Stem cells transplanted into the brains of mice generate more numerous and more mature nerve cells if the brain cells called astrocytes are not activated. This discovery at the Sahlgrenska Academy is an important step forward for stem cell research.
The study was performed by a research team at the Center for Brain Repair and Rehabilitation at the Sahlgrenska Academy. The findings are being published in the journal Stem Cells.
Many see the transplantation of stem cells and activation of the body's own stem cells as a promising future treatment for several neurological disorders.
"Intensive research is under way around the world to find ways to get stem cells to develop into the right kind of cells, to migrate through brain tissue to the right place and then survive. Even though much work remains to be done before patients benefit from this knowledge, our findings are an important step in that direction," says Milos Pekny, professor at the Sahlgrenska Academy, Göteborg University in Sweden.
Astrocytes are a type of cells in the central nervous system that control many neurological functions, including the capacity of the brain to repair itself. The research team has previously shown that reduced activation of astrocytes leads to prolonged healing of the damage, but that ultimately the regeneration of the nerve fibers and synapses of nerve cells is enhanced. Decreased activation of astrocytes also yields better results when cells are transplanted into the retina.
"Astrocytes are also activated when stem cells are transplanted into the brain, and we show that this negatively affects the development of the stem cells," says Milos Pekny.
The scientists used genetically modified mice whose astrocytes are unable to produce two proteins called GFAP and vimentin. Such astrocytes have a limited capacity to become activated. When neural stem cells are cultured with these modified astrocytes, the generation of nerve cells was increased by 65 percent. At the same time, the formation of new astrocytes rose by 124 percent.
In the study, stem cells were transplanted into the mouse hippocampus, an area where new nerve cells are generated also in adults. When mice with limited astrocyte activation were used as recipients, there was an increase in the number of nerve cells and astrocytes generated from the transplanted stem cells. The newly generated nerve cells were also more mature than those in normal mice.
"These studies were carried out in collaboration with Professor Peter Eriksson, a great friend, a fantastic colleague, and a pioneer in human neural stem cell research, whom we lost very suddenly just a few days ago," says Milos Pekny.
Reference: Journal: Stem Cells, Title of article: Increased Neurogenesis and Astrogenesis from Neural Progenitor Cells Grafted in the Hippocampus of GFAP-/-Vimentin-/- Mice, Authors: Ĺsa Widestrand, Jonas Faijerson, Ulrika Wilhelmsson, Peter L. P. Smith, Lizhen Li, Carina Sihlbom, Peter S. Eriksson, Milos Pekny
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