Stories about: Regenerative medicine

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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Transplant surgeon seeks to avoid transplants

First in a two-part series on metabolic liver disease. Read part 2.

Khashayar Vakili, MDIn the clinical world, Boston Children’s Hospital surgeon Khashayar Vakili, MD, specializes in liver, kidney and intestinal transplant surgeries, while in the lab he is doing work which, for some patients, could eliminate the need for a transplant surgeon altogether.

Vakili has been working at Boston Children’s for six years. During his transplant surgery fellowship, he spent several months learning about pediatric liver transplantation from Heung Bae Kim, MD, director of the Boston Children’s Pediatric Transplant Center, which prompted his interest in the field.

“When the opportunity to join the transplant team presented itself, I did not hesitate to accept,” he says.

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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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Fast-regenerating mice offer clues for stroke, spinal cord and optic nerve injury

axon regeneration CNS
The CAST mouse from Thailand–genetically distinct from most lab mice–may have the right ingredients for nerve regeneration. (Courtesy Jackson Laboratory)

Second in a two-part series on nerve regeneration. Read part 1.

The search for therapies to spur regeneration after spinal cord injury, stroke and other central nervous system injuries hasn’t been all that successful to date. Getting nerve fibers (axons) to regenerate in mammals, typically lab mice, has often involved manipulating oncogenes or tumor suppressor genes to encourage growth, a move that could greatly increase a person’s risk of cancer.

A study published online last week by Neuron, led by the F.M. Kirby Neurobiology Center at Boston Children’s Hospital, took a completely different tactic.

Seeing little success at first, the researchers wondered whether they were working with the wrong mice.

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Proteomics provides new leads into nerve regeneration

Nerve regeneration. From Santiago Ramón y Cajal’s “Estudios sobre la degeneración y regeneración del sistema nervioso” (1913-14). Via Scholarpedia.

nerve regeneration proteomicsFirst in a two-part series on nerve regeneration. Read part 2

Researchers have tried for a century to get injured nerves in the brain and spinal cord to regenerate. Various combinations of growth-promoting and growth-inhibiting molecules have been found helpful, but results have often been hard to replicate. There have been some notable glimmers of hope in recent years, but the goal of regenerating a nerve fiber enough to wire up properly in the brain and actually function again has been largely elusive.

“The majority of axons still cannot regenerate,” says Zhigang He, PhD, a member of the F.M. Kirby Neurobiology Center at Boston Children’s Hospital. “This suggests we need to find additional molecules, additional mechanisms.”

Microarray analyses—which show what genes are transcribed (turned on) in injured nerves—have helped to some extent, but the plentiful leads they turn up are hard to analyze and often don’t pan out. The problem, says Judith Steen, PhD, who runs a proteomics lab at the Kirby Center, is that even when the genes are transcribed, the cell may not actually build the proteins they encode.

That’s where proteomics comes in. “By measuring proteins, you get a more direct, downstream readout of the system,” Steen says.

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The silk scaffold: A promising road to hollow organ reconstruction

Silk photo_black backgroundSilk production and global interest in the lustrous fiber date back to prehistoric times. Today, the natural protein is solidifying itself as a biomaterials alternative in the world of regenerative medicine.

A recent study conducted by Boston Children’s Hospital urologist Carlos Estrada, MD and bioengineer Joshua Mauney, PhD, shows two-layer, biodegradable silk scaffolds to be a promising cell-free, “off-the-shelf” alternative to traditional implants for the reconstruction of hollow gastrointestinal structures such as the esophagus.

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Pediatric innovators showcase highlights inventions

Innovators Showcase Boston Children's HospitalSome 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)

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First six months of life are best for stimulating child heart growth

heart-regeneration-study2
In these sample sections of mouse heart, the color blue signifies scar tissue. Damage from scarring was minimized by early administration of the drug neuregulin.

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.

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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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Induced pluripotent stem cells: Choosing a reprogramming method

options for making induced pluripotent stem cells

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.

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