Agency for Science, Technology and Research |
Researchers at the Institute of Bioengineering and Nanotechnology
(IBN) have successfully generated human kidney cells from human
embryonic stem cells in vitro1. Specifically, they produced the renal
cells under artificial conditions in the lab without using animals or
organs. This has not been possible until now. According to IBN Executive Director, Professor Jackie Y. Ying, “This
discovery has wide-reaching implications for in vitro toxicology, drug
screening, disease models and regenerative medicine. In particular, we
are interested in applying our technology to develop predictive in vitro
drug testing and renal toxicity models as alternatives to animal
testing.” IBN Team Leader and Principal Research Scientist Dr Daniele Zink
elaborated, “The kidney is a major target organ for drug-induced toxic
effects. Therefore, it is important for pharmaceutical companies to find
out early in the development phase whether their drugs would cause
nephrotoxicity in humans. However, animal models are of limited
predictability, and there is currently no regulatory accepted in vitro
assay based on renal cells to predict nephrotoxic effects. A major
problem is the lack of suitable renal cells, which may now be resolved
through our discovery.” At present, human kidney cells are extracted directly from human
kidney samples. However, this method is not efficient because such
samples are limited, and the extracted cells die after a few cell
divisions in the petri dish. Also, cells obtained from different samples
would display variable features, depending on age, gender, health
status and other conditions of the donor. Therefore, cells that have
been isolated from human samples are of limited suitability for research
and applications in industry and translational medicine, which require
large cell numbers. An alternative approach is to use human renal cell lines that have
been rendered immortal, i.e. they can be reproduced indefinitely in the
lab. However, such cells may not be used in many applications due to
safety issues, and their functional features have usually been changed
so profoundly that they may no longer be useful toward predicting cell
behaviour in the human body. IBN’s technique, on the other hand, enables human embryonic stem
cells to differentiate into renal proximal tubular-like cells. This
particular kidney cell type plays an important role in kidney
disease-related processes and drug clearance. Results showed that the
renal proximal tubular-like cells generated by IBN were similar to the
renal proximal tubular cells isolated from fresh human kidney samples.
For example, they displayed very similar gene and protein expression
patterns. Also, since human embryonic stem cells may grow indefinitely
in cell culture, the IBN researchers have discovered a potentially
unlimited source of human kidney cells. “We are currently adapting our approach to use induced pluripotent
stem cells as the source,” shared Dr Karthikeyan Narayanan, IBN Senior
Research Scientist. “We are also planning to modify our protocol in
order to generate other renal cell types from stem cells.” The IBN researchers have tested the renal cells they generated in in
vitro nephrotoxicology models developed by the Institute, and have
obtained very promising test results. They welcome industry partners to
collaborate with IBN on commercializing this technology. IBN has recently received a grant from A*STAR’s Joint Council Office
Development Program to further develop predictive in vitro models for
liver- and kidney-specific toxicity. This project will be conducted in
collaboration with the Experimental Therapeutics Centre, the
Bioinformatics Institute and the National University Health System.
Editor's Note: Original news release can be found here.
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Friday, February 22, 2013
Developing human kidney cells
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