Stem cell-based gut-on-a-chip: a new path to personalized medicine

“Personalized medicine” is a trendy phrase these days, frequently used in TV ads for hospitals, newspaper articles about medicine’s future and even here in the Stem Cellar. The basic gist is that by analyzing a patient’s unique biology, a physician can use disease treatments that are most likely to work in that individual.

RMI163285_webcrop

Emulate’s Organ-on-a-Chip device.
Image: Emulate, Inc.

This concept is pretty straight-forward but it’s not always clear to me how it would play out as a routine clinical service for patients. A recent publication in Cellular and Molecular Gastroenterology and Hepatology by scientists at Cedars-Sinai and Emulate, Inc. paints a clearer picture. The report describes a device, Emulate’s Intestine-Chip, that aims to personalize drug treatments for people suffering from gastrointestinal diseases like inflammatory bowel disease and Chrohn’s disease.

Intestine-Chip combines the cutting-edge technologies of induced pluripotent stem cells (iPSCs) and microfluidic engineering. For the iPSC part of the equation, skin or blood samples are collected from a patient and reprogrammed into stem cells that can mature into almost any cell type in the body. Grown under the right conditions in a lab dish, the iPSCs self-organize into 3D intestinal organoids, structures made up of a few thousand cells with many of the hallmarks of a bona fide intestine.

RMI HOI

Miniature versions of a human intestinal lining, known as organoids, derived from induced pluripotent stem cells (iPSCs).
Image: Cedars-Sinai Board of Governors Regenerative Medicine Institute

These iPSC-derived organoids have been described in previous studies and represent a breakthrough for studying human intestinal diseases. Yet, they vary a lot in shape and size, making it difficult to capture consistent results. And because the intestinal organoids form into hollow tubes, it’s a challenge to get drugs inside the organoid, a necessary step to systematically test the effects of various drugs on the intestine.

The Intestine-Chip remedies these drawbacks. About the size of a double A battery, the Chip is made up of specialized plastic engineered with tiny tunnels, or micro-channels. The research team placed the iPSC-derived intestinal organoid cells into the micro-channels and showed that passing fluids with a defined set of ingredients through the device can prod the cells to mimic the human intestine.

RMI IntestinalChip

Cells of a human intestinal lining, after being placed in an Intestine-Chip, form intestinal folds as they do in the human body. Image: Cedars-Sinai Board of Governors Regenerative Medicine Institute

The Intestine-Chip not only looks like a human intestine but acts like one too. A protein known to be at high levels in inflammatory bowel disease was passed through the microchannel and the impact on the intestinal cells matched what is seen in patients. Clive Svendsen, Ph.D., a co-author on the study and director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute, explained the exciting applications that the Intestine-Chip opens up for patients:

Svendsen

Clive Svendsen

“This pairing of biology and engineering allows us to re-create an intestinal lining that matches that of a patient with a specific intestinal disease—without performing invasive surgery to obtain a tissue sample,” he said in a press release. “We can produce an unlimited number of copies of this tissue and use them to evaluate potential therapies. This is an important advance in personalized medicine.”

Emulate’s sights are not just set on the human intestine but for the many other organs affected by disease. And because disease rarely impacts only one organ, a series of Organs-on-Chips for a particular patient could be examined together. Geraldine A. Hamilton, Ph.D., president and chief scientific officer of Emulate, Inc. summed up this point in a companion press release:

EMULATE_GERALDINE_HAMILTON_5_1024X1024-RGB-800x800

Geraldine Hamilton

“By creating a personalized Patient-on-a-Chip, we can really begin to understand how diseases, medicines, chemicals and foods affect an individual’s health.”

 

 

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google+ photo

You are commenting using your Google+ account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

w

Connecting to %s