THE IMPROVEMENT OF INFARCTED MYOCARDIAL CONTRACTILE FORCE AFTER AUTOLOGOUS SKELETAL MUSCLE SATELLITE CELL IMPLANTATION

Objective To study the improvement of infarcted myocardial contractile force after autologous skeletal muscle satellite cell implantation via intracoronary arterial perfusion. Methods Skeletal muscle cells were harvested from gluteus max of adult mongrel dogs and the cells were cultured and expanded before being labeled with DAPI (4’, 6-diamidino-2-phenylindone). The labeled cells were then implanted into the acute myocardial infarct site via the ligated left anterior descending (LAD) coronary artery. Specimens were taken at 2nd, 4th, 8th week after myoblast implantation for histologic and contractile force evaluation, respectively. Results The satellite cells with fluorescence had been observed in the infarct site and also in papi- llary muscle with consistent oriented direction of host myocardium. A portion of the implanted cells had differen- tiated into muscle fibers. Two weeks after implantation, the myocardial contractile force showed no significant difference between the cell implant group and control group. At 4 and 8 week, the contractile force in the cell implant group was better than that in control group. Conclusion The skeletal muscle satellite cells, implanted into infarct myocardium by intracoronary arterial perfusion, could disseminate through the entire infarcted zone with myocardial regeneration and improve the contractile function of the infarcted myocardium.

Understanding the interplay between cell force and cell adhesion processes

Cells,wrapped among their neighbors and surrounding extracellular matrix(ECM),form cell-cell adhesions and cell-ECM adhesions.Extracellular biophysical cues exert a far-reaching influence on a sweeping of cell behaviors,including signal transduction,gene expression,and fate determination.Cell-cell adhesions mediated by inter-cellular adhesion molecules bridge the membranes of adjacent cells through either heterophilic or homophilic adhesive interactions,playing a critical part in multicellular structural maintenance and,therefore,a foundation for multicellular organisms.Cell-ECM adhesions are derived from the interaction between cell adhesion receptors and multi-adhesive matrix proteins to ensure cell and tissue cohesion.Whereas cells not only unilaterally respond to certain cues from extracellular environment but can also alter the physicochemical profiles of the externalities and hence hold important implications for clinical applications.The essential function of cell adhesions has cre-ated tremendous interests in developing methods for measuring and studying cell adhesion properties,namely,cellular force.Here,we describe the collection of cell adhesive inputs on cellular signaling cascades and the“crosstalk”between cell-cell adhesions and cell-ECM adhesions.Furthermore,we provide the summary of the current methods to measure such cell adhesive forces.

Atomic force microscopy studies on cellular elastic and viscoelastic properties

In this work, a method based on atomic force microscopy (AFM) approach-reside-retract experiments was established to simultaneously quantify the elastic and viscoelastic properties of single cells. First, the elastic and viscoelastic properties of normal breast cells and cancerous breast cells were measured, showing significant differences in Young’s modulus and relaxation times between normal and cancerous breast cells. Remarkable differences in cellular topography between normal and cancerous breast cells were also revealed by AFM imaging. Next, the elastic and viscoelasitc properties of three other types of cell lines and primary normal B lymphocytes were measured; results demonstrated the potential of cellular viscoelastic properties in complementing cellular Young’s modulus for discerning different states of cells. This research provides a novel way to quantify the mechanical properties of cells by AFM, which allows investigation of the biomechanical behaviors of single cells from multiple aspects.

Changes of Bone Remodeling-related Factors of HPDLF Regulated by Estrogen and Tensile Strain

Estrogen deficiency has been proposed as a risk factor for alveolar bone loss, but whether or not estrogen will influcence the bone rebuilting process during orthodontic tooth movement and what the mechanisms involved remain unclear. The paper aims to provide new information that may elucidate the modulatory effect of estrogen on the bone-resorbing cytokines RANKL and its anti-resorptive factor OPG secrected by HPLFs which are already force-stimulated. The expression of OPG mRNA is rising after mechanical loading either with or without stimulated by estrogen before. But HPDL cells exposured to estrogen for 24 h before loaded tend to express more OPG mRNA. Compared with the no-estrogen group, the inhibit trend of RANKL mRNA is much more apparent in with-estrogen group. Moreover, estrogen and mechanic force time-dependently increased OPG expression and attenuated the RANKL expression.

A chemotaxis model to explain WHIM neutrophil accumulation in the bone marrow of WHIM mouse model

Neutrophils are essential immune cells that defend the host against pathogenic microbial agents.Neutrophils are produced in the bone marrow and are retained there through CXCR4–CXCL12 signaling.However,patients with the Warts,Hypogammaglobulinemia,Infections,and Myelokathexis(WHIM)syndrome are prone to infections due to increased accumulation of neutrophils in the bone marrow leading to low numbers of circulating neutrophils.How neutrophils accumulate in the bone marrow in this condition is poorly understood.To better understand factors involved in neutrophil accumulation in the bone marrow,neutrophils from wildtype and WHIM mouse models were characterized in their response to CXCL12 stimulation.WHIM neutrophils were found to exert stronger traction forces,formed significantly more lamellipodia-type protrusions and migrated with increased speed and displacement upon CXCL12 stimulation as compared to wildtype cells.Migration speed of WHIM neutrophils showed a larger initial increase upon CXCL12 stimulation,which decayed over a longer time period as compared to wildtype cells.We proposed a computational model based on the chemotactic behavior of neutrophils that indicated increased CXCL12 sensitivity and prolonged CXCR4 internalization adaptation time in WHIM neutrophils as being responsible for increased accumulation in the bone marrow.These findings provide a mechanistic understanding of bone marrow neutrophil accumulation in WHIM condition and novel insights into restoring neutrophil regulation in WHIM patients.