Background and objectives:Exosomes therapy is a promising technique that can decrease the concern related to the fate of transplanted stem cells to the fistula location. The unique properties of mesenchymal stem cells (MSCs)-derived exosomes can improve fistula healing because of their high ability to regulate and modify immune responses. This project aims to examine the safety and efficacy of implementing MSCs-exosomes in treating refractory fistulas in inflammatory bowel disease (IBD) patients.Methods:The exosomes were isolated from umbilical cord-derived MSCs and characterized using flow cytometry, western blotting, and transmittance electron microscope (TEM). Five patients (three men and two women) with refractory perianal Crohn's disease with an average age of 35.4 years old were included. The patients did not match the exclusion criteria, and the presence of refractory fistulas was the main inclusion criteria. These patients have their exosomes injections in the operation room. The therapy responses of patients were assessed using physical examination, face-to-face interviews, computerized tomography (CT) scan, and magnetic resonance imaging (MRI) six months later.Result:The Following injection, patients reported a 70% improvement on average. Two patients claimed complete healing after exosome injections, while one patient reported no improvement and active discharge from the fistula site. In addition, five patients reported no adverse effects, both systemic or on the injection site.Conclusion: Injection of exosomes extracted from MSCs shows total safety and a satisfactory therapeutic impact, as shown in this and other research, and could play a significant role in the treatment of gastrointestinal fistulas in the future.

The potential use of gene- modified cell therapy in hematologic malignancies is often limited by complications related to effectively engineering and manufacturing cells with conventional delivery systems and is challenge specifically for immune cells. In fact, this life-saving therapy requires use of inefficient reagents and specialized equipment that can drive up the price of the treatment. Herein, we compared two different approaches for gene transfer into target cells: Nucleofection as a 2D gene delivery and microfluidic device as a 3D gene transfer technology. In fact, we developed and used serpentine microfluidic chip for cell membrane penetration that permits delivery of DNA into Multiple myeloma cells. We achieved high transfection efficiency (55.7% GFP) in myeloma cells with high cell viability (by PI staining) 24-48 hours after microfluidic processing compared to nucleofection that is toxic and rate of dead cells is very high. The significant differences in outcomes from the two techniques underscores the importance of understanding the impact of intracellular delivery techniques on cell function for research and clinical applications. Altogether, these results highlight the use of microfluidic device as a rapid and gentle delivery method with promising potential to engineer primary human cells for research and clinical applications.

Co-transplantation of MSCs and HSCs has showed controversial results for treatment of GvHD. In this study, the level of predictor factors and GvHD biomarkers have been checked. The co-transplantation of HSCs and MSCs did not show a significant difference compared to the group received MSCs alone.