Tuesday, June 20, 2006

NBC reports "stem cell breakthrough" on June 20, 2006

On Tuesday, June 20, 2006, NBC Nightly News featured work [on spinal cord injured mice] of Dr. Douglas Kerr, a neurologist at Johns Hopkins University who led the research separately being published [next] Monday in the journal Annals of Neurology.

The new research details a complex recipe of growth factors and other chemicals that entice the delicate cells to form correctly and make the right connections. Miss a single ingredient, and the cells wander aimlessly, unable to reach the muscle and make it move.

An AP report obliquely compared this work to other work in rats. The Hopkins experiment isn’t the first to use stem cells to help paralyzed rodents move. But previous work bridged damage inside the spinal cord that blocked nerve cells from delivering their “move” messages to muscles, sort of like fixing the circuit that brings electricity to a fan. The new work essentially installs new wiring: replacing motor neurons — specialized nerve cells for movement — that have died to make a new circuit that grows neuronal connections out of the spinal cord and down to a leg muscle.

Unlike the UCal/Irvine work that used HUMAN embryonic stem cells, Kerr mixed embryonic stem cells FROM MICE with chemicals that caused them to turn into motor neurons. He transplanted them into the spinal cords of partially paralyzed rats [mice].

A post on IPBiz had presented reporting by "60 Minutes" of work by Hans Keirstead at UC/Irvine. The work by Keirsted used HUMAN embryonic stem cells [Here, we show that transplantation of human embryonic stem cell (hESC)-derived oligodendrocyte progenitor cells (OPCs) into adult rat spinal cord injuries enhances remyelination and promotes improvement of motor function.] Curiously, the stem cell line used was pre-August 2001 and thus "Bush-approved."

Bloomberg reported:

In the study, stem cells taken from mouse embryos were chemically transformed in a lab into motor neurons, cells that carry impulses from the brain and spinal cord to receptors in the muscles. Researchers then injected the neurons into the mice in such a way that three in every four animals were able to bear weight on their hind legs and take steps after six months.

The study, to be published in the Annals of Neurology next week, was funded in part by the NIH. It suggests similar techniques may eventually be useful for treating such disorders as spinal cord injury and Lou Gehrig's Disease, also known as ALS, both of which leave people unable to use their limbs, the researchers said. They cautioned that such an advance in humans remains many years away.

The research used a cocktail of chemicals that help build nerves while inhibiting the body's ability to protect itself from the new cells. The cocktail allows the motor neurons to re- connect, essentially re-establishing the circuitry that allows the body to signal muscles that they're needed.

Forbes noted:

"In the simplest [neuronal] relay, a brain cell talks to the motor neuron in the spinal cord and says, 'Move that muscle,' " Kleitman explained. "Then, the motor neuron reaches out of the spinal cord to the muscle using these long fibers called axons. They communicate with the muscle, send an impulse, and the muscle contracts."

But this seemingly simple network relies on a complex partnership of growth factors and signaling chemicals -- each vital to the process. So, research aimed at deciphering these players and their connections has continued.

"It's like a detective story where if you don't put all the clues in order, you wind up going off in the wrong direction," Kleitman said.

Starting in the laboratory, Kerr first used specific growth factors to spur mouse embryonic stem cells to differentiate into motor neurons. Then they added two chemicals -- retinoic acid and sonic hedgehog protein -- to help these new cells feel more at home in the spinal-cord environment.

The next step was to deliver these primed cells into the spinal cords of mice previously paralyzed by a viral infection.

But another roadblock loomed.

"We know that there are proteins in this area that inhibit axons from growing in adult animals," Kleitman explained. The proteins are linked to the protective myelin sheath that coats nerve fibers. "They're part of how we keep our nervous system from going haywire during normal function," she said.

To overcome this resistance, the Hopkins team added two agents -- cyclic AMP (cAMP) and the drug rolipram -- to the mix. According to Kleitman, these molecules "block the 'stop sign,' so that now the axons can grow."

But there was one more hurdle -- it's one thing to allow axons the freedom to grow, but to grow where? "You've got pretty long distances to cover, so one of the things you need is a 'target' that's screaming out like a neon sign, 'Come here!' " Kleitman said.

The Hopkins group created just such a target by applying a powerful neural growth factor, called GDNF, to the remains of nearby, deadened sciatic nerve cells. The GDNF -- derived from fetal mouse neural stem cells -- essentially "called out" to the growing axons, urging them to make the connection.


Post a Comment

<< Home