Stem cells locate brain injury and form replacement neurons in rats.
Transplants of human fetal stem-cells may help repair stroke-induced brain damage. This has long been a goal of stem-cell researchers, and now a study in rats has produced the most promising result yet, by showing that grafted cells can home in on injured brain regions and form replacement nerve cells.
The next step is to prove that the cells can reverse paralysis in the rodents, before moving on to primate and human trials. "We're not saying we can treat patients immediately, but it is a big step forwards," says Gary Steinberg from Stanford University, who led the study.
Stroke is the main cause of disability in adults, and is the third biggest cause of death in the United States. The condition occurs when a blood vessel carrying oxygen and nutrients to the brain becomes blocked or bursts. Brain cells then start to suffocate and die.
It is hoped that stem cells, which can turn into many different types of cell, will be able to replace the damaged tissue.
Alive and well
Steinberg's team took neural stem-cells from 16- to 20-week-old human fetuses and cultured them with growth-promoting chemicals to generate millions of cells for transplantation.
Seven days after surgically inducing a stroke in rats, the researchers transplanted around 300,000 cells into each rodent's brain. One month later, an average of 100,000 of the grafted cells were still alive in the rats' brains and nearly half of them had turned into neurons, the team reports in the Proceedings of the National Academy of Sciences1.
The remaining cells still looked like stem cells or had turned into astrocytes, a type of brain cell that supports neurons. Some grafted cells had migrated a millimetre or more away from the injection site towards the damaged part of the brain.
These are all positive signs, the team says. They suggest that the grafted cells have located the site of damage, and are homing in on it and turning into the types of cells that are needed to repair the injury.
Steinberg says that fetal stem cells have advantages over adult and embryonic alternatives. Adult stem cells do exist in the brain, but they are difficult to obtain, survive less well after transplantation and may be less versatile than their younger counterparts.
Human embryonic stem cells, taken from the very early stages of development, have the potential to turn into any type of adult cell. But they are ethically contentious and in the US, only a limited number of embryonic stem cell lines are available for academic research.
Way to grow
"It's encouraging work," says stem-cell researcher Erik Miljan from the British biotechnology company ReNeuron, who are also developing stem cells for stroke therapy.
There is a lot of work still to be done, however. Hundreds of millions of cells would need to be grown for human clinical trials and it is not clear whether these cells are capable of growth on that scale. Prolonged culture periods can slow cell growth and may give the cells a chance to pick up random genetic abnormalities.
Another approach would be to add a gene to the stem cells that boosts growth and prevents the formation of genetic defects, says Miljan. Such altered cells could then be used for the treatments of stroke and other neurodegenerative disorders, such as Parkinson's and Alzheimer's disease.
KellyS., et al. journal, PNAS Early Edition. doi:10.1073/pnas.0404474101 (2004).
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Pilcher, H. Transplant hope for stroke sufferers. Nature (2004). https://doi.org/10.1038/news040726-2