Stem cells and hydrogels

Discuss stem cells, adult and embryonic, and their therapeutic potential for MS here.

Stem cells and hydrogels

Postby dignan » Wed Mar 29, 2006 9:31 am

Not MS-specific, but looks like an important step in figuring out how to fix severly damaged spinal cords...



Jell-O Fix for Spinal Cords

By Elizabeth Svoboda - Mar 29, 2006 - Stem cells embedded in futuristic materials may heal decades-old spinal cord injuries and rescue patients from paralysis, if recent experiments in rodents can be replicated in humans.

Stem cells have cured many rats of spinal cord injuries, but the treatment has yet to benefit humans. When it does, most scientists say the first treatments will benefit only the newly injured.

But Pavla Jendelova, a biologist at the Institute of Experimental Medicine in Prague, Czech Republic, found that adding stem cells to spinal implants made of hydrogels -- jelly-like polymers consisting of latticed networks of amino acids -- could build a bridge in spinal cords even with older injuries, and help patients to regain function.

"In chronic spinal cord injuries, there's a large cavity that develops over time in the injured area," she said. "We want to see if the hydrogels can breach this gap."

Hydrogels resemble the soft tissue that surrounds a human spinal cord as it develops in the womb, Jendelova said. Neurons grow through pores in the material, creating a scaffold that supports delicate cells. The pores are also large enough to allow the transmission of chemical signals that orchestrate neural development.

Jendelova believes hydrogels' physical properties, which are similar to those of Jell-O, increase the likelihood that stem cells will integrate successfully with existing spinal tissue.

"An ideal matrix for neurons would be soft, chemically inert and would have a high water content like a sponge -- something that resembles the natural environment around developing neural tissue," she said. Made of up to 99 percent water, hydrogels come closer to meeting these criteria than any other artificial material.

The Institute of Experimental Medicine team induced spinal cord lesions in 28 rats by removing small sections of the cord or compressing spinal cord tissue. They then filled the spinal cavity around the injured area with blocks of hydrogel laced with stem cells from rat bone marrow.

Four weeks later, the scientists analyzed the treated areas and found that the stem cells had successfully built new spinal cord tissue with nerve fibers that grew through the gaps in the hydrogel's amino-acid lattice. "We observed significant growth of neural tissue into the hydrogels," Jendelova said. "There were neurofilaments, axons and connective tissue growing into the whole area of the lesion."

Not only did the rats show unprecedented neural regrowth, they also recovered much of the limb function they had lost when the researchers initially injured them. Jendelova presented her findings last month at the Cambridge Healthtech Institute's molecular medicine conference in San Francisco.

"If you create a physical architecture, cells will often follow it," said Erin Lavik, a biomedical engineer at Yale University who is developing hydrogels that can be used as matrices to build blood vessel networks. The technique could prove crucial in tissue and spinal cord repair procedures.

Scientists have also tried nanofibers as frameworks for stem cell growth, Lavik said, but because they are engineered to be strong and tough, they are less flexible and don't readily mold to a lesion.

The nervous system is not a particularly hospitable environment for nerve regeneration to begin with, said Itzhak Fischer, a molecular neurobiologist at Drexel University who specializes in spinal cord repair. "But if you can insert a scaffold that directs neural cells exactly where you want them, you're going to have a much better result," Fischer said.

For several years, Fischer has been investigating which hydrogel formulations best facilitate neural tissue growth. He is currently experimenting with "permissive peptides" -- protein strands attached to the gel's surface that attract newly developing nerve fibers.

In late 2004, Fischer and his colleagues implanted hydrogels drenched with a growth-factor compound similar to that secreted by stem cells into the severed spinal cords of 24 adult rats. The rats grew new, mature neurons, which are necessary for spinal cord development.

Despite his and Jendelova's early success, Fischer foresees future roadblocks. "It's tricky to make stem cells compatible with the nervous system environment," he said. Even if a hydrogel scaffold works beautifully, the body's immune system still might reject the foreign cells.

Like Fischer, Jendelova is cautious -- she estimates gel-based spinal cord repair clinical trials will begin within the next five years, but it's too soon to predict whether the treatment will translate into humans.

"The problem with transferring results from rodents to humans is that there are so many size differences," she said. "The hydrogels may be fine for a rat's small spinal cord, but we can't say whether they will work as well in a human one, which is more than 10 times thicker." Recently, however, she conducted hydrogel experiments in five pigs with injured spinal cords. The results suggest the gel implants may scale up better than she expected.

Several other stem cell-based techniques have cured rats of paralysis, but scientists have yet to try the techniques in humans. Hans Keirstead, an assistant professor of anatomy and neurobiology at the Reeve-Irvine Research Center, is one of them. His work is funded by Geron, and the company's chief scientific officer, Tom Okarma, said his scientists could begin human clinical trials using Keirstead's technique in 2007 -- but the first study will focus on newly injured patients.

Evan Snyder has also restored movement to previously paralyzed rats using a stem cell therapy.

Ultimately, according to Aileen Anderson, a neurobiologist at the University of California at Irvine, hydrogels could emerge as front-runners among the many stem cell-based spinal cord repair strategies being developed.

"There have certainly been experiments showing that you don't have to have a hydrogel scaffold to achieve some spinal cord regeneration," she said. "But they might be really useful in certain situations -- especially in injuries where the spinal cord is completely cut in two, and the scaffold forms a bridge between the sections."

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