Neuroinflammation is regarded as one of the pathogenic factors of Alzheimer disease (AD). Previously, we showed that mice regularly injected with bacterial lipopolysaccharide (LPS) possessed the AD-like symptoms like episodic memory decline, elevated amounts of amyloid beta (Aβ) peptide (1–42), and decreased levels of nicotinic acetylcholine receptors (nAChRs) in the brain. The use of mesenchymal stem cells (MSCs), which can differentiate into multiple cell types, including neurons, is an attractive idea of regenerative medicine, in particular, for neurodegenerative disorders like AD. In the present study, we aimed to investigate whether pathogenic effect of LPS on the brain and behavior of mice can be prevented or treated by injection of MSCs or MSC-produced soluble factors. Fluorescently-labeled MSCs, injected intravenously, were found in the brain blood vessels of LPS-treated mice. Mice co-injected with LPS and MSCs did not demonstrate episodic memory impairment, Aβ (1–42) accumulation, and nAChR decrease in the brain and brain mitochondria. Their mitochondria released less cytochrome
c
under the effect of Ca
2+
compared to mitochondria of LPS-only-treated mice. Moreover, MSCs could reverse the pathogenic symptoms developed 3 weeks after LPS injection. Cultured MSCs produced IL-6 in response to LPS and MSCs effect
in vivo
was accompanied by additional stimulation of both micro- and macroglia. Xenogeneic (human) MSCs were almost as efficient as allogeneic (mouse) ones and regular injections of human MSC-conditioned medium also produced positive effect. These data allow suggesting MSCs as a potential therapeutic tool to cure neuroinflammation-related cognitive pathology.
The study of opportunities to use stem cells of different origins in the treatment and rehabilitation of patients with perinatal pathology of the central neural system (CNS) is important.The aim of our study was to evaluate the effects of transplantation of multipotent mesenchymal stromal cells (MMSСs) from adipose tissue in mice with experimental model of cerebral palsy – periventricular leukomalacia (PVL).Materials and methods. PVL was modeled by unilateral coagulation of common carotid artery in mice line FVB on sixth day after birth followed by exposure to hypoxia (6 % O2) with intraperitoneal injection of the endotoxin lipopolysaccharide 1 mg/kg. For transplantation we used MMSСs from adipose tissue of the 2nd passage derived from mice FVB-Cg-Tg(GFPU)5Nagy/J. Syngeneic transplantation of GFP-positive MMSСs suspension into seven-day-old (P7) animals with a model of perinatal brain damage was performed stereotactically into right hemisphere in 24 hours after PVL. Corticospinal function of the control animals and the mice with PVL was assessed by testing reaching and retrieval of food rewards.Results. After modeling PVL operated animals lagged in development, had less weight, height and disorders of static and kinetic reflex compared to non-operated control mice. Animals with PVL had lower rates of successful attempts at obtaining food: the percentage of successful attempts in control animals was 58 ± 3 % and in animals with PVL – 23 ± 4 %. In the group of animals with MMSСs transplantation after PVL modeling corticospinal function recovery was observed and the number of successful attempts was 43 ± 4 %.Conclusions. Syngeneic stereotactic transplantation of multipotent mesenchymal stromal cells from adipose tissue contributes to the restoration of behavioral responses in animals after PVL and improves cytoarchitectonics in the focus of brain damage
Today it is important to introduce new approaches to the treatment of the elderly, which are aimed at the use of not only pharmacological drugs, but also advanced technologies of regenerative medicine using cell and tissue therapy. The particular interest of researchers and clinicians is attracted by the application of adipose-derived stem cells (ADSCs) as one of the safest and most accessible sources. Due to the multipotent potential of linear differentiation into specialized cells of different types (adipose tissue, bone, cartilage), they are widely used in plastic and reconstructive surgery of soft tissues and musculoskeletal system, in the treatment of endothelial dysfunction at critical limb ischemia and diabetes, ischemic heart disease, endocrine dysfunction etc. Morphofunctional properties of adipose-derived multipotent mesenchymal stromal cells in vitro in ovariectomized mice of different ages
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.