骨髓间充质干细胞移植治疗犬急性放射性肠病临床观察

目的建立比格犬急性放射性肠病的损伤模型,观察骨髓间充质干细胞移植治疗犬急性放射性肠病的临床效果。方法将35只比格犬随机分为空白对照组(A组)、10 Gy单独照射组(B组)、12 Gy单独照射组(C组)、14 Gy单独照射组(D组)、10 Gy照射后干细胞治疗组(E组)、12 Gy照射后干细胞治疗组(F组)及14 Gy照射后干细胞治疗组(G组),每组5只。对比格犬腹部进行X线调强照射,观察单独照射、照射后干细胞治疗的比格犬的临床特点、肠镜表现、生存时间,并采用组织病理学评分对放射造成的肠损伤程度进行评估。结果比格犬肠损伤程度与放射剂量呈正相关。E、F组干细胞治疗后肠损伤组织病理学评分明显低于治疗前(P<0.05);G组治疗前后比较,差异无统计学意义(P>0.05)。比格犬生存时间与放射剂量呈负相关。F组生存时间明显长于C组(P<0.05);E组与B组、G组与D组比较,差异无统计学意义(P>0.05)。结论随着放射剂量增大,比格犬急性放射性肠病加重,生存时间缩短。骨髓间充质干细胞移植在12 Gy剂量的急性放射性肠病的治疗中发挥积极作用。     

骨髓间充质干细胞对放创复合伤创面的促愈作用

目的 探讨骨髓间充质干细胞对放创复合伤创面的促愈作用。方法 利用自体骨髓来源的间充质干细胞移植于局部合并放射损伤的创面，采用荧光示踪技术、形态学观察、胶原染色、成纤维细胞和毛细血管计数、羟脯氨酸含量测定等多种指标，观察了间充质干细胞对放创复合伤创面的促愈使用。结果 间充质干细胞能加快创面愈合，促进肉芽组织生长和胶原合成。结论 骨髓间充质干细胞对放创复合伤创面有明显的促愈效应。     

脐带间充质干细胞制剂的质量管理及有效性和安全性

在临床应用时,脐带间充质干细胞制剂的质量直接影响其安全性和有效性。在脐带间充质干细胞分离纯化、制剂制备、储存以及运输等环节,需要建立相应的质量标准、质量检测方法和质量管理流程,确保制剂中干细胞的数量、活性达到临床要求,并且不含有细菌、乙型肝炎病毒、丙型肝炎病毒、艾滋病病毒、EB病毒、巨细胞病毒、人类嗜T淋巴细胞病毒、真菌、支原体、衣原体、梅毒螺旋体、寄生虫、内毒素等病原体以及其他未经批准用于临床的物质。脐带间充质干细胞可用于自身免疫性疾病、退行性疾病、衰老性疾病、遗传缺陷性疾病、放射性疾病、炎症、组织器官损伤等病症的治疗,并且具有明确的疗效。脐带间充质干细胞用于临床治疗是安全的,除极少数患者轻度腰部酸痛、头昏、头痛、发热外,无其他任何严重不良反应。但是,也有一些患者不宜进行脐带间充质干细胞治疗。     

极重度骨髓型与肠型急性放射病的救治进展

极重度骨髓型与肠型急性放射病(ARS)一直是医学难以攻克的热点问题。本文从4个方面概括ARS治疗的新进展:①WR-2721作为细胞防护剂的机制和早期应用,可能阻断组织器官的不可逆性放射损伤;②细胞因子治疗放射病的新进展,提出重视造血恢复后患者的免疫重建;③造血干细胞移植的适应证,骨髓间充质干细胞对放射病有重要治疗意义;④放射病的抗感染防护和治疗,临床真菌感染症状出现前,抗真菌用药的适应证。     

间充质干细胞修复放射性肠损伤的机制探讨

放射性肠损伤在临床上常见。然而,针对放射性肠损伤的治疗手段有限。随着组织工程研究不断进展,现已证实间充质干细胞对放射性肠损伤具有修复作用,其中以脐带、骨髓来源的间充质干细胞应用研究居多^[1-6]。这些研究证实了间充质干细胞能够促进受损肠上皮细胞的再生,维持受照上皮的完整性。     

不同来源间充质干细胞构建组织工程肌腱的可行性评估

骨关节外科患者肌腱损伤非常普遍,传统治疗不仅愈合时间长,且常发生并发症.采用组织工程技术构建组织工程肌腱为治疗肌腱损伤带来了新的希望,提供了一种新的治疗策略.既往已报道利用间充质干细胞进行组织修复,因此,利用间充质干细胞构建组织工程肌腱修复受损肌腱可能是一个行之有效的办法.本文主要综述了利用常见来源间充质干细胞构建组织工程肌腱的研究现状,并评估临床应用的可行性.     

牛间充质干细胞及其应用研究进展

间充质干细胞(Mesenchymal Stem Cells,MSCs)是一种成体多能干细胞,其自我更新、长时间增殖、免疫调节和多谱系分化等特性为人类和动物诸多疾病的治疗开辟了新的道路.在各种干细胞类型中,间充质干细胞由于来源广泛、易于获取以及在特定培养条件下仍然具有分化为各胚层细胞的能力而受到广泛关注.近年来,家畜特别是牛的间充质干细胞研究取得了进展,对牛间充质干细胞的来源、培养条件以及实际应用都有了长足进展.但是,依旧存在间充质干细胞来源狭窄,传代次数有限,分化潜能有争议,实验数据不足导致相关机制不明晰等问题.提出了拓展充质干细胞来源、优化培养条件、增加资助力度和临床试验等建议.旨在为以后相关研究提供帮助..     

基因修饰的间充质干细胞在放射性肺损伤治疗中的实验研究进展

放射性肺损伤是胸部恶性肿瘤放疗、核事故重症损伤的常见并发症,目前缺乏有效的治疗手段。间充质干细胞（MSCs）是具有多向分化潜能的细胞群,其通过归巢至损伤部位并分化成受损组织、分泌细胞因子和免疫调节起到防护肺组织辐射损伤的作用。此外,通过对间充质干细胞进行基因修饰,使其不仅具有MSCs的主要特性,而且能够高效稳定表达或敲低某些目的基因,从而增强或降低间充质干细胞对各种生理刺激的敏感性,加强其在放射性肺损伤中治疗的疗效,为临床治疗提供了新思路和新途径。本文就近年来相关进展进行综述。     

间充质干细胞治疗肺损伤研究进展

呼吸系统疾病发病率和病死率的不断上升,使其成为一个全球性公共卫生问题。随着再生医学的发展,细胞疗法成为治疗肺部疾病的新策略。间充质干细胞是一种多能成体干细胞,具有强大的自我更新和分化能力,因其生物学特性、低免疫原性和来源丰富等特点,成为治疗急慢性肺部疾病的理想种子细胞。该文对间充质干细胞治疗新型冠状病毒肺炎、急性肺损伤/急性呼吸窘迫综合征、慢性阻塞性肺疾病、哮喘等急慢性肺损伤的可能机制及研究现状进行了综述。     

骨髓间充质干细胞对冈田酸致神经细胞损伤的修复作用

目的 观察人骨髓间充质干细胞对冈田酸(OA)损伤的神经细胞是否具有修复作用.方法 应用冈田酸损伤神经母细胞瘤细胞系SH-SY5Y细胞,建立阿尔茨海默病体外模型.将细胞分成正常组、损伤组和治疗组,损伤组用20nmol/L冈田酸损伤24h,治疗组在损伤24h后加入骨髓间充质于细胞的条件培养基治疗24h.采用CCK-8法检测各组细胞活力,免疫荧光染色微管微丝测定细胞树突长度和荧光面积,Western blotting检测磷酸化Tau蛋白和总Tau蛋白含量.结果 冈田酸能损伤SH-SY5Y细胞,使其胞体皱缩、塌陷,出现空泡,树突缩短、断裂,微管微丝排列紊乱,而骨髓间充质干细胞条件培养基可使SH-SY5Y细胞胞体变得圆润,树突重新恢复变长,微管、微丝致密规则,荧光变强;并且能有效降低冈田酸诱导的Tau蛋白过度磷酸化水平.结论 骨髓间充质干细胞对冈田酸损伤的神经细胞具有明显的修复作用.     

Mobilisation of mesenchymal cells into blood in response to skeletal muscle injury

Mesenchymal cells recruited to damaged tissues must circulate through the bloodstream. The absolute numbers of circulating mesenchymal stem cells (cMSCs) in two different models of acute and chronic skeletal muscle injury were determined. cMSCs were present in significantly higher numbers in both models than in healthy controls. These results support the hypothesis that MSCs are mobilised into the bloodstream after skeletal muscle tissue damage. These two models (acute and chronic) would be of value in the search for molecular mediators of mobilisation of MSCs into the circulation.     

间充质干细胞外泌体治疗脊髓损伤作用机制的研究进展

脊髓损伤后继发性损伤及胶质瘢痕,使神经细胞在微环境中出现再生障碍.导致治疗困难.间充质干细胞(MSCs)具有多向分化、自我更新能力、参与免疫调节等功能,可用于治疗脊髓损伤.但存在不易通过血脊屏障、高致瘤性等缺点、MSCs外泌体是由MSCs分泌的纳米级外囊泡.包裹多种活性物质.在脊髓损伤研究中具有极强的神经修复作用,且具有易通透性、稳定性及低致瘤等优点,弥补了MSCs治疗的缺点.有望替代MSCs用于治疗脊髓损伤.笔者对MSCs外泌体的生物学特性及其在脊髓损伤治疗中的作用机制作一综述,为脊髓损伤的治疗提供参考.     

The radiation protection and therapy effects of mesenchymal stem cells in mice with acute radiation injury

The aim of this study was to investigate the effects and mechanisms of mesenchymal stem cells (MSCs) on haematopoietic reconstitution in reducing bone marrow cell apoptosis effects in irradiated mice, and to research the safe and effective dosage of MSCs in mice with total body irradiation (TBI). After BALB/c mice were irradiated with 5.5 Gy cobalt-60 γ-rays, the following were observed: peripheral blood cell count, apoptosis rate, cell cycle, colony-forming unit-granulocyte macrophage (CFU-GM) and colony-forming unit-fibroblast (CFU-F) counts of bone marrow cells and pathological changes in the medulla. The survival of mice infused with three doses of MSCs after 8.0 Gy or 10 Gy TBI was examined. The blood cells recovered rapidly in the MSC groups. The apoptotic ratio of bone marrow cells in the control group was higher at 24 h after radiation. A lower ratio of G0/G1 cell cycle phases and a higher ratio of G2/M and S phases, as well as a greater number of haematopoietic islands and megalokaryocytes in the bone marrow, were observed in the MSC-treated groups. MSCs induced recovery of CFU-GM and CFU-GM and improved the survival of mice after 8 Gy TBI, but 1.5 × 10⁸ kg⁻¹ of MSCs increased mortality. These results indicate that MSCs protected and treated irradiated mice by inducing haematopoiesis and reducing apoptosis. MSCs may be a succedaneous or intensive method of haematopoietic stem cell transplantation under certain radiation dosages, and could provide a valuable strategy for acute radiation syndrome.Currently, substantial progress has been made in the treatment of acute radiation syndrome (ARS) [1–6]. The study of haematopoietic growth factors and haematopoietic stem cell transplantation (SCT) has already progressed to the molecular and genetic level [4, 7, 8]. However, there are still some problems associated with SCT for ARS, such as donor deficiency, a high mortality for conditioning and complications resulting from transplantation. Thus, some experts continue to question the effect of transplantation on ARS. It is known that the microenvironment in bone marrow plays a key role in haematopoietic recovery after irradiation injury. The haematopoietic stem cells (HSCs) and the microenvironment, in a pathological state, often damage and aggravate mutually [9]. Therefore, the treatment of both is indispensable in ARS. Mesenchymal stem cells (MSCs) are adherent cells capable of self renewal and multilineage differentiation [10]. In addition, MSCs can produce several essential haematopoietic growth factors, including interleukin (IL)-6, IL-11, leukemia inhibitor factor (LIF), stem cell factor (SCF), Flt3 ligand and stromal derived factor (SDF) [11]. The microenvironment in bone marrow consists of stroma cells derived from MSCs. Cytokine and extracellular matrices are important factors in HSC growth and multiplication [12]. Transplantation of MSCs is used for both autologous and allogeneic transplant [13, 14], but there are fewer reports on the radiation protection and therapy effects of MSCs on mice with acute radiation injury [15, 16]. The present study was undertaken to examine the effects of three dosages of MSCs on the survival of mice exposed to lethal doses of total body irradiation (TBI), and to explore the mechanisms by which MSCs significantly improve haematopoietic recovery. This was accomplished by observing peripheral blood counts, apoptosis, p53 expression, CFU-GM and CFU-F counts, the cell cycle of bone marrow cells, and pathological changes in variety of the medulla.     

骨髓间充质干细胞治疗急性腹膜纤维化的作用方式探讨

目的 探讨骨髓间充质干细胞(MSCs)治疗急性腹膜纤维化的作用方式.方法 取SD大鼠114只,制作急性膜腹粘连模型,其中6只在腹膜刮伤后24h经尾静脉(n=3)或腹腔(n=3)注入MS(s,采用活体成像示踪法观察MSCs的分布并对两种方式注射后MSCs的示踪效果进行比较；其余108只大鼠随机分为无血清条件培养基(CM)...     

干细胞在放射医学研究中的进展

电离辐射作用于机体后,可致机体发生急性放射病。辐射损伤的远后效应之一是白血病,含有干细胞的骨髓细胞移植是目前挽救急性放射病病人生命的惟一有效的治疗方法。近年来随着干细胞研究的突破性进展,其多向分化潜能及干细胞相互转化可能为辐射损伤病人提供新的干细胞来源;同时随着辐射防护剂研究的深入,促进了损伤后干细胞的恢复。     

细胞因子在急性辐射损伤治疗中的作用

急性辐射损伤以及肿瘤患者在放疗或化疗后,均可发生程度不等的骨髓功能抑制。一些细胞因子通过刺激不同分化时期、不同类型的靶细胞影响其增殖和分化,从而对骨髓造血细胞起辐射防护和促进骨髓造血恢复的作用。随着基因工程的发展,人们可以获得越来越多的高纯度重组造血因子,这些因子在急性辐射损伤的实验研究和临床救治中发挥了极其重要的作用。同时,细胞因子治疗也存在一些问题,有待进一步研究和解决。     

间充质干细胞促进半相合骨髓移植治疗急性放射病小鼠的实验研究

目的 探讨骨髓间充质干细胞(MSCs)促进半相合造血干细胞移植(haploid-SCT)治疗急性放射病小鼠的作用及机制。方法 ⁶⁰Co γ射线照射BALB/C(H-2^d)雌性小鼠8Gy,单独输注半相合CB6F1(H-2 bd) 雄性小鼠骨髓细胞1×10⁹/kg(I组),或联合CB6F1 雌性小鼠MSCs不同数量级1.5×10⁸/kg (a组)、5×10⁷/kg (b组)和2.5×10⁷/kg (c组)治疗,比较放射病小鼠的生存分析。同时,MSCs组小鼠尾静脉输注经cm-DiI膜染剂标记的CB6F1雌性小鼠MSCs和CB6F1雄性小鼠的骨髓细胞,与只输注CB6F1骨髓细胞的对照组比较,观察移植后不同时间供者细胞在受者骨髓的植入率、供者MSCs在受者体内发布、外周血象、T淋巴细胞亚群、胸骨骨髓病理和慢性移植物抗宿主病(GVHD)发生情况。结果 a组小鼠早期死亡率增加;b和c组存活率高于I组(P<0.05),但二组之间差异无统计学意义。移植后30 d,MSCs组受者骨髓的sry基因高于对照组。移植后MSCs主要集中在胸腺、骨髓、肝和小肠中,有形态改变。MSCs组的白细胞、血小板恢复较快。照射后15和30 d,MSCs组小鼠骨髓腔中的巨核细胞明显高于对照组。移植后7、14和30 d,MSCs组CD3高于对照组(P<0.05);移植后14和30 d,MSCs组CD4阳性细胞率和CD4/CD8值高于对照组(P<0.05)。MSC组慢性GVHD症状出现较对照组晚30 d。结论 MSCs通过促进干细胞植入,改善造血微环境,促进造血恢复,加快T淋巴细胞的恢复,延缓GVHD的发生时间和促进放射损伤的组织器官的修复,加强了半相合骨髓移植对急性放射病的治疗作用。     

In vivo MRI monitoring nerve regeneration of acute peripheral nerve traction injury following mesenchymal stem cell transplantation

Objective

To assess the continuous process of nerve regeneration in acute peripheral nerve traction injury treated with mesenchymal stem cells (MSCs) transplantation using MRI.

Materials and methods

1 week after acute nerve traction injury was established in the sciatic nerve of 48 New Zealand white rabbits, 5 × 10⁵ MSCs and vehicle alone were grafted to the acutely distracted sciatic nerves each in 24 animals. Serial MRI and T1 and T2 measurements of the injured nerves were performed with a 1.5-T scanner and functional recovery was recorded over a 10-week follow-up period, with histological assessments performed at regular intervals.

Results

Compared with vehicle control, nerves grafted with MSCs had better functional recovery and showed improved nerve regeneration, with a sustained increase of T1 and T2 values during the phase of regeneration.

Conclusion

MRI could be used to monitor the enhanced nerve regeneration in acute peripheral nerve traction injury treated with MSC transplantation, reflected by a prolonged increase in T1 and T2 values of the injured nerves.