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Background Exosome administration is a novel medical approach that promises excellent immunomodulatory properties without the conventional side effects of current antitumor necrosis factor drugs and stem cells. This study aimed to assess the safety and efficacy of using mesenchymal stem cell (MSC) exosomes to treat refractory fistulas in patients with inflammatory bowel disease. Methods MSCs were derived from the umbilical cords and their exosomes were isolated. Five patients with refractory perianal Crohn’s disease fistulas with a median age of 35 years (range 31–47 years) were enrolled in the study. Exosome injections were administered in the operating room to patients with refractory fistula (fistulas that are irresponsive to anti-tumor necrosis factor-α administration within 6 months). Six months later, a physical examination, face-to-face interviews, and magnetic resonance imaging were employed to evaluate the therapy responses of patients. Results The outcomes within 6 months after initiation of therapy showed that four patients had responded to therapy. Three patients who received exosome injections exhibited complete healing, while one reported no improvement and active discharge from the fistula site. In addition, five patients (100%) reported neither systemic nor local adverse effects. Conclusions Injection of exosomes extracted from MSCs demonstrates safety and a satisfactory therapeutic effect, as evidenced in this and other studies, and may play a significant role in the future treatment of gastrointestinal fistulas.

Microfluidics is a promising approach for the facile and large-scale fabrication of monodispersed droplets for various applications in biomedicine. This technology has demonstrated great potential to address the limitations of regenerative medicine. Microfluidics provides safe, accurate, reliable, and cost-effective methods for encapsulating different stem cells, gametes, biomaterials, biomolecules, reagents, genes, and nanoparticles inside picoliter-sized droplets or droplet-derived microgels for different applications. Moreover, microenvironments made using such droplets can mimic niches of stem cells for cell therapy purposes, simulate native extracellular matrix (ECM) for tissue engineering applications, and remove challenges in cell encapsulation and three-dimensional (3D) culture methods. The fabrication of droplets using microfluidics also provides controllable microenvironments for manipulating gametes, fertilization, and embryo cultures for reproductive medicine. This review focuses on the relevant studies, and the latest progress in applying droplets in stem cell therapy, tissue engineering, reproductive biology, and gene therapy are separately evaluated. In the end, we discuss the challenges ahead in the field of microfluidics-based droplets for advanced regenerative medicine.

Background and Aim:A perianal fistula is an abnormal tract that connects anal canal to skin. Current medical and surgical interventions have a high failure rate particularly in complex and refractory cases. MSC-derived exosomes have demonstrated immunomodulatory effects without the conventional complications; hence, in this study, we evaluated the safety of their application for complex perianal fistula. Methods: Placenta-derived MSCs were cultured, and exosomes were isolated using ultracentrifugation. Exosome injections were administered in the operating room to 11 patients with complex perianal fistula (presence of fistulas for at least 1 year alongside medical and surgical treatment). The patients were followed for 6 months, and the patients were evaluated using physical examination, face-to-face interviews, and magnetic resonance imaging (MRI). Results: Among 11 patients only one did not show any improvement upon physical examination. Five patients showed complete tract resolve. While the discharge was stopped in eight patients, two patients showed only reduction. None of the patients showed any acute or latent allergic reaction or injection related complications. Conclusion: Administration of exosomes isolated from MSCs demonstrates safety and a satisfactory therapeutic effect in treatment complex perianal fistulae; therefore, it can be a candidate for future studies and might play a significant role in treatment.Ethical approval: This study was submitted to and ethically approved by the Iranian clinical registry system and committee under the reference number "IRCT20200413047063N3." This study was also approved by the Research Deputy and the Ethics Committee of the Tehran University of Medical Sciences (Reference number: IR.TUMS.IKHC. REC.1400.184). This study was also approved by the US Clinical Trial Registry (reference number: NCT05402748) and was carried out per the ethical standards outlined in the 1964 Declaration of Helsinki and all subsequent revisions. All participants signed a written informed consent form. Informed consent: All patients signed informed consent forms. Financial support: This study was self-funded by its authors and received no funding from any government/non-governmental organization. 1 Haleh Pak and Alireza Hadizadeh contributed equally to this study.