Exosomes derived from umbilical cord mesenchymal stem cells promote healing of complex perianal fistulas in rats

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Background Complex perianal fistulas, challenging to treat and prone to recurrence, often require surgical intervention that may cause fecal incontinence and lower quality of life due to large surgical wounds and potential sphincter damage. Human umbilical cord-derived MSCs (hUC-MSCs) and their exosomes (hUCMSCs-Exo) may promote wound healing. Methods This study assessed the efficacy, mechanisms, and safety of these exosomes in treating complex perianal fistulas in SD rats. We established a rat model, divided rats with fistulas into the control and the exosome groups. We assessed treatment efficacy through ultrasound, clinical observations, and histopathological analysis. We also evaluated the activation of the HIF-1α/TGF-β/Smad signaling pathway via PCR and Western blot and assessed serological markers for HIF-1α and inflammatory indices through ELISA. We analyzed gut microbiota and the systemic metabolic environment via untargeted metabolomics. Results The hUCMSCs-Exo effectively promoted healing of wound, regulated the immune balance enhanced collagen synthesis and angiogenesis in the perianal fistulas model of rats, and regulated the gut microbiota and metabolomic profiles. Results of PCR and Western blot analyses indicated that the exosomes activated HIF-1α/TGF-β/Smad signaling pathways. To the dosages tested, the 10ug/100ul concentration (medium dose) was found to be the

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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