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