Biology subjects

Esfandiari, L.

Publications and source records attributed to Esfandiari, L..

7 recordsLinked to original sources

bioRxiv2026

Defining characteristics of mesenchymal stem cell-derived matrix-bound nanovesicles compared to conditioned culture medium extracellular vesicles

Matrix-bound nanovesicles (MBVs) are a type of small extracellular vesicle (EV) embedded in the extracellular matrix (ECM) throughout the body. MBVs have been previously isolated from various tissues and in vitro-cultured cell sheets, demonstrating remarkable attributes in regenerative medicine. However, differences between MBVs and conditioned culture medium-derived EVs (liquid-EVs) have yet to be characterized, and the field currently lacks specific protein markers that can identify MBVs from other EV subtypes. Here, we isolate MBVs and liquid-EVs from bone marrow mesenchymal stem cell (MSC) sheets and define differences in size, protein, and zeta potential between these EVs. We show that there is a correlation between cell-driven ECM deposition and MBV and liquid-EV production. We also find that MBVs are smaller, contain less protein per particle, and possess lower zeta potential than liquid-EVs. Interestingly, MBVs also comprise a distinct tetraspanin profile compared to liquid-EVs, with MBVs containing more CD63 and little to no CD81. Finally, we define that CD63, LAMP1, Alix, ITG{beta}1, and GRP94 and their abundance, may be markers specifically used to identify MBVs from liquid-EVs. Our study paves the way for the characteristic differentiation between MBVs from liquid-EVs, elucidates their differences in biogenesis, and reveals a potential connection between EV and ECM production.

bioengineering↗

bioRxiv2025

Stage-specific extracellular vesicle cargo from Schwann cells orchestrates peripheral nerve regeneration

Schwann cells (SCs) play a critical role in peripheral nerve regeneration, undergoing dynamic phenotype transitioning from myelinating to repair stages following injury. While SC-derived extracellular vesicles (SC-EVs) have emerged as key mediators of intercellular communication during nerve repair, their stage-specific molecular cargo and functional roles remained incomplete understood. Here, we delineate protein, microRNA and lncRNA landscapes of SC-EVs across distinct differentiation stages, including immature, myelinating, and repair phenotypes, using an in vitro model of primary rat SCs. We show that myelinating SC-EVs are enriched with reprogramming factor SOX2 and neurotrophin receptor p75NTR, while repair SC-EVs carry distinct microRNAs predicted to modulate genes involved in myelin ensheathment, neuronal differentiation and neurogenesis. Moreover, repair SC-EVs contain long non-coding RNAs (lncRNAs) that may regulate miRNA activity. These findings reveal a novel mechanism by which SC-EVs orchestrate neuronal regeneration through stage-specific molecular cargo, and establishes a foundational model for investigating SC plasticity in peripheral nerve repair.

neuroscience↗

bioRxiv2025

Label-free monitoring of therapy response in 3D spheroids using lab-on-a-chip impedance spectroscopy

The high incidence and mortality of cancer continue to drive research and development of effective therapies. Lab-on-a-Chip (LOC) platforms have emerged as powerful alternatives to traditional biological evaluation methods, offering reduced complexity, lower costs, and improved throughput. In parallel, the integration of non-invasive and non-destructive sensing techniques have expanded opportunities for real-time and label-free analysis. Electrical impedance spectroscopy (EIS), which exploits the intrinsic dielectric properties of cells, has shown promise for the quantitative evaluation of 3D cellular structures. In this study, we demonstrate the application of LOC-based EIS to assess the bioeffects of radiotherapy on 3D head and neck cancer spheroids. Our results establish EIS as a viable tool for real-time monitoring of treatment-induced changes in 3D tumor models, supporting its potential in preclinical cancer research and therapeutic screening.

cancer biology↗

bioRxiv2025

Matrix stiffness modulated release of spheroid-derived extracellular vesicles and discovery of Piezo1 cargo

Augmented extracellular matrix (ECM) stiffness is a mechanical hallmark of cancer. Mechanotransduction studies have extensively probed the mechanisms by which ECM stiffness regulates intracellular communication. However, the influence of stiffness on intercellular communication aiding tumor progression in three-dimensional microenvironments remains unknown. Small extracellular vesicles (EVs) are communicators of altered biophysical cues to distant sites through EV-ECM interactions and EV-mediated recipient cell-ECM interactions. Here we demonstrate stiffness-mediated modulation of small EVs secretion and cargo from three-dimensional oral squamous cell carcinoma spheroids. Using a spheroid culture platform with varying matrix stiffness properties, we show that small EVs carry parental biomolecular cargo, including mechanosensitive Piezo1 ion channel and adhesion molecule CD44. We comprehensively validate the presence of both markers in our EV populations using proteomic and genetic analysis. Transcriptomic analysis of microRNA and long non-coding RNA cargo of small EVs released from soft and stiff ECM spheroids revealed enrichment of tumorigenic and metastatic profiles in EVs from stiff ECM cultures compared to that of soft ones. Gene set enrichment analysis of a comparative dataset obtained by overlaying spheroid mRNA and EV miRNA profiles identified key oncogenic pathways involved in cell-EV crosstalk in the spheroid model.

cancer biology↗

bioRxiv2024

Enhanced Piezoelectric Performance of PVDF-TrFE Nanofibers through Annealing for Tissue Engineering Applications

This study investigates bioelectric stimulations role in tissue regeneration by enhancing the piezoelectric properties of tissue-engineered grafts using annealed poly(vinylidene fluoride-trifluoroethylene) (PVDF-TrFE) scaffolds. Annealing at temperatures of 80{degrees}C, 100{degrees}C, 120{degrees}C, and 140{degrees}C was assessed for its impact on material properties and physiological utility. Analytical techniques such as Differential Scanning Calorimetry (DSC), Fourier-Transform Infrared Spectroscopy (FTIR), and X-ray Diffraction (XRD) revealed increased crystallinity with higher annealing temperatures, peaking in {beta}-phase content and crystallinity at 140{degrees}C. Scanning Electron Microscopy (SEM) showed that 140{degrees}C annealed scaffolds had enhanced lamellar structures, increased porosity, and maximum piezoelectric response. Mechanical tests indicated that 140{degrees}C annealing improved elastic modulus, tensile strength, and substrate stiffness, aligning these properties with physiological soft tissues. In vitro assessments in Schwann cells demonstrated favorable responses, with increased cell proliferation, contraction, and extracellular matrix attachment. Additionally, genes linked to extracellular matrix production, vascularization, and calcium signaling were upregulated. The foreign body response in C57BL/6 mice, evaluated through Hematoxylin and Eosin (H&E) and Picrosirius Red staining, showed no differences between scaffold groups, supporting the potential for future functional evaluation of the annealed group in tissue repair.

bioengineering↗

bioRxiv2024

Promoting Human Intestinal Organoid Formation and Stimulation Using Piezoelectric Nanofiber Matrices

Human organoid model systems have changed the landscape of developmental biology and basic science. They serve as a great tool for human specific interrogation. In order to advance our organoid technology, we aimed to test the compatibility of a piezoelectric material with organoid generation, because it will create a new platform with the potential for sensing and actuating organoids in physiologically relevant ways. We differentiated human pluripotent stem cells into spheroids following the traditional human intestinal organoid (HIO) protocol atop a piezoelectric nanofiber scaffold. We observed that exposure to the biocompatible piezoelectric nanofibers promoted spheroid morphology three days sooner than with the conventional methodology. At day 28 of culture, HIOs grown on the scaffold appeared similar. Both groups were readily transplantable and developed well-organized laminated structures. Graft sizes between groups were similar. Upon characterizing the tissue further, we found no detrimental effects of the piezoelectric nanofibers on intestinal patterning or maturation. Furthermore, to test the practical feasibility of the material, HIOs were also matured on the nanofiber scaffolds and treated with ultrasound, which lead to increased cellular proliferation which is critical for organoid development and tissue maintenance. This study establishes a proof of concept for integrating piezoelectric materials as a customizable platform for on-demand electrical stimulation of cells using remote ultrasonic waveforms in regenerative medicine.

bioengineering↗

bioRxiv2024

Machine Learning Approaches in Label-Free Small Extracellular Vesicles Analysis with Surface-Enhanced Raman Scattering (SERS) for Cancer Diagnostics

Early diagnosis remains of pivotal importance in reducing patient morbidity and mortality in cancer. To this end, liquid biopsy is emerging as a tool to perform broad cancer screenings. Small extracellular vesicles (sEVs), also called exosomes, found in bodily fluids can serve as important cancer biomarkers in these screenings. Our group has recently developed a label-free electrokinetic microchip to purify sEVs from blood. Herein, we demonstrate the feasibility to integrate this approach with surface-enhanced Raman scattering (SERS) analysis. SERS can be used to characterized extracted sEVs through their vibrational fingerprint that changes depending on the origin of sEVs. While these changes are not easily identified in spectra, they can be modeled with machine learning (ML) approaches. Common ML approaches in the field of spectral analysis use dimensionality reduction method that often function as a black box. To avoid this pitfall, we used Shapley additive explanations (SHAP) is a type of explainable AI (XAI) that bridges ML models and human comprehension by calculating the specific contribution of individual features to a models predictions, directly correlating model/decisions with the original data. Using these approaches we demonstrated a proof-of-concept model predictive of cancer from isolated sEVs, integrating the electrokinetic device and SERS. This work explores the use of explainable AI to perform diagnostic analysis on complex SERS data of clinical samples, while reporting interpretable biochemical information. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=74 SRC="FIGDIR/small/581099v2_ufig1.gif" ALT="Figure 1"> View larger version (18K): org.highwire.dtl.DTLVardef@1cbcb8aorg.highwire.dtl.DTLVardef@9ffc00org.highwire.dtl.DTLVardef@15999a9org.highwire.dtl.DTLVardef@1775726_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗