Discovery that migrating cells 'turn right' has implications for engineering tissues, organs

February 17, 2012

What if we could engineer a liver or kidney from a patient's own stem cells? How about helping regenerate tissue damaged by diseases such as osteoporosis and arthritis? A new UCLA study bring scientists a little closer to these possibilities by providing a better understanding how tissue is formed and organized in the body.

A UCLA research team discovered that migrating cells prefer to turn right when encountering changes in their environment. The researchers were then able to translate what was happening in the cells to recreate this left–right asymmetry on a level. Such asymmetry is important in creating differences between the right and left sides of structures like the brain and the hand.

The research, a collaboration between the David Geffen School of Medicine at UCLA and the Center for Cell Control at UCLA's Henry Samueli School of Engineering and Applied Science, appears in the Feb. 17 issue of the journal Circulation Research.

"Our findings suggest a mechanism and design principle for the engineering of tissue," said senior author Dr. Linda L. Demer, a professor of medicine, physiology and bioengineering and executive vice chair of the department of medicine at the Geffen School of Medicine. "Tissue and organs are not simply collections of cells but require careful architecture and design to function normally. Our findings help explain how cells can distinguish and develop highly specific left–right asymmetry, which is an important foundation in tissue and organ creation."

Using microtechnology, the team engineered a culture surface in the lab with alternating strips of protein substrates that were cell-adhesive or cell-repellent, analogous to a floor with narrow horizontal stripes of alternating carpet and tile. Cells may encounter such surface changes when they travel through the body.

The researchers observed that as the migrating cells crossed the interface between "carpet" and "tile" sections, they exhibited a significant tendency to turn right by 20 degrees, and, like a marching band, lined up in long, parallel rows, producing diagonal stripes over the entire surface.

"We had been noticing how these vascular cells would spontaneously form structures in cultures and wanted to study the process," said first author Ting-Hsuan Chen, a graduate student researcher in the department of mechanical and aerospace engineering at UCLA Engineering. "We had no idea our substrates would trigger the left–right asymmetry that we observed in the cells. It was completely unexpected.

"We found that cells demonstrated the ability to distinguish right from left and to self-organize in response to mechanical changes in the surfaces that they encounter. This provides insight into how to communicate with cells in their language and how to begin to instruct them to produce tissue-like architecture."

According to the researchers, the cells can sense the substrates beneath them, and this influences the direction of their migration and what shapes they form in the body. Of most interest, the researchers said, was the fact that the cells responded to the horizontal stripes by reorganizing themselves into diagonal stripes.

The team hopes to harness this phenomenon to use substrate interfaces to communicate with cells and instruct them to produce desired tissue structures for replacement. By adjusting the substrates, the researchers say, they have the potential to guide what structures the cells and tissue form.

The next stage of the research will be to control and guide cells to self-organize into two-dimensional and, eventually, three-dimensional patterns chosen by the researchers.

According to the research team, this is one of the first studies to demonstrate that encountering a change in substrate can trigger a cell's preference for turning left or right. It is also one of the first studies showing that can integrate left–right asymmetry into a patterned structure of parallel diagonal stripes resembling tissue architecture.

"Applications for this research may help in future engineering of organs from a patient's own ," Demer said. "This would be especially important given the limited supply of donor organs for transplant and problems with immune rejection."

Explore further: Extracting stem cells from fat for tissue regeneration

Related Stories

Extracting stem cells from fat for tissue regeneration

May 3, 2011
Stem cells extracted from body fat may pave the way for the development of new regenerative therapies including soft tissue reconstruction following tumor removal or breast mastectomy surgery, the development of tissue-engineered ...

Adult stem cells use special pathways to repair damaged muscle (w/ Video)

December 1, 2011
When a muscle is damaged, dormant adult stem cells called satellite cells are signaled to "wake up" and contribute to repairing the muscle. University of Missouri researchers recently found how even distant satellite cells ...

Expression of pluripotency-associated gene marks many types of adult stem cells

October 6, 2011
Investigators at the Massachusetts General Hospital (MGH) Center for Regenerative Medicine and the Harvard Stem Cell Institute (HSCI) have found that Sox2 – one of the transcription factors used in the conversion of ...

Recommended for you

Prototype equipment can detect rheumatoid arthritis

September 28, 2017
According to a first clinical study published in the scientific journal Photoacoustics, the University of Twente and various European partners have designed a device that shows the difference between healthy fingers and arthritic ...

Improving the recognition of anxiety and depression in rheumatoid arthritis

August 28, 2017
A study conducted by Keele University shows that patients with rheumatoid arthritis who are also suffering with anxiety or depression may avoid talking to their GP about their mental health symptoms.

How you think about your arthritis makes a difference

August 24, 2017
(HealthDay)—How well you cope with knee arthritis depends a lot on your mental outlook, a new study suggests.

Treating arthritis with algae

August 23, 2017
Researchers at ETH Zurich, Empa and the Norwegian research institute SINTEF are pursuing a new approach to treating arthritis. This is based on a polysaccharide, a long-chain sugar molecule, originating from brown algae. ...

Study shows prevalence of knee osteoarthritis has doubled since World War II

August 14, 2017
The average American today is twice as likely to be diagnosed with knee osteoarthritis than in the years before World War II, Harvard scientists say, but that increase can't be blamed on the reasons most might think.

Researchers find arthritis drug could treat blood cancer patients

August 3, 2017
Blood cancer sufferers could be treated with a simple arthritis drug, scientists at the University of Sheffield have discovered.

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

210
not rated yet Feb 18, 2012
"Tissue design"...like...'DESIGN' design?
"Tissue and organs are not simply collections of cells but require careful architecture and design to function normally. Our findings help explain how cells can distinguish and develop highly specific leftright asymmetry, which is an important foundation in tissue and organ creation."Biological structures are simply astounding! Life is so complex and yet obeys, as in this case, simple traffic, texture, and geometric, cues...who would have thunk it! Impressive....

word-to-ya-muthas

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.