Lu Yafei, Huangfu Shaohua, Ma Chuanxue, Ding Yan, Zhang Yajie, Zhou Chungen, Liao Lianming, Li Ming, You Jia, Chen Yuting, Wang Dawei, Chen Ao, Jiang Bin
National Colorectal Disease CenterNanjing Hospital of Chinese Medicine, Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210022, Jiangsu, People's Republic of China.
Central Laboratory, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210022, Jiangsu, People's Republic of China.
Stem Cell Res Ther. 2024 Dec 29;15(1):414. doi: 10.1186/s13287-024-04028-0.
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.
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.
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 most effective to the treatment of complex perianal fistulas.
The hUCMSCs-Exo significantly promoted the healing of wound in perianal fistulas of rats and demonstrated higher safety. The underlying mechanism facilitating the healing process was likely associated with the activation of the HIF-1α/TGF-β/Smad signaling pathway.
复杂肛周瘘治疗具有挑战性且易于复发，通常需要手术干预，但由于手术创面大及可能损伤括约肌，会导致大便失禁及生活质量下降。人脐带间充质干细胞（hUC-MSCs）及其外泌体（hUCMSCs-Exo）可能促进伤口愈合。
本研究评估了这些外泌体治疗SD大鼠复杂肛周瘘的疗效、机制及安全性。我们建立了大鼠模型，将有瘘管的大鼠分为对照组和外泌体组。我们通过超声、临床观察及组织病理学分析评估治疗效果。我们还通过PCR和蛋白质免疫印迹法评估HIF-1α/TGF-β/Smad信号通路的激活情况，并通过酶联免疫吸附测定法评估HIF-1α的血清学标志物及炎症指标。我们通过非靶向代谢组学分析肠道微生物群和全身代谢环境。
hUCMSCs-Exo有效促进伤口愈合，调节免疫平衡，增强大鼠肛周瘘模型中的胶原蛋白合成和血管生成，并调节肠道微生物群和代谢组学谱。PCR和蛋白质免疫印迹分析结果表明，外泌体激活了HIF-1α/TGF-β/Smad信号通路。在所测试的剂量中，发现10μg/100μl浓度（中等剂量）对治疗复杂肛周瘘最有效。
hUCMSCs-Exo显著促进大鼠肛周瘘伤口愈合，并显示出更高的安全性。促进愈合过程的潜在机制可能与HIF-1α/TGF-β/Smad信号通路的激活有关。
