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What's new in HSCI research

Different autism risk genes, same effects on brain development

Organoid of the developing human brain.
Autism spectrum disorder has been associated with hundreds of different genes, but how these distinct genetic mutations converge on similar symptoms in patients has remained a mystery. HSCI Principal Faculty member Paola Arlotta studied three autism risk genes whose exact functions have been unclear.
  • What they did: The researchers created miniature 3D models, or “organoids,” of the human cerebral cortex, the part of the brain responsible for cognition, perception, and language. The organoids contained a mutation in one of the autism risk genes.
  • What they found: The three different risk genes affected similar aspects of development and the same types of neurons, although each gene acted through unique molecular mechanisms. Additionally, a person’s specific genetic background fine-tuned the genes’ effects.
  • Why it matters: These results advance our understanding of autism spectrum disorder and are a first step toward finding treatments for the condition.

Biohybrid fish made from human cardiac cells swims like the heart beats

Lab models are an important tool to study heart disease and work toward building an artificial replacement heart, but most of them replicate either the heart’s simple beating or basic structure. HSCI Principal Faculty member Kevin Kit Parker created a more complex bioengineered device to study the biophysical properties of the heart.
  • What they did: Inspired by the swimming motion of zebrafish, researchers grew two layers of heart muscle cells that were made from stem cells, one on each side of the device’s tail fin. When one side contracted, the other one stretched, automatically triggered by a protein that is sensitive to mechanical forces. The researchers also added a pacemaker to control the frequency and rhythm of the contractions.
  • What they found: The bioengineered system propelled the fish’s movement for over 100 days, with the muscle contractions and coordination improving over time.
  • Why it matters: By modeling the mechanical and electrical signals of the pumping heart, researchers are one step closer to developing a more complex artificial muscular pump, as well as a platform to study heart diseases like arrhythmia.

Harvard licenses bioengineering technologies to companies for therapy development

Organoid of kidney cells connected by a blood vessel network.
Two bioengineering technologies pioneered by HSCI researchers have been licensed to companies, bringing the lab innovations closer to the clinic.
  • HSCI faculty Jennifer Lewis and Ryuji Morizane, in collaboration with Joseph Bonventre, combined stem cell organoid and 3D bioprinting methods to grow kidney tissue that contains blood vessels. Licensed by Harvard to Trestle Biotherapeutics, the technology paves the way to create fully functional tissue for treating chronic kidney diseases and addressing the shortage of transplantable organs.
  • Harvard licensed a novel technology to Alkem Laboratories Limited to help treat diabetic neuropathy, foot ulcers, peripheral arterial disease, and other injuries caused by vascular disease. Developed by HSCI’s David Mooney, the technology is an injectable biocompatible scaffold that slowly releases tissue-regenerative molecules. In multiple animal models of ischemia and injury, the technology restored blood flow, muscle strength, and nerve damage.
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