Adipose-Derived Stem Cells of Blind Mole Rat Spalax Exhibit Reduced Homing Ability: Molecular Mechanisms and Potential Role in Cancer Suppression.

Adipose-derived stem cells (ADSCs) are recruited by cancer cells from the adjacent tissue, and they become an integral part of the tumor microenvironment. Here, we report that ADSCs from the long-living, tumor-resistant blind mole rat, Spalax, have a low ability to migrate toward cancer cells compared with cells from its Rattus counterpart. Tracking 5-ethynyl-2'-deoxyuridine (EdU)-labeled ADSCs, introduced to tumor-bearing nude mice, toward the xenografts, we found that rat ADSCs intensively migrated and penetrated the tumors, whereas only a few Spalax ADSCs reached the tumors. Moreover, rat ADSCs, but not Spalax ADSCs, acquired endothelial-like phenotype and incorporated in the intratumoral reticular structure resembling a vasculature. Likewise, endothelial-like cells differentiated from Spalax and rat ADSCs could form capillary-like structures; however, the tube densities were higher in rat-derived cells. Using time-lapse microscopy, in vitro wound-healing, and transwell migration assays, we demonstrated the impaired motility and low polarization ability of Spalax ADSCs. To assess whether the phosphorylated status of myosin light chain (MLC) is involved in the decreased motility of Spalax ADSCs, we inhibited MLC phosphorylation by blocking of Rho-kinase (ROCK). Inhibition of ROCK resulted in the suppression of MLC phosphorylation, acquisition of actin polarization, and activation of motility and migration of Spalax ADSCs. We propose that reduced ADSCs migration to cancer and poor intratumoral angiogenesis play a role in Spalax's cancer resistance. Learning more about the molecular strategy of noncancerous cells in Spalax to resist oncogenic stimuli and maintain a nonpermissive tumor milieu may lead us to developing new cancer-preventive strategy in humans. Stem Cells 2018;36:1630-1642.

Association of left atrial deformation indices with left atrial appendage thrombus in patients with non valvular atrial fibrillation.

AIM: Assessment of the value of left atrial deformation indices for prediction of left atrial appendage functioning patients with non-valvular atrial fibrillation. METHOD: The study included 250 patients with non-valvular atrial fibrillation and normal left atrial dimension. Trans-thoracic and trans-esophageal echocardiography were performed. Patients were divided into two groups; patients with LAA thrombus (group I) and patients without LAA thrombus (group II), a correlation between trans-esophageal and trans-thoracic data was analyzed. RESULTS: Group I included110 patients (44%) and Group II 140 patients (56%). By TDI mean LA strain and strain rate were lower in group I (21.89 ± 7.75% vs 35.14 ± 9.28%; p < 0.001) and (1.15/sec, IQR 0.12-3/sec versus 2.1/sec, IQR 0.21-3/sec, p < 0.001) respectively. By speckle tracking PALS and strain rate were lower in group I (24.79 ± 7.78% vs 37.63 ± 8.64%; p value < 0.001) and (0.95 ± 0.32/sec. Vs 1.27 ± 0.32/sec p, value < 0.001) respectively. By TEE; group I had lower LAA EF (39.2 ± 13.55% vs 53.86 ± 12.7%); p < 0.001, and lower LAA emptying velocity (17.53 cm/s, IQR 9.54-77.4 vs 63.5 cm/s, IQR 7.89-86.4; p < 0.001). There was a good correlation between LA TDI and speckle tracking PALS and PALSR and LAA EF% and velocity p < 0.001. TDI and PALS and PALSR were found to be significant predictors for LAA thrombus (P < 0.05) with good sensitivity and specificity. CONCLUSION: Left atrium deformation indices are predictors of LAA thrombus or SEC in patients with non-valvular AF with accepted sensitivity and specificity.