间充质干细胞对新型冠状病毒肺炎免疫损伤潜在修复作用的研究进展

针对新型冠状病毒肆虐以及暂无特效药物治疗的情况,多地已开展间充质干细胞(MSCs)在新型冠状病毒感染重症救治方面的临床研究,在规范应用的前提下,经过严格的临床检验后,对若干重型患者进行治疗并取得了一定效果。MSCs能抑制免疫系统过度激活,通过改善微环境促进内源性修复、抑制肺部炎症的进展达到缓解呼吸窘迫症状的目的。本文就新型冠状病毒免疫损伤的发生机制、治疗现状以及MSCs在治疗新型冠状病毒感染的潜在治疗机制作一介绍。     

骨髓间充质干细胞对肾移植受者T淋巴细胞分化和miRNA-155表达的影响

目的探讨骨髓间充质干细胞（MSCs）对肾移植受者T淋巴细胞分化和miRNA-155表达的影响。 方法选取2013年1月至2017年12月于福州总医院接受MSCs诱导+同种异体肾移植术的受者20例（MSCs组）,对照组为同期配对的异体肾移植受者20例。两组患者术后免疫抑制方案均为霉酚酸酯+他克莫司+强的松。两组患者分别于移植术前、术后第15天抽取静脉血,流式细胞仪检测外周血CD4⁺ CD25⁺ FoxP3⁺ Treg细胞/?CD4⁺细胞亚群比值;ELISA检测白细胞介素2（IL-2）、肿瘤坏死因子α（TNF-α）和白细胞介素10（IL-10）浓度;免疫磁珠分选外周血T淋巴细胞后,Rea1-time PCR法检测外周血T淋巴细胞中miRNA-?155的表达。两组间均数比较采用独立t检验,治疗前后均数比较采用配对t检验。 结果移植前两组肾移植受者外周血CD4⁺ CD25⁺ FoxP3⁺ Treg细胞/?CD4⁺细胞比值、IL-2、IL-?10、TNF-α、T淋巴细胞miRNA-155表达水平差异均无统计学意义（P均> 0.05）;术后第15天,与对照组相比,MSCs组外周血CD4⁺ CD25⁺ FoxP3⁺ Treg细胞/?CD4⁺细胞亚群比值（30.44﹪?± 4.23﹪? vs 26.06﹪?±4.77﹪,t = 2.365,P = 0.042）、IL-10水平（20.35?ng/?L?±?5.10?ng/?L? vs 16.63?ng/?L±6.26?ng/?L,t = 2.062,P?=?0.046）上升,而IL-2（27.47ng/?L±4.30 ng/?L vs 31.40?ng/?L±5.33 ng/L,t = 2.252,P = 0.015）、TNF-α（41.52?ng/?L±8.32?ng/L vs 46.67?ng/?L±6.71?ng/L,t = 2.157,P = 0.037）和T淋巴细胞miRNA-155表达水平（1.61±0.31 vs 1.89±0.15,t = 3.688,P?= 0.001）则降低。 结论MSCs能够升高肾移植受者外周血CD4⁺ CD25⁺ FoxP3⁺ Treg细胞/?CD4⁺细胞比值和IL-10水平,降低IL-2、TNF-α和T淋巴细胞miRNA-155表达水平,与MSCs的免疫耐受诱导有关。     

<i>AHNAK</i>基因高表达与老年急性髓系白血病患者预后不良相关

目的基于单细胞RNA测序（scRNA-seq）筛选老年急性髓系白血病（AML）造血干细胞（HSCs）中的关键基因,分析其对预后的影响。 方法对3例初诊老年AML患者骨髓细胞进行scRNA-seq,采用统一流形逼近与投影（UMAP）算法聚类确定骨髓细胞类型。进一步根据拷贝数变异（CNV）分析、干性分析、拟时序分析、差异表达基因分析和富集分析揭示HSCs亚群的特点,筛选差异表达基因。通过癌症基因组图谱计划（TCGA）数据库/基因型-组织表达（GTEx）数据库以及实时荧光定量聚合酶链反应（RT-qPCR）对收集的老年AML患者、年轻AML患者和健康人骨髓样本检测,对筛选出的关键基因表达进行验证。采用单因素方差分析和Dunnett-t检验进行比较,生存分析用Log-rank检验。 结果3例老年AML患者的骨髓细胞UMAP聚类分为11类细胞,其中HSCs比例差异较大;重新UMAP聚类HSCs,得到5个HSCs亚群。HSCs_2和4在细胞命运2 （Fate2）分支,CNV评分较高,且富集通路类似,因此归为一组,HSCs_1、3和5归为另一组;差异表达基因分析结果显示肺腺癌转移相关转录本1 （MALAT1）、AHNAK核蛋白（AHNAK）、Dmx like蛋白2 （DMXL2）和磷脂转运ATP酶8B4 （ATP8B4）基因差异显著。TCGA数据库/GTEx数据库分析结果显示,与健康人比较,MALAT1、AHNAK和ATP8B4基因在AML患者中高表达（P < 0.05）,DMXL2基因表达在AML患者和健康人中比较差异无统计学意义。RT-qPCR结果显示AHNAK和ATP8B4 mRNA水平在老年AML患者中高于年轻AML患者和健康人（P < 0.05）[AHNAK mRNA：（0.74 ± 0.14）比（4.28 ± 1.06）,（1.05 ± 0.11）比（4.28 ± 1.06）,ATP8B4 mRNA：（0.03 ± 0.01）比（0.64 ± 0.14）,（0.07 ± 0.02）比（0.64 ± 0.14）]。MALAT1 mRNA水平在老年AML患者中高于年轻AML患者[（0.45 ± 0.16）比（1.27 ±0.23）]（P < 0.05）,但与健康人的差异无统计学意义。DMXL2 mRNA水平在老年AML患者中与年轻AML患者、健康人比较差异无统计学意义。生存分析显示AHNAK基因高表达与老年AML患者生存负相关。 结论AHNAK基因在老年AML患者HSCs中高表达,且与预后不良相关。     

Microenvironment at tissue injury, a key focus for efficient stem cell therapy: A discussion of mesenchymal stem cells

Stem cell therapy is not a new field, as indicated by the success of hematopoietic stem cell reconstitution for various hematological malignancies and immune-mediated disorders. In the case of tissue repair, the major issue is whether stem cells should be implanted, regardless of the type and degree of injury. Mesenchymal stem cells have thus far shown evidence of safety, based on numerous clinical trials, particularly for immune-mediated disorders. The premise behind these trials is to regulate the stimulatory immune responses negatively. To apply stem cells for other disorders, such as acute injuries caused by insults from surgical trauma and myocardial infarction, would require other scientific considerations. This does not imply that such injuries are not accompanied by immune responses. Indeed, acute injuries could accompany infiltration of immune cells to the sites of injuries. The implantation of stem cells within a milieu of inflammation will establish an immediate crosstalk among the stem cells, microenvironmental molecules, and resident and infiltrating immune cells. The responses at the microenvironment of tissue injury could affect distant and nearby organs. This editorial argues that the microenvironment of any tissue injury is a key consideration for effective stem cell therapy.     

间充质干细胞外泌体在阿尔兹海默症治疗中的研究进展

阿尔兹海默症（AD）是一种病理机制复杂,以进行性认知功能障碍为主的中枢神经系统疾病,目前仍缺乏有效的治疗方法。多项研究结果显示,间充质干细胞（MSCs）外泌体能够促进抗炎、调节免疫功能、加强Aβ降解、促进神经细胞轴突生长等,能很好地针对AD的核心病理机制发挥效果从而达到治疗效果。本文主要介绍MSCs外泌体在各项AD病理机制治疗中的研究进展。     

Immune regulatory properties of multipotent mesenchymal stromal cells: Where do we stand?

Multipotent mesenchymal stromal cells (MSC) can be isolated and efficiently expanded from almost every single body tissue and have the ability of self-renewal and differentiation into various mesodermal cell lineages. Moreover, these cells are considered immunologically privileged, related to a lack of surface expression of costimulatory molecules required for complete T cell activation. Recently, it has been observed that MSC are capable of suppressing the immune response by inhibiting the maturation of dendritic cells and suppressing the function of T lymphocytes, B lymphocytes and natural killer cells in autoimmune and inflammatory diseases as a new strategy for immunosuppression. The understanding of immune regulation mechanisms by MSC is necessary for their use as immunotherapy in clinical applications for several diseases.