Two recent studies report a mixed outlook for cell transplantation as a therapy for Parkinson's disease this week, while a third reports on an improved way to track the transplanted cells.

The first cell transplants on Parkinson's patients were performed decades ago, but the procedure has yet to become anywhere near standard clinical practice: it's just not very good yet. Randomized clinical trials have shown a benefit only to younger patients, and then only in the morning, after a night without medication.

When patients were at their best, right after receiving a dose of anti-Parkinson's medication, cell transplantation does not improve their symptoms over and above what medicine is able to do.

Nevertheless, average effects aside, transplantation can work very well. And so, the search for ways to make it more uniformly beneficial continues.

In the May 30, 2007 issue of the Journal of Neuroscience, scientists from the University of Lund in Sweden and Hannover Medical School in Germany report clues to why some patients may do better than others with cell transplants in the first place.

The neurons affected in Parkinson's disease are dopamine-containing neurons in the substantia nigra. But replacement cells are not transplanted into the substantia nigra. Instead, they go into the striatum - the major area that substantia nigra neurons project to.

But not the only area - the substantia nigra projects to a greater area of the striatum than the cell transplants can normally replace, as well as to other areas in the cortex and limbic system.

In their paper, the researchers compared rats whose substantia nigra striatum connection had been partially destroyed, which is typical of early stage Parkinson's, to those with more extensive lesions that included the entire striatum as well as the cortical and limbic system connections. They found that the animals with more extensive lesions benefitted very little from cell transplants.

The authors drew two conclusions from their work: "First, patients with advanced disease involving the ventral striatum and/or nonstriatal DA projections would be unlikely to respond well to intrastriatal DA grafts and, second, to retain the full benefit of the grafts, progression of the disease should be avoided by, for example, combining cell therapy with a neuroprotective approach."

A similar conclusion about the importance of remaining cells in Parkinson's patients is reached in a second paper, published in the June 12, 2007 issue of the early online edition of the Proceedings of the National Academy of Sciences by a research team from Yale University, Harvard University, the University of Colorado and the Burnham Institute.

The scientists transplanted human neural stem cells into a total of 27 monkeys with symptoms of advanced Parkinson's disease, and followed them for up to eight months.

The transplanted monkeys showed improvements in their Parkinson's symptoms compared to control animals. However, in immunohistochemical experiments, the researchers found that only a small number of stem cells had turned into dopamine-containing neurons. Instead, the transplanted cells appeared to have branched out in terms of their functional roles.

The authors wrote that "a much larger number of [human neural stem cell]-derived cells that did not express neuronal or DA markers was found arrayed along the persisting nigrostriatal path, juxtaposed with host cells." The cells express factors that are protective for dopaminergic neurons and "were therefore well positioned to influence host . . . cells and mediate other homeostatic adjustments," including the preservation of host nigrostriatal cells, and a normalizing effect on the aggregation of certain proteins.

The authors of the primate paper had to kill their animals to get data on what sorts of cell types arose from the grafts. But an improved way to track such cells also was published just a week earlier.

Writing in the June 5, 2007 early online edition of PNAS, researchers from Stanford University and Palo Alto, Calif.-based biotechnology company StemCells Inc. reported that it is possible to label human neural stem cells in a way that does not affect their biological properties in vivo or in vitro.

The authors used superparamagnetic iron oxide or SPIO-containing nanoparticles to label human neural stem cells, and tested the effects on their survival, differentiation, migration abilities and firing properties. Labeled stem cells behaved no differently from unlabeled ones, and the authors were able to track their migration through the repeated use of magnetic resonance imaging.

The team concluded that "implementation of noninvasive stem cell tracking might help to improve the design of future clinical neural stem cell transplantation."