Biology subjects

Tehrani, K. F.

Publications and source records attributed to Tehrani, K. F..

3 recordsLinked to original sources

bioRxiv2022

Integration of imaging modalities with lipidomic characterization to investigate MSCs potency metrics

Mesenchymal stem cells (MSCs) are widely used as therapeutics targets for numerous autoimmune diseases. However, MSC therapies have had limited success so far in clinical trials, mainly being heterogenous population it is difficult to determine MSCs efficiencies. It is critical to understand internal signaling of individual MSCs population that directly affect the cell phenotype. Lipid signaling is closely associated with cell shape so, a holistic approach to understand how changes in lipid metabolites trickles all the way to single cell phenotype could reveal deeper understanding of MSCs functional regulation. So, we aim to evaluate lipid metabolic profiles of single cell MSCs with known variability in immune regulation and explore the phenotypic changes that occur because of differences in lipid signaling. We use longitudinal label free phase imaging strategies to obtain cell phenotypic features which are directly correlated with single cell lipid metabolome obtained using advanced MALDI-MSI technique. Correlation maps indicate associations between lipid signaling and phenotypic changes in MSCs. Moreover, a novel machine learning clustering approach detects the heterogeneity in the MSCs subpopulation then methodically see how each heterogenous population is being impacted by the changes in lipid profiles which could be linked to the functional behaviors of the cell.

cell biology↗

bioRxiv2019

PGC-1α overexpression partially rescues impaired oxidative and contractile pathophysiology following volumetric muscle loss injury

Volumetric muscle loss (VML) injury is characterized by a non-recoverable loss of muscle fibers due to ablative surgery or severe orthopaedic trauma, that results in chronic functional impairments of the soft tissue. Currently, the effects of VML on the oxidative capacity and adaptability of the remaining injured muscle are unclear. A better understanding of this pathophysiology could significantly shape how VML-injured patients and clinicians approach regenerative medicine and rehabilitation following injury. Herein, the data indicated that VML-injured muscle has diminished mitochondrial content and function (i.e. oxidative capacity), loss of mitochondrial network organization, and attenuated oxidative adaptations to exercise. However, forced PGC-1 over-expression rescued the deficits in oxidative capacity and muscle strength. This implicates physiological activation of PGC1- as a limiting factor in VML-injured muscle adaptive capacity and provides a mechanistic target for regenerative rehabilitation approaches to address the skeletal muscle dysfunction.

physiology↗

bioRxiv2018

Chronic Electrical Stimulation Promotes the Excitability and Plasticity of ESC-derived Neurons following Glutamate-induced Inhibition In vitro

Functional electrical stimulation (FES) is rapidly gaining traction as a therapeutic tool for mediating the repair and recovery of the injured central nervous system (CNS). However, the underlying mechanisms and impact of these stimulation paradigms at a molecular, cellular and network level remain largely unknown. In this study, we used embryonic stem cell (ESC)-derived neuron and glial cocultures to investigate network maturation following acute administration of L-glutamate, which is a known mediator of excitotoxicity following CNS injury. We then modulated network maturation using chronic low frequency stimulation (LFS) and direct current stimulation (DCS) protocols. We demonstrated that L-glutamate impaired the rate of maturation of ESC-derived neurons and glia immediately and over a week following acute treatment. The administration of chronic LFS and DCS protocols individually following L-glutamate infusion significantly promoted the excitability of neurons as well as network synchrony, while the combination of LFS/DCS did not. qRT-PCR analysis revealed that LFS and DCS alone significantly up-regulated the expression of excitability and plasticity-related transcripts encoding N-methyl-D-aspartate (NMDA) receptor subunit (NR2A), brain-derived neurotrophic factor (BDNF) and Ras-related protein (RAB3A). In contrast, the simultaneous administration of LFS/DCS down-regulated BDNF and RAB3A expression. Our results demonstrate that LFS and DCS stimulation can modulate network maturation excitability and synchrony following the acute administration of an inhibitory dose of L-glutamate, as well as an upregulation of NR2A, BDNF and RAB3A gene expression. Our study also provides a novel framework for investigating the effects of electrical stimulation on neuronal responses and network formation/repair after traumatic brain injury.

neuroscience↗