July 23, 2015
Scientists have successfully created a model of early human heart development using stem cells derived from human skin cells.
The heart-on-a-chip model is one of the latest in a growing technology known as “organ chips” which uses human cells in a dynamic micro-environment to simulate natural physiology. This latest heart chip is unique in its potential to evaluate the effects of drugs on the developing human heart, including prenatally.
To test its ability for screening drugs that may have an adverse impact on fetal development, UC Berkeley researchers and scientists at the Gladstone Institutes exposed the developing cells to thalidomide, known for its ability to cause severe birth defects. They were able to demonstrate that the drug impaired cell development, including normal muscle contractions and beat rate.
Grown on a geometrically confined surface, human iPC stem cells go
through differentiation to form developing cardiac cells.
(Photo credit: Zhen Ma, UC Berkeley)
Because the most commonly reported birth defects involve the heart, this latest chip can help address the problem of drug exposure posing fetal risk to as many as 280,000 pregnant women each year.
Just four months ago, UC Berkeley bioengineering professor Kevin Healy and his collaborators unveiled a heart-on-a-chip that successfully modeled cardiac physiology for screening drug toxicity. In contrast, this latest model uses cells that are in the process of differentiating into adult cells, and can mimic the developing heart.
The researchers began with stem cells engineered from adult skin tissue and progressed to cardiac cells that naturally differentiated and self-assembled in 3D, forming small chambers with beating cells, much like the human heart.
Dr. Healy and his research team believe that this latest heart chip could eventually replace animal experiments to study the effects of drugs on cardiac development.
“The fact that we used patient-derived human pluripotent stem cells in our work represents a sea change in the field,” said Dr. Healy. “Previous studies of cardiac microtissues primarily used harvested rat cardiomyocytes, which is an imperfect model for human disease.”
By their design, animal studies of developmental effects involve multitudes of animals, including pregnant animals, lactating mothers, and unborn babies, who are typically removed by killing the mothers and babies. Efforts to use non-animal methods would spare the lives of millions of animals.
This latest chip of the developing heart was created through an expansive program by the National Institutes of Health to create organ chips for use in drug development. Recognizing the failure of animal tests to predict safe and effective drugs, the National Center for Advancing Translational Sciences, a division of NIH, is leading the development of bio-engineered living human cells and tissues into organs-on-chips.
A scientist holds an organ chip in this video about the Tissue Chip Program at NCATS
Click to watch the video (Credit: NCATS)
The multi-million dollar program, which awarded $17 million in 2014, is being carried out in conjunction with the Food and Drug Administration and the Defense Advanced Research Projects Agency. The goal is to pursue the development and implementation of advanced models using human cells that will enable the safe and cost-effective way to test vaccines, drugs or other biologic agents without using animals.
Citizens for Alternatives to Animal Research (CAARE), is a 501(c)(3) non-profit organization, established to highlight and promote research without animals.
CAARE’s mission is to reduce animal suffering by disseminating information about the power and progress of research without animals.