Sunday Apr 21st, 2002
by Tabitha M. Powledge
Although human embryonic stem cells preoccupy politicians and journalists, nobody was talking about them at a stem cell symposium today. Instead, researchers are trying to turn other kinds of stem cells, ones that won't raise political hackles, into real-world cures.
Darwin Prockop, professor of biochemistry at Tulane University, is betting on MSCs - adult stem cells from bone marrow stroma - with the nervous system, bone, cartilage, heart, kidney, liver, and maybe blood vessels, as possible clinical targets.
Prockop and his colleagues have come up with new conditions for growing as many as 16 million MSCs in just two weeks. The secret, he says, is to plate them at low density. At 10 cells/cm2, 95% of the cells form an individual colony, and all clones differentiate - thus far, into bone and fat.
Because MSCs home in on damaged tissue, they probably function as a repair system, Prockop suggests. MSCs are also appealing because they are relatively easy to isolate and grow in large numbers, and easy to genetically manipulate and differentiate.
Among their other virtues, the cells have been studied for 30 years, do not cause tumors, and can be obtained from patients and grown quickly, bypassing immune system problems.
But the data on functional improvement in animal models using MSCs is still tentative, Prockop notes, adding they appear to be of some benefit in spinal cord injuries and Parkinson's disease.
"Animal model results are never quite as encouraging as we'd like them to be," he said. The researchers are "pretty sure" they are seeing astrocytes in CNS studies, but have yet to observe functional neurons.
Rather than use pluripotent cells like bone marrow, other researchers are trying to identify a specific cell for a specific disease. Neuropharmacologist Paul Carvey and his colleagues have been chosen progenitor cells from the midbrain of fetal rats, cells that could be coaxed into becoming dopamine neurons, to treat Parkinson's disease.
The primary signal that instructs a progenitor cell to become a neuron is the cytokine interleukin-1, says Carvey, director of the Neuropharmacology Research Laboratories at Rush University in Chicago.
The researchers watched the cells develop, and selected and cloned cells that were near-neurons. They then grafted the cells into brains of rats suffering from a Parkinson's-like disorder and effectively cured the symptoms, Carvey says. He and his colleagues are now looking for progenitor neurons in monkey fetuses.
"Is this really a dopamine neuron? We don't know for sure," Carvey acknowledged. "But this is first time in my career that we're potentially looking at a cure."
Recent studies suggest that in mouse models of CNS injury and degeneration, neural stem cells migrate to the injury and differentiate toward replacement of dying cells, not all of which are neurons, notes Evan Snyder assistant professor of neurology at Harvard Medical School.
"Maybe the smartest way to fix problems in the nervous system is to
recapitulate development," Snyder said. "You want multiple cell types,
which may be one appealing aspect of having a multipotent cell."
Experimental Biology 2002
© Elsevier Science Limited 2002