Olfactory epithelial stem cells will restore the brain
Researchers from the French National Center for Scientific Research, working under the leadership of François S. Roman, have demonstrated in experiments on mice that transplantation of olfactory epithelial stem cells of the nasal sinuses promotes the healing of brain damage and the restoration of associative thinking and memory. After being injected directly into brain tissue or cerebrospinal fluid, ectomesenchymal stem cells (eMSCs) of the olfactory epithelium migrate to the injury zone, differentiate into neurons and stimulate neurogenesis (formation of new neurons).
Ectomesenchymal stem cells of the olfactory epithelium are localized in their own plate of the mucous membrane (a layer of connective tissue located under the epithelium) of the nasal sinuses and are isolated using a simple procedure performed under local anesthesia. These cells (basal cells) are similar in many ways to mesenchymal stem cells of the bone marrow. Their main difference lies in the high degree of expression of genes involved in neurogenesis.
Earlier work on animal models carried out by different research groups demonstrated the positive effect of transplantation of ectomesenchymal stem cells of the olfactory epithelium on the symptoms of brain damage caused by various factors, including Alzheimer's and Parkinson's diseases. Particular attention should be paid to restoring the plasticity of the hippocampus, a region of the brain involved in the mechanisms of learning, emotion formation and memory, and also known for its ability to neurogenesis throughout life. However, according to the authors, so far no one has been able to restore the normal functioning of the neural pathways of the adult hippocampus with the help of transplantation of adult human stem cells.
To assess the neurogenic potential of human ectomesenchymal stem cells of the olfactory epithelium in a living organism, they conducted a series of experiments on a mouse model of excitotoxically (under the action of neurotransmitters causing excessive stimulation of neurons) induced cell death simulating the effects of stroke-induced ischemia/hypoxia of the hippocampus.
First, human ectomesenchymal stem cells expressing green fluorescent protein were injected into the mouse hippocampus and demonstrated their ability to differentiate into nerve cells in an environment alien to them.
After that, ibotenic acid (a hallucinogenic toxin of fly agarics) was injected into the hippocampus of mice using a thin capillary, which led to the death of part of the neurons. Such mice lost the ability to memorize even the simplest associations of the "stimulus-reward" type, instantly grasped by normal animals. Four weeks after the introduction of ectomesenchymal stem cells of the human olfactory epithelium labeled with green fluorescent protein into the hippocampus, there was a marked improvement in the ability to associative thinking in experimental animals, which was not observed in animals of the control group who were injected with placebo. Five sessions of specially designed training practically leveled the level of associative thinking of experimental animals with normal indicators.
In the second group of mice with similar brain tissue injuries, transplantation of human cells into the hippocampus significantly improved the indicators of visual-spatial perception and long-term memory. The study of animal brain tissue five weeks after the procedure confirmed that the transplanted cells successfully took root in the hippocampus.
About 80% of these cells expressed the marker of immature neurons III-beta-tubulin and about 1.3% – the marker of mature neurons MAR2. None of the cells expressed glial cell markers. Neurons formed from transplanted cells were also registered in other regions of the brain, while they were not found in any of the analyzed peripheral organs (kidneys, liver, lungs, etc.). The researchers also note that, contrary to the data published by other groups, none of the cells differentiated into astrocytes either during preliminary experiments in laboratory conditions or during subsequent transplantation to animals.
In the second series of experiments, human ectomesenchymal stem cells were injected into the cerebrospinal fluid of the lateral ventricles of the brain of experimental animals. The results obtained were identical to the results of the first series of experiments. Moreover, the analysis of animal brain tissue showed clear signs of neurogenesis – the formation of new neurons from their own nerve stem cells.
The researchers believe that their results demonstrate the possibility of using their own ectomesenchymal stem cells of the human olfactory epithelium to restore the brain damaged as a result of injuries or diseases.
Article by Emmanuel Nivet et al. The engagement of human nasalfactory stem cells restores neuroplasticity in mice with hippocampal lesions was published on June 13 in The Journal of Clinical Investigation.
Evgeniya Ryabtseva
Portal "Eternal youth" www.vechnayamolodost.ru based on the materials of GEM: Researchers Say Human Nasal Cavity Stem Cells Repair Brain Damage in Mice.
20.06.2011