Featured Research

from universities, journals, and other organizations

Signal gradients in 3-D guide stem cell behavior

Date:
September 18, 2013
Source:
Case Western Reserve University
Summary:
Researchers have developed an easy and versatile way of forming physical and biochemical gradients in three dimensions -- a step toward identifying the recipes that induce stem cells to generate specific tissues, including multiple tissues, such as a bone-cartilage interface. Ultimately, one of their goals is to engineer systems to manipulate stem cells to repair or replace damaged tissues and organs.

Scientists know that physical and biochemical signals can guide cells to make, for example, muscle, blood vessels or bone. But the exact recipes to produce the desired tissues have proved elusive.

Now, researchers at Case Western Reserve University have taken a step toward identifying that mix by developing an easy and versatile way of forming physical and biochemical gradients in three dimensions.

Ultimately, one of their goals is to engineer systems to manipulate stem cells to repair or replace damaged tissues and organs.

"If we can control the spatial presentation of signals, we may be able to have more control over cell behavior and enhance the rate and quality of tissue formation," said Eben Alsberg, an associate professor of biomedical engineering and orthopaedic surgery at Case Western Reserve and senior author of the research. "Many tissues form during development and healing processes at least in part due to gradients of signals: gradients of growth factors, gradients of physical triggers."

Alsberg, postdoctoral scholar Oju Jeon and graduate student Daniel S. Alt of Case Western Reserve, and Stephen W. Linderman, a visiting undergraduate on a National Science Foundation Research Experience for Undergraduates summer fellowship, tested their system on mesenchymal stem cells, turning them toward bone or cartilage cells. They report their findings in Advanced Materials.

Regulating the presentation of certain signals in three-dimensional space may be a key to engineering complex tissues, such as repairing osteochondral defects, damaged cartilage and bone in osteoarthritic joints, Alsberg said.

"There must be a transition from bone to cartilage," he said, "and that may require control over multiple signals to induce the stem cells to change into the different kinds of cells to form tissues where you need them."

In their first test, the researchers found that stem cells changed into cartilage or bone cells in the directions of two opposing soluble growth factor gradients: one that promotes cartilage, called TGF-beta 1, and another that promotes bone, called BMP-2. The stem cells were placed in a solution of modified alginate, a material derived from seaweed that can form a jello-like material called a hydrogel when exposed to low level ultraviolet light.

The solution was divided between two computer-controlled syringe pumps, with BMP-2 in one syringe and TGF-beta 1 in the other. By controlling the rate of injection with the pumps and using a mixing unit, a hydrogel with a BMP-2 gradient starting with a large amount and tapering to nearly none and an opposing TGF-beta 1 gradient from low-to-high was formed.

The hydrogels were further modified in such a way that the growth factors were retained for a longer period of time. This enabled prolonged exposure of stem cells to the growth factors and further control over their differentiation into bone or cartilage cells.

The researchers then modified the hydrogel with a gradient of adhesion ligands, molecular strings that allow the stem cells to attach to the hydrogel itself. After two weeks of culturing the cells, they found the highest number of cells in the hydrogel region where the concentration of ligands was highest.

In a third test, they created a gradient of crosslink density within the hydrogels. Crosslinks provide structure to the gels. The lower the density, the more flexible the hydrogel; the higher, the stiffer the gel. After two weeks, more cells were found in the most flexible gel regions within the gradient. The flexibility may allow for more free movement of nutrients and removal of waste products, Alsberg explained.

"This is exciting," Alsberg said. "We can look at this work as a proof of principle. Using this approach, you can use any growth factor or any adhesion ligand that influences cell behavior and study the role of gradient presentation. We can also examine multiple different parameters in one system to investigate the role of these gradients in combination on cell behavior."

If the technology enables them to unravel recipes that generate complex tissues, the biodegradable hydrogel mix could be implanted or injected at the site of an injury, the researchers say. The recipe would guide cell behavior until new tissue is formed, restoring function.


Story Source:

The above story is based on materials provided by Case Western Reserve University. Note: Materials may be edited for content and length.


Journal Reference:

  1. Oju Jeon, Daniel S. Alt, Stephen W. Linderman, Eben Alsberg. Biochemical and Physical Signal Gradients in Hydrogels to Control Stem Cell Behavior. Advanced Materials, 2013; DOI: 10.1002/adma.201302364

Cite This Page:

Case Western Reserve University. "Signal gradients in 3-D guide stem cell behavior." ScienceDaily. ScienceDaily, 18 September 2013. <www.sciencedaily.com/releases/2013/09/130918101954.htm>.
Case Western Reserve University. (2013, September 18). Signal gradients in 3-D guide stem cell behavior. ScienceDaily. Retrieved July 23, 2014 from www.sciencedaily.com/releases/2013/09/130918101954.htm
Case Western Reserve University. "Signal gradients in 3-D guide stem cell behavior." ScienceDaily. www.sciencedaily.com/releases/2013/09/130918101954.htm (accessed July 23, 2014).

Share This




More Health & Medicine News

Wednesday, July 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Courts Conflicted Over Healthcare Law

Courts Conflicted Over Healthcare Law

AP (July 22, 2014) Two federal appeals courts issued conflicting rulings Tuesday on the legality of the federally-run healthcare exchange that operates in 36 states. (July 22) Video provided by AP
Powered by NewsLook.com
Why Do People Believe We Only Use 10 Percent Of Our Brains?

Why Do People Believe We Only Use 10 Percent Of Our Brains?

Newsy (July 22, 2014) The new sci-fi thriller "Lucy" is making people question whether we really use all our brainpower. But, as scientists have insisted for years, we do. Video provided by Newsy
Powered by NewsLook.com
Scientists Find New Way To Make Human Platelets

Scientists Find New Way To Make Human Platelets

Newsy (July 22, 2014) Boston scientists have discovered a new way to create fully functioning human platelets using a bioreactor and human stem cells. Video provided by Newsy
Powered by NewsLook.com
Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

TheStreet (July 21, 2014) New research shows Gilead Science's drug Sovaldi helps in curing hepatitis C in those who suffer from HIV. In a medical study, the combination of Gilead's Hep C drug with anti-viral drug Ribavirin cured 76% of HIV-positive patients suffering from the most common hepatitis C strain. Hepatitis C and related complications have been a top cause of death in HIV-positive patients. Typical medication used to treat the disease, including interferon proteins, tended to react badly with HIV drugs. However, Sovaldi's %1,000-a-pill price tag could limit the number of patients able to access the treatment. TheStreet's Keris Lahiff reports from New York. Video provided by TheStreet
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins