Some great inventions were on view this week at the second annual Boston Children’s Hospital Innovators Showcase. Hosted by the hospital’s Innovation Acceleration Program and Technology & Innovation Development Office, the event featured everything from virtual reality goggles with gesture control to biomedical technologies. Below are a few new projects that caught Vector’s eye (expect to hear more about them in the coming months), a kid-friendly interview about the SimLab and list of inventions kids themselves would like to see. (Photos by Katherine Cohen except as noted)
Developing a child-centric approach to treating heart failure is no easy task. For one thing, the underlying causes of decreased cardiac function in children vastly differ from those in adults. While most adults with heart failure have suffered a heart attack, heart failure in children is more likely the result of congenital heart disease (CHD), or a structural defect present at birth that impairs heart function. And most therapies designed for adults haven’t proven equally effective in children.
Stimulating heart muscle cells to regenerate is one way cardiac researchers at Boston Children’s Hospital’s Translational Research Center hope to restore function to children’s ailing hearts. In this area, children actually have an advantage over adults: their young heart cells are better suited for regrowth.
Reporting in the April 1 Science Translational Medicine, Brian Polizzotti, PhD, and Bernhard Kuhn, MD, demonstrate that not only does the drug neuregulin trigger heart cell regeneration and improve overall heart function in newborn mice, but its effects are most potent for humans within the first six months of life.
Last 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.
Alexander DeVine is a research assistant in the Stem Cell Research Program at Boston Children’s Hospital.
Few discoveries have so transformed human stem cell research as have induced pluripotent stem cells (iPSCs). Like embryonic stem cells (ESCs), iPSCs possess, in principle, the potential to produce any of the cells in the human body—hence the term pluripotent. Because they can be derived by “reprogramming” easily accessible cell types (e.g., blood or skin cells) from any patient, rather than by creating and dissecting an embryo from donated sperm and eggs, iPSCs are more readily available to researchers than ESCs and better poised for clinical application.
In the seven years since Shinya Yamanaka, Jamie Thomson, and Boston Children’s Hospital’s own George Daley independently described the first methods for generating human iPSCs, these versatile cells have taken stem cell laboratories by storm. Today, they are used around the globe to study human development and to model a plethora of common and rare genetic conditions, from Parkinson’s disease to Fanconi anemia to type I diabetes. iPSCs are also starting to enter the clinic: in Japan, patients are already being recruited to a clinical trial to test the safety and efficacy of iPSC-derived therapeutics for the treatment of blindness.
For years, the lab of Leonard Zon, MD, director of the Stem Cell Research Program at Boston Children’s Hospital, has sought ways to enhance bone marrow transplants for patients with cancer, serious immune deficiencies and blood disorders. Using zebrafish as a drug-screening platform, the lab has found a number of promising compounds, including one called ProHema that is now in clinical trials.
But truthfully, until now, Zon and his colleagues have largely been flying blind.
“Stem cell and bone marrow transplants are still very much a black box: cells are introduced into a patient and later on we can measure recovery of their blood system, but what happens in between can’t be seen,” says Owen Tamplin, PhD, in the Zon Lab. “Now we have a system where we can actually watch that middle step.”
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
Monique Yoakim-Turk, PhD, is a partner of the Technology Development Fund and associate director of the Technology and Innovation Development Office at Boston Children’s Hospital
Since 2009, Boston Children’s Hospital has committed $6.2 million to support 58 hospital innovations ranging from therapeutics, diagnostics, medical devices and vaccines to regenerative medicine and healthcare IT projects. What a difference six years makes.
The Technology Development Fund (TDF) was proposed to Boston Children’s senior leadership in 2008 after months of research. As a catalyst fund, the TDF is designed to transform seed-stage academic technologies at the hospital into independently validated, later-stage, high-impact opportunities sought by licensees and investors. In addition to funds, investigators get access to mentors, product development experts and technical support through a network of contract research organizations and development partners. TDF also provides assistance with strategic planning, intellectual property protection, regulatory requirements and business models.
Seeking some “metrics of success” beyond licensing numbers and royalties (which can come a decade or so after a license), I asked recipients of past TDF awards to report back any successes that owed at least in part to data generated with TDF funds. While we expected some of the results, we would have never anticipated such a large impact.
Labs the world over are jumping onto the gene editing bandwagon (and into the inevitable patent arguments). And it’s hard to blame them. As these technologies have evolved over the last two decades starting with the zinc finger nucleases (ZFNs), followed by transcription activator-like effector nucleases (TALENs) and CRISPR—they’ve become ever more powerful and easier to use.
But one question keeps coming up: How precise are these systems? After all, a method that selectively mutates, deletes or swaps specific gene sequences (and now can even turn genes on) is only as good as its accuracy.
Algorithms can predict the likely “off-target” edits based on the target’s DNA sequence, but they’re based on limited data. “The algorithms are getting better,” says Richard Frock, PhD, a fellow in the laboratory of Frederick Alt, PhD, at Boston Children’s Hospital. “But you still worry about the one rare off-target effect that’s not predicted but falls in a coding region and totally debilitates a gene.”
Frock, Alt (who leads Boston Children’s Program in Cellular and Molecular Medicine, or PCMM), fellow Jiazhi Hu, PhD, and their collaborators recently turned a method first developed in Alt’s lab for studying broken chromosomes into a quality assurance tool for genome editing. As a bonus, the method—called high-throughput genome translocation sequencing (HTGTS)—also reveals the “collateral damage” gene editing methods might create in a cell’s genome, information that could help researchers make better choices when designing gene editing experiments.
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.
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.