In laboratories, across the world, scientists are actively trying to apply the principles of biomedical engineering to develop artificial tissue and miniature organs, mainly for the purpose of drug testing and organ transplantation. So far, researchers have managed to grow fully-functioning trachea, ear, nose, urinary bladder and even contracting muscle tissue, from human stem cells. And now, as part of a recent project, conducted by the University of California, Berkeley, in collaboration with the Gladstone Institute of Cardiovascular Disease, scientists have successfully developed microscopic beating “hearts”, complete with tiny cardiac chambers, in the lab.
In the research, published this week in the Nature Communications journal, the scientists have adopted an innovative approach for growing beating heart tissues, from induced pluripotent stem cells (iPSCs). The lab-grown cardiac tissue could, one day, serve as a model for studying early heart development and also as a drug-testing tool to ensure safer pregnancies. Unlike similar research, in the past, the newly-devised method uses specific biophysical and biochemical cues that in turn help regulate cell differentiation and organization.
To build the miniature hearts, the scientists reproduced the intricate process of human tissue formation, using undifferentiated stem cells derived from adult skin tissue. For the research, the iPS cells were carefully placed onto a tissue culture dish, featuring a circular-patterned surface. These specially-designed circular patterns actually serve as physical guides that regulate the process of cell differentiation and development. At the end of two weeks, the cells had transformed from two-dimensional layers into complex 3D structures, complete with pulsating microchambers. Furthermore, with the help of physical and chemical cues, the cells managed to reorganize themselves, according to the ring-like patterns. The cells, at the center, developed into fully-functional cardiac tissue, while those, towards the edge of the colony, evolved into fibroblasts, a special type of cell that forms the connective tissue.
To test the efficacy of the system as a drug-testing tool, the team exposed the lab-grown cardiac muscle tissue to thalidomide, a drug that famously caused severe congenital defects in over 5,000 infants, back in the 1950s. According to the researchers, exposure to normal doses of the sedative actually led to the development of smaller microchambers, with abnormal muscle contraction and reduced beat rates, especially in comparison to the controls. Dr. Bruce Conklin, of UC San Francisco, explained:
We chose drug cardiac developmental toxicity screening to demonstrate a clinically relevant application of the cardiac microchambers. Each year, as many as 280,000 pregnant women are exposed to drugs with evidence of potential fetal risk. The most commonly reported birth defects involve the heart, and the potential for generating cardiac defects is of utmost concern in determining drug safety during pregnancy.
Interestingly, while the said study is based on the analysis of the heart tissue, the scientists are also looking forward to the advancement of technology that could lead to development of other organs. As Kevin Healy, a UC Berkeley professor of bioengineering, said –
Our focus here has been on early heart development, but the basic principles of patterning of human pluripotent stem cells, and subsequently differentiating them, can be readily expanded into a broad range of tissues for understanding embryogenesis and tissue morphogenesis.
Source: Berkeley News