A group of researchers from The Skaggs Institute for Chemical Biology at The Scripps Research Institute and from the Genomics Institute of the Novartis Research Foundation (GNF) has identified a small synthetic molecule that can control the fate of embryonic stem cells.
This compound, called cardiogenol C, causes mouse embryonic stem cells to selectively differentiate into "cardiomyocytes," or heart muscle cells, an important step on the road to developing new therapies for repairing damaged heart tissue.
Normally, cells develop along a pathway of increasing specialization. In humans and other mammals, these developmental events are controlled by mechanisms and signaling pathways we are only beginning to understand. One of scientists' great challenges is to find ways to selectively differentiate stem cells into specific cell types.
"It's hard to control which specific lineage the stem cells differentiate into," says Xu Wu, who is a doctoral candidate in the Kellogg School of Science and Technology at Scripps Research. "We have discovered small molecules that can [turn] embryonic stem cells into heart muscle cells."
Wu is the first author of the study to be published in an upcoming issue of the Journal of the American Chemical Society and which was conducted under the direction of Peter G. Schultz, Ph.D., who is a professor of chemistry and Scripps Family Chair of the Skaggs Institute for Chemical Biology at The Scripps Research Institute, and Sheng Ding, Ph.D, who is an assistant professor in the Department of Chemistry at Scripps Research.
Regenerative Medicine and Stem Cell Therapy
Likewise, a damaged heart, which is composed mainly of cardiac muscle cells that the body may be unable to replace once lost, could potentially be repaired with new muscle cells derived from stem cells.
Scripps Research scientists reasoned that if stem cells were exposed to certain synthetic chemicals, they might selectively differentiate into particular types of cells. In order to test this hypothesis, the scientists screened some 100,000 small molecules from a combinatorial small molecule library that they synthesized. Just as a common library is filled with different books, this combinatorial library is filled with different small organic compounds.
From this assortment, Wu, Ding, and Schultz designed a method to identify molecules able to differentiate the mouse embryonic stem cells into heart muscle cells. They engineered embryonal carcinoma (EC) cells with a reporter gene encoding a protein called luciferase, and they inserted this luciferase gene downstream of the promoter sequence of a gene that is only expressed in cardiomyocytes.
Then they placed these EC cells into separate wells and added different chemicals from the library to each. Any engineered EC cells induced to become heart muscle cells expressed luciferase. This made the well glow, distinguishing it from tens of thousands of other wells when examined with state-of-the-art high-throughput screening equipment. These candidates were confirmed using more rigorous assays.
In the end, Wu, Ding, Schultz, and their colleagues found a number of molecules that were able to induce the differentiation of EC cells into cardiomyocytes, and they chose one, called Cardiogenol C, for further studies. Cardiogenol C proved to be effective at directing embryonic stem cells into cardiomyocytes.
Using Cardiogenol C, the scientists report that they could selectively induce more than half of the stem cells in their tests to differentiate into cardiac muscle cells. Existing methods for making heart muscle cells from embryonic stem cells are reported to result in merely five percent of the stem cells becoming the desired cell type.
Now Wu, Ding, Schultz, and their colleagues are working on understanding the exact biochemical mechanism whereby Cardiogenol C causes the stem cells to differentiate into cardiomyocytes, as well as attempting to improve the efficiency of the process.
Scripps Research Institute
Subscribe To SpaceDaily Express
Making Of Mouse Marks Move Toward Mmitochondrial Medicine
Rochester - Feb 11, 2004
There sits in most mammalian cells what amounts to a lock-box of DNA tucked away from the bulk of genetic material. While scientists routinely cut and paste snippets of life's blueprint to learn more about life and to treat disease, crucial DNA within cellular structures known as mitochondria has remained off-limits.
|The content herein, unless otherwise known to be public domain, are Copyright 1995-2016 - Space Media Network. All websites are published in Australia and are solely subject to Australian law and governed by Fair Use principals for news reporting and research purposes. AFP, UPI and IANS news wire stories are copyright Agence France-Presse, United Press International and Indo-Asia News Service. ESA news reports are copyright European Space Agency. All NASA sourced material is public domain. Additional copyrights may apply in whole or part to other bona fide parties. Advertising does not imply endorsement, agreement or approval of any opinions, statements or information provided by Space Media Network on any Web page published or hosted by Space Media Network. Privacy Statement All images and articles appearing on Space Media Network have been edited or digitally altered in some way. Any requests to remove copyright material will be acted upon in a timely and appropriate manner. Any attempt to extort money from Space Media Network will be ignored and reported to Australian Law Enforcement Agencies as a potential case of financial fraud involving the use of a telephonic carriage device or postal service.|