Immunomodulatory Activity of Human Bone Marrow and Adipose-Derived Mesenchymal Stem Cells Prolongs Allogenic Skin Graft Survival in Nonhuman Primates.

OBJECTIVE: In the present study, we examined the tolerance-inducing effects of human adipose-derived mesenchymal stem cells (hAD-MSCs) and bone marrow-derived MSCs (hBM-MSCs) on a nonhuman primate model of skin transplantation. MATERIALS AND METHODS: In this experimental study, allogenic and xenogeneic of immunomodulatory properties of human AD-MSCs and BM-MSCs were evaluated by mixed lymphocyte reaction (MLR) assays. Human MSCs were obtained from BM or AD tissues (from individuals of either sex with an age range of 35 to 65 years) and intravenously injected (2×106 MSCs/kg) after allogeneic skin grafting in a nonhuman primate model. The skin sections were evaluated by H and E staining for histopathological evaluations, particularly inflammation and rejection reaction of grafts after 96 hours of cell injection. At the mRNA and protein levels, cellular mediators of inflammation, such as CD4+IL-17+ (T helper 17; Th17) and CD4+INF-γ+ (T helper 1, Th1) cells, along with CD4+FoxP3+ cells (Treg), as the mediators of immunomodulation, were measured by RT-PCR and flow cytometry analyses. RESULTS: A significant Treg cells expansion was observed in MSCs-treated animals which reached the zenith at 24 hours and remained at a high concentration for 96 hours; however, Th1 and Th17 cells were significantly decreased. Our results showed that human MSCs significantly decrease Th1 and Th17 cell proliferation by decreasing interleukin-17 (IL-17) and interferon-γ (INF-γ) production and significantly increase Treg cell proliferation by increasing FoxP3 production. They also extend the allogenic skin graft survival in nonhuman primates. Histological evaluations showed no obvious presence of inflammatory cells or skin redness or even bulging after MSCs injection up to 96 hours, compared to the group without MSCs. There were no significant differences between hBM-MSCs and hAD-MSCs in terms of histopathological scores and inflammatory responses (P<0.05). CONCLUSION: It seems that MSCs could be regarded as a valuable immunomodulatory tool to reduce the use of immunosuppressive agents.

Microwave-assisted green synthesis of 4,5-dihydro-1H-pyrazole-1-carbothioamides in water.

Rapid, efficient, simple and green procedure for the synthesis of 4,5-dihydro-1H-pyrazole-1-carbothioamides via the multicomponent reaction of aryl aldehydes, acetophenones and thiosemicarbazide in water in the presence of tetrabutylammonium hydroxide under microwave irradiation is reported.

Effects of Memantine, an NMDA Antagonist, on Metabolic Syndromes in Female NMRI Mice.

INTRODUCTION: The brain glutamate neurotransmitter system and its NMDA (N-methyl-D-aspartate) receptors in the nucleus accumbens play an important role in the incidence of sensitivity and addiction. The present study examined the inhibitory effect of glutamate NMDA receptors in the nucleus accumbens in response to chronic stress. METHODS: After the unilateral and bilateral placement of cannula(e) in the nucleus accumbens, one group of the animals received different doses of intra-accumbens memantine (0.1, 0.5 and 1 µg/mouse) 5 minutes before receiving the electric shock stress at their soles (using a Communication Box) and the other group received intraperitoneal memantine (doses of 0.1, 0.5 and 1mg/kg) 30 minutes before receiving the same shock. Chronic stress increased the animals' weight, plasma corticosterone, food and water intake, but reduced their defecation rates and eating latency. RESULTS: The intraperitoneal administration of memantine increased plasma corticosterone, water intake, fecal weight, and eating latency, but had no effect on food intake or weight. The dose and site-dependent intra-accumbens administration of memantine either exacerbated the effects of stress on plasma corticosterone levels, water and food intake, or had no effect on these parameters. Furthermore, the administration of memantine had no effect on animal's weight and inhibited the effects of stress on fecal weight and eating latency. DISCUSSION: The inhibition of glutamate NMDA receptors in the nucleus accumbens can inhibit and/or exacerbate the dose and site-dependent effects of chronic stress, and gender plays a significant role in producing this effect too.

Potential uses for cord blood mesenchymal stem cells.

Stem cell therapy is a powerful technique for the treatment of a number of diseases. Stem cells are derived from different tissue sources, the most important of which are the bone marrow (BM), umbilical cord (UC) blood and liver. Human UC mesenchymal stem cells (hUC-MSCs) are multipotent, non-hematopoietic stem cells that have the ability to self-renew and differentiate into other cells and tissues such as osteoblasts, adipocytes and chondroblasts. In a number of reports, human and mouse models of disease have hUC-MSCs treatments. In this article, we review studies that pertain to the use of hUC-MSCs as treatment for diseases.