干细胞移植在炎症性肠病治疗中的应用

随着干细胞和炎症性肠病(IBD)研究的深入,干细胞移植在IBD治疗中的应用取得一些进展。此文主要介绍了自体造血干细胞移植,同种异基因造血干细胞移植和间充质干细胞移植在IBD治疗中的应用。     

生物学制剂和干细胞移植治疗炎症性肠病的进展

炎症性肠病（IBD）是一种病因复杂的肠道慢性炎症性疾病。治疗IBD的传统药物虽能控制症状,但多数患者反复发作迁延不愈。新近研究的生物学制剂、干细胞移植等疗法已逐渐用于临床,较传统药物凸显出一定的优势,成为近年来IBD治疗学的研究热点,该文就此两种新疗法进行概述。     

炎症性肠病及其干细胞移植再生修复

炎症性肠病(IBD)在我国发病率逐步升高,其相关病理学研究和再生修复成为研究的热点.炎症性肠病存在易感基因NOD2,发病与感染、饮食、药物、肠道菌群变化及免疫因素有关.肠道干细胞,具有自我更新与增殖能力.肠黏膜被破坏时,陷窝残存的干细胞向外生长并移行,重建绒毛直至肠黏膜恢复正常.肠道干细胞的增殖和分化与多种细胞因子作用有关.造血干细胞移植治疗IBD是最近出现的一种新型治疗方法,自体与异体移植均有较好临床疗效,基础研究已经证实移植的造血干细胞可以定居于肠道上皮,但移植修复损伤肠道黏膜的详细机制则有待于深入研究.     

干细胞治疗炎症性肠病的研究进展

炎症性肠病的患病人数在我国高速增长，传统药物治疗难以改变病程，且2/3的患者存在生物制剂失应答，亟需开发新疗法实现黏膜愈合。隐窝肠干细胞可分化成肠上皮细胞，并与肠上皮细胞协同修复肠道黏膜，维持肠道内稳态。炎症性肠病患者免疫功能紊乱，破坏肠道干细胞池自我更新，阻止黏膜修复再生导致黏膜屏障受损。近年来随着类器官共培养技术与单细胞测序技术的应用，免疫细胞与干细胞之间相关调控关系越加明确。干细胞移植有望重建黏膜屏障实现黏膜愈合，目前已开展多项干细胞临床研究并取得一定临床突破。本文综述免疫细胞与肠干细胞相关调控关系及干细胞临床研究前沿进展。     

干细胞与消化系统疾病的治疗

随着现代科技的发展,学者们在干细胞移植研究领域陆续取得了重大突破,尤其是在干细胞移植治疗消化系统疾病方面.目前针对干细胞移植治疗消化系统疾病的研究主要集中在胃肠动力障碍性疾病、炎症性肠病、终末期肝病、急慢性胰腺炎及消化系统肿瘤等领域;其中部分研究已应用于临床.此文就干细胞移植治疗消化系统疾病方面作一综述.     

骨髓干细胞移植治疗炎症性肠病的前景可观

炎症性肠病（IBD）在我国的发病率逐年增加，现有的治疗手段和疗效有限，骨髓干细胞移植治疗IBD具有很好的疗效,但有待更大样本的前瞻性、随机、对照研究，并进一步完善其机制，以指导临床实践。本文结合目前国内外干细胞移植治疗IBD的临床和基础研究,对骨髓干细胞移植治疗IBD的可能机制进行述评。     

造血干细胞移植治疗炎症性肠病进展

炎症性肠病(IBD)是胃肠道慢性炎性肉芽肿性疾病,其发病与环境、遗传因素相关,传统治疗包括抗炎和抑制免疫等治疗.新近的研究提示造血干细胞移植(HSCT)治疗IBD有效,此文就HSCT治疗IBD的研究现状和存在的问题进行概述.     

寄生虫感染治疗炎症性肠病的研究进展

人口流行病学证据表明,炎症性肠病的发病率与寄生虫感染率呈负相关,提示寄生虫感染具有治疗炎症性肠病的潜力。目前对待寄生虫的视角,逐渐从消除寄生虫,转向到利用寄生虫或其排泄分泌物开发安全、有效的炎症性肠病疗法。本文就近年来运用寄生虫模型治疗炎症性肠病的效果及机制的研究进展做一综述。     

骨髓间质干细胞对炎症性肠病肠上皮重建的作用机制

骨髓间质干细胞（MSCs）移植是治疗炎症性肠病（IBD）的一种新方法,其可通过促进肠上皮重建修复受损组织,但其作用机制仍未完全明确。相关机制的研究主要集中在MSCs的多向分化、分泌细胞因子、调节肠道干细胞微环境三个方面。本文就相关研究进展作一综述。     

干细胞治疗在炎症性肠病中的研究进展

我国炎症性肠病(IBD)发病率近年来呈明显上升趋势,危重病例也逐渐增多。现有的IBD治疗主要着眼于控制活动性炎症和调节免疫紊乱,常用药物有5-氨基水杨酸类制剂、糖皮质激素、免疫抑制剂等,对危重及难治性病例疗效有限,且存在许多不良反应。干细胞移植治疗是一种新兴的治疗方法,也是近年来IBD治疗领域的研究热点之一。本文对既往干细胞移植治疗IBD的临床和基础研究进行回顾,着重介绍近年来该领域的新进展。     

骨髓干细胞治疗炎症性肠病的研究进展

炎症性肠病（inflammatory bowel disease,IBD）是一种侵及胃肠道的特发的炎症反应,包括溃疡性结肠炎（ulcerative colitis,UC）和克罗恩病（Crohn’s disease,CD）,在中国的发病率逐年上升,其可能与现代生活方式、基因遗传、肠道菌群的免疫耐受缺失、免疫反应激活等因素有关。目前的治疗在于控制活动性炎症和调节免疫紊乱,包括抗炎药物、激素、免疫抑制剂、生物治疗等多种治疗手段,但无一具有长期疗效且副作用颇多。而近年来干细胞再生、营养、免疫调节等方面的研究给IBD的治疗带来了新的希望。本文讨论了骨髓间充质干细胞及造血干细胞在IBD治疗中的新发现,回顾了干细胞在IBD治疗中可能的作用机制。     

Modern management of chronic granulomatous disease

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder of phagocytic cells resulting in failure to kill a characteristic spectrum of bacteria and fungi and in defective degradation of inflammatory mediators with concomitant granuloma formation. Current prophylaxis with trimethoprim-sulfamethoxazole, itraconazole and in selected cases additional interferon gamma is efficient, but imperfect. A significant recent progress towards new antibiotic (e.g. linezolid) and antifungal (e.g. voriconazole and posaconazole) therapy will allow survival of most patients into adulthood. Adolescent and adult CGD is increasingly characterized by inflammatory complications, such as granulomatous lung and inflammatory bowel disease, requiring immunosupressive therapy. Allogeneic haematopoietic stem cell transplantation from a human leucocyte antigen identical donor is currently the only proven curative treatment for CGD and can be offered to the selected patients. Gene-replacement therapy for patients lacking a suitable stem cell donor is still experimental and faces major obstacles and risks. However, it may offer some transitory benefits and has helped in a few cases to overcome life-threatening infections.     

Fulminant Crohn's colitis after allogeneic stem cell transplantation

We report a case of fulminant Crohn's colitis that occurred following non-myeloablative allogeneic stem cell transplantation for Hodgkin's lymphoma. Adoptive transfer of inflammatory bowel disease by haematopoietic cells is recognised in several animal models of inflammatory bowel disease and remission of Crohn's disease has been reported in patients who have received a bone marrow transplant. However, adoptive transfer of Crohn's disease susceptibility leading to phenotypic manifestation of the disease after transplantation has not been previously reported. Having ruled out an infective cause of a colitis in this case, we speculated that adoptive transfer of Crohn's disease may have occurred and performed a genetic analysis of known susceptibility loci for significant donor-recipient mismatches. The donor and recipient had several haplotype mismatches in HLA class III genes at the IBD3 locus. In addition, the donor (but not the recipient) had a polymorphism of the 5' UTR of NOD2/CARD15 that may be associated with Crohn's disease. This case highlights the question of whether adoptive transfer of Crohn's disease can occur between allogeneic stem cell transplant donor and recipient, in a similar fashion to that reported for other autoimmune diseases. This report should also stimulate debate regarding the need for stem cell transplant donor screening for inflammatory bowel disease.     

Disappointing outcome of autologous stem cell transplantation for enteropathy-associated T-cell lymphoma

BACKGROUND: Despite treatment, enteropathy-associated T-cell lymphoma has a very poor outcome. Chemotherapy can be complicated by small bowel perforation, gastrointestinal bleeding and development of enterocolic fistulae. Here we report on the feasibility, safety and efficacy of high-dose chemotherapy followed by autologous stem cell transplantation in patients with enteropathy-associated T-cell lymphoma (three upfront and one at relapse), with or without prior partial small bowel resection. METHODS: Four patients [two males, two females, mean age 65 years (range 60-69 years)] received high-dose chemotherapy followed by autologous stem cell transplantation. Partial small bowel resection has been performed in three patients. RESULTS: All four patients completed the mobilization and leucopheresis procedures successfully and subsequently received conditioning chemotherapy and transplantation. Engraftment occurred in all patients. No major non-haematological toxicity or transplantation-related mortality was observed. One patient has ongoing complete remission 32 months after transplantation. Three patients died from relapse within few months after autologous stem cell transplantation. CONCLUSIONS: Autologous stem cell transplantation seems unsatisfactory for patients with enteropathy-associated T-cell lymphoma. More intensive conditioning and aggressive chemotherapy with/or without targeted immunotherapy as well as allogenous stem cell transplantation needs to be explored.     

Stem cell transplantation for Crohn's disease

There is much interest in the possibility that haematopoietic stem cell transplantation might benefit patients with inflammatory bowel disease, with an emphasis on Crohn's disease. Case reports of patients with Crohn's disease undergoing stem cell transplantation for other reasons, or specifically for Crohn's disease, support the view that major improvements can be achieved, with even the possibility of a cure in a small number of, but certainly not all, cases. The development of Crohn's disease in a previously normal patient receiving an allogeneic transplant from an individual with the NOD2 mutation illustrates the importance of the genotype of the immune system. Population of the lamina propria by myofibroblasts with the donor's phenotype shows that non-immune mechanisms make also play a part. A clinical trial to determine the value of stem cell transplantation in Crohn's disease has been set up under the supervision of the European Group for Blood and Marrow Transplantation.     

Can allogeneic haematopoietic cell transplantation be curative in classical Crohn's disease?

The article by Moser et al. details the outcomes of 11 patients with inflammatory bowel disease (IBD) as the main manifestation of their immune deficiency syndrome who are treated with allogeneic transplantation. The authors report low rates of complications (including graft-versus-host disease) and resolution of symptoms. Here we outline whether allogeneic transplantation should be considered more broadly for IBD. Commentary on : Moser et al. Treatment of inborn errors of immunity patients with inflammatory bowel disease phenotype by allogeneic stem cell transplantation. Br J Haematol 2023;200:595-607.