Regulatory Effects of Mesenchymal Stem Cells in Brain
Abstract
The question on various functional effects of mesenchymal stem cells
(MSCs) during different pathological processes development in brain was
considered. Attention was paid to ability of MSCs to be involved in
control of reparative processes in nerve tissue due to expression of
many neurotrophic factors. Such feature of MSCs enhances their positive
effects by realization of another potential - ability to progress in
neuron-like direction. They also have an impressive ability to interact
with immune competent cells in brain tissue to increase antitumor
effect. It was shown that MSCs are able to synthesize and express lots
of regulatory factors which inhibit growth of glioma cells. Therefore,
vision of MSCs functional heterogeneity was expanded and their various
regulatory effects were combined in realization of protective function
both in health and disease.
Keywords: Antitumor Effects; Brain
Plasticity; Defensive Reactions; Neurotrophic Factors; Reparative
Processes; Stem Cells; Transcription Factors
Abbreviations: Ad-HMSCs: Adipose Human
Mesenchymal Stem Cells; BDNF: Brain Derived Neurotrophic Factor; GDNF:
Glial Cell Derived Neurotrophic Factor; NGF: Nerve Growth factor; NGFR:
Nerve Growth Factor Receptor; MSCs: Mesenchymal Stem Cells; SCs: Stem
Cells; Sox: (Sry-Related HMG Box) Genes Encode Transcription Factors
Introduction
Cellular technologies are being widely implemented into many spheres
of practical medicine recently. The number of advanced technologies
involving stem cells (SCs) progressively increases in treatment of brain
diseases. Specialists think SCs are able to grow in neuron-like
direction in damaged brain regions showing various regulatory effects in
health and disease (Alzheimer’s disease, stroke, brain trauma, glioma,
glioblastoma) [1-6]. Mesenchymal stem cells (MSCs) seem the most
promising besides residential brain cells. MSCs are administered mainly
systemically for correction of impaired brain functions in the
development of pathological processes. For example, MSCs have wide
potential for the treatment of Alzheimer’s disease [1,7]. It has been
suggested that reparative processes in the brain are activated by
secretion of nerve growth factor (NGF), brain-derived neurotrophic
factor (BDNF), and vascular endothelial growth factor (VEGF) from neural
SCs [8].The search for “Neurotrophic Effect Stem Cells Brain” and
“Neurotrophic Effect Mesenchymal Stem Cells Brain” in PubMed on November
7th, 2018 showed 491 and 153 articles, respectively, and the interest
started to grow only eight-nine years ago. Scientists and physicians are
interested in two aspects of MSCs functional role in brain: reparative
potential of MSCs, and antitumor potential of MSCs.
Reparative Potential of MSCs
First of all, enhancement of reparative potential of residential stem
cells in patient’s brain by autologous MSCs is a promising field. Only
27 articles have been found in PubMed while searching for “Neurotrophic
Effect Mesenchymal Stem Cells Brain repair”. Their authors stress that
despite of low amount of publications cellular technologies of MSCs use
are promising addition to current methods of neurodestructive processes
treatment [3,4,6,9-11]. According to range of authors, intravenous
injection of allogeneic MSCs from adipose tissue in patients with acute
stroke can be safe therapy and increase recovery of nerve tissue and
blood flow in cerebral vessels [8]. Brain-derived neurotrophic factor
(BDNF) is mentioned as one of the key trophic factors which MSCs express
in damaged brain area [8,9]. It was assumed, following experimental
modeling of neonatal stroke in rats, that intranasal administration of
MSCs could be useful in brain functions recovery after stroke [3,4,6].
The technique of intranasal administration of MSCs after modeling of
neurodestructive processes in different parts of brain and spinal cord
was thoroughly substantiated [2-4]. Somatotopic principle of MSCs
migration to damaged brain region was established for the first time:
MSCs move along chosen cranial nerve to anterior or
posterior cranial fossae depending on damage localization [4].
Antitumor Potential of MSCs
Secondly, recent results showed that MSCs have potential for
inhibition of glioma cells growth [12,13]. It was based on revealed
MSCs taxis to tumor cells [6]. PubMed search for “Neurotrophic
Effect Mesenchymal Stem Cells Brain glioma” and “Mesenchymal
Stem Cells Brain glioma” on November 7th, 2018 revealed one and
386 articles, respectively. Articles demonstrate how MSCs actively
interact with components of immune system and show both antiinflammatory
and antitumor effects [13].
MSCs serve as attractive instrument for cellular therapy
of cancer due to their ability to migrate to tumors and express
bioactive molecules. However, influence of MSCs on tumor growth
was not completely established. Authors [2,7,13] performed
systemic injection of MSCs to femoral vein, or carotid artery. Same
authors [14] showed that intracerebral injection of Ad-hMSC
significantly improved survival rate of rats with heterotransplants
U87MG. This effect was associated with decrease of tumor growth
due to limitation of tumor cells proliferation and decrease of
microvessel density. Fetal injection of Ad-hMSC lowered population
of tumor cells and initiated migration of residential microglia cells
in GSC1 heterotransplants. It is known that Sox21 inhibits glioma
progression, because Sox21 decrease the stem-like cell properties
of the tumor cells [15]. Induction of Sox21 in the glioma resulted in
a significant smaller tumor size [15]. But, still there is no clarity in
the answer to the question of how the intercellular, perineural and
perivascular spaces of the brain create conditions for the migration
of stem cells [16].
Gathered data can say for broadening of MSCs antitumor
potential use in combination with standard surgical, radio- and
chemotherapeutical, and especially with such methods which
are aimed at activation of immune system [17,18], delivery of
metabolizing genes and/or oncolytic viruses [19].
Conclusion
Functional heterogeneity of MSCs which is demonstrated in
various regulatory effects is the basis for extension of stem cells
use in guidelines dedicated to treatment of socially important
diseases. It should be mentioned that lots of MSCs effects are still
underexplored. For example, we don’t know all of side effects,
including possibility of MSCs to transform to cancerogenic cells.
Deepening of knowledge on fundamental and applied aspects of
MSCs use in experiments and practice will allow reasonable use of
protective function of MSCs in health and disease.
Acknowledgement
Our research project was partially sponsored by SSTP “New
methods of medical care”, section “Transplantation of cells, tissues
and organs” (2016-2020), and by grant OOO “Synergy”.
The Possibility of Urinary Tract Infection
in Primary School Students with A Diagnosis
of Febrile Pharyngotonsillitis - https://biomedres01.blogspot.com/2020/02/the-possibility-of-urinary-tract.html
More BJSTR Articles : https://biomedres01.blogspot.com
No comments:
Post a Comment
Note: Only a member of this blog may post a comment.