Simple Chemical Procedure Augments Therapeutic Potential Of Stem Cells

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Simple Chemical Procedure Augments Therapeutic Potential Of Stem Cells

http://medicalnewscenter.com/out/out.cgi?

http://www.sciencedaily.com/releases/2008/10/081031102049.htm

Adult stem cells resemble couch potatoes if they hang out and divide

in a dish for too long. They get fat and lose key surface proteins,

which interferes with their movement and reduces their therapeutic

potential. Now, via a simple chemical procedure, researchers have

found a way to get these cells off the couch and over to their

therapeutic target.

To do this, they simply added a molecule called SLeX to the surface

of the cells. The procedure took just 45 minutes and restored an

important biological function.

" Delivery remains one of the biggest hurdles to stem cell therapy, "

explains senior author Karp, an instructor at the Harvard-MIT

Division of Health Sciences and Technology. " The blood stream offers

a natural delivery vehicle, but stem cells don't move through blood

vessels normally after being expanded in culture. Our procedure

promises to overcome this obstacle. "

These findings will be published online in the journal Bioconjugate

Chemistry on Oct. 31.

In order for cells injected into the blood stream to be

therapeutically useful, they need to take initiative to reach target

tissues. But instead, cultured stem cells go with the flow. They move

through the body quickly, carried by the current, which means they

seldom contact the sides of blood vessels. Thus, they have fewer

opportunities to escape into the surrounding tissue by squeezing

between cells of the vessel wall. Adult stem cells must escape before

they can colonize surrounding tissue and rebuild damaged structures.

In February of 2008, HMS associate professor Sackstein (at

Brigham and Women's Hospital) and colleagues showed they could

correct this problem by adding a particular molecule to the surface

of adult stem cells. This molecule—a cousin of SLeX—formed temporary

connections with proteins on the blood vessel wall, serving as a kind

of weak tape. But Sackstein's method involved enzymes, which made the

chemistry complicated. Karp's team achieved the same result without

enzymes.

Karp lab postdoc Debanjan Sarkar simply flooded a dish of cells with

three molecules—biotin, streptavidin, and SLeX—one after the other.

The biotin and streptavidin anchored SLeX to the cell surface. Sarkar

tweaked the concentrations of each molecule to maximize the cell's

ability to roll along the interior of the blood vessel, rather than

getting lost in the flow. He also confirmed that the altered cells

were still viable.

" The method is very simple, " says Sarkar, who is first author on the

paper. " Plus, biotin and streptavidin work with many molecules, so

labs can use this universal anchor we discovered to tackle other

problems. They're not limited to sticking SLeX on cells. "

The team worked with human cells extracted from the bone marrow. The

cultures included mesenchymal stem cells (MSCs), which can form fat

cells, cartilage, bone, tendon and ligaments, muscle cells, and even

nerve cells. When injected into the bloodstream of patients, MSCs can

home to the site of an injury and replace damaged tissue. But just a

fraction of cultured MSCs currently reach their target in clinical

trials. Karp's procedure might improve their homing abilities.

Karp cautions that his lab's discovery must be validated in animals,

before doctors can apply it in the clinic. He's collaborating with

another lab to test the homing ability of the SLeX-dotted cells in

mice.

" We need to confirm that this rolling behavior translates into

increased homing and tissue repair, " explains Karp. " We may need to

tweak the cells further. "

" This is definitely an approach that should be tried, " adds Pamela

Robey, chief of the Craniofacial and Skeletal Diseases Branch of the

National Institute of Dental and Craniofacial Research. Robey is

working to reconstruct three-dimensional tissues with MSCs. " Jeff

hasn't tested the altered MSCs inside animals, and that's really the

gold-standard, but his in vitro data looks promising. "

This research is supported by Brigham and Women's Hospital.