Biology subjects

Al Amir Dache, Z.

Publications and source records attributed to Al Amir Dache, Z..

3 recordsLinked to original sources

bioRxiv2024

Therapeutic potential of human mesenchymal stromal cell-derived mitochondria in a rat model of post-surgical digestive fistula: towards an energetic nano-biotherapy

BackgroundTissue regeneration heavily relies on cellular energy production, with mitochondria playing a crucial role. Dysfunctional mitochondria are implicated in various degenerative diseases, driving interest in targeting mitochondrial transplantation for tissue repair. Wound healing is highly compromised in gastrointestinal conditions resulting in fistula development, particularly after sleeve gastrectomy. Human mesenchymal stem/stromal cells (hMSCs) and their cell-free products such as mitochondria offer potential benefits due to their therapeutic properties on cellular energy production. Here we investigated the therapeutic advantage of hMSCs-derived mitochondria nano-biotherapy in a rat model of post-surgical fistula healing. MethodsViable and structurally intact mitochondria were isolated from hMSCs before exposure to human colonic epithelial cells (HCEC-1CT) culture or transplantation into a rat model of post-operative fistula. ResultsOur findings reveal significant dose-dependent improvement on cellular metabolic activity and ATP content of the recipient cells. Assessment of the external fistula orifice developed following post sleeve gastrectomy fistula, revealed a substantial healing in all transplanted rats compared to control group. ConclusionOur findings highlight the therapeutic potential of hMSCs-derived mitochondria in post-surgical fistula healing. This research contributes to advancing cell-free regenerative strategies for gastrointestinal conditions, offering new insights into mitochondrial-based therapies for enhancing wound healing and tissue repair.

systems biology↗

bioRxiv2022

Cholesterol and ceramide facilitate SARS-CoV-2 Spike protein-mediated membrane fusion

SARS-CoV-2 entry into host cells is mediated by the Spike (S) protein of the viral envelope. The S protein is composed of two subunits: S1 that induces binding to the host cell via its interaction with the ACE2 receptor of the cell surface and S2 that triggers fusion between viral and cellular membranes. Fusion by S2 depends on its heptad repeat domains that bring membranes close together, and its fusion peptide (FP) that interacts with and perturb the membrane structure to trigger fusion. Recent studies suggest that cholesterol and ceramide lipids from the cell surface may facilitate SARS-CoV-2 entry into host cells, but their exact mode of action remains unknown. We have used a combination of in vitro liposome-liposome and in situ cell-cell fusion assays to study the lipid determinants of S-mediated membrane fusion. We found that cholesterol and ceramide both facilitated fusion, suggesting that targeting lipids could be effective against SARS-CoV-2. As proof of concept, we examined the effect of chlorpromazine (CPZ), an antipsychotic drug known to perturb membrane structure. We found that CPZ inhibited S-mediated membrane fusion and thus potentially SARS-CoV-2 entry.

biophysics↗

bioRxiv2021

Plasma derived cell-free mitochondrial DNA originates mainly from circulating cell-free mitochondria

Circulating mitochondrial DNA (cir-mtDNA) could have a potential comparable to circulating nuclear DNA (cir-nDNA), with numerous applications. However, research and development in this area have fallen behind, particularly considering its origin and structural features. To tackle this, we initially combined Q-PCR and low-pass whole genome sequencing in the same analytical strategy previously and successfully used for cir-nDNA. This revealed unexplained structural patterns and led us to correlate these data with observations made during physical examinations such as filtration, and differential centrifugation in various plasma preparations. Both the integrity index and number of reads revealed a very minor proportion of low size-ranged fragments (<1000 bp) in plasma obtained with a standard preparation (0.06%). Filtration and high speed second step centrifugation revealed that 98.7 and 99.4% corresponded to extracellular mitochondria either free or in large extracellular vesicles. When avoiding platelet activation during plasma preparation, the proportion of both types of entities was still preponderant (76-80%), but the amount of detected mitochondrial DNA decreased 67-fold. In correlation with our previous study on the presence of circulating cell-free mitochondria in blood, our differential centrifugation procedure suggested that cir-mtDNA is also associated with approximately 18% small extracellular vesicles, 1.7% exosomes and 4% protein complexes.

genomics↗