A new approach to the treatment of Alzheimer's disease and to the treatment of consequences of traumatic brain injury will be studied at the Research Centre for Medical Genetics

Researchers of the Laboratory of Stem Cell Genetics of the Research Centre for Medical Genetics will study the mechanism of restoration of nervous tissue using extracellular vesicles of glial cells obtained from human induced pluripotent stem cells (iPSCs) for the first time in Russia. The study was funded by a grant obtained from the Russian Science Foundation (Russian Science Foundation Project No. 22-25-00354, “Study of the mechanism of the therapeutic action of extracellular vesicles obtained from glial derivatives of induced human pluripotent stem cells”).

It is assumed that extracellular vesicles can play an important role in the regulation of neuroregeneration. Their use can have a significant therapeutic effect in the treatment of neurodegenerative diseases such as Alzheimer's disease, cognitive disorders of various origins, rehabilitation after a stroke etc., that constitute a significant burden to society.

Cell-based therapy is one of the most promising approaches to the development of a new method of treatment of traumatic brain injury. This direction is of great interest among scientific groups around the world. Numerous studies have shown that human stem cells transplanted into an experimental model of traumatic brain injury have a positive therapeutic effect, but the mechanism of such therapy is poorly understood. According to some data, neural stem cells transplanted into the rat brain show sufficient capacities for survival, division and migration toward sites of injury, but have a limited ability to differentiate into glial cells or electrically active neurons.

Dmitry Goldstein, Head of the Laboratory of Stem Cell Genetics of the Research Centre for Medical Genetics, Doctor of Biological Sciences, Professor: “We believe that the therapeutic effect of cell therapy is not due to the incorporation of transplanted cells into the nervous tissue, but rather to the paracrine action of the vesicles and proteins secreted by these cells.”

Extracellular vesicles are about 80 nm in size, they carry proteins, peptides, nucleic acids. Cells secrete these vesicles into the external environment and they are carried throughout the body with the bloodstream. Today, the role of extracellular vesicles in the complex processes of information transfer between cells of different tissues is being actively studied. In addition to transmitting information, different types of vesicles are known to be involved in many other processes, such as signal transmission from neurons to muscles. Nobel Prize in Physiology or Medicine in 2013 has been awarded for the discoveries in vesicle traffic.

Glial cells are part of the nervous tissue; they occupy the space between neurons. Their number is many times greater than the number of neurons.

In addition to studying the role of extracellular vesicles of iPSC-derived glial cells in the regulation of regenerative processes in nervous tissue, the Laboratory of Stem Cell Genetics of the Research Centre for Medical Genetics is also studying the mechanism of their interaction with the primary culture of cerebellar neurons and evaluating the therapeutic efficacy of extracellular vesicles in an experimental model of traumatic brain injury. The vesicles are expected to have immunomodulatory, anti-inflammatory, neuroprotective and angiogenic properties that will also be evaluated in the study.

The data obtained may be an experimental rationale for the use of extracellular vesicles derived from glial cell precursors for the treatment of neurological diseases. This approach will have a number of advantages over cell therapy. Mainly, it minimizes the risk of embolism and immune rejection. In addition, transplanted cells that are used in cell therapy, in some cases, are capable of malignant transformation. In the case of using extracellular vesicles, such risks will not arise.

Dmitry Goldstein: "Extracellular vesicles are a drug of the future that can be obtained in biotechnological production and used to treat neurological diseases."

Previously, the participation of neuronal and glial cells derived from iPSCs in the processes of nervous tissue repair was studied at the Laboratory of Stem Cell Genetics of the Research Centre for Medical Genetics. A positive effect was demonstrated as early as a week after the intra-arterial injection of neural stem cells, when they could not yet differentiate and integrate into the brain tissue of the recipient.