes.

“DNA damage doesn’t just arise from mistakes during replication,” explains Derrick Rossi, PhD, a stem cell biology researcher with Boston Children’s Hospital’s Program in Cellular and Molecular Medicine. “There are many ways for damage to occur during periods of inactivity, such as reactions with byproducts of our oxidative metabolism.”

The canonical view has been that HSCs always keep one eye open for DNA damage and repair it, even when dormant. But in a study recently published in Cell Stem Cell, Rossi and his team found evidence to the contrary­­—which might tell us something about age-related blood cancers and blood disorders. Full story »

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Tracking patients between clinical visits

A randomized trial will soon test whether web-based updates from parents and teachers improve outcomes in ADHD, autism and more.

Eugenia Chan, MD, MPH, is a developmental-behavioral pediatrician and health services researcher in the Division of Developmental Medicine at Boston Children’s Hospital. She runs the Developmental Medicine Centers ADHD Program and is co-developer of ICISS Health, a web-based disease monitoring and management system.

When I set out with my collaborator Eric Fleegler, MD, MPH, to build a web-based tracking system for children with attention deficit hyperactivity disorder (ADHD), we focused on a single problem—getting parents and teachers to fill out symptom questionnaires in time to help doctors make informed clinical decisions at follow-up visits. We had no inkling of the possibilities that this kind of software platform could hold, or how it might grow in the future. Full story »

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spina bifida myelomeningocele

Prenatal cell therapy could avoid the need for invasive surgery to repair myelomeningocele.

The neural tube, which becomes the spinal cord and brain, is supposed to close during the first month of prenatal development. In children with spina bifida, it doesn’t close completely, leaving the nerves of the spinal cord exposed and subject to damage. The most common and serious form of spina bifida, myelomeningocele, sets a child up for lifelong disability, causing complications such as hydrocephalus, leg paralysis, and loss of bladder and bowel control.

New research from Boston Children’s Hospital, though still in animal models, suggests that standard amniocentesis, followed by one or more injections of cells into the womb, could be enough to at least partially repair spina bifida prenatally.

Currently, the standard procedure is to operate on infants soon after delivery. Full story »

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