Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet and University Hospital, Stockholm, Sweden.
Gastroenterology unit, Department of Gastroenterology, Dermatovenereology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden.
Nat Rev Gastroenterol Hepatol. 2022 Aug;19(8):493-507. doi: 10.1038/s41575-022-00604-y. Epub 2022 Apr 19.
Almost all currently available treatments for inflammatory bowel disease (IBD) act by inhibiting inflammation, often blocking specific inflammatory molecules. However, given the infectious and neoplastic disease burden associated with chronic immunosuppressive therapy, the goal of attaining mucosal healing without immunosuppression is attractive. The absence of treatments that directly promote mucosal healing and regeneration in IBD could be linked to the lack of understanding of the underlying pathways. The range of potential strategies to achieve mucosal healing is diverse. However, the targeting of regenerative mechanisms has not yet been achieved for IBD. Stem cells provide hope as a regenerative treatment and are used in limited clinical situations. Growth factors are available for the treatment of short bowel syndrome but have not yet been applied in IBD. The therapeutic application of organoid culture and stem cell therapy to generate new intestinal tissue could provide a novel mechanism to restore barrier function in IBD. Furthermore, blocking key effectors of barrier dysfunction (such as MLCK or damage-associated molecular pattern molecules) has shown promise in experimental IBD. Here, we review the diversity of molecular targets available to directly promote mucosal healing, experimental models to identify new potential pathways and some of the anticipated potential therapies for IBD.
几乎所有目前可用的治疗炎症性肠病（IBD）的方法都通过抑制炎症起作用，通常是阻断特定的炎症分子。然而，鉴于慢性免疫抑制治疗相关的传染性和肿瘤性疾病负担，实现无免疫抑制的黏膜愈合的目标很有吸引力。IBD 中缺乏直接促进黏膜愈合和再生的治疗方法可能与对潜在途径缺乏了解有关。实现黏膜愈合的潜在策略范围多种多样。然而，再生机制的靶向尚未在 IBD 中实现。干细胞作为一种再生治疗方法提供了希望，并在有限的临床情况下使用。生长因子可用于治疗短肠综合征，但尚未应用于 IBD。类器官培养和干细胞治疗的治疗应用可产生新的肠道组织，为恢复 IBD 的屏障功能提供新的机制。此外，阻断屏障功能障碍的关键效应物（如 MLCK 或损伤相关分子模式分子）在实验性 IBD 中显示出有希望的结果。在这里，我们回顾了可直接促进黏膜愈合的分子靶标的多样性、用于鉴定新的潜在途径的实验模型以及一些预期的 IBD 潜在治疗方法。
