免疫干预联合骨髓干细胞移植治疗早发1型糖尿病的前景

1型糖尿病是由于胰岛β细胞进行性自身免疫性破坏所引起的,其治疗需要自身免疫件反应的逆转、胰岛β细胞的再牛和功能恢复.适度的免疫抑制剂治疗早发1型糖尿病可阻止胰岛β细胞进一步损失、减少胰岛素的使用,但不能阻止并发症的恶化.最近许多研究报道,免疫干预联合骨髓干细胞移植可维持较长的胰岛素非依赖时间,然而其能有效治疗早发1型槠尿病的机制尚未清楚.     

自体造血干细胞移植治疗1型糖尿病的研究进展

1型糖尿病(T1DM)是一种T细胞介导的自身免疫性疾病,以胰腺B细胞选择性破坏,导致患者体内胰岛素分泌绝对不足为特征[1]。目前,T1DM的治疗主要以外源性胰岛素替代治疗为主,患者需每日注射胰岛素,但胰岛素的使用只是延缓疾病的发展却并不能治愈糖尿病。T1DM的最终治疗需要去除免疫     

造血干细胞移植治疗1型糖尿病获得成功

造血干细胞移植治疗1型糖尿病在南京鼓楼医院获得成功，接受治疗的患者已停止使用胰岛素注射4个多月。     

造血干细胞移植治疗1型糖尿病

造血干细胞移植治疗自身免疫性疾病的由来自体或异基因造血干细胞移植治疗自身免疫性疾病的概念已提出数年。其基本原理是通过对患者进行大剂量化学治疗(化疗)或结合全身放射治疗(放疗)进行预处理,以最大限度地清除体内自身反应性克隆,使患者达到过度的免疫抑制或免疫     

间充质干细胞联合胰岛细胞治疗1型糖尿病研究进展

近年来,国内外兴起的胰岛移植术治疗l型糖尿病,因炎症介导的免疫反应以及营养因子缺乏而导致移植后3-5年内仍需注射小剂量的胰岛素,而间充质干细胞与胰岛细胞联合,不仅具有免疫调节作用还能分泌营养因子促进胰岛细胞活性和功能,但其在体内的致瘤性以及促进肿瘤细胞转移这些潜在不良反应会一定程度影响其临床应用.本文就间充质干细胞与胰...     

自体造血干细胞移植治疗1型糖尿病的前景与出路

1A型糖尿病的“根治性”治疗方向在于免疫紊乱的纠正和受损胰岛β细胞的完全修复.前者借助于免疫干预治疗,后者借助于细胞替代治疗.自体造血干细胞移植(AHSCT)在使用了大剂量免疫抑制剂和自体预先采集的造血干细胞回输后,拟通过造血和免疫系统的重建和干细胞对胰岛β细胞促进再生作用,来达到长期缓解糖尿病的临床治疗目的.其目前适用的人群仅限于1A型初发糖尿病患者,伴有残存的胰岛功能.同时,AHSCT的具体机制尚不明朗,临床疗效个体差异较大,其未来和出路还面临着巨大挑战.     

自体造血干细胞移植治疗1型糖尿病--附一例报告

目的初步探讨自体非清髓性造血干细胞移植（AHST）治疗1型糖尿病（T1DM）的有效性与安全性。方法首先，环磷酰胺及粒细胞集落刺激因子动员造血干细胞至外周血，采用白细胞分离术分离、处理造血干细胞并予以冻存；其次，采用环磷酰胺＋兔抗胸腺细胞球蛋白方案预处理后，经静脉回输造血干细胞。观察移植前后胰岛素注射剂量、HbA1c水平、胰岛功能、胰岛自身抗体滴度等变化；记录治疗过程中及治疗后的不良反应。结果自回输干细胞后，（1）患者已停用胰岛素达15月余；（2）HbA1c降至7.0%以下；（3）胰岛功能较前明显改善；（4）未出现骨髓抑制、出血性膀胱炎等严重不良反应。结论AHST治疗T1DM一例，初步显示出一定的临床有效性，但仍需大样本量前瞻性研究，以进一步评估此疗法的远期疗效与安全性。     

1型糖尿病的免疫耐受治疗

1型糖尿病的发病机制是自身免疫性胰岛炎.其胰岛素缺乏是由于胰腺中大量胰岛β细胞被免疫系统攻击所致.通过各种不同的途径建立胰岛β细胞免疫耐受,包括造血干细胞的移植、过继不同功能状态的树突状细胞、口服胰岛素及其相关疫苗的输入、谷氨酸脱羧酶65疫苗、抗CD3、CD20单克隆抗体以及联合免疫干预等免疫耐受治疗,可延缓l型糖尿病...     

自体造血干细胞移植治疗1型糖尿病的疗效和安全性评价

目的 对初发的新诊断1型自身免疫性糖尿病患者施行自体外周造血干细胞移植术,评估该治疗方式的安全性和有效性.方法 共有18例患者符合入选条件,获得知情同意后接受移植治疗.利用环磷酰胺和粒细胞集落刺激因子促进外周造血干细胞产生,干细胞富集后采集冷冻保存.通过环磷酰胺和抗胸腺球蛋白获取免疫抑制,于上述两种给药后即行干细胞回输.术前后监测血糖、血清C肽、HbA1C、谷氨酸脱羧酶抗体(GAD-Ab)水平和记录不良事件,对干细胞移植的疗效和安全性进行评估.结果 18例患者(6例男性,12例女性2)平均年龄(18.8±4.4)岁,平均随访天数(414±150)d.67%(12/18)患者术后停用胰岛素,最短在术后2周,最长在术后6个月.12例中有4例因上感等原因出现血糖上升而重新使用胰岛素.目前有44.4%(8/18)患者完全脱离胰岛素治疗,其余患者胰岛素用量的减量幅度平均为67.3%±22.4%.18例患者的GAD-Ab水平明显下降,转阴率33.3%(6/18).空腹C肽和餐后2 h C肽水平在术后明显上升,C肽曲线下面积(AUCC)上升更为显著,且可维持1年.在移植治疗过程中,所有患者均出现不同程度的胃肠道反应,脱发,发热,骨髓抑制等不良反应,有5例患者接受了成份血输注.未观察到明显的心、肝、肾等脏器功能受损.不良反应在干细胞回输后的2～4周逐步消失,粒细胞减少的恢复最为缓慢.结论 自体造血干细胞移植治疗有胰岛功能残存的初发1型糖尿病患者有一定的疗效,安全性较高,临床可行性强.对其治疗机制还有待进一步研究.     

1型糖尿病的免疫防治

1型糖尿病(T1DM)是遗传与环境因素共同作用所致的自身免疫性疾病.为预防和延缓T1DM高危人群自身免疫性胰岛炎的发生,阻止新发T1DM残存胰岛β细胞进一步遭受免疫破坏,T1DM的免疫防治有了较大进展.根据干预实施时机的不同,分为一级、二级和三级预防.主要通过饮食干预、自身抗原疫苗接种及单克隆抗体治疗等措施诱导自身免疫耐受,改善免疫调节,减少胰岛β细胞凋亡.许多临床研究对T1DM的免疫干预进行了探索,并进行了谷氨酸脱羧酶(GAD)疫苗、抗CD3单克隆抗体、DiaPep277等药物的临床研究,为T1DM的防治提供了新启示.     

Transplantation for the treatment of type 1 diabetes

Transplantation of pancreatic tissue, as either the intact whole pancreas or isolated pancreatic islets has become a clinical option to be considered in the treatment of patients with type 1 insulin-dependant diabetes mellitus. A successful whole pancreas or islet transplant offers the advantages of attaining normal or near normal blood glucose control and normal hemoglobin Alc levels without the risks of severe hypoglycemia associate with intensive insulin therapy. Both forms of transplants are also effective at eliminating the occurrence of significant hypoglycemic events （even with only partial islet function evident）. Whereas whole pancreas transplantation has also been shown to be very effective at maintaining a euglycemic state over a sustained period of time, thus providing an opportunity for a recipient to benefit from improvement of their blood glucose control, it is associated with a significant risk of surgical and post-operative complications. Islet transplantation is attractive as a less invasive alternative to whole pancreas transplant and offers the future promise of immunosuppression-free transplantation through pretransplant culture. Islet transplantation however, may not always achieve the sustained level of tight glucose control necessary for reducing the risk of secondary diabetic complications and exposes the patient to the adverse effects of immunosuppression. Although recent advances have led to an increased rate of obtaining insulin-independence following islet transplantation, further developments are needed to improve the longterm viability and function of the graft to maintain improved glucose control over time.     

骨髓移植与1型糖尿病

自体和同种异体骨髓移植治疗难治性自身免疫性疾病是近年来研究的热点。1型糖尿病是最常见的器官特异性自身免疫性疾病之一,自体骨髓移植能够缓解自身免疫性胰岛炎,重建相对正常的免疫系统;而同种异体骨髓移植则不仅能纠正自身免疫状态,而且能对供者的胰岛产生特异性免疫耐受。因此,骨髓移植对1型糖尿病的防治以及胰岛移植等都具有重要的价值。     

1型糖尿病的DiaPep277免疫治疗

1型糖尿病（T1DM）的病理基础是胰岛β细胞的自身免疫性破坏,因此阻止该免疫进程对预防或治疗T1DM尤为重要.DiaPep277是一种由24个氨基酸组成的肽段,衍生于热休克蛋白60（HSP60）的C-末端区域.研究证明,它对糖尿病动物模型的自身免疫性T细胞具有免疫调节作用.临床研究表明,DiaPep277对初发T1DM患者的胰岛β细胞有保护作用,并具有安全性.     

Clinical benefits of autologous haematopoietic stem cell transplantation in type 1 diabetes patients

Type 1 diabetes (T1D) is characterized by severe damage to pancreas islet function through immunological attack; therefore, it is also called ‘insulin-dependent diabetes’. The present study aimed to evaluate the safety and clinical efficacy of autologous haematopoietic stem cell transplantation (AHSCT) in adolescent patients with newly diagnosed T1D. A phase-II prospective, parallel-assignment, non-randomized trial was conducted from March 2008 to December 2011 with 40 T1D patients, of whom 20 received AHSCT therapy and 20 were treated only with insulin injections. Of these patients, 14 (70%) in the AHSCT group became insulin-independent for 1.5 to 48 months compared with only one patient in the Insulin group. Of these 14 AHSCT patients, 11 relapsed within a median time of 19.5 (range 5.5–1) months and resumed insulin use. By the end of the 4-year follow-up, the difference in daily insulin dosages between the AHSCT and Insulin groups had become smaller (0.49 ± 0.32 IU/kg/day vs. 0.79 ± 0.18 IU/kg/day, respectively; P < 0.01). C-peptide levels increased significantly at 3 months in both groups and later decreased, with the insulin group showing more rapid deterioration. Most of the adverse events in the AHSCT group were transplantation complications. Our data suggest that AHSCT treatment was well tolerated and slowed deterioration of islet β-cell function while significantly decreasing daily insulin dosages. However, because of the high relapse rate, more information on longer-term outcomes is needed before AHSCT can be routinely considered for T1D patients. Significance: although this was a non-randomized clinical study, this phase-II trial demonstrated the beneficial effects of AHSCT in patients with newly diagnosed T1D by increasing C-peptide levels and inducing insulin independence, while showing its safety and good tolerability compared with conventional intensive insulin therapy. Thus, these results are helpful for increasing our understanding of the use of haematopoietic stem cell therapy in the treatment of T1D and for evaluating whether it can become more widespread in future.     

调节性T细胞在1型糖尿病和胰岛移植中的作用

调节性T细胞是一种免疫抑制性细胞,在维持免疫耐受中起重要作用.研究相继发现了多种调节性T细胞的表面标记和调节性T细胞的作用机制.调节性T细胞的数量和(或)功能缺陷与1型糖尿病的发生、发展密切相关.输注调节性T细胞可以预防和治疗1型糖尿病,延长移植胰岛的存活时间和改善移植物功能.目前,关于调节性T细胞治疗的临床试验研究已经开展,如果后续实验能证实调节性T细胞体内输注治疗的安全性及有效性,调节性T细胞免疫治疗将成为治疗1型糖尿病和预防胰岛移植后免疫排斥的有效方法.     

Novel therapy for type 1 diabetes: Autologous hematopoietic stem cell transplantation

Type 1 diabetes is characterized pathologically by autoimmune insulitis‐related islet β‐cell destruction. Although intensive insulin therapy for patients with type 1 diabetes can correct hyperglycemia, this therapy does not prevent all diabetes‐related complications. Recent studies have shown that autologous hematopoietic stem cell transplantation (HSCT) is a promising new approach for the treatment of type 1 diabetes by reconstitution of immunotolerance and preservation of islet β‐cell function. Herein we discuss the therapeutic efficacy and potential mechanisms underlying the action of HSCT and other perspectives in the clinical management of type 1 diabetes.