脐带血干细胞移植治疗非恶性血液病进展

异基因造血干细胞移植（allo-HSCT）是治愈多种非恶性病的有效方法。脐带血干细胞（UCB）具有免疫原性低、人类白细胞抗原不合耐受性好、移植物抗宿主反应发生率低以及获取相对快捷等特点,可作为非恶性血液疾病患者allo-HSCT的来源。本文简要综述脐血干细胞移植在原发性免疫缺陷病、遗传性骨髓衰竭、遗传代谢病以及自身免疫性疾病等非恶性血液疾病的治疗效果。     

脐带血干细胞的基础与应用研究

作为造血干/祖细胞(hematopoieticstemcells/hematopoieticprogenitorcells,HSCs/HPCs)的另一来源,脐带血已经应用于临床治疗多种恶性和非恶性疾病。脐带血中HSCs/HPCs的质与量是决定其临床应用效果的最重要因素。同时,脐带血中还存在多种非造血的干细胞和前体细胞,如间充质干细胞(mesenchymalstemcells,MSCs)、内皮前体细胞(endothelialprogenitorcells,EPCs)和非限制性体干细胞(unrestrictedsomaticstemcells,USSCs)等,这些细胞可能会在未来的细胞治疗和再生医学中发挥重要作用。本综述还讨论了脐带血的临床应用及HSCs/HPCs的体外扩增、增加HSCs归巢和再植能力等提高其临床应用能力的相关研究。     

脐带血造血干细胞治疗糖尿病的研究进展

脐带血造血干细胞具有极强的自我更新和多向分化潜能,为治疗糖尿病开辟了新的途径,造血干细胞在生成胰岛素分泌细胞前需要经过诱导分化、细胞选择和细胞成熟三个阶段。目前,脐带血造血干细胞在治疗糖尿病中已取得一定进展,将造血干细胞定向分化为胰岛β细胞成为了治疗的关键。本文通过对脐带血的特征、造血干细胞的制备和移植、糖尿病的治疗以及脐带血造血干细胞移植的利与弊等方面进行的归纳总结,分析脐带血造血干细胞在治疗糖尿病方面的进展和应用前景。     

间充质干细胞促进脐带血干细胞体外扩增的研究进展

非亲缘脐带血移植是治疗造血系统疾病的重要移植方式之一,但脐带血移植面临的最大挑战是造血干细胞(HSCs)数量不足,特别是成人患者受到脐带血干细胞数量的限制,导致造血及免疫恢复延迟,非复发死亡率升高。体外扩增脐带血HSCs(UCB-HSCs)是解决该问题的途径之一。研究发现可以通过模拟骨髓造血龛(niche)这一生态位使HSCs在体外进行自我更新增殖,而间充质干细胞(MSCs)正是造血龛的重要的组成细胞之一。本文将探讨MSCs在UCB-HSCs体外扩增中的应用。重点以MSCs促造血的特点、机制,促进脐带血干细胞增殖的各种策略以及其临床应用和前景做一综述。     

间充质干细胞在造血干细胞移植中的应用

间充质干细胞(MSCs)是一种具有自我更新和多向分化潜能的成体干细胞,存在于骨髓、脂肪组织、脐血及多种胎儿组织.它可分泌多种细胞因子及生长因子,促进造血干细胞(HSC)的增殖与分化.MSCs还具有免疫调节、抗炎和组织修复作用,可减轻移植物抗宿主病(GVHD)及其他移植相关并发症.     

无关供者脐带血干细胞移植概况

脐带血作为造血干细胞的一大来源,已逐渐获得医学界的认可,随着临床实践的不断展开,对脐带血的使用也趋于标准化。我们通过移植物抗宿主病和治愈情况对骨髓移植与脐带血移植进行了比较,提供了移植用脐带血的择优选取办法及移植的最低细胞剂量,对双份脐带血的选择给出建议,同时对非亲缘脐血与骨髓共输注临床使用情况和嵌合体检测做了介绍与评价。可以看出,在治疗恶性血液病时,脐带血移植是一个可靠的方法。     

脐带血干细胞的低温保存研究

脐带血干细胞在医学上具有广阔的应用前景.本文对其低温保存进行了理论和实验研究.在以5%和10%的二甲亚砜做低温保护剂时,实验得到干细胞分别在冷却速率为10℃/min和10.5℃/min时细胞具有最高的存活率,与理论预测的最佳冷却速率十分接近.     

自体造血干细胞移植治疗急性白血病:历史传承、体系建设与优化

自体造血干细胞移植(autologous hematopoietic stem cell transplantation,ASCT)是急性白血病(acute leukemia,AL)缓解后治疗的重要方法,尤其是对首次完全缓解(first complete remission,CR1)的低危、中危急性髓系白血病(acute myeloid leukemia,AML),复发后再次完全缓解(CR2)的急性早幼粒白血病(acute promyelocytic leukemia,APL)及费城染色体阳性急性淋巴细胞白血病(Philadelphia chromosome-positive acute lymphoblastic leukemia,Ph⁺ ALL)的患者而言,ASCT具有良好的临床疗效。微小残留疾病(minimal residual disease,MRD)状态、预处理方案、移植后维持治疗等因素与ASCT后的疾病预后密切相关。中国医学科学院血液病医院实施了中国第一例ASCT,并结合基础与临床研究逐渐形成和不断完善了ASCT治疗AL的诊疗体系,取得了良好的临床疗效...     

人脐带血来源造血干细胞体外扩增的研究进展

造血干细胞（HSCs）是血液系统中的一类成体干细胞群,具有自我更新和多谱系分化两个基本特征。造血干细胞移植（HSCT）可以治疗退行性疾病和多种血液系统疾病。脐带血来源造血干细胞（CB HSCs）是降低HLA配型要求的突破点,但单份脐带血中HSCs数量不能满足使用要求,为了获得足够数量的CB HSCs,体外扩增是一种可行的方法。近几年,学者们探索了多种体外扩增方法,包括优化细胞生长因子混合物、与基质细胞共培养及加入小分子化合物（SMCs）激动剂等。目前应用细胞因子联合小分子的扩增方法在多个临床试验中获得成功。本文对目前体外扩增CB HSCs的研究进展做一综述。     

GM—CSF和IL—3对脐带血CD34＋细胞植入骨髓基质的促进作用

利用抗ＣＤ３４单克隆抗体吸附磁性微球的方法分离纯化脐带血ＣＤ３４＾＋细胞,将其种入照射后的成年骨髓基质。比较ｒｈＧＭ－ＣＳＦ、ＩＬ－３及两者的联合对植入效率的促进作用。结果表明：经２ｈ铺展贴壁后,对照组只有３６％的ＣＤ３４＾＋细胞植入基质,而生长因子预处理组则有６８－８９．６％的ＣＤ３４＾＋细胞植入基质。在长期液体培养体系中则显示了植入ＣＤ３４＾＋细胞多的处理组造血重建快速而持久。表明ＧＭ－ＣＳＦ     

Hyperbaric oxygen treatment effects on in vitro cultured umbilical cord blood CD34+ cells

Background aims

Umbilical cord blood (UCB) provides an alternative source for hematopoietic stem/progenitor cells (HSPCs) in the treatment of hematological malignancies. However, clinical usage is limited due to the low quantity of HSPCs in each unit of cord blood and defects in bone marrow homing. Hyperbaric oxygen (HBO) is among the more recently explored methods used to improve UCB homing and engraftment. HBO works by lowering the host erythropoietin before UCB infusion to facilitate UCB HSPC homing, because such UCB cells are not directly exposed to HBO. In this study, we examined how direct treatment of UCB-CD34⁺ cells with HBO influences their differentiation, proliferation and in vitro transmigration.

Complete nationwide survey on umbilical cord blood freezing bag breakage in Japan

Background aimsAlthough umbilical cord blood (UCB) has now become a common stem cell source, UCB bag breakage is a known risk in UCB transplantation (UCBT). This survey provides the first comprehensive data on the frequency and causes of UCB bag breakage in Japan.MethodsData regarding UCB bag breakage from all causes, identified between April 1, 2010, and September 3, 2013, were collected from all transplant centers registered for UCBT (209 hospitals) and all public cord blood banks (CBBs) (8 CBBs) in Japan.ResultsSeventeen incidents of UCB bag breakage at CBBs were confirmed, none of which resulted in bags being shipped to transplant centers. From among 3836 UCBT, 16 incidents (0.4%) of UCB bag breakage were confirmed at transplant centers. Although all these bags were used for transplantation, no direct health hazard was reported. The major cause of UCB bag breakage confirmed at transplant centers was considered to be external force (75%). In addition, 11 incidents of unexplained UCB bag breakage at sealing between compartments were reported.ConclusionsUCB bag breakage was confirmed at both CBBs and transplant centers. UCB bags should be handled with particular care and attention.     

The umbilical cord matrix is a better source of mesenchymal stem cells (MSC) than the umbilical cord blood

Many studies have drawn attention to the emerging role of MSC (mesenchymal stem cells) as a promising population supporting new clinical concepts in cellular therapy. However, the sources from which these cells can be isolated are still under discussion. Whereas BM (bone marrow) is presented as the main source of MSC, despite the invasive procedure related to this source, the possibility of isolating sufficient numbers of these cells from UCB (umbilical cord blood) remains controversial. Here, we present the results of experiments aimed at isolating MSC from UCB, BM and UCM (umbilical cord matrix) using different methods of isolation and various culture media that summarize the main procedures and criteria reported in the literature. Whereas isolation of MSC were successful from BM (10:10) and (UCM) (8:8), only one cord blood sample (1:15) gave rise to MSC using various culture media [DMEM (Dulbecco's modified Eagle's medium) +5% platelet lysate, DMEM+10% FBS (fetal bovine serum), DMEM+10% human UCB serum, MSCGM®] and different isolation methods [plastic adherence of total MNC (mononuclear cells), CD3⁺/CD19⁺/CD14⁺/CD38⁺‐depleted MNC and CD133⁺‐ or LNGFR⁺‐enriched MNC]. MSC from UCM and BM were able to differentiate into adipocytes, osteocytes and hepatocytes. The expansion potential was highest for MSC from UCM. The two cell populations had CD90⁺/CD73⁺/CD105⁺ phenotype with the additional expression of SSEA4 and LNGFR for BM MSC. These results clearly exclude UCB from the list of MSC sources for clinical use and propose instead UCM as a rich, non‐invasive and abundant source of MSC.     

Expanded umbilical cord blood T cells used as donor lymphocyte infusions after umbilical cord blood transplantation

BackgroundUmbilical cord blood (UCB) is an alternative graft source for hematopoietic stem cell transplantation and has been shown to give results comparable to transplantation with other stem cell sources. Donor lymphocyte infusion (DLI) is an effective treatment for relapsed malignancies after hematopoietic stem cell transplantation. However, DLI is not available after UCB transplantation.MethodsIn this study, in vitro–cultured T cells from the UCB graft were explored as an alternative to conventional DLI. The main aim was to study the safety of the cultured UCB T cells used as DLI because such cell preparations have not been used in this context previously. We also assessed potential benefits of the treatment.ResultsThe cultured UCB T cells (UCB DLI) were given to 4 patients with mixed chimerism (n = 2), minimal residual disease (n = 1) and graft failure (n = 1). No adverse reactions were seen at transfusion. Three of the patients did not show any signs of graft-versus-host disease (GVHD) after UCB DLI, but GVHD could not be excluded in the last patient. In the patient with minimal residual disease treated with UCB DLI, the malignant cell clone was detectable shortly before infusion but undetectable at treatment and for 3 months after infusion. In 1 patient with mixed chimerism, the percentage of recipient cells decreased in temporal association with UCB DLI treatment.ConclusionsWe saw no certain adverse effects of treatment with UCB DLI. Events that could indicate possible benefits were seen but with no certain causal association with the treatment.     

人脐带间充质干细胞移植治疗脊髓损伤的研究进展

脊髓损伤（SCI）由于复杂病理生理和神经修复再生困难,至今仍旧是难以攻克的医学难题,而干细胞因其神经再生和神经保护特性被认为是治疗SCI最有希望的方法。其中人脐带间充质干细胞（HUC-MSCs）近年培养分化方法不断改进、神经修复机制初步阐明,联合移植等综合治疗方案也不断实践,使HUC-MSCs移植治疗效果提高。另外关于HUC-MSCs治疗SCI的临床试验逐渐开展,术后患者神经功能恢复改善且无严重并发症出现,表明干细胞移植应用于人体是安全有效的。本文就HUC-MSCs治疗SCI的研究状况及进展进行综述。     

Human umbilical cord mesenchymal stem cell transplantation restores damaged ovaries

Ovarian injury because of chemotherapy can decrease the levels of sexual hormones and potentia generandi of patients, thereby greatly reducing quality of life. The goal of this study was to investigate which transplantation method for human umbilical cord mesenchymal stem cells (HUMSCs) can recover ovarian function that has been damaged by chemotherapy. A rat model of ovarian injury was established using an intraperitoneal injection of cyclophosphamide. Membrane‐labelled HUMSCs were subsequently injected directly into ovary tissue or tail vein. The distribution of fluorescently labelled HUMSCs, estrous cycle, sexual hormone levels, and potentia generandi of treated and control rats were then examined. HUMSCs injected into the ovary only distributed to the ovary and uterus, while HUMSCs injected via tail vein were detected in the ovary, uterus, kidney, liver and lung. The estrous cycle, levels of sex hormones and potentia generandi of the treated rats were also recovered to a certain degree. Moreover, in some transplanted rats, fertility was restored and their offspring developed normally. While ovary injection could recover ovarian function faster, both methods produced similar results in the later stages of observation. Therefore, our results suggest that transplantation of HUMSCs by tail vein injection represents a minimally invasive and effective treatment method for ovarian injury.     

Concentrations of heavy metals in maternal and umbilical cord blood

Concentrations of lead, cadmium, methylmercury and total mercury were measured in maternal and umbilical cord blood using graphite atomic absorption spectrometry. Two essential metals, copper and zinc, were also determined using ion chromatography. Lead, copper and zinc were found to be lower in the cord blood, whereas methylmercury and total mercury were higher in cord blood than in maternal blood. Little differences were noted for cadmium in maternal and cord blood. Significant positive correlations were observed between the concentrations in maternal and cord blood with regard to lead (correlation coefficient, r = 0.44), copper (r = 0.34), zinc (r = 0.29), methylmercury (r = 0.44) and total mercury (r = 0.58). These results suggest that, like essential metals, most heavy metals can move rather freely across the human placenta. The potential health effects of heavy metal transfer from mothers to young infants cannot be discounted.