Biology subjects

Mousavi, A.

Publications and source records attributed to Mousavi, A..

5 recordsLinked to original sources

bioRxiv2025

Patient-Specific 3D Heart-On-a-Chip Model of Dilated Cardiomyopathy with Embedded Bead-Based Mapping of Tissue Contractility

Dilated cardiomyopathy (DCM) is the leading cause of heart transplantation, with a 50% risk of progression to heart failure within five years. Conventional disease modeling approaches fail to recapitulate the sophisticated function of the human heart. Alternatively, heart-on-a-chip (HOC) platforms enable real-time monitoring of disease progression and drug responses using miniaturized engineered heart tissues. Here, we developed a functional HOC model using patient-specific human induced pluripotent stem cells (hiPSCs), reprogrammed from the patients blood samples. The chip contains two cell-seeding chambers with flexible silicone pillars to support tissue formation. Healthy and DCM hiPSCs were differentiated into cardiomyocytes, combined with an optimized ratio of human cardiac fibroblasts, encapsulated in a fibrin/Geltrex hydrogel (containing fluorescent beads), and seeded in the device chambers. The tissue gradually compacted and started beating spontaneously. Immunofluorescence assay revealed structural abnormalities in DCM tissues, including reduced cell alignment and elongation. The tissue functional responses (e.g., calcium transients and beating) were investigated after 2 weeks of culture, revealing ventricular tachycardia in DCM tissue and highlighting functional hallmarks of the disease. Finally, the model was validated using a drug with known inotropic and chronotropic effects (i.e., norepinephrine). Our platform demonstrated great potential in drug screening, disease modeling, and personalized medicine.

bioengineering↗

bioRxiv2025

Heart-On-a-Chip with Integrated Ultrasoft Mechanosensors for Continuous Measurement of Cell- and Tissue-scale Contractile Stresses

Heart-on-a-chip platforms aim to miniaturize and replicate the complex structure and function of cardiac tissue. Traditionally, microfabricated pillar pairs have been employed in these systems to provide tissue anchorage and determine contractility parameters based on pillar deflection. However, this approach lacks the spatial resolution required to capture local cell- and tissue-scale mechanical stresses. In this study, we established a non-destructive optical method for continuous micro- and macro-scale contractile force measurements. We utilized our previously developed edge-labeled micro-spherical stress gauges (eMSGs) to map the stresses within a heart-on-a-chip. These ultrasoft mechanosensors visibly deform in response to stresses generated by cells and the extracellular matrix (ECM). The chip consisted of two cell-seeding chambers, each containing flexible silicone pillar pairs to support tissue formation and compaction. Neonatal rat cardiomyocytes (CMs) were encapsulated in a fibrin/Geltrex hydrogel mixture containing eMSGs and seeded into each chamber. Over time, the tissue compacted and began beating spontaneously, demonstrating structural alignment and functional cardiac hallmarks, such as calcium transients and tissue-scale beating. The effects of ECM composition on tissue function were examined, revealing that lower fibrin concentrations significantly enhanced contractile frequency, regularity, and stress generation. Local cell- and ECM-scale mechanics were further investigated by analyzing the shape changes of the dispersible sensors. Lateral and longitudinal stresses were calculated for each sensor, highlighting the critical role of tissue compaction and contraction in cell-generated forces. Finally, the platform was validated using two known drug candidates, with their effects on contractility clearly demonstrated.

bioengineering↗

bioRxiv2024

Evaluation of Iron Oxide Nanoparticles for Lymph Node Detection with Magnetomotive Ultrasound- A Pilot Study in Rats

IntroductionThe inadequate detection of lymph node metastases by current imaging methods has led to overtreatment in rectal cancer. Magnetomotive ultrasound (MMUS) has the potential of being a more accurate diagnostic imaging method for lymph node metastases. This method is based on the detection of tissue movement that is induced by the vibration of iron oxide nanoparticles, caused by an external alternating magnetic field. This study investigated the suitability of the subcutaneous administration of two iron oxide nanoparticles--Ferrotran(R) and Magtrace(R)--and their distribution in lymph nodes, with regard to the possibility of identifying lymph node metastases in rectal cancer by MMUS. MethodsMale Sprague Dawley rats were injected subcutaneously with 10.7 mg Ferrotran(R) (n=9), 10.5 mg Magtrace(R) (n=9), or saline (n=3) dorsally at the root of the tail. On euthanization of the rats after 1, 5, and 24 hours, the proximal and distal lymph nodes were harvested and analyzed by histology [hematoxylin/eosin, Perls Prussian Blue (PPB)] and inductively coupled plasma-optical emission spectroscopy. The primary aim was to evaluate the distribution of the iron oxide nanoparticles throughout the lymphatic system; the general health of the rats after subcutaneous administration of these nanoparticles was also monitored. ResultsAt 1 hour after subcutaneous injection, Ferrotran(R) and Magtrace(R) accumulated in the proximal lymph nodes. After 24 hours, both particles had spread to distal lymph nodes, but only Ferrotran(R) reached the mesenteric and mandibular lymph nodes. In addition, Ferrotran(R) penetrated the lymph nodes more deeply than Magtrace(R) at 24 hours. No toxicity was observed with either nanoparticle. ConclusionAlthough both compounds disseminated well, Ferrotran(R) accumulated better and more rapidly in lymph nodes than Magtrace(R). Because accumulation and time are important parameters for imaging, our data indicate that Ferrotran(R) is a potentially more suitable particle for MMUS in clinical use.

biophysics↗

bioRxiv2024

The Surgical Method of Craniectomy Differentially Affects Acute Seizures, Brain Deformation and Behavior in a TBI Animal Model

Traumatic brain injury (TBI) is the leading cause of morbidity and mortality worldwide. Multiple injury models have been developed to study this neurological disorder. One such model is the lateral fluid-percussion injury (LFPI) rodent model. The LFPI model can be generated with different surgical procedures that could affect the injury and be reflected in neurobehavioral dysfunction and acute EEG changes. A craniectomy was performed either with a trephine hand drill or with a trephine electric drill that was centered over the left hemisphere of adult, male Sprague Dawley rats. Sham craniectomy groups were assessed by hand-drilled (ShamHMRI) and electric-drilled (ShamEMRI) to evaluate by MRI. Then, TBI was induced in separate groups (TBIH) and (TBIE) using a fluid-percussion device. Sham-injured rats (ShamH/ShamE) underwent the same surgical procedures as the TBI rats. During the same surgery session, rats were implanted with screw and microwire electrodes positioned in the neocortex and hippocampus and the EEG activity was recorded 24 hours for the first 7 days after TBI for assessing the acute EEG seizure and Gamma Event Coupling (GEC). The electric drilling craniectomy induced greater tissue damage and sensorimotor deficits compared to the hand drill. Analysis of the EEG revealed acute seizures in at least one animal from each group after the procedure. Both TBI and Sham rats from the electric drill groups had a significant greater total number of seizures than the animals that were craniectomized manually (p<0.05). Similarly, EEG functional connectivity was lower in ShamE compared to ShamH rats. These results suggest that electrical versus hand drilling craniectomies produce cortical injury in addition to the LFPI which increases the likelihood for acute post-traumatic seizures. Differences in the surgical approach could be one reason for the variability in the injury that makes it difficult to replicate results between preclinical TBI studies.

neuroscience↗

bioRxiv2022

TEMPRANILLO homologs in apple regulate flowering time in the woodland strawberry Fragaria vesca

Many economically valuable fruit trees belong to the Rosaceae family. The long juvenile period of fruit trees makes their breeding costly and time-consuming. Therefore, flowering time regulation and shortening the juvenile phase have been a breeding priority for genetic improvement of fruit tree crops. TEMPRANILLO genes act as floral inhibitors in Arabidopsis and so, two orthologs of this gene were isolated here from apple (Malus domestica) and functionally analysed in Arabidopsis and woodland strawberry by being overexpressed in both model plants, and partially silenced in strawberry. The overexpression of MdTEM genes down-regulated FvFT1, FvGA3OX1, and FvGA3OX2 genes in strawberry. The overexpression lines exhibited delayed flowering, both in terms of days to flowering and the number of leaves at flowering. RNAi-mediated silencing of TEM resulted in early flowering plants. These plants flowered approximately five days earlier than wild type plants with a lower number of leaves. However, the overexpression of MdTEM genes could not functionally rescue the Arabidopsis mutants. According to the results, it can be concluded that MdTEM1 and MdTEM2 are orthologs of FvTEM gene, which play an important role in regulating the juvenile phase and flowering time through controlling FT and GA biosynthetic gene expression.

plant biology↗