Researchers in Singapore, for the first time, have recreated two key processes essential for fetal formation in vitro. The team has not only controlled the differentiation of stem cells into other cell types, but they have also demonstrated the successful migration of these transformed cells.
Singapore, October 9, 2015 – For the first time, researchers from the Institute of Bioengineering and Nanotechnology (IBN) of Agency for Science, Technology and Research (A*STAR) in Singapore have recreated two key processes essential for fetal formation in vitro. The IBN team has not only controlled the differentiation of stem cells into other cell types, but they have also demonstrated the successful migration of these transformed cells. The latter has remained elusive to researchers until now, and makes it possible for researchers to build a better embryo development model for testing drugs causing birth defects.
|Image 1: IBN Postdoctoral Fellow Dr Jiangwa Xing (seated) and IBN Group Leader Prof Hanry Yu, who recreated key processes of embryonic development “in a dish”. Copyright: IBN A*STAR
IBN Executive Director Professor Jackie Y. Ying says, “Unintended exposure to compounds that can disrupt fetal development, such as Thalidomide, may lead to birth defects or even miscarriage. Our breakthrough is a major step toward identifying such compounds and understanding how they affect embryonic growth, and we hope that it will eventually help to mitigate the risk of fetal exposure to these destructive agents.”
Teratogens are compounds that are known to cause malformation in embryos. Currently, researchers rely on animal testing to assess the hazard of teratogens, but this method is expensive, time-consuming and unreliable due to inter-species variability. To overcome these problems, researchers have focused on developing alternative tests using human pluripotent stem cells (hPSCs).
According to IBN Group Leader Professor Hanry Yu, “Embryonic development does not only consist of the transformation of stem cells into other cell types, such as bone, muscle or nerve cells. It also involves the migration of these transformed cells to the right places in the body where they will develop into properly functioning organs as intended. This is why we believed it was important to develop a model encompassing both cell differentiation and migration that would give us a more complete and accurate picture of the effects of teratogens on the developing embryo.”
In the IBN model, the researchers confined the environment in which the embryonic stem cells transformed into other cell types, and restricted the ensuing migration of the micropatterned hPSC colonies so that the resulting mesoendoderm cells would form a consistent circular or ring pattern. Due to this geometric restriction, it was possible for the researchers to study the effect of teratogens, which may alter the shape and even the eventual position of the mesoendoderm layer.
“A key feature of our model that would facilitate its application as a drug screening platform is the consistency with which we can generate the circular mesoendoderm layer. This provides a reliable starting point and straightforward indicator for measuring drug-induced effects,” shared Professor Yu.
The IBN researchers have developed image processing and statistical algorithms to quantify and classify the teratogenic potential of different compounds. Using their micropatterned hPSC model, they have successfully distinguished between teratogenic compounds (i.e. Thalidomide) and non-teratogenic compounds (i.e. Penicillin G), and could also measure dose-dependent effects, which is essential for identifying a teratogenic agent’s clinically relevant dose.
The team is currently looking for clinical and industrial partners to further develop and validate their technology.
 Mesoendoderm cells refer to a combination of mesoderm (associated with internal organs such as muscle, spine and circulatory system) and endoderm (e.g. digestive system) cells.
J. Xing, Y.-C. Toh, S. Xu and H. Yu, “A Method for Human Teratogenic Detection by Geometrically Confined Cell Differentiation and Migration,” Scientific Reports, 5 (2015) 10038.
Elena Tan Nidyah Sani
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About the Institute of Bioengineering and Nanotechnology
Established in 2003, the Institute of Bioengineering and Nanotechnology (IBN) is the world’s first bioengineering and nanotechnology research institute. IBN’s mission is to conduct multidisciplinary research across science, engineering, and medicine for breakthroughs to improve healthcare and quality of life.
IBN’s research activities are focused in the following areas:
· Nanomedicine, where functionalized polymers, hydrogels and biologics are developed as therapeutics and carriers for the controlled release and targeted delivery of therapeutics to diseased cells and organs.
· Synthetic Biosystems, where biomimetic materials, innovative cell culture, 3D printing technologies, microfluidic systems and bioimaging are combined to develop novel approaches for regenerative medicine, in vitro compound screening, and disease modeling.
· Biodevices and Diagnostics, which involve nanotechnology and microfabricated platforms for high-throughput biomarker and drug screening, automated biologics synthesis, and rapid disease diagnosis.
· Green Chemistry and Energy, which encompass the green synthesis of chemicals and pharmaceuticals, catalytic conversion of biomass, utilization of carbon dioxide, and new nanocomposite materials for energy applications.
· More than 1,000 papers published in leading scientific journals
· Over 1,100 seminars and presentations at international conferences, including over 700 invited, keynote and plenary lectures
· Organized premier scientific meetings such as the International Conference on Bioengineering and Nanotechnology, Nano Today Conference, and the IBN International Symposium
Technological and Commercialization Impact
· 341 active patents and patent applications
· 84 licensed patents and patent applications
· 9 spin-off companies
· 153 active research collaborations with industrial, clinical and academic partners
Nurturing Future Research Talents
· Trained 116 PhD students
· More than 90,300 students and teachers from 290 local and overseas schools/universities have participated in IBN’s Youth Research Program
· Over 2,200 students and teachers have completed research attachments at IBN
For more information on IBN, please visit www.ibn.a-star.edu.sg.
About the Agency for Science, Technology and Research (A*STAR)
The Agency for Science, Technology and Research (A*STAR) is Singapore's lead public sector agency that spearheads economic oriented research to advance scientific discovery and develop innovative technology. Through open innovation, we collaborate with our partners in both the public and private sectors to benefit society.
As a Science and Technology Organisation, A*STAR bridges the gap between academia and industry. Our research creates economic growth and jobs for Singapore, and enhances lives by contributing to societal benefits such as improving outcomes in healthcare, urban living, and sustainability.
We play a key role in nurturing and developing a diversity of talent and leaders in our Agency and Research Institutes, the wider research community and industry. A*STAR oversees 18 biomedical sciences and physical sciences and engineering research entities primarily located in Biopolis and Fusionopolis.
For more information on A*STAR, please visit www.a-star.edu.sg.
|Image 2: Phase and T immunofluorescence images of mesoendoderm patterns in different drug test groups on day 3. The morphology of the mesoendoderm pattern was significantly disrupted under teratogen (Thalidomide, RA, D-penicillamine and VPA) treatment in a dose-dependent manner; whereas under non-teratogen (Penicillin G) treatment, the structure of the mesoendoderm pattern remained unchanged. Scale bar = 200 μm. Copyright: IBN A*STAR
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