2 research outputs found
THERAPEUTIC POTENTIAL OF MESENCHYMAL STEM CELLS IN ATHEROSCLEROSIS: PROGRESS AND FUTURE PERSPECTIVES
Atherosclerosis is a chronic inflammatory disease of the arterial intima characterized by the formation of
athermanous plaques leading to the occlusion of arteries. In these regards, atherosclerosis is at the core
of cardiovascular diseases that lead to myocardial infarction, coronary heart disease, stroke and lower
limb ischemia. Despite the available drug therapy that is designed to reduce cholesterol and low-density
lipoprotein in the blood of patients, atherosclerosis is the most common cause of disability and premature
mortality of the population around the world. Taking into consideration inflammation of endothelium
as one of the main processes involved in all stages of atherosclerosis, suppressing inflammation and
balancing immunity was a promising treatment strategy for atherosclerosis. Mesenchymal stem cells
(MSCs) are multipotent stromal cells that can be derived from various tissues including bone marrow,
muscle, adipose tissue, umbilical cord blood, dental pulp, placenta and gingival. MSCs have unique features
of self-renewing, immune-tolerance and differentiation into a number of specialized cell types such
as adipocytes, osteoblasts, chondrocytes, muscle and endothelial cells. Moreover, recent studies reveal
that MSCs possess strong anti-inflammatory and immunomodulatory properties as well as participate
in the lipid metabolism, reducing plasma cholesterol during the development of atherosclerosis. Thus,
MSCs have attracted the attention of scientists and clinicians as a novel therapeutic tool for treatment of
atherosclerosis. A number of animal studies demonstrated that transplantation of MSCs occur beneficial
therapeutic effects on atherosclerosis development such as restoring endothelial function, suppressing
inflammatory processes, reducing plaque formation and dyslipidemia. However, these effects of MSCs
on development of atherosclerosis still remain limited. Thus, how to enhance the therapeutic potential
of MSCs for effective atherosclerosis treatment is the key current issue. In this report, we summarize the
current literatures on MSCs and their potential application for preventing and regressing atherosclerosis
as well as discuss preconditioning strategies for improving the efficacy of MSC-based therapy
NEW TREATMENT STRATEGY AGAINST ISCHEMIC BRAIN DAMAGE BASED ON COMBINED APPLICATION OF STEM CELL THERAPY AND PLANT POLYPHENOLS
Introduction: There is a number of data indicating that plant polyphenols can provide protection
against neurodegenerative changes associated with cerebral ischemia. On the other hand, it has been
shown that application of bone marrow-derived mesenchymal stem cells (BM-MSCs) resulted in an improved
functional recovery in animal models of cerebral ischemia and stroke by modulating the inflammatory
response, and stimulating endogenous neurogenesis and angiogenesis. Thus, we hypothesized
that neuroregenerative potential of mesenchymal stem cell therapy could be significantly improved if
applied in combination with plant polyphenols. We applied extract of Limonium Gmelinii (a plant widespread
in Kazakhstan) as a source of plant polyphenols.
Methods: 25 female Wistar rats were used in this study (weight 280-300g). Ischemic stroke was induced
in 20 animals by occlusion of the middle cerebral artery (MCAO); 15 animals received either Limonium
Gmelini, or BM-MSCs, and both; untreated and intact animals served as controls. The day before the
induction of stroke, the next day, on the 14th and 28th days after MCAO the sensorimotor functions of
the animals were evaluated. Before transplantation, BM-MSCs were transfected with lentiviral particles.
Results: The distribution of the transfected MSCs inside the body of laboratory animal with MCAO
was shown to be different from the distribution of MSCs inside the body of intact rats (control group).
In control rats all the MSCs were localized in visceral organs, while in rats with surgically induced MCAO
some amount of cells was found in the brains. Daily treatment of rat with 200 mg/kg of Limonium Gmelinii
extract for 28 days or single transplantation of MSC (5x10e6 cells) showed partial restoration of the
locomotor function of the animals while combined therapy with Limonium Gmelinii and MSCs completely
restores it by 28th day.
Conclusion: Combined therapy with extract of Limonium Gmelinii and mesenchymal stem cells is a
more effective approach in comparison to monotherapy