System Bits: Sept. 30

Scientists at Harvard have created a tissue-level model of the human airway musculature that could lead to development of patient-specific asthma treatments; Purdue University researchers have developed a chip capable of simulating a tumor’s “microenvironment” as part of a system to test the effectiveness of nanoparticles and drugs that target cancer.

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Airway muscle-on-a-chip mimics asthma
A Harvard University research team has developed a human airway muscle-on-a-chip that could be used to test new drugs as it accurately mimics the way smooth muscle contracts in the human airway, under normal circumstances and when exposed to asthma triggers.

The chip also gives a window into the cellular and even subcellular responses within the tissue during an asthmatic event.

The chip is a soft polymer well that is mounted on a glass substrate and contains a planar array of microscale, engineered human airway muscles, designed to mimic the laminar structure of the muscular layers of the human airway.

To mimic a typical allergic asthma response, the team first introduces a natural protein often found in the airway of asthmatic patients that mediates the response of smooth muscle to an allergen. Then they introduced a neurotransmitter that causes smooth muscle to contract. As such, the airway muscle on the chip hypercontracted—and the soft chip curled up—in response to higher doses of the neurotransmitter.

They achieved the reverse effect as well and triggered the muscle to relax using drugs called β-agonists, which are used in inhalers.

Interestingly, they were able to measure the contractile stress of the muscle tissue as it responded to varying doses of the drugs, which means the chip gives a simple, reliable and direct way to measure human responses to an asthma trigger.

The researchers mimicked an asthmatic airway on their airway muscle-on-a-chip by first introducing Interleukin-13 (IL-13), a natural protein often found in the airway of asthmatic patients. Then they used a neurotransmitter called acetylcholine to trigger the smooth muscle to hypercontract, and a bronchodilator used in inhalers called a β-agonist to elicit muscle relaxation. (Source: Wyss Institute and Harvard SEAS)

The researchers mimicked an asthmatic airway on their airway muscle-on-a-chip by first introducing Interleukin-13 (IL-13), a natural protein often found in the airway of asthmatic patients. Then they used a neurotransmitter called acetylcholine to trigger the smooth muscle to hypercontract, and a bronchodilator used in inhalers called a β-agonist to elicit muscle relaxation. (Source: Wyss Institute and Harvard SEAS)

Tumor-targeting chip
Also in the medical space, Purdue University researchers have developed a chip capable of simulating a tumor’s “microenvironment” as part of a system to test the effectiveness of nanoparticles and drugs that target cancer.
http://www.purdue.edu/newsroom/releases/2014/Q3/new-chip-promising-for-tumor-targeting-research.html

The system is called a tumor-microenvironment-on-chip (T-MOC) device and allows researchers to study the complex environment surrounding tumors and the barriers that prevent the targeted delivery of therapeutic agents.

Researchers are trying to perfect “targeted delivery” methods using various agents, including an assortment of tiny nanometer-size structures, to selectively attack tumor tissue, the researcher said. One approach is to design nanoparticles small enough to pass through pores in blood vessels surrounding tumors but too large to pass though the pores of vessels in healthy tissue. The endothelial cells that make up healthy blood vessels are well organized and have small pores in the tight junctions between them. However, the endothelial cells in blood vessels around tumors are irregular and misshapen, with larger pores in the gaps between the cells. It was thought that if nanoparticles were designed to be the right size they could selectively move toward only the tumor.

The researchers believe the T-MOC system is capable of simulating the complex environment around tumors and providing detailed information about how nanoparticles move through this environment and that such information could aid efforts to perfect targeted delivery methods.

The T-MOC chip is about 4.5 centimeters (1.8 inches) square and contains “microfluidic” channels where tumor cells and endothelial cells are cultured. The chip also incorporates extracellular matrix – a spongy, scaffold-like material made of collagen found between cells in living tissue.

The new chip offers an alternative to conventional experimental methods. Studies using cancer cells in petri plates exclude the complex microenvironment surrounding tumors, and research with animals does not show precisely how proposed therapies might work in people. But the T-MOC system has the potential to mimic cancer in humans and the technology has been tested using human breast cancer and endothelial cells.

Future work will expand to the study of anticancer drugs. Eventually, the devices might be used to grow tumor cells from patients to gauge the effectiveness of specific drugs in those people.

This illustration shows the design of a new chip capable of simulating a tumor's "microenvironment" to test the effectiveness of nanoparticles and drugs that target cancer. The new system, called a tumor-microenvironment-on-chip device, will allow researchers to study the complex environment surrounding tumors and the barriers that prevent the targeted delivery of therapeutic agents.  (Source: Purdue University)

This illustration shows the design of a new chip capable of simulating a tumor’s “microenvironment” to test the effectiveness of nanoparticles and drugs that target cancer. The new system, called a tumor-microenvironment-on-chip device, will allow researchers to study the complex environment surrounding tumors and the barriers that prevent the targeted delivery of therapeutic agents. (Source: Purdue University)