Modulating endothelial adhesion and migration impacts stem cell therapies efficacy

Background: Limited knowledge of stem cell therapies‘ mechanisms of action hampers their sustainable implementation into the clinic. Specifically, the interactions of transplanted stem cells with the host vasculature and its implications for their therapeutic efficacy are not elucidated. We tested whether adhesion receptors and chemokine receptors on stem cells can be functionally modulated, and consequently if such modulation may substantially affect therapeutically relevant stem cell interactions with the host endothelium. Methods: We investigated the effects of cationic molecule polyethylenimine (PEI) treatment with or without nanoparticles on the functions of adhesion receptors and chemokine receptors of human bone marrow-derived Mesenchymal Stem Cells (MSC). Analyses included MSC functions in vitro, as well as homing and therapeutic efficacy in rodent models of central nervous system´s pathologies in vivo. Findings: PEI treatment did not affect viability, immunomodulation or differentiation potential of MSC, but increased the CCR4 expression and functionally blocked their adhesion receptors, thus decreasing their adhesion capacity in vitro. Intravenously applied in a rat model of brain injury, the homing rate of PEI-MSC in the brain was highly increased with decreased numbers of adherent PEI-MSC in the lung vasculature. Moreover, in comparison to untreated MSC, PEI-MSC featured increased tumour directed migration in a mouse glioblastoma model, and superior therapeutic efficacy in a murine model of stroke. Interpretation: Balanced stem cell adhesion and migration in different parts of the vasculature and tissues together with the local microenvironment impacts their therapeutic efficacy. Funding: Robert Bosch Stiftung, IZEPHA grant, EU grant 7 FP Healt

Electron-topological, energetic and π-electron delocalization analysis of ketoenamine-enolimine tautomeric equilibrium

The ketoenamine-enolimine tautometic equilibrium has been studied by the analysis of aromaticity and electron-topological parameters. The influence of substituents on the energy of the transition state and of the tautomeric forms has been investigated for different positions of chelate chain. The quantum theory of atoms in molecules method (QTAIM) has been applied to study changes in the electron-topological parameters of the molecule with respect to the tautomeric equilibrium in intramolecular hydrogen bond. Dependencies of the HOMA aromaticity index and electron density at the critical points defining aromaticity and electronic state of the chelate chain on the transition state (TS), OH and HN tautomeric forms have been obtained

Repair, regenerative and supportive therapies of the annulus fibrosus: achievements and challenges

Lumbar discectomy is a very effective therapy for neurological decompression in patients suffering from sciatica due to hernia nuclei pulposus. However, high recurrence rates and persisting post-operative low back pain in these patients require serious attention. In the past decade, tissue engineering strategies have been developed mainly targeted to the regeneration of the nucleus pulposus (NP) of the intervertebral disc. Accompanying techniques that deal with the damaged annulus fibrous are now increasingly recognised as mandatory in order to prevent re-herniation to increase the potential of NP repair and to confine NP replacement therapies. In the current review, the requirements, achievements and challenges in this quickly emerging field of research are discussed

Measures for the eu as part of the support of non-individual entities in rural areas of Kuyavian-Pomeranian voivodship

Artykuł przedstawia wielkość oraz strukturę środków pomocowych UE wykorzystanych przez podmioty nieindywidualne w ramach realizacji Wspólnej Polityki Rolnej na obszarach wiejskich województwa kujawsko-pomorskiego. Wskazuje także przestrzenne zróżnicowanie płatności oraz główne przyczyny, które je powodują. Płatności podmiotów nieindywidualnych korzystających z programów WPR analizowane są pod kątem źródła płatności (płatno- ści bezpośrednie, płatności z tytułu rozwoju obszarów wiejskich oraz inne), jak również według grup benefi cjentów.Total payments obtained by the non-individual benefi ciaries during 16.10.2007-15.10.2008 in Kuyavian-Pomeranian province, amounted to nearly 261 million PLN, that is 31.6% of all aid measures from the EU, which arrived to the region in the framework of the programmes under the CAP. The size and structure of the EU funds used by non-individual entities show large variations in spatial planning in rural areas. Most of them – over 211 million PLN (81.2% of all measures for nonindividual entities) was in the group “companies depart ment and other”. In the group “other payments” intervention programs related to the operation of the market, the market in fruit and vegetables, etc. Non-individual benefi ciaries received more than 208 million PLN, of which sum up 182.8 million PLN went to Toruń (87.7% of the total amount), and the main benefi ciary was the company Krajowa Spółka Cukrowa SA, which received appropriations amounting to more than 181 million PLN