Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi's sarcoma

Emerging evidence suggests that both human stem cells and mature stromal cells can play an important role in the development and growth of human malignancies. In contrast to these tumor-promoting properties, we observed that in an in vivo model of Kaposi's sarcoma (KS), intravenously (i.v.) injected human mesenchymal stem cells (MSCs) home to sites of tumorigenesis and potently inhibit tumor growth. We further show that human MSCs can inhibit the in vitro activation of the Akt protein kinase within some but not all tumor and primary cell lines. The inhibition of Akt activity requires the MSCs to make direct cell–cell contact and can be inhibited by a neutralizing antibody against E-cadherin. We further demonstrate that in vivo, Akt activation within KS cells is potently down-regulated in areas adjacent to MSC infiltration. Finally, the in vivo tumor-suppressive effects of MSCs correlates with their ability to inhibit target cell Akt activity, and KS tumors engineered to express a constitutively activated Akt construct are no longer sensitive to i.v. MSC administration. These results suggest that in contrast to other stem cells or normal stromal cells, MSCs possess intrinsic antineoplastic properties and that this stem cell population might be of particular utility for treating those human malignancies characterized by dysregulated Akt

Nitrite Therapy After Cardiac Arrest Reduces Reactive Oxygen Species Generation, Improves Cardiac and Neurological Function, and Enhances Survival via Reversible Inhibition of Mitochondrial Complex I

Three-fourths of cardiac arrest survivors die prior to hospital discharge or suffer significant neurological injury. Excepting therapeutic hypothermia and revascularization, no novel therapies have been developed that improve survival or cardiac and neurological function after resuscitation. Nitrite (NO2−) increases cellular resilience to focal ischemia-reperfusion injury in multiple organs. We hypothesized that nitrite therapy may improve outcomes after the unique global ischemia-reperfusion insult of cardiopulmonary arrest

Effects of surface chemistry on the porous structure of coal. Technical progress report, September 1994--October 1995

The primary objective of this work is to use {sup 129}Xe NMR to characterize the microporous structure of coals. As an aide in this characterization, another objective is to combine this technique with volumetric adsorption techniques and track the effect of controlled opening of the micropores in a microporous carbon by oxygen chemisorption/desorption. The primary goal of the NMR work is to measure the micropore sizes in coal; more broadly, it is to better tailor the {sup 129}Xe NMR method for use with coal, and to investigate other ways it may be used to describe pore structure in coal, with emphasis on determining whether micropores in coal are connected or isolated. In terms of the primary objectives of the project, the {sup 129}Xe NMR spectra with pressure variation have been completed for four coals, and N{sub 2} and C0{sub 2} adsorption isotherms with surface area measurement have been completed for three coals. A microporous carbon has been subjected to one oxygen chemisorption/desorption cycle and examined by {sup 129}Xe NMR

Color Transformation and Fluorescence of Prussian Blue–Positive Cells: Implications for Histologic Verification of Cells Labeled with Superparamagnetic Iron Oxide Nanoparticles

Superparamagnetic iron oxide (SPIO) nanoparticles, either modified or in combination with other macromolecules, are being used for magnetic labeling of stem cells and other cells to monitor cell trafficking by magnetic resonance imaging (MRI) in experimental models. The correlation of histology to MRI depends on the ability to detect SPIO-labeled cells using Prussian blue (PB) stain and fluorescent tags to cell surface markers. Exposure of PB-positive sections to ultraviolet light at a wavelength of 365 nm commonly used fluorescence microscopy can result in color transformation of PB-positive material from blue to brown. Although the PB color transformation is primarily an artifact that may occur during fluorescence microscopy, the transformation can be manipulated using imaging process software for the detection of low levels of iron labeled cells in tissues sample

Detection of migration of locally implanted AC133+ stem cells by cellular magnetic resonance imaging with histological findings

This study investigated the factors responsible for migration and homing of magnetically labeled AC133+ cells at the sites of active angiogenesis in tumor. AC133+ cells labeled with ferumoxide-protamine sulfate were mixed with either rat glioma or human melanoma cells and implanted in flank of nude mice. An MRI of the tumors including surrounding tissues was performed. Tumor sections were stained for Prussian blue (PB), platelet-derived growth factor (PDGF), hypoxia-inducible factor-1α (HIF-1α), stromal cell derived factor-1 (SDF-1), matrix metalloproteinase-2 (MMP-2), vascular endothelial growth factor (VEGF), and endothelial markers. Fresh snap-frozen strips from the central and peripheral parts of the tumor were collected for Western blotting. MRIs demonstrated hypointense regions at the periphery of the tumors where the PB+/AC133+ cells were positive for endothelial cells markers. At the sites of PB+/AC133+ cells, both HIF-1α and SDF-1 were strongly positive and PDGF and MMP-2 showed generalized expression in the tumor and surrounding tissues. There was no significant association of PB+/AC133+ cell localization and VEGF expression in tumor cells. Western blot demonstrated strong expression of the SDF-1, MMP-2, and PDGF at the peripheral parts of the tumors. HIF-1α was expressed at both the periphery and central parts of the tumor. This work demonstrates that magnetically labeled cells can be used as probes for MRI and histological identification of administered cells.—Arbab, A. S., Janic, B., Knight, R. A., Anderson, S. A., Pawelczyk, E., Rad, A. M., Read, E. J., Pandit, S. D., Frank, J. A. Detection of migration of locally implanted AC133+ stem cells by cellular magnetic resonance imaging with histological findings