The Role of Adipose Tissue Mesenchymal Stem Cells in Colonic Anastomosis Healing in Inflammatory Bowel Disease: Experimental Study in Rats.

(1) Background: A surgical operation on an inflamed bowel is, diachronically, a challenge for the surgeon, especially for patients with inflammatory bowel disease. Adipose tissue-derived mesenchymal stromal cells are already in use in clinical settings for their anti-inflammatory properties. The rationale of the current study was to use AdMSCs in high-risk anastomoses to monitor if they attenuate inflammation and prevent anastomotic leak. (2) Methods: a total of 4 groups of rats were subjected to a surgical transection of the large intestine and primary anastomosis. In two groups, DSS 5% was administered for 7 days prior to the procedure, to induce acute intestinal inflammation. After the anastomosis, 5 × 106 autologous AdMSCs or an acellular solution was injected locally. Macroscopic evaluation, bursting pressure, hydroxyproline, and inflammatory cytokine expression were the parameters measured on the 8th post-operative day. (3) Results: Significantly less intra-abdominal complications, higher bursting pressures, and a decrease in pro-inflammatory markers were found in the groups that received AdMSCs. No difference in VEGF expression was observed on the 8th post-operative day. (4) Conclusions: AdMSCs attenuate inflammation in cases of acutely inflamed anastomosis.

Induced differentiation and molecular characterization of monocytes-derived multipotential cells generated from commonly discarded leukapheresis filters.

Monocyte-derived multipotential cells (MOMCs) are a subpopulation of monocytes that appear to be capable of differentiating into many cell populations, thus MOMCs can be an ideal autologous transplantable cell source for regenerative medicine. In this study, we generated MOMCs from leukapheresis filters, evaluated their ability to differentiate to endothelium and osteocytes and performed their molecular characterization. For this purpose, leukapheresis filters were collected from a hospital blood donation department and used for leukocytes isolation. The isolated leukocytes were cultured in a medium supplemented with SDF-1a for MOMCs generation. We evaluated the expression of the multipotency genes ZNF217, ZNF878, ESRRB, SALL4, KLF4, SOX2, NANOG, OCT4, GAPDH, CD34 and c- MYC in MOMCs with real-time reverse transcription PCR (qRT-PCR) and the differentiation capacity of MOMCs to osteocytes and endothelium with qRT-PCR. The results suggest that MOMCs can be generated using leukocytes isolated from leukapheresis filters in the presence of SDF-1a. Furthermore, MOMCs expressed all the tested factors responsible to activate the networks of pluripotency of cells and can differentiate into endothelium and osteocytes. Therefore, the blood donors could benefit and be rewarded with the potential use of their own immune system cells for future treatment in the frame of personalized regenerative medicine.

The cytotoxicity effect of a bis-MPA-based dendron, a bis-MPA-PEG dendrimer and a magnetite nanoparticle on stimulated and non-stimulated human blood lymphocytes.

Dendrimers and dendrons offer a high surface area and nanoscale size and magnetic nanoparticles can be easily detected and manipulated due to their magnetic properties. The aim of the present study is to investigate the in vitro toxicity of Polyester-8-hydroxyl-1-carboxyl bis-MPA dendron, generation 3 (bis-MPA), Hyperbranched G4-PEG6k-OH (PEG) dendrimer and magnetite nanoparticle (Fe3O4), in human lymphocytes. Cell viability assays were performed on non-stimulated and lipopolysaccharide (LPS) stimulated lymphocytes, after exposure to various concentrations of the nanoparticles, using the Trypan blue assay, Flow Cytometry with 7-Amino Actinomycin D fluorescent dye (7-AAD), as well as the 3-[4,5-dimethylthiazol-2-yl] 2,5 diphenyl tetrazolium bromide (MTT) colorimetric method. The results collectively showed that after 24 h both the dendron and dendrimer at 50 µM concentration exhibited low cytotoxicity to non-stimulated and stimulated lymphocytes. Magnetite nanoparticle (Fe3O4) in concentrations 50-1000 µg/mL revealed negligible cytotoxicity to stimulated and non-stimulated lymphocytes. Moreover, the amount of intercellular Reactive Oxygen Species with or without treatment was assessed by means of the DCFH-DA to evaluate the presence of any oxidative stress. We propose herein simple cytotoxicity tests which indicate that these nanoparticles, after further studying, can serve as ideal drug carriers.

A Randomized Clinical Trial of Greek High Phenolic Early Harvest Extra Virgin Olive Oil in Mild Cognitive Impairment: The MICOIL Pilot Study.

BACKGROUND: Extra virgin olive oil (EVOO) constitutes a natural compound with high protection over cognitive function. OBJECTIVE: To investigate for the first time the effect of Greek High Phenolic Early Harvest Extra Virgin Olive Oil (HP-EH-EVOO) versus Moderate Phenolic (MP-EVOO) and Mediterranean Diet (MeDi) in people with mild cognitive impairment (MCI). METHODS: We conducted a randomized prospective study so as to examine the HP-EH-EVOO and MP-EVOO versus MeDi in MCI. Genetic predisposition (APOEɛ4) to Alzheimer's disease (AD) was tested and an extensive neuropsychological battery was administered at baseline and after 12 months. Each participant was randomized and assigned one of three groups: 1) Group 1 received the HP-EH-EVOO (50 mL/day); 2) Group 2 received the MP-EVOO (50 mL/day), and 3) Group 3 received only the MeDi instructions. RESULTS: Better follow-up performance was found in Group 1 compared to Group 2 and Group 3 in the almost all cognitive domains. Moreover, Group 2 showed also significant improvement compared to Group 3 in ADAS-cog (p = 0.001) and MMSE (p = 0.05), whereas Group 3 exhibited worse or similar to baseline performance in almost all domains. In particular, Group 1 and Group 2 had better outcomes with regards to ADAS-cog (p = 0.003), Digit Span (p = 0.006), and Letter fluency (p = 0.003). Moreover, there was a significant difference (p = 0.001) in the presence of APOEɛ4 between the Groups 1 and 2 versus Group 3. CONCLUSION: Long-term intervention with HP-EH-EVOO or MP-EVOO was associated with significant improvement in cognitive function compared to MeDi, independent of the presence of APOEɛ4.