间充质干细胞移植治疗系统性红斑狼疮的研究进展

间充质干细胞是来源于发育早期中胚层的成体干细胞,具有高度增殖、自我更新能力、多向分化潜能、损伤组织修复功能和免疫抑制能力。该文综述间充质干细胞,主要是脐带间充质干细胞和骨髓间充质干细胞用于治疗系统性红斑狼疮的研究进展,并提示间充质干细胞移植在未来的细胞治疗中是非常有前景的一种方法。     

间充质干细胞移植治疗自身免疫性疾病的进展

间充质干细胞(MSC)是来源于发育早期中胚层的成体干细胞,具有高度增殖、自我更新能力、多向分化潜能、损伤组织修复功能和免疫抑制能力.该文综述间充质干细胞,主要是脐带间充质干细胞(hUMSCs)和骨髓间充质干细胞(BMMSC),用于移植治疗系统性红斑狼疮(SLE)、类风湿关节炎(RA)、硬皮病(SSc)、皮肌炎(DM)的研究进展,并显示间充质干细胞移植(MSCT)在未来的分子治疗中是非常有前景的一种方法.     

干细胞移植治疗天疱疮研究进展

天疱疮是一种可累及全身皮肤、黏膜的有潜在致死性的自身免疫性皮肤病。传统治疗方案包括糖皮质激素、免疫抑制剂、生物制剂等。疗效肯定且不断改进,但存在长期使用不良反应大、价格高昂等缺点,仍有其局限性。应用干细胞移植治疗重症天疱疮突破了传统治疗的局限,使根治天疱疮成为可能,正在成为新的研究热点。近年来的应用实例表明干细胞移植治疗天疱疮可行并且有效,而对移植相关的免疫学机制也有了初步的认识。     

自体外周血造血干细胞移植治疗难治性寻常型天疱疮1例

目的观察自体外周血造血干细胞移植治疗难治性寻常型天疱疮1例的效果。方法患者男,45岁。口腔、头面部、躯干、四肢水疱、糜烂6年。诊断为寻常型天疱疮。经糖皮质激素和免疫抑制剂及抗CD20单克隆抗体治疗,疾病反复发作。同时合并糖尿病和高血压。半年前,全身水疱加重,行自体外周血造血干细胞移植。应用环磷酰胺、粒细胞集落刺激因子（G-CSF）进行动员。用环磷酰胺（CTX）＋磷酸氟达拉滨（Flud）＋抗胸腺细胞球蛋白（ATG）进行预处理。结果患者移植结束后,皮疹消退,自身抗体滴度明显降低。移植2个月后皮疹轻度反复,小量糖皮质激素联合甲氨蝶呤可以控制。目前移植后6个月,病情稳定。结论自体外周血造血干细胞移植治疗难治性寻常天疱疮疗效显著。可作为治疗难治性寻常型天疱疮的一种新方法。但其远期治疗效果需进一步观察。     

CT引导行骨髓源性间充质干细胞术的配合与护理

通过不断的创新研究,武警总医院神经干细胞移植科在治疗脊髓损伤后遗症方面除延用传统的"腰椎穿刺干细胞移植"和"脊髓探查+神经干细胞移植"的手术方法,采用了CT引导下行骨髓源性间充质干细胞移植,它是一种新的移植方法,具有创伤小、定位准确、疗效好的优点[1],现将本科脊髓损伤后遗症患者CT引导下行骨髓源性间充质干细胞术围手术期的护理报道如下.     

无血清培养体系分离培养人脐带间充质干细胞

目的用体外无血清培养体系分离培养人脐带间充质干细胞。方法取1例足月妊娠剖宫产健康胎儿脐带,采用组织块贴壁培养,使用无血清培养体系培养获得人脐带间充质干细胞。通过形态学观察,成脂、成骨、成软骨诱导分化能力检测及流式细胞术免疫表型检测进行鉴定。结果组织块贴壁培养6天后可见细胞从组织块边沿爬出;培养15天后,达到80%汇合,生长状况良好,细胞呈梭形,为典型的成纤维细胞形态,极性整齐排列,集落呈涡旋状,形态较均一。传代培养的第三代细胞CD29、CD44、CD90、CD105均为阳性表达,不表达CD34和CD45,均具有成脂、成骨、成软骨分化的能力。结论无血清培养体系组织块贴壁法分离培养人脐带间充质干细胞法成功率高,其生物学特性稳定,并能消除由未确定的病原体引起的风险。     

自体外周血造血干细胞移植治疗重症天疱疮三例

目的 探讨自体外周血造血干细胞移植治疗天疱疮的疗效及安全性.方法 选择经糖皮质激素、免疫抑制剂等治疗6个月以上病情仍难以控制或病情进展、且出现治疗相关并发症的3例寻常型天疱疮患者进行自体外周血造血干细胞移植治疗,并随访5年以上.3例中男1例,女2例,平均年龄27.3(21～39)岁.造血干细胞的动员方案为环磷酰胺4g/m2、重组人粒细胞集落刺激因子(G-CSF)、利妥昔单抗375 mg/m2;预处理方案为环磷酰胺50 mg·kg-1·d-1连用4d(移植前第6天到移植前第3天)、抗胸腺细胞球蛋白2.5 mg·kg-1·d-1连用4d(移植前第3天至移植当天)、利妥昔单抗600 mg/d于移植当天和移植后第7天静脉滴注.结果 3例天疱疮患者均获得成功植入,平均植活时间白细胞13.3 d(11 ～ 16d),血小板16.3 d(16～ 17d).监测各项免疫指标及相关抗体未见异常,免疫重建良好.随访期间,所有患者无严重并发症,生活质量较前明显提高.结论 自体外周血造血干细胞移植可能是治疗天疱疮有效且安全的新方法之一.     

基因联合间充质干细胞移植治疗老年性ED的研究进展

勃起功能障碍(erectile dysfunction,ED)的发病率与年龄相关,随着老龄人口的增加,老年ED患者也不断增多。目前仍未找到最适当的治疗方法治愈或阻止ED的发生发展。虽然老年性ED的基因治疗是一个新兴的热点,但是联合间充质干细胞(Mesenchymal stem cells,MSCs)移植更是对运用基因治疗ED的升华,本文将对各种基因联合间充质干细胞移植治疗老年性ED进行综述。     

间充质干细胞移植治疗系统性红斑狼疮的研究

系统性红斑狼疮(SLE)是自身免疫性疾病,传统治疗方法主要有糖皮质激素和免疫抑制剂等,由于长期用药部分患者出现继发感染、复发及疗程长、药物不良反应等问题,对难治性、重症SLE效果欠佳。近年来,越来越多的证据表明SLE患者有间充质干细胞(MSCs)功能异常。因此,MSCs移植治疗SLE成为一种新的方法。该文简要介绍了SLE的发病机制、MSCs的免疫学特性以及干细胞移植治疗SLE的现状。     

间充质干细胞与自身免疫性疾病

自身免疫性疾病的治疗一直以糖皮质激素和免疫抑制剂为主,但一些患者对糖皮质激素和免疫抑制剂反应不好或不能耐受,间充质干细胞可能成为一种新的辅助治疗手段.本文对间充质干细胞的特性及与自身免疫性疾病的关系进行综述.     

生物制剂和生物技术治疗天疱疮进展

天疱疮是一种慢性、复发性表皮内棘层松解性大疱性皮肤病,生物制剂和生物工程技术在天疱疮治疗中发挥一定作用。利妥昔单抗作为一种生物制剂,被国际专家共识推荐为天疱疮一线治疗方案。造血干细胞移植可重建患者的免疫系统,基于前期临床试验确切的疗效,造血干细胞移植已被应用于难治性天疱疮的治疗。调节性T细胞（regulatory T cells,Tregs）在维持自身免疫耐受和避免免疫反应过度损伤中发挥重要作用,应用Tregs过继回输治疗天疱疮前期试验疗效显著。本文综述了利妥昔单抗、干细胞技术以及Tregs过继治疗天疱疮的进展。     

自体外周血干细胞移植治疗难治性天疱疮一例

目的 探讨自体外周血干细胞移植治疗天疱疮的可能性.病历资料男性患者,35岁,全身反复大疱4年余,根据临床表现、组织病理和免疫荧光检查确诊为天疱疮.经糖皮质激素和免疫抑制剂治疗效果不佳,2月前出现髓关节疼痛,经X线和CT检查诊断为股骨头无菌性坏死.采取环磷酞胺及粒细胞集落刺激因子作为动员剂,利妥昔单抗联合净化.用环磷酞胺联合抗胸腺细胞球蛋白、利妥昔单抗进行预处理,同时碱化和水化尿液,保护心、肝和肾功能.观察移植后临床表现、造血和免疫指标等的变化.结果 患者移植结束即停用糖皮质激素,3周后自觉双侧靛关节疼痛减轻,复查CT示股骨头缺血性改变减轻.移植6周后直接免疫荧光和间接免疫荧光检查转阴并持续阴性.经一年复诊,临床及免疫学检查均无复发迹象.结论 本研究结果提示自体外周血干细胞移植治疗天疙疮近期疗效显著,可能是治疗存在治疗抵抗的重症天疤疮潜在的“根治”方法,但其风险收益比尚需进一步评价.     

Two cases of mycosis fungoides treated by reduced-intensity cord blood transplantation

Mycosis fungoides is a cutaneous T-cell lymphoma, which is clinically divided into three stages: patch, plaque and tumor. Despite a variety of treatments the prognosis is poor in advanced mycosis fungoides. Recently, allogeneic hematopoietic stem cell transplantation has been successfully applied for such cases. We performed reduced-intensity umbilical cord blood transplantation for two advanced mycosis fungoides patients. Case 1 was a 56-year-old man and case 2 was a 30-year-old woman. Tumors of each case were refractory to conventional chemotherapy. Although radiation therapy was considerably effective, tumors relapsed after several months. Reduced-intensity umbilical cord blood transplantation was performed because case 1 had no human leukocyte antigen-identical siblings and the sibling of case 2 did not agree to be the donor. The male patient died of pulmonary failure 23 days after reduced-intensity umbilical cord blood transplantation. The case 2 patient succeeded in reduced-intensity umbilical cord blood transplantation and remained in complete/partial remission for 13 months. However, chemotherapy-resistant tumors relapsed, and allogeneic hematopoietic stem cell transplantation was performed at 17 months. She died of cerebral hemorrhage 23 days after the procedure. Reduced-intensity umbilical cord blood transplantation may be included in the treatments for advanced mycosis fungoides, where graft-versus-lymphoma effect seems to be a significant factor for the success of the treatment.     

Immunoablative high-dose cyclophosphamide without stem cell rescue in a patient with pemphigus vulgaris

The use of ablative intravenous cyclophosphamide (50 mg/kg per day for 4 days) without stem cell rescue has been described in patients with refractory autoimmune diseases such as paraneoplastic pemphigus, systemic lupus erythematosus, and aplastic anemia. We describe a 33-year-old patient with pemphigus vulgaris recalcitrant to multiple therapies. The patient presented with numerous oral ulcerations, erosions, and hyperpigmented crusted plaques on his face, trunk, and arms. Findings of a skin biopsy and direct immunofluorescence were consistent with pemphigus vulgaris. The circulating pemphigus vulgaris autoantibodies were present at a titer of 1:640. The patient received immunoablative therapy (50 mg/kg of cyclophosphamide for a total of 4 days) and tolerated the regimen well. Complications such as thrombocytopenia and Pseudomonas septicemia were quickly treated. Four months after the 4-day therapy, his oral and skin lesions completely healed, and his pemphigus titers have decreased to zero. He is no longer receiving prednisone and no new lesions have developed. This provides further evidence that this regimen is relatively safe and provides a potential "cure" for refractory autoimmune diseases such as pemphigus vulgaris.     

Immunoablative high-dose cyclophosphamide without stem cell rescue in pemphigus foliaceus

BACKGROUND: There is growing evidence that immunoablative high-dose cyclophosphamide without stem cell rescue is effective and safe in patients with refractory autoimmune diseases such as paraneoplastic pemphigus, systemic lupus erythematosus, aplastic anemia, and more recently pemphigus vulgaris. METHODS: We report a 51-year-old patient with severe pemphigus foliaceus, which was recalcitrant to multiple medical regimes. The patient presented with multiple thick hyperpigmented and scaly, ill-defined plaques on the face. In addition, she had multiple superficial erosions and crusts on her scalp, thorax, upper and lower extremities. The patient also had a few discrete intact flaccid bullae. A skin biopsy and direct immunofluorescence was consistent with pemphigus foliaceus. The patient's circulating pemphigus autoantibodies were present at a titer of 1 : 2560. The patient received immunoablative high-dose cyclophosphamide (50 mg/kg/day) for 4 consecutive days, and tolerated the regime well. RESULTS: Approximately 3 months after therapy, the skin lesions had healed and her prednisone, which had been as high as 80 mg daily, was tapered to 30 mg daily. In addition, her circulating autoantibodies decreased after treatment. Nearly 10 months after treatment, the patient did relapse. However, her disease was less severe and more easily managed with lower doses of immunosuppressive therapy. CONCLUSION: This case contributes to the growing evidence of high-dose cyclophosphamide's efficacy without stem cell rescue in recalcitrant autoimmune diseases, including pemphigus foliaceus.     

皮肤间质干细胞

皮肤干细胞的研究长期限定在表皮和毛囊隆突区,皮肤间质来源的干细胞和造血干细胞同样具有分化成脂肪细胞、平滑肌细胞、骨细胞、软骨细胞,甚至神经元和神经胶质细胞的潜能.毛囊周围结缔组织鞘、毛乳头和毛囊间真皮都可能含有多潜能干细胞,未来可能作为自体移植细胞治疗的潜在供体.主要概述皮肤问质干细胞的定位、表面标记、功能和潜在的临床应用价值.

Abstract：

For a long time,skin stem cell research has been focused on the epidermis and hair follicle bulge.It has been demonstrated that stem cells and hematopoietic stem cells from the mesenchymal compartments of the skin have the potential to differentiate into adipocytes,smooth muscle cells,osteocytes,chondrocytes,and even neurons and glia.The perifollicular connective tissue sheath,papilla and interfollicular dermis crystallize as the likely anatomic niche for these multipotent dermal cells; hence,they have the potential to function as an easily accessible,autologous source for stem cell transplantation.This article describes the location,surface antigens,function and potential applications of skin-derived mesenchymal stem cells.     

天疱疮121例临床分析

目的：加强对天疱疮的认识,提高治疗水平。方法：回顾性分析121例天疱疮患者的临床资料。结果：大部分天疱疮患者通过激素及免疫抑制剂的治疗均能获得临床缓解,免疫抑制剂、血浆置换、大剂量丙种免疫球蛋白冲击治疗等＂辅助疗法＂能减少激素用量及其所产生的远期并发症,自体外周血造血干细胞移植有望根治难治性天疱疮。结论：目前天疱疮的治疗药物仍以激素为主,但由于其副作用,一些新型的治疗方案的研究正积极展开。     

Development of pemphigus herpetiformis in a patient with psoriasis receiving UV-light treatment

BACKGROUND: Pemphigus is an autoimmune blistering disease of the skin and mucous membranes. Pemphigus herpetiformis, a rare variant of pemphigus, is characterized by erythematous, vesicular, bullous, or papular lesions in a herpetiform pattern, often associated with pruritus. Clinical cases documenting the development of pemphigus in patients with a history of psoriasis have been reported in the literature. METHODS: We used immunological methods to study a case in which pemphigus herpetiformis occurred in a woman with a history of psoriasis, shortly after a course of ultraviolet B (UVB) therapy. RESULTS: Histopathology revealed a subcorneal blister with prominent neutrophilic infiltration. Immunopathology detected in situ bound and circulating immunoglobulin G (IgG) autoantibodies to epithelial cell surfaces and circulating IgG autoantibodies against desmoglein 1. The patient was also found to have Hashimoto's thyroiditis. CONCLUSIONS: This case illuminates a possible role of UV therapy in the induction of pemphigus herpetiformis through an epitope-spreading mechanism. The patient's autoimmune thyroiditis may also contribute to the predisposition for pemphigus development. The histopathological findings in pemphigus patients with a history of psoriasis may resemble Munro's microabscesses of psoriasis and should therefore alert pathologists and clinicians in considering additional diagnostic methods such as direct and indirect immunofluorescence.     

Pemphigus in Korea: clinical manifestations and treatment protocol

Pemphigus, a rare, chronic blistering disease of the skin and mucous membranes with severe morbidity and occasional mortality, is the most common autoimmune bullous disease in Korea. The purpose of this study was to evaluate the clinical features and propose a treatment strategy for patients with pemphigus. A retrospective analysis was conducted of 51 pemphigus patients seen between 1993 and 2001. Pemphigus vulgaris (PV) was the most common type with 32 cases, followed by 19 cases of pemphigus foliaceus (PF). The male to female ratio was 1:1.3, with females predominating, particularly among PV patients (PV, 1:1.5; PF, 1:1.1). The average ages at onset of PV and PF were 44.3 and 51.0 years old, respectively. Mucosal involvement was noted in 27 cases (84.4%) of PV but in only 3 cases (15.8%) of PF. Most patients initially received relatively low to intermediate doses (0.3-1.0 mg/kg/day) of prednisolone, and 23 (71.9%) PV patients and 10 (52.6%) PF patients also received immunosuppressive agents. Oral prednisolone and azathioprine (100 mg/day) formed the mainstay of treatment for our patients (47.1%). At the time of writing, 25.5% (13/51) of patients are in complete remission, and 72.5% (37/51) are undergoing maintenance therapy. One patient died due to sepsis during the treatment. For the treatment of pemphigus, a course of the lowest possible corticosteroid dosage in combination with immunosuppressive agents appears to be effective and less toxic than a high corticosteroid dosage.     

Pemphigus treatment in Japan

Pemphigus is a group of autoimmune blistering diseases characterized by blisters and erosive lesions on the skin and mucous membranes due to loss of cell and cell adhesion of keratinocytes. In 2010, new Japanese guidelines for the management of pemphigus were published for dermatologists. Systemic corticosteroids are the gold standard and the first choice of treatment of pemphigus.