Biomedical subjects

Mitra Lavasani

Publications and source records attributed to Mitra Lavasani.

3 recordsLinked to original sources

PubMed2006

Nerve growth factor improves the muscle regeneration capacity of muscle stem cells in dystrophic muscle.

Researchers have attempted to use gene- and cell-based therapies to restore dystrophin and alleviate the muscle weakness that results from Duchenne muscular dystrophy (DMD). Our research group has isolated populations of muscle-derived stem cells (MDSCs) from the postnatal skeletal muscle of mice. In comparison with satellite cells, MDSCs display an improved transplantation capacity in dystrophic mdx muscle that we attribute to their ability to undergo long-term proliferation, self-renewal, and multipotent differentiation, including differentiation toward endothelial and neuronal lineages. Here we tested whether the use of nerve growth factor (NGF) improves the transplantation efficiency of MDSCs. We used two methods of in vitro NGF stimulation: retroviral transduction of MDSCs with a CL-NGF vector and direct stimulation of MDSCs with NGF protein. Neither method of NGF treatment changed the marker profile or proliferation behavior of the MDSCs, but direct stimulation with NGF protein significantly reduced the in vitro differentiation ability of the cells. NGF stimulation also significantly enhanced the engraftment efficiency of MDSCs transplanted within the dystrophic muscle of mdx mice, resulting in the regeneration of numerous dystrophin-positive muscle fibers. These findings highlight the importance of NGF as a modulatory molecule, the study of which will broaden our understanding of its biologic role in the regeneration and repair of skeletal muscle by musclederived cells.

Animals↗

PubMed2003

Fiber orientation and cell-cell coupling influence ventricular fibrillation dynamics.

UNLABELLED: Cell Coupling Influences VF Dynamics. INTRODUCTION: The structure of ventricular fibrillation (VF) is influenced by regional differences in action potential durations and perhaps restitution kinetics and fiber anisotropy. The spatial organization of VF was investigated by measuring the cross-correlation (CC) and mutual information (MI) of membrane potential (Vm) oscillations recorded from multiple sites. METHODS AND RESULTS: Rabbit hearts (n = 6) were retrogradely perfused and stained with di-4-ANEPPS, and VF was elicited by burst pacing. Vm oscillations were recorded optically from multiple locations on the epicardium using a 16 x 16 photodiode array or a 72 x 78 CCD camera. The spatial organization of VF was investigated by calculating the maximum CC (CCmax) and MI (MImax) that can be obtained between any two sites. CCmax and MImax were extended to all pixels and served as indices of the similarities between Vm transients at a reference pixel and all other pixels on the map. We found that maps of CCmax and MImax did not contain discrete regions with high CC or MI. However, CCmax and MImax decreased monotonically with increasing distance between any arbitrarily chosen reference pixel and all other pixels. In VF, maps of CCmax and MImax revealed elliptical gradients of CC and MI that were closely aligned with fiber orientation, with major axis at 127 degrees +/- 8 degrees on the left ventricles. CONCLUSION: CC and MI analysis in fibrillation provides new evidence that anisotropy of fiber orientation and cell-cell coupling have a direct influence on VF dynamics.

Action Potentials↗

PubMed2002

Environmental factors in Parkinson's disease.

Evidence discussed in this review article lends strong support in favor of an etiologic role of environmentalfactors in Parkinson's disease. First, thanks to the discovery of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), it is now clear that, by targeting the nigrostriatal system, neurotoxicants can reproduce the neurochemical and pathological features of idiopathic parkinsonism. The sequence of toxic events triggered by MPTP has also provided us with intriguing clues concerning mechanisms of toxicant selectivity and nigrostriatal vulnerability. Relevant examples are (i) the role of the plasma membrane dopamine transporter in facilitating the access of potentially toxic species into dopaminergic neurons; (ii) the vulnerability of the nigrostriatal system to failure of mitochondrial energy metabolism; and (iii) the contribution of inflammatory processes to tissue lesioning. Epidemiological and experimental data suggest the potential involvement of specific agents as neurotoxicants (e.g. pesticides) or neuroprotective compounds (e.g. tobacco products) in the pathogenesis of nigrostriatal degeneration, further supporting a relationship between the environment and Parkinson's disease. A likely scenario that emerges from our current knowledge is that neurodegeneration results from multiple events and interactive mechanisms. These may include (i) the synergistic action of endogenous and exogenous toxins (e.g. the ability of the pesticide diethyldithiocarbamate to promote the toxicity of other compounds); (ii) the interactions of toxic agents with endogenous elements (e.g. the protein alpha-synuclein); (iii) the tissue response to an initial toxic insult; and, last but not least, (iv) the effects of environmental factors on the background of genetic predisposition and aging.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗