Better Cell Culture System

http://www.hhmi.org/news/anseth20090402.html

by Kristi S. Anseth

Howard Hughes Medical Institute-HHMI researchers have created a new type of "intelligent scaffold" for growing human cells that mimics conditions inside the body better than the standard, flat petri dishes often used in laboratories.

Anseth's team constructed their scaffold from hydrogels, which are polymer based compounds that absorb water. The scientists built the hydrogel using a light sensitive molecule that permitted them to snip apart the scaffolding with the flick of a laser beam.  They can use laser to alter 

1. the gel's stiffness, 
2. sculpt out chambers and channels 
3. release signaling molecules inside the gel matrix
   

The researchers have already used their light sensitive hydrogels to study the  behavior of cancer cells and cartilage forming stem cells. These hydrogels are useful for studying cell behavior because they mimic the natural environment in the body better than flat petri dishes. 

• for example, cancer cells migrate very differently when they are  on a two dimensional surface than in three dimensions.
• Ansth and her colleagues incorporated nitrobenzyl ether, a molecule that can be cleaved with wavelengths of light that do not damage cells. 
• Attaching this molecule was a critical step, because it gave the scientists the ability to remodel the hydrogel  even after cells had begun growing in it.
  
• Also it responds in seconds to minutes which enables us to alter that microenvironment on the same time scale as cellular events.
• In one experiment, researchers embedded mesenchymal stem cells- immature cells that can differenctiate into bond, cartilage, fat, muscle and pancreatic cells in the hydrogel. The msesenchymal cells were compact and round when packed inside the hydrogel. But when the researchers used light to partially degrade the gel structure- making it more pliable the cells quickly spread into a new shape.
• This experiment showed that we have the ability to control the local structure of the gel surrounding the cell
• Imagine, then , that we could use focused light to selectively degrade the material between two cells and then study their interaction.
• In another set of experiments the researchers selectively eroded material around living cells to "herd" cells within the gel without affecting their viability. Cell migration is of major interest to cancer researchers and team used fibrosarcoma cells which cause tumors of connective tissue .
• They also demonstrated that they could control biochemical signaling inside the hydrogel.They used the photodegradable molecule to tether a short sequence of amino acids to polymer. That sequence promotes the survival of mesenchymal stem cells but it also inhibits them from differentiating into the more specialized cartilage forming cells- Chondrocytes. Anseth's team wanted to see what would happen to the cells if they suddenly lost that signal , so after the cells had grown in the hydrogel for ten days, they released the amino acid sequence with a laser beam. The biochemical signal rapidly diffused out of the hydrogel and mesenchymal stem cells were able to differentiate into chondrocytes.
• This make hydrogel a powerful tool for designing vehicles for drug delivery and engineering new tissues in the laboratory.