Stem Cell Researchers Inch toward Therapeutic Applications

by Brenda Patoine

January, 2006

Sometimes lost amid the political and ethical controversies surrounding stem cells and cloning for therapeutic purposes are the tough scientific hurdles that must be over-come before stem cell-based therapies are a reality.

Yet worldwide, scientists at universities and private companies are tackling these hurdles from every angle, inching forward in their quest to tap the seemingly limitless potential of stem cells, in all their varieties, to treat human diseases. More than 400 of the presentations and posters at the conference focused on stem cells of one type or another, an indicator of the breadth of research ongoing in this area.

“Research is advancing incredibly quickly,” said David Steindler, a University of Florida neuroscientist who led a discussion highlighting recent findings. “The potential therapies that are on the horizon are very exciting.”

Routine clinical use of stem cells to treat disease is still years away, as scientists strive to understand how best to harness their therapeutic potential. Among the foremost challenges scientists face are understanding the mechanisms that regulate the “fate” of stem or precursor cells—that is, what type of cells they will differentiate into—and developing methods for generating sufficient quantities of cells for therapeutic use.

Researchers are making noteworthy progress on both fronts. Nobuko Uchida, a scientist with Stem Cells Inc. in Palo Alto, Calif., presented findings from the company’s work with human neural stem cells, precursor cells that can differentiate into different brain cells based on the chemical signals they encounter in the brain.

Uchida’s team transplanted neural stem cells into the spinal cords of genetically altered mice that could not make myelin, the protective sheath surrounding nerve fibers that speeds nerve transmission. After about seven weeks, the transplanted cells developed into fully functioning oligodendrocytes, support cells in the brain that produce myelin, and the violent shaking symptoms of the mice were ameliorated.

“The animals’ recovery was directly linked to the transplanted cells,” Uchida said. Her team also characterized

“Research is advancing incredibly quickly. The potential therapies that are on the horizon are very exciting.”

the specific steps that the neural stem cells underwent following transplantation, work that could help scientists direct the cells’ differentiation for therapeutic use in disorders that affect myelin, including spinal cord injury, cerebral palsy, multiple sclerosis, and a group of rare genetic diseases that result in myelin deficiency.

Many researchers are focusing on ways to activate the brain’s endogenous (built-in) stem cells to replace cells lost or damaged because of disease. This approach would obviate the need for large populations of stem cells for trans-plantation and avoid any risk of a patient’s body rejecting transplanted cells that are not a perfect genetic match.

Limitless Potential?

“One stem cell could potentially repopulate every human brain on Earth a thousand times over,” said Brent Reynolds, a stem cell researcher at the University of Queensland in Australia. Driven by this seemingly limitless potential, several biotechnology companies and international research teams are racing to develop drugs or “cocktails” of biochemicals that would make it clinically feasible to activate one’s own stem cells for therapeutic purposes.

Reynolds’ team, for example, has discovered that growth hormone is an important regulator of adult neural stem cells. When growth hormone was added to neural stem cells in a culture dish, the number of cells increased. Also, laboratory animals that lack receptors for growth hormone have reduced numbers of neural stem cells.

This work has potential implications for neurological and psychiatric diseases that have been linked to shrinkage in the hippocampus, the primary brain region where neural stem cells are generated, including schizophrenia, long-term major depression, and post-traumatic stress disorder.

“Given that the absolute numbers of neural stem cells are thought to decline with age, stimulation of such cells via growth hormone or its receptor may represent a novel means by which to reverse or prevent the deleterious effects of aging,” the researchers wrote in the conference abstract reporting their work.

A team from the University of Calgary, led by Trudi Stickland, tested the ability of a cocktail of growth factors to mobilize endogenous neural stem cells and improve recovery of movement in a rat model of stroke. The researchers used tiny pumps to infuse epidermal growth factor into the animals’ brains for seven days, then erythropoietin, a natural hormone that promotes blood cell growth, for another seven days.

A few weeks after the treatment, they examined the rats and found that cortical tissue had regrown where the stroke lesion had been. Behavioral tests revealed that the treatment effectively diminished deficits in forepaw function in the animals, though the specific mechanisms underlying this recovery are not yet known.

Meanwhile, a Swedish biotech company, NeuroNova, is testing the capacity of an experimental drug to activate endogenous stem cells to compensate for those lost in Parkinson’s disease. Using a mouse model of parkinsonism, company scientists infused the drug directly into the animals’ ventricles (fluid-filled spaces in the cerebrum) via implanted pumps. One of the scientists, Anders Haegerstrand, reported that treatment with the drug resulted in a two- to five-fold increase in the number of cells in the ventricles and the striatum, the part of the brain affected in Parkinson’s. The company is continuing to observe the mice to determine if the treatment is improving their Parkinson’s-like symptoms.