Division of Gastroenterology and Hepatology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.
Sci Adv. 2023 Jan 4;9(1):eade1067. doi: 10.1126/sciadv.ade1067.
Perianal fistulas (PAFs) represent a severe complication of Crohn's disease (CD). Despite the advent of biologic and small-molecule therapeutics for luminal disease, PAFs in CD (CD-PAF) are relatively resistant to treatment, with less than 50% responding to any therapy. We report an injectable, biodegradable, mechanically fragmented nanofiber-hydrogel composite (mfNHC) loaded with adipose-derived stem cells (ADSCs) for the treatment of fistulas in a rat model of CD-PAF. The ADSC-loaded mfNHC results in a higher degree of healing when compared to surgical treatment of fistulas, which is a standard treatment. The volume of fistulas treated with mfNHC is decreased sixfold compared to the surgical treatment control. Molecular studies reveal that utilization of mfNHC reduced local inflammation and improved tissue regeneration. This study demonstrates that ADSC-loaded mfNHC is a promising therapy for CD-PAF, and warrants further studies to advance mfNHC toward clinical translation.
肛周瘘管（PAFs）是克罗恩病（CD）的严重并发症。尽管生物制剂和小分子治疗药物已用于腔道疾病，但 CD 相关的 PAFs（CD-PAF）对治疗相对耐药，不到 50%的患者对任何治疗有反应。我们报告了一种可注射、可生物降解、机械断裂的纳米纤维-水凝胶复合材料（mfNHC），其中负载脂肪来源的干细胞（ADSCs），用于治疗 CD-PAF 大鼠模型中的瘘管。与瘘管的手术治疗（一种标准治疗）相比，负载 ADSC 的 mfNHC 导致更高程度的愈合。与手术治疗对照组相比，mfNHC 治疗的瘘管体积减少了六倍。分子研究表明，mfNHC 的使用减少了局部炎症并改善了组织再生。这项研究表明，负载 ADSC 的 mfNHC 是治疗 CD-PAF 的一种有前途的疗法，值得进一步研究以推进 mfNHC 向临床转化。
