Researchers reverse some lung diseases in mice by coaxing production of healthy cells

January 30, 2014
Using a novel 3D culture method, Kim and colleagues were able to prod bronchioalveolar stem cells to produce colonies containing airway (bronchiolar) epithelial cells, alveolar epithelial cells or both cell types. Credit: Joo-hyeon Lee, Boston Children's Hospital

It may be possible one day to treat several lung diseases by introducing proteins that direct lung stem cells to grow the specific cell types needed to repair the lung injuries involved in the conditions, according to new research at Boston Children's Hospital.

Reporting in the January 30th issue of Cell, researchers led by Carla Kim, PhD, and Joo-Hyeon Lee, PhD, of the Stem Cell Research Program at Boston Children's, describe a new pathway in the lung, activated by injury, that directs to transform into specific types of cells. By enhancing this natural pathway in a mouse model, they successfully increased production of alveolar epithelial cells, which line the small sacs (alveoli) where gas exchange takes place. These cells are irreversibly damaged in diseases like pulmonary fibrosis and emphysema.

By inhibiting the same pathway, the researchers ramped up production of airway epithelial cells, which become damaged in diseases affecting the lung's airways, such as asthma and bronchiolitis obliterans.

Using a novel 3D culture model that mimics the environment of the lung, the researchers showed that even a single lung stem cell could be coaxed into producing alveolar and bronchiolar . By adding a protein known as thrombospondin-1 (TSP-1) to these cultures, they prodded the stem cells to generate alveolar cells.

Kim and Lee conducted experiments using a live mouse model of fibrosis. By simply taking the endothelial cells that line the lung's many small blood vessels—which naturally produce TSP-1—and directly injecting the liquid surrounding the into the mice, they were able to reverse the lung damage.

Conversely, when the team used lung endothelial cells that lacked TSP-1 in the 3D cultures, the stem cells produced more . In live mice engineered to lack TSP-1, airway repair was enhanced after injury.

"When are injured, there seems to be a cross talk between the damaged cells, the lung endothelial cells and the stem cells," says Lee, who is first author on the paper.

"We think that lung endothelial produce a lot of repair factors besides TSP-1," adds Kim, the paper's senior author. "We want to find all these molecules, which could provide additional therapeutic targets."

Explore further: US researchers identify first human lung stem cell

Related Stories

US researchers identify first human lung stem cell

May 11, 2011

For the first time, researchers at Brigham and Women's Hospital (BWH) have identified a human lung stem cell that is self-renewing and capable of forming and integrating multiple biological structures of the lung including ...

Stem cells, signaling pathways identified in lung repair

October 11, 2011

(Medical Xpress) -- Researchers at National Jewish Health have identified cells and signaling molecules that trigger the repair of injured lungs. Stijn De Langhe, PhD, and his colleagues report October 10, 2011, online in ...

Tracking nanodiamond-tagged stem cells

August 5, 2013

A method that is used to track the fate of a single stem cell within mouse lung tissue is reported in a study published online this week in Nature Nanotechnology. The method may offer insights into the factors that determine ...

Recommended for you

We've all got a blind spot, but it can be shrunk

August 31, 2015

You've probably never noticed, but the human eye includes an unavoidable blind spot. That's because the optic nerve that sends visual signals to the brain must pass through the retina, which creates a hole in that light-sensitive ...

Biologists identify mechanisms of embryonic wound repair

August 31, 2015

It's like something out of a science-fiction movie - time-lapse photography showing how wounds in embryos of fruit flies heal themselves. The images are not only real; they shed light on ways to improve wound recovery in ...

New 'Tissue Velcro' could help repair damaged hearts

August 28, 2015

Engineers at the University of Toronto just made assembling functional heart tissue as easy as fastening your shoes. The team has created a biocompatible scaffold that allows sheets of beating heart cells to snap together ...

Research identifies protein that regulates body clock

August 26, 2015

New research into circadian rhythms by researchers at the University of Toronto Mississauga shows that the GRK2 protein plays a major role in regulating the body's internal clock and points the way to remedies for jet lag ...

Fertilization discovery: Do sperm wield tiny harpoons?

August 26, 2015

Could the sperm harpoon the egg to facilitate fertilization? That's the intriguing possibility raised by the University of Virginia School of Medicine's discovery that a protein within the head of the sperm forms spiky filaments, ...

0 comments

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.