自体外周血干细胞移植治疗周围神经损伤

背景：关于神经干细胞对周围神经损伤的治疗已有多篇报道,但外周血干细胞对周围神经损伤治疗鲜有报道。 目的：探讨自体外周血干细胞移植治疗周围神经损伤使失神经骨骼肌重获神经再支配的临床应用。 方法：应用外周血干细胞治疗周围神经损伤6例,同时与周围神经损伤单纯行神经断端吻合或神经移植10例比较。2组患者术后常规肌注鼠神经生长因子一两个疗程,同时给予针灸、理疗、经皮电刺激治疗及功能康复训练。 结果与结论：两组患者随访均超过6个月。干细胞移植组运动神经传导速度和感觉神经传导速度的恢复率要明显高于单纯神经吻合组。提示周围神经损伤后给予修复局部用外周血干细胞移植能够使远端失神经骨骼肌早期重新获得神经再支配。     

自体造血干细胞移植治疗多发性硬化的疗效及免疫学改变

目的研究自体造血干细胞移植(ASCT)治疗进展型多发性硬化(MS)临床应用的可行性及免疫学改变。方法对10例处于继发进展期的MS患者进行了ASCT。移植后依据扩展疾病状态(EDSS)评分、发作次数、核磁共振(MRI)检查及免疫抑制药物的需求指标评定疗效。用流式细胞仪方法动态检测移植前后MS患者T淋巴细胞亚群、CD4 CD25 细胞及Th2细胞的改变。结果移植相关死亡率为零。随访观察9~26个月(平均17.9个月),至随访截止时有1例患者出现复发;4例患者处于疾病无进展状态;5例患者病情明显好转。除1例复发者外,全部患者在ASCT后不需要免疫抑制剂治疗。移植前、后相同观察期内发作次数由24次减至1次。移植后6个月MRI检查病灶由移植前的92处减少至6处。移植后1a(n=6)CD3 细胞、CD8 细胞及CD4 CD25 细胞的恢复高于移植前水平;CD4 细胞及CD3 CD4-CD8-细胞的恢复未达到移植前水平。结论ASCT治疗进展型MS患者是安全、有效的;移植后CD4 细胞及CD4-CD8-细胞的恢复较慢,CD4 CD25 细胞的恢复高于移植前水平。     

异基因造血干细胞移植后的相关并发症及危险因素

背景：有效预防和治疗异基因造血干细胞移植后并发症是提高患者存活率的重要因素。 目的：分析异基因造血干细胞移植后相关并发症的发生和危险因素。 方法：应用文献检索的方法获取异基因造血干细胞移植后相关并发症研究的文献,对符合研究标准的文献进行深入的数据分析,文章选取异基因造血干细胞移植后极易发生的并发症进行分析,如肺部并发症、真菌性败血症、巨细胞病毒感染以及中枢神经系统并发症等。 结果与结论：异基因造血干细胞移植后易出现肺部并发症,而且死亡率较高,肺部并发症的发病机制可能与移植物抗宿主病和巨细胞病毒抗原血症相关。异基因造血干细胞移植后真菌性败血症病原菌以假丝酵母菌属为主,死亡率较高,应二级预防性和早期经验性抗真菌治疗。更昔洛韦、膦甲酸钠对异基因造血干细胞移植后巨细胞病毒感染的治疗有效。中枢神经系统并发症在异基因造血干细胞移植后发生率较低,但在治疗过程也不容忽视。异基因造血干细胞移植后相关并发症的发生与多种危险因素有关,在临床治疗过程中要对相关因素采取预防措施,减少并发症的发生,提高患者的存活率。     

The role of innate immune cells in systemic sclerosis in the context of autologous hematopoietic stem cell transplantation

Systemic sclerosis (SSc) is a complex, heterogeneous autoimmune connective tissue disease. Autologous hematopoietic stem-cell transplantation (AHSCT) has emerged as a valuable treatment option for rapidly progressive diffuse cutaneous SSc (dcSSc) patients, and thus far is the only treatment that has been shown to have a long-term clinical benefit. AHSCT is thought to reintroduce immune homeostasis through elimination of pathogenic self-reactive immune cells and reconstitution of a new, tolerant immune system. However, the mechanism of action underlying this reset to tolerance remains largely unknown. In this study we review the immune mechanisms underlying AHSCT for SSc, with a focus on the role of the innate immune cells, including monocytes and natural killer (NK) cells, in restoring immune balance after AHSCT.     

Regulatory T cells in autologous stem cell transplantation for autoimmune disease

Since a decade autologous stem cell transplantation (ASCT) is successfully performed to treat patients with severe autoimmune disease. However, the mechanism of action of this intervention remains largely unknown. Scarce data from animal studies and human clinical trials indicate that, besides extensive immune ablation, restoration of regulatory immune networks is of critical importance. This review focuses on the role of naturally occurring and induced regulatory T cells in controlling immune reconstitution and restoration of immune tolerance and in preventing relapses of disease following ASCT.     

临床病例讨论（step by step）——自体干细胞移植后发热、呼吸困难

 植入综合征 (ES) 系造血干细胞移植过程中严重并发症,主要发生在造血干细胞移植后中性粒细胞恢复早期。ES以发热、皮疹、非心源性肺水肿为主要特征。ES以往与高移植相关死亡率相关,多数患者死于呼吸衰竭和多器官功能不全。早期诊断并合理应用皮质激素可以显著降低移植相关死亡率。本文报道了一个年轻女性NHL患者,在自体外周血干细胞移植后粒细胞恢复早期出现发热、呼吸困难、肺水肿,早期诊断为ES并及时应用皮质激素后病情获得完全缓解。     

Mesenchymal Stem Cells versus Mesenchymal Stem Cells Combined with Cord Blood for Engraftment Failure after Autologous Hematopoietic Stem Cell Transplantation: A Pilot Prospective,Open-Label,Randomized Trial

Engraftment failure (EF) after autologous hematopoietic stem cell transplantation is a serious complication. We prospectively evaluated the effects and safeties of mesenchymal stem cells (MSCs) alone and MSCs combined with cord blood (CB) for EF. Twenty-two patients were randomized to receive MSCs (MSC group; n = 11) or MSCs plus CB (CB group; n = 11). Patients with no response (NR) to MSCs received the therapeutic schedule in the CB group, and those patients with partial response (PR) in the MSC group and patients without complete remission (CR) in the CB group received another cycle of MSC treatment. Patients who did not achieve CR after 2 cycles of treatments received other treatments, including allogeneic HSCT. After the first treatment cycle, response was seen in 7 of 11 patients in the MSC group and in 9 of 11 in the CB group (P = .635), with a significant difference in neutrophil reconstruction between the 2 groups (P = .030). After 2 treatment cycles, 16 patients achieved CR, 3 achieved PR, and 3 had NR. No patient experienced graft-versus-host disease (GVHD). With a median follow-up of 345 d (range, 129 to 784 d) post-transplantation, 18 patients remained alive and 4 had died (3 from primary disease relapse and 1 from cytomegalovirus pneumonia). The 2-year overall survival, disease-free survival, and cumulative incidence of tumor relapse post-transplantation were 75.2% ± 12.0%, 79.5% ± 9.4%, and 20.5% ± 9.4%, respectively. Our data indicate that the 2 strategies are effective for EF and do not result in GVHD or increase the risk of tumor relapse, but the MSC plus CB regimen has a superior effect on neutrophil reconstruction.     

Autologous stem cell transplantation for systemic sclerosis

Systemic sclerosis (SSc) is a generalised autoimmune disease, of yet unknown origin, with two major clinical subsets: the limited (lcSSc) and the diffuse cutaneous (dcSSc) forms, which can be distinguished by the extent of skin involvement, the autoantibody profile and the pattern of organ involvement. With an incidence of 1/10(5), SSc affects around 250,000 people in Europe and is responsible for significant morbidity with a 5-year mortality rate of at least 30% of all patients. In patients with rapidly progressive dcSSc, the 5-year mortality is estimated to be 40-50%. Hematopoietic stem cell transplantation (HSCT), mostly autologous but also allogeneic in some specific cases, has been employed worldwide since 1996 as a new therapeutic strategy in patients with a poor prognosis. In 2007, 150 HSCT procedures have been reported in the EBMT data base. We review herein both the short and the long-term reports from the various European and North American phase I-II studies, which have shown that autologous HSCT in selected patients with severe dcSSc results in sustained improvement of skin thickening and stabilisation of organ function up to seven years after transplantation. Based on these promising results, ongoing phase III trials have been designed in parallel, both in Europe (ASTIS) and in North America (SCOTT) aiming to analyse the respective benefits from autologous HSCT respectively without or with high dose irradiation. This review reports the current data concerning the effects of HSCT on survival, skin, and major organ function in patients with severe dcSSc.     

造血干细胞移植在血液系统疾病的临床应用

本文阐述了关于造血干细胞的特点和造血干细胞移植的新观点。移植需要的造血干细胞不仅应包括造血干细胞、造血祖细胞,还应该包括间充质干细胞。造血干细胞来源呈现多样化局面,当没有配型相合的供者时,配型相合的非血缘志愿者、脐带血和配型不合的亲缘供者都可以作为常规供者。造血干细胞适应证、供者、移植方式、移植时机的选择以及移植合并症的处理都趋向个体化。造血干细胞移植技术日趋成熟,已经逐渐发展成为一个相对独立的学科领域。     

Autologous Hematopoietic Stem Cell Transplantation for Systemic Sclerosis: A Systematic Review and Meta-Analysis

Autologous hematopoietic stem cell transplantation (AHSCT) has been proposed as a therapeutic modality for severe systemic sclerosis (SSc). We set out to systematically review and meta-analyze the efficacy and safety of AHSCT in SSc. Randomized controlled trials (RCTs) and retrospective studies comparing AHSCT with standard immunosuppressive therapy were included. Of 363 titles screened from multiple databases, 15 were extracted for further investigation, and 4 met inclusion criteria (3 RCTs and 1 retrospective analysis). The control arm was monthly cyclophosphamide in all the RCTs and the majority of patients in the retrospective analysis (69%). Compared with the control, AHSCT reduced all-cause mortality (risk ratio [RR], .5 [95% confidence interval, .33 to .75]) and improved skin thickness (modified Rodnan skin score mean difference [MD], 10.62 [95% CI, ?14.21 to 7.03]), forced vital capacity (MD, 9.58 [95% CI, 3.89 to 15.18]), total lung capacity (MD, 6.36 [95% CI, 1.23 to 11.49]), and quality of life (physical 36-Item Short Form Health Survey [MD, 6.99 (95% CI, 2.79 to 11.18)]). Treatment-related mortality considerably varied between trials but was overall higher with AHSCT (RR, 9.00 [95% CI, 1.57 to 51.69]). The risk of bias for studies included in the analysis was low. Overall, AHSCT reduces the risk of all-cause mortality and has properties of a disease-modifying antirheumatic treatment in SSc. Further investigation is warranted for refining patient selection and timing of transplantation.     

造血干细胞移植治疗再生障碍性贫血的现状

文题释义：预处理：指在移植前对患者进行的放、化疗和免疫抑制治疗。再生障碍性贫血预处理的重点为免疫抑制,常采用非清髓和减低剂量预处理。 移植物抗宿主病：是异基因造血干细胞移植最常见的并发症,分为急性和慢性2种类型。目前认为移植物含有免疫活性细胞、供受者之间存在组织不相容性、受者不排斥植入的细胞是发生移植物抗宿主病3个必备条件。 背景：异基因造血干细胞移植治疗再生障碍性贫血的研究近年来取得很大的进步,但是移植后移植物抗宿主病、移植失败等仍是患者非复发死亡的主要原因,严重影响患者生存。 目的：总结异基因造血干细胞移植治疗再生障碍性贫血的现状及进展。 方法：中文检索词为“再生障碍性贫血,同胞全合异基因造血干细胞移植,无关供者造血干细胞移植,单倍体造血干细胞移植,脐血造血干细胞移植”,英文检索词为“aplastic anemia,matched sibling donor hematopoietic stem cell transplantation,unrelated donor hematopoietic stem cell transplantation,haploidentical hematopoietic stem cell transplantation,cord blood transplantation”,由第一作者检索1990年1月至2019年9月在PubMed、中国知网、万方、维普等数据库中发表的与造血干细胞移植治疗再生障碍性贫血相关的文献,最终选择55篇文献进行分析。 结果与结论：同胞全合异基因造血干细胞移植仍是目前首选的移植方式;对于无同胞全合供者的重型再生障碍性贫血患儿,一线治疗可以选择无关供者相合异基因造血干细胞移植;缺乏全合供者时,单倍体移植和脐血移植亦为不错的选择。 ORCID: 0000-0003-3931-8385(黄东平) 中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

富集自体外周血单个核细胞移植治疗肝硬化

背景：与骨髓移植相比较,外周血干细胞移植有其自身的优点,外周血中干细胞资源多、收集方便易行、无需麻醉、创伤小、易被患者接受、安全性高、患者的造血系统易恢复等。 目的：观察自体外周血单个核细胞对失代偿期肝硬化患者的治疗作用及安全性。 方法：选择2010年11月至2011年7月于大连医科大学附属第一医院住院的4例失代偿期肝硬化患者,其中乙型肝炎后失代偿期肝硬化3例,自身免疫性肝病后失代偿期肝硬化1例,年龄31-67岁,平均年龄44岁。经粒细胞集落刺激因子动员后采集外周血干细胞,行肝动脉插管自体外周血单个核细胞移植治疗。 结果与结论：外周血单个核细胞采集、肝动脉内干细胞移植过程中及移植后无发热、出血、恶心等不良反应发生,行自体外周血单个核细胞移植第 1,3,6个月后,纳差、乏力、食欲、腹胀等临床症状得到不同程度的改善。实验室检测肝功能和肝纤维化指标得到一定程度的改善。     

造血干细胞移植治疗自身免疫性疾病

自从1995年造血干细胞移植（HSCT）应用于难治复发性自身免疫性疾病（AID）的治疗以来,取得了令人鼓舞的疗效,最近已经进入Ⅲ期临床试验阶段。AID可能是一种造血干细胞异常所致疾病,本文主要就自体或异体HSCT治疗AID的原理及自体HSCT治疗几种主要AID的临床试验结果做一综述。     

T‐cell responses after haematopoietic stem cell transplantation for aggressive relapsing–remitting multiple sclerosis

Autologous haematopoietic stem cell transplantation (HSCT) for relapsing–remitting multiple sclerosis is a potentially curative treatment, which can give rise to long‐term disease remission. However, the mode of action is not yet fully understood. The aim of the study was to evaluate similarities and differences of the CD4⁺ T‐cell populations between HSCT‐treated patients (n = 12) and healthy controls (n = 9). Phenotyping of memory T cells, regulatory T (Treg) cells and T helper type 1 (Th1) and type 17 (Th17) cells was performed. Further, T‐cell reactivity to a tentative antigen, myelin oligodendrocyte glycoprotein, was investigated in these patient populations. Patients treated with natalizumab (n = 15) were included as a comparative group. White blood cells were analysed with flow cytometry and T‐cell culture supernatants were analysed with magnetic bead panel immunoassays. HSCT‐treated patients had similar levels of Treg cells and of Th1 and Th17 cells as healthy subjects, whereas natalizumab‐treated patients had lower frequencies of Treg cells, and higher frequencies of Th1 and Th17 cells. Cells from HSCT‐treated patients cultured with overlapping peptides from myelin oligodendrocyte glycoprotein produced more transforming growth factor‐β₁ than natalizumab‐treated patients, which suggests a suppressive response. Conversely, T cells from natalizumab‐treated patients cultured with those peptides produced more interleukin‐17 (IL‐17), IL‐1 and IL‐10, indicating a Th17 response. In conclusion, we demonstrate circumstantial evidence for the removal of autoreactive T‐cell clones as well as development of tolerance after HSCT. These results parallel the long‐term disease remission seen after HSCT.     

自体外周血干细胞移植治疗下肢缺血性疾病

目的 观察自体干细胞移植治疗下肢缺血性疾病的临床疗效及部分影响因素.方法 下肢缺血性疾病病人15例,其中男性8例,女性7例;年龄44～77岁,平均年龄67.3岁.病人移植前均内科常规治疗半年以上,临床症状、体征未改善.应用自体干细胞移植治疗,按照操作规范和病人实际情况采集外周血干细胞(PBSC),全部病人均给予重组人粒细胞集落刺激因子300～600μg/d,皮下注射,行自体PBSC动员3～5d,然后用费森尤斯血细胞分离机采集PBSc,将干细胞悬液按3×3cm距离进行肢体移植术.术后第1天至3个月定期观察各项指标综合评估.结果 PBSC移植后3个月进行评价,全部病例下肢疼痛明显缓解,皮温升高,下肢冷感消失,14例感染得到控制,溃疡或足趾坏疽明显好转或愈合,足趾颜色由青紫色转为正常,肿胀消失,无1例病人行截肢术;有2例病人趾头已坏死在移植同时行截趾术;移植后所有病人均未出现并发症和明显不良反应.结论 自体PBSC移植治疗糖尿病下肢缺血性疾病是一种安全、有效的手段,可使一部分病人免除截肢,改善生活质量.     

自体造血干细胞移植治疗多发性骨髓瘤的新进展

背景：自体造血干细胞移植是治疗多发性骨髓瘤的有效手段,诱导化疗后行自体造血干细胞移植已成为多发性骨髓瘤的标准治疗方案,多单位、多中心进行了大规模的研究报道。如何减少药物毒副反应、移植相关并发症及改善长期生存是目前关注的重点。 目的：综述自体造血干细胞移植治疗多发性骨髓瘤的新进展。 方法：应用计算机检索2006年1月至2012年11月PubMed、CNKI数据库、维普数据库、万方数据库、free medicaljournals.com网络资源关于自体造血干细胞移植治疗多发性骨髓瘤的文献。英文检索词“Autologous hematopoietic stem cell transplantation, multiple myeloma”;中文检索词“自体造血干细胞移植,多发性骨髓瘤”。选中相关性强的46篇进行综述。 结果与结论：大剂量化疗联合自体造血干细胞移植治疗多发性骨髓瘤的疗效优于传统化疗。但单次自体造血干细胞移植后仍有许多患者不能得到很好的缓解,疾病最终难免复发;异基因造血干细胞移植受到供体来源限制,且治疗相关病死率高,运用受到限制。因此目前的新发展方向包括：在单次自体造血干细胞移植的基础上进行2次自体造血干细胞移植、自体联合减低预处理强度的异体移植以及药物巩固维持治疗。新型药物蛋白酶体抑制剂及免疫调节剂在诱导缓解、预处理、尤其是巩固维持阶段的使用,使多发性骨髓瘤的治疗总体反应率及长期生存得到显著改善。     

ABO血型不合对HLA相合异基因外周血干细胞移植的影响

目的在非血缘移植比例增加、移植物抗宿主病（GVHD）发生率增加、免疫抑制剂用量加大的情况下,分析ABO血型不合对HLA相合异基因外周血干细胞移植（allo-BPSCT）的影响。方法将43例ABO血型不合的allo-PBSCT患者与同期49例ABO血型相合的受者进行比较。结果 ABO血型不合组与相合组输注红细胞量分别为（7.73±7.61）u和（4.33±3.24）u（P=0.040）,ABO血型不合组与相合组血红蛋白恢复到100g/L的时间分别为（54.08±45.24）d和（32.46±16.95）d（P=0.009）。ABO血型不合组较相合组红细胞输注量多,红系恢复时间长。两组间移植相关并发症差异无统计学意义。结论 ABO血型不合不影响造血干细胞移植的植活、主要合并症及预后。ABO血型不合组较相合组红细胞输注量多,红系恢复较慢。     

外周血造血干细胞移植治疗3例重型β地中海贫血和1例特发性溶血性贫血

目的探讨异基因外周血造血干细胞移植(allogeneic peripheral blood stem cell transplantation,Allo-PBSCT)治疗遗传性溶血性贫血(hereditary haemolytic     

非清髓异基因造血干细胞移植治疗低增生性MDS1例并文献复习

目的探讨非清髓性异基因外周血造血干细胞移植治疗低增生性骨髓增生异常综合征（MDS）的疗效,观察其植入及并发症的发生情况。方法我院诊断为低增生性MDS患者1例,采用氟达拉滨＋阿糖胞苷＋环磷酰胺的非清髓预处理方案,环孢素A＋甲氨蝶呤＋骁悉预防移植物抗宿主病。结果 STR-PCR证实移植后30d及3个月骨髓植入为完全供者型,移植后3个月发生多发性脑梗塞,6个月出现面部皮疹及口腔溃疡,通过调整免疫抑制剂及输注间充质干细胞（5×10^7/次,2次）后症状明显好转。结论非清髓性异基因外周血造血干细胞移植治疗低增生性MDS获得较好的疗效。     

自体外周血造血干细胞动员采集的影响因素

背景:自体外周血造血干细胞移植因患者年龄范围宽、移植后并发症少、费用低,临床应用日益广泛.移植后造血功能的重建主要取决于输入造血干细胞的数量和质量.文章从临床实际出发,分析影响外周血造血干细胞采集的各种因素,并计算出适宜采集的血常规标准,对提高临床外周血造血干细胞采集成功率进而提高自体移植成功率有重要意义.目的:分析血...