Tools to Accelerate Discovery

HSCI scientists develop innovative stem cell technologies that are changing the way we study disease. In 2019, HSCI researchers found new ways to reprogram stem cells to become specific tissues, for example taking skin cells from a patient and reprogramming them to become nerve cells in a dish. This makes it possible to model a patient’s specific disease in the lab, study it to identify a potential therapy, and test that intervention safely in a dish before administering it to the patient.

Advances in engineered miniature kidneys

Kidney organoids connected by a network of blood vessels.

Stem cells can be grown in the lab and bioengineered to become miniature, three-dimensional organs, called organoids. Human organoids have opened up a new way to model and study human diseases directly. In 2019, an interdisciplinary study led by bioengineer Jennifer Lewis, Sc.D. and stem cell biologist Ryuji Morizane, M.D., Ph.D. led to the creation of kidney organoids that are vastly improved over initial models.

Lewis and Morizane grew their kidney organoids while exposing them to the frictional force of flowing biological fluids, mimicking the natural conditions of the body, As a result, the organoids developed networks of blood vessels that could circulate oxygen and nutrients, remove waste, and send messages between different cell types.

Whether they are used in drug screening or for understanding organ development and disease mechanisms, these new models will yield far more relevant and accurate results than past models.

Reproducible human brain organoids

Animal studies of human neurological disorders rarely lead to results that translate to therapies for people, because differences in the brain are too great. In a major step forward for neuropsychiatric disease research, Paola Arlotta, Ph.D. and her colleagues created human brain organoids that consistently follow the growth patterns observed in the developing human brain. The optimized process allows organoids to grow for long enough that key cell types can form, opening the door to studies of a broad range of brain disorders.

The HSCI scientists used multiple stem-cell lines to form organoids of the cerebral cortex, the part of the brain responsible for cognition, language, and sensation. They found that across the different organoids, the same cell types were made in the same way, in the correct order.

Researchers can now use this reproducible experimental system to test drugs for neurological diseases like Alzheimer’s disease, autism spectrum disorder and schizophrenia directly in human tissues.

Pancreas on a chip

Pancreas-on-a-chip device combines microfluidics
technology and insulin-producing beta cells.

Kevin Kit Parker, Ph.D. and Douglas Melton, Ph.D. collaborated on the design of a new device that will expand diabetes research, and that could improve beta-cell transplantation in diabetes patients.

The new “islet on a chip,” inspired by the human pancreas, combines microfluidics and human, insulin-producing beta cells. It automates the process of monitoring whether or not islets are releasing insulin, and whether they are functioning as expected.

The device can make it easier for scientists to screen beta cells before transplanting them into a patient. It can also be used to test insulin-stimulating compounds, and to study the fundamental biology of diabetes.

Finding a gene therapy for heart arrhythmia

William Pu, M.D. and Kevin Kit Parker, Ph.D. combined stem cell science and bioengineering to develop a potential gene therapy for a type of heart arrhythmia, a condition marked by racing and irregular heartbeats.

The researchers made heart muscle cells using the stem cells of patients, and put the new cells on an engineered surface, creating a tissue that modeled the disease. Using the disease model, they identified a gene as a potential therapeutic target. They targeted the gene in an animal model and succeeded in suppressing the arrhythmia.

Beyond heart arrhythmia, the gene therapy could be applied to other types of heart disease where the targeted biological pathway is involved. In addition, the combined approach shows the power of stem cell technology to discover therapeutic targets — a process that often takes many years.