Five years closer to a cure
W.M. Keck Center celebrates its fifth anniversary
Archived article from Oct 7, 2002
By Joseph Blumberg
Page 2 of 3
Grumet and his co-workers are studying all aspects of these stem cells, from their molecular makeup to their behavior in the body. He expects to work out the principles behind their structure and function, and then use them as tools in spinal cord injury repair.
On yet another front, Grumet is looking at why cells are dying in and around a spinal cord injury. "Many therapies are geared to taking stem cells or other kinds of cells and transplanting them into an injured cord to make the nerves regenerate," he explains. "But it won't do any good to introduce these cells if something in the injury's immediate environment is killing them."
In the lab, Grumet has taken extracts from injured cords and demonstrated that these kill cells, while extracts from normal cords do not. "We have just started down the path to define the factors that are doing the killing. Once we know what they are, we think we can control them and thereby help the transplanted cells survive to participate in the healing process," he says.
Ron Hart
"Depending on what's going on and where, inflammation can be a good thing," says Professor Ron Hart, a 17-year Rutgers–Newark veteran. Hart's move to the Keck Center is facilitating his collaborations with Wise Young, including a project on inflammatory responses to spinal cord injury.
When you hit your thumb with a hammer, you get inflammation. It turns red, hurts and swells up in a process that leads to healing. Damaged cells and tissue are then replaced by fresh tissue.
Inflammation in the spinal cord, however, is more problematic. Since it is enclosed in the spinal column, the spinal cord has nowhere to expand when it swells up. The bone around it chokes off the blood supply and the injury gets worse. "Some inflammatory response can create a better environment for regeneration," says Hart, "but too much inflammation can just cause more damage. It is a very, very fine line to walk."
Hart is investigating various mechanisms that trigger inflammation when the spinal cord is injured and testing drugs that might inhibit these mechanisms. Methylprednisolone, the best drug in use for treating spinal cord injury and the one whose use Young has advocated, is one such anti-inflammatory. Hart is comparing this drug with other anti-inflammatory treatments to identify the ways in which they may act to help preserve spinal cord function.
Hart is also concerned with how genes trigger cell regeneration. Why is it, he wonders, that the genes trigger some cells to grow back and reconnect but not those related to the spinal cord? "This may be due in part to what genes are available and whether they are being expressed after spinal cord injury rather than in peripheral nerve injury," he suggests.
Hart and his collaborators needed a tool to help them discover which genes are involved in spinal cord injury responses. This, they note, is a first step toward designing drugs that specifically stimulate the appropriate genes.
The tool Hart created is a special gene chip or microarray, essentially a glass microscope slide that, in this case, is robotically spotted with 5,000 genes. This tool can be used to measure expression from the 5,000 different genes at once in order to help define the ones involved.
Hart's microarray design has been so successful that other researchers from Israel, Korea, Brazil, Canada and from all over the United States have been sending him samples to test. The vast amount of microarray data collected is being compiled in a database on the Web so that collaborators outside the lab can have access.
"Through our testing, we will gain a more complete understanding of which genes are involved and what they are doing. Then we can develop drugs to target these functions," he says.
Crista Adamson
Crista Adamson's own spinal cord injury, sustained in 1985, has not diminished her enthusiasm for scientific research. She earned her doctorate at Rutgers in March 2001 and became a postdoctoral fellow at the center in April of that year.
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