Myelinating cells of the highest quality
Stem cells give hope for the restoration of nervous tissue
with multiple sclerosis and other myelopathies
Progenitor cells were obtained from ESCs,
differentiating into highly active oligodendrocytesLifeSciencesToday based on University of California – Davis: UC Davis team "spikes" stem cells to generate myelin
Having developed a technology for producing functional brain cells that produce myelin, which forms the insulating shell of neurons, scientists have brought the use of stem cells in the treatment of multiple sclerosis and other myelopathies, as well as spinal cord injuries, closer.
"Our results represent an important conceptual step in stem cell research," says the head of the work, Wenbin Deng, PhD, associate professor of the Department of Biochemistry and Molecular Medicine at the University of California, Davis. "Using bioengineering methods, we have for the first time obtained myelin-producing cells with excellent regenerative capacity."
Brain tissue mainly consists of two types of cells: neurons and glial cells. Neurons are considered responsible for thinking and feeling, glial cells surround, support and interact with neurons, helping to process and transmit information using electrical and chemical signals. Cells of one of the types of glia – oligodendrocytes – produce a substance of the membranes of neurons called myelin, which provides isolation, mainly, of the axons of neurons. Myelin, often compared to the insulation of electrical wires that prevents short circuits, is necessary for normal neural conduction. The most well–known diseases, the causes of which are disorders in the production of myelin or its loss, are multiple sclerosis and leukodystrophy.
American scientists have developed a new protocol for the effective induction of differentiation of embryonic stem cells (ESCs) into oligodendroglial progenitor cells (OPCs) – early progenitor cells that normally develop into oligodendrocytes. Although protocols for obtaining such cells have been developed by other scientists, Dr. Dan's method allows for a cleaner population of oligodendrocyte precursors, with fewer cells of other types.
Comparing the electrophysiological properties of the obtained OPCs with the natural precursors of oligodendrocytes, the researchers found that, unlike natural OPCs, there were no sodium ion channels in the membranes of OPCs obtained from embryonic stem cells, which deprived them of the ability to generate spikes during electrical stimulation.
The Anglicism "spikes" (spike – peak) here and further should be understood as "action potentials" – periodic jumps in the potential difference between the cell and the environment, characteristic of full–fledged neurons - VM
Using the method of viral transduction, they introduced DNA encoding sodium channels into the ESC derivatives of OPCs. The resulting OPCs expressed ion channels and had the ability to generate spikes.
Myelination of spike and non-spike progenitor cells of oligodendrocytes,
derived from mouse embryonic stem cells. (Photo: © UC Regents)According to Dr. Dan, this is the first time that scientists have managed to create OPCs with so-called spike properties.
This achievement allowed them to compare the capabilities of spike and non-spike cells.
In experiments on cell cultures, they found that only spike OPCs received an electrical impulse from neurons; they also showed a higher ability to differentiate into mature oligodendrocytes.
The researchers transplanted spike and non-spike OPCs into the spinal cord and brain of mice genetically unable to produce myelin. Both types of OPCs had the ability to differentiate into oligodendrocytes and synthesize myelin, but oligodendrocytes from spike OPCs formed a longer and thicker myelin sheath around the axons.
"In fact, we have developed "super cells" with a greater ability to generate spikes than natural cells," Dr. Dan comments on his results. "This apparently gives them an advantage in maturing into oligodendrocytes and in producing higher–quality myelin."
It is well known that the mature nervous tissue of the human body has a very low capacity for natural regeneration. Although oligodendrocyte progenitor cells are present in it, there is no effective tissue repair in diseases and injuries.
Dr. Dan believes that replacing glial cells with oligodendrocyte precursors with increased spike activity may become a more effective strategy for treating neural injuries and diseases than replacing neurons, which are usually more problematic to work with. Providing a favorable environment for the vital activity of neurons may be the best approach to the regeneration of nervous tissue. In addition, the scientist notes, currently a certain role of myelin is recognized in the development of many diseases, including schizophrenia, epilepsy and amyotrophic lateral sclerosis, which have not been traditionally considered myelopathies until now.
Article by Jiang et al. Generation and characterization of spiking and non-spiking oligodendroglial progenitor cells from embryonic stem cells is published in the journal Stem Cells.
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