Simple chemical procedure augments therapeutic potential of stem cells

Oct 31, 2008

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 Jeffrey 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 Robert 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."

Source: Harvard Medical School

Explore further: Oat breakfast cereals may contain a common mold-related toxin

add to favorites email to friend print save as pdf

Related Stories

Engineers put the 'squeeze' on human stem cells

Feb 10, 2015

After using optical tweezers to squeeze a tiny bead attached to the outside of a human stem cell, researchers now know how mechanical forces can trigger a key signaling pathway in the cells.

Nano-antioxidants prove their potential

Feb 09, 2015

Injectable nanoparticles that could protect an injured person from further damage due to oxidative stress have proven to be astoundingly effective in tests to study their mechanism.

Recommended for you

The construction of ordered nanostructures from benzene

2 hours ago

A way to link benzene rings together in a highly ordered three-dimensional helical structure using a straightforward polymerization procedure has been discovered by researchers from RIKEN Center for Sustainable ...

Superatomic nickel core and unusual molecular reactivity

2 hours ago

A superatom is a combination of two or more atoms that form a stable structural fragment and possess unique physical and chemical properties. Systems, that contain superatoms, open a number of amazing possibilities ...

Oat breakfast cereals may contain a common mold-related toxin

Feb 25, 2015

Oats are often touted for boosting heart health, but scientists warn that the grain and its products might need closer monitoring for potential mold contamination. They report in ACS' Journal of Agricultural and Food Chemistry that s ...

NETL invents improved oxygen carriers

Feb 24, 2015

One of the keys to the successful deployment of chemical looping technologies is the development of affordable, high performance oxygen carriers. One potential solution is the naturally-occurring iron oxide, ...

User comments : 1

Adjust slider to filter visible comments by rank

Display comments: newest first

NeilFarbstein
1 / 5 (1) Oct 31, 2008
If your apparatus suffers from leaks or if toxic fumes are escaping reagent bottles in your lab.. Get Suction funnel adhesive. Its' new and it works when funnel collars and rubber stoppers dont. http://www.prlog....5443.pdf

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.