Nuevo Biochip Podría Reemplazar la Experimentación Con Animales

Escrito por UC Berkeley.

Foto: Moo-Yeal Lee/Rensselaer Polytechnic Institute Dado que la industria de los cosméticos se enfrentará en el 2009 con una prohibición europea para la comprobación en animales de los efectos de sus productos, un biochip recientemente desarrollado podría proporcionar los análisis rápidos necesarios para asegurar que los productos químicos en los cosméticos no son tóxicos para los humanos

Nuevo Biochip Podría Reemplazar la Experimentación Con Animales
28 de Enero de 2008.

Foto: Moo-Yeal Lee/Rensselaer Polytechnic InstituteDado que la industria de los cosméticos se enfrentará en el 2009 con una prohibición europea para la comprobación en animales de los efectos de sus productos, un biochip recientemente desarrollado podría proporcionar los análisis rápidos necesarios para asegurar que los productos químicos en los cosméticos no son tóxicos para los humanos.

El biochip contiene una suspensión de más de mil cultivos de células humanas en un gel tridimensional. Cada cultivo celular es capaz de evaluar la toxicidad de un producto químico diferente.

Según investigadores de la Universidad de California en Berkeley, el Instituto Politécnico Rensselaer y la empresa Solidus Biosciences, Inc., de Troy, Nueva York, los cultivos de células de la piel en este biochip, denominado DataChip, podrían utilizarse para comprobar con rapidez si los nuevos productos químicos son tóxicos o pueden irritar la piel.

Agregando otros tipos de células, como las del pulmón o las del corazón, y combinando el DataChip con otro biochip (el MetaChip) que los investigadores crearon hace varios años, las compañías de cosméticos o productos químicos también podrían probar si sus productos son tóxicos para otros órganos, no sólo para la piel.

El DataChip extiende las capacidades del MetaChip y le permite probar los efectos tóxicos de los productos químicos y sus metabolitos en todo el cuerpo. Éste es un paso importante hacia el reemplazo de los animales para evaluar la seguridad de un producto, así como hacia un sistema personalizado que pueda predecir la toxicidad de los medicamentos en individuos concretos.

Para las compañías farmacéuticas, la combinación del MetaChip y el DataChip ofrece una forma rápida de predecir si un producto candidato para ser utilizado como medicamento, o sus metabolitos, son tóxicos. Los chips también permitirán a las compañías químicas cumplir con la nueva legislación que estipula la aplicación de análisis de toxicidad a los productos químicos.

Las compañías farmacéuticas son sólo uno de los tipos de usuarios potenciales.

Dentro de los próximos 5 a 10 años, cuando el costo de secuenciar todos los genes de una persona se vuelva bastante asequible, las personas podrán disponer del análisis de su genoma individual para así obtener la información sobre los tipos y niveles de las enzimas del hígado que determinan cómo reaccionarán a medicamentos específicos, y reproducir entonces este perfil en un MetaChip para que éste revise todos los medicamentos antes de que se les administren, determinando las dosis eficaces y seguras.

Press Release

UC Berkeley Press Release

New biochip could replace animal testing

By Robert Sanders, Media Relations | 18 December 2007

BERKELEY – With the cosmetics industry facing a European ban on animal testing in 2009, a newly developed biochip could provide the rapid analysis needed to insure that the chemicals in cosmetics are nontoxic to humans.

human cells on DataChip spot
Close up of a DataChip spot. Human cells (green live, red dead) are encapsulated in an algae extract and treated with chemicals or liver metabolites of chemicals to assess toxicity. (Moo-Yeal Lee/Rensselaer Polytechnic Institute )

The biochip, announced this week in the online edition of the Proceedings of the National Academy of Sciences, is a suspension of more than a thousand human cell cultures in a three-dimensional gel on a standard microscope slide. Each cell culture is capable of assessing the toxicity of a different chemical. According to researchers from the University of California, Berkeley, Rensselaer Polytechnic Institute and Solidus Biosciences, Inc. of Troy, N.Y., cultures of skin cells in this so-called DataChip could be used to rapidly screen new chemicals for skin toxicity or irritability.

By adding other types of cells, such as lung or heart cells, and combining the DataChip with another biochip - the MetaChip - that the researchers created several years ago, cosmetics or chemical companies could also test whether chemicals are toxic to other organs, not just skin.

"The DataChip expands the capabilities of the MetaChip and enables it to test for toxic effects of chemicals and their metabolites throughout the body," said co-lead author Douglas S. Clark, UC Berkeley professor of chemical engineering and co-founder of Solidus Biosciences, the company that is working to commercialize the chips. "It is one step closer to a replacement for animals in evaluating product safety, as well as to a personalized system that can predict the toxicity of drugs in individual patients."

The MetaChip that was reported two years ago contains liver enzymes immobilized on a microscope slide. Liver enzymes can sometimes alter seemingly safe chemicals and make them toxic. The MetaChip mimicks this process, quickly metabolizing a chemical to produce compounds the liver itself would produce. The DataChip provides an equally fast way to determine the effect of these metabolites on cells.

For drug companies, the combination of the MetaChip and the DataChip offers a rapid way to predict whether a drug candidate or its metabolite is toxic. The chips will also enable chemical companies to comply with new legislation stipulating that chemicals undergo toxicity analysis.

"We looked at the issues facing companies and realized that we needed to develop something that was low-cost, high-throughput, easily automatable and did not involve animals" said co-lead author and Solidus Biosciences co-founder Jonathan S. Dordick, the Howard P. Isermann '42 Professor of Chemical and Biological Engineering at Rensselaer. "We developed the MetaChip and DataChip to deal with the two most important issues that need to be assessed when examining the toxicity of a compound - the effect on different cells in our body and how toxicity is altered when the compound is metabolized in our bodies."

The collaborative team sees the combined chips as an efficient, more accurate way to test drug compounds for toxicity earlier in the discovery process, before a lot of money has been invested in a drug candidate. However, according to Clark, pharmaceutical companies are only one potential user, and not necessarily the first.

"Obviously cosmetics need to be safe, and ensuring the safety of new compounds without testing them on animals presents a new challenge to the industry, especially as the number of compounds increases," said Clark. "These chips can meet this challenge by providing comprehensive toxicity data very quickly and cheaply."

Within the next 5 to 10 years, assuming the cost of sequencing all of a person's genes becomes generally affordable, people will be able to mine their personal genomes for information on the types and levels of liver enzymes that determine how they react to specific drugs and then reproduce this profile on a MetaChip to prescreen all drugs before they're administered to determine safe and effective doses.

human liver cells on new DataChip
Human liver cells are dotted across the new DataChip to quickly determine if various chemicals, drugs, and drug candidates are toxic. When coupled with the MetaChip, the two biochips could provide a highly predictive alternative to animal testing. (Moo-Yeal Lee/Rensselaer Polytechnic Institute)
The DataChip currently contains 1,080 human cell cultures arranged within a gel made of collagen or algae extract, approximating how cells are arranged in organs of the human body. For now, the DataChip establishes a drug's toxicity by whether it kills cells or inhibits their growth. Through fundamental research, however, Clark and Dordick hope to adapt this methodology to test for other biological responses, not just cell death.

"We have the fundamental platform and concept, and there is the potential to expand considerably beyond that to test for many different biological responses, such as allergic responses or binding of a chemical to a receptor to trigger a reaction," Clark said. "For personalized medicine, that is exactly what you'd want to do."

Dordick and Clark were joined in the research by Moo-Yeal Lee and Michael G. Hogg of Solidus Biosciences; R. Anand Kumar of UC Berkeley; and Sumitra M. Sukumaran of Rensselaer.

The research was funded by the National Institutes of Health and the New York State Office of Science and Technology (NYSTAR).

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