In a new experiment on rats, a team of researchers at Lund University has shown that by transplanting human induced pluripotent stem (iPS) cell-derived neurons into rat brains, it is possible to restore mobility and sensation of touch in the stroke-injured animals.
Intracortical grafts of human long-term self-renewing neuroepithelial-like stem (lt-NES) cell-derived cortical neurons project extensively in stroke-injured rat brain: (A) location of illustrated areas; (B-D) fibers immunoreactive for human cytoplasmic marker STEM121 in the transplant core (B), corpus callosum (C), and peri-infarct area (D). Scale bar – 200 μm. Image credit: Palma-Tortosa et al, doi: 10.1073/pnas.2000690117.
Many stroke patients exhibit long-term disability. Transplantation of stem cells is a new therapeutic strategy to promote recovery.
However, little is known about whether these cells can form functionally integrated connections with neurons in the stroke-injured recipient’s brain.
“Six months after the transplantation, we could see how the new cells had repaired the damage that a stroke had caused in the rats’ brains,” said senior author Professor Zaal Kokaia, a researcher in the Laboratory of Stem Cells and Restorative Neurology at the Lund Stem Cell Center, Lund University.
Professor Kokaia and colleagues transplanted human iPS cell-derived cortical neurons into the cerebral cortex of rats with ischemic cortical stroke.
“We’ve used tracking techniques, electron microscopy and other methods, such as light to switch off activity in the transplanted cells, as a way to show that they really have connected correctly in the damaged nerve circuits,” Professor Kokaia said.
“We’ve been able to see that the fibers from the transplanted cells have grown to the other side of the brain, the side where we did not transplant any cells, and created connections. No previous study has shown this.”
“It is remarkable to find that it is actually possible to repair a stroke-damaged brain and recreate nerve connections that have been lost.”
“The study kindles hope that in the future it could be possible to replace dead nerve cells with new healthy nerve cells also in stroke patients, even though there is a long way to go before achieving that,” said co-author Dr. Olle Lindvall, also from the Laboratory of Stem Cells and Restorative Neurology at the Lund Stem Cell Center, Lund University.
“We want to know more about how the transplanted cells affect the opposite hemisphere of the brain,” Professor Kokaia said.
“We also want to take a closer look at how a transplant affects intellectual functions such as memory.”
“In addition, we will study possible side effects. Safety is, of course, extremely important for cell transplantation if it is going to be used clinically in the future.”
The team’s work was published in the Proceedings of the National Academy of Sciences.
_____
Sara Palma-Tortosa et al. Activity in grafted human iPS cell-derived cortical neurons integrated in stroke-injured rat brain regulates motor behavior. PNAS, published online April 6, 2020; doi: 10.1073/pnas.2000690117
