干细胞在细胞移植法治疗心肌损伤中的应用

干细胞是指同时具有自我更新和产生分化细胞的增殖性细胞.干细胞具有分化成多种机体组织细胞,包括心肌细胞的潜能.把胚胎干细胞和成熟组织干细胞分化成心肌细胞的体内和体外实验,以及把这些分化出的心肌细胞用于细胞移植来治疗心肌损伤的可能性加以总结.虽然干细胞用于治疗心肌损伤的细胞移植疗法具有广阔的前景,但在临床应用方面仍有很多问题尚待解决.     

脊髓损伤治疗中的细胞移植策略及预处理研究进展

急性脊髓损伤是骨科常见的严重疾患,伤后神经功能恢复及重建是近年来研究的热点,其中细胞移植的研究得到广泛的关注并取得较大的研究进展。本文介绍了细胞移植治疗脊髓损伤治疗的研究现状,其中对移植细胞的来源,移植的时机,移植的途径以及细胞移植存活的问题及应对策略做了重点阐述。同时对增加移植细胞存活率的预处理方法做了简要综述。     

胰岛素分泌细胞移植治疗Ⅰ型糖尿病的研究进展

Ⅰ型糖尿病(typeⅠ diabetes mellitus,T1DM)是目前严重危害人类健康的常见病、多发病,全世界约有2%~5%的人患有此种疾病,且呈逐年增长趋势,多见于儿童和青少年。从降糖药物到胰岛素,从胰腺移植到胰岛移植,T1DM的治疗经历了一个漫长的过程。近年来研究发现,由胚胎干细胞(embryonicstemcells,ESC)、胰腺干细胞及其它组织干细胞等诱导分化为胰岛素分泌细胞(insulin-serectingcells,ISC),可望解决移植过程中存在的供体不足的问题。着重介绍了几种ISC的来源和诱导分化途径,分析了各种途径的优势及不足。     

干细胞移植治疗心力衰竭的研究进展

由于心肌梗死发作等原因可造成心肌受损、心力衰竭。干细胞可以向心肌细胞定向分化,这使得通过细胞移植治疗心力衰竭成为可能。简要综述了有望用于移植的干细胞,以及目前实验与临床研究进展和面临的问题。     

异基因造血干细胞移植中的树突状细胞

树突状细胞(DC)是目前已知的启动免疫反应最强大的抗原呈递细胞(APC),也是惟一能激活初始T细胞的APC。近年来,DC在移植免疫中的作用已成为研究的焦点。简要综述了DC在异基因造血干细胞移植中的研究进展。     

细胞重编程和移植技术用于帕金森病治疗的研究进展

帕金森病(Parkinson disease,PD)是一种复杂的中枢神经系统退行性疾病,主要病理特征为黑质致密部多巴胺神经元的进行性丧失.目前PD主要治疗手段包括药物和手术.但药物存在神经保护活性不足、缺乏对因治疗、晚期无药可用等问题,手术治疗风险较大.近年来,细胞重编程技术取得突破性进展,由重编程产生的诱导多能干细胞(induced pluripotent stem cells,iPSCs)、诱导多巴胺神经元(induced dopamine neurons,iDNs)和诱导神经干细胞(induced neural stem cells,i NSCs)可用于治疗PD.移植iPSCs分化而来的多巴胺能神经元、iDNs和iNSCs至相应脑区,可起到神经替代与修复作用,有效治疗PD.本文重点介绍细胞重编程的机制,总结iPSCs、iDNs和iNSCs治疗PD的优缺点,并阐述尚存在的挑战,探讨可能的解决方案.     

一种有效区分移植细胞和宿主细胞脑损伤模型的建立

为了区分移植神经细胞和宿主细胞,便于将来在宿主体内对移植细胞进行在体的电生理记录以及其它方面的研究,通过机械损毁的方法,建立了一种特殊的脑损伤模型。结果发现,通过机械损毁的方法,在大鼠大脑皮层形成形态规则的损伤空洞,其模型稳定,重复性好;在空洞内进行干细胞移植,能够长时间存活,移植神经干细胞绝大部分细胞分化为神经元,只有少量细胞分化为胶质细胞,而且移植细胞与宿主细胞分界明显;对移植细胞进行单细胞电生理记录,记录到神经元放电信号。这些结果表明,通过机械损毁的方法,在大鼠大脑皮层成功建立了一个稳定、精确定位移植细胞与宿主细胞界限的脑损伤模型。     

Ⅰ型糖尿病的细胞治疗

糖尿病是一种代谢系统紊乱疾病,全世界大约有2％—5％的人口患有此种疾病。Ⅰ型糖尿病病因在于中枢及外周免疫系统B细胞特异性分子免疫耐受的丧失,破坏B细胞,为此需要依赖外源性胰岛素治疗。Ⅰ型糖尿病的传统治疗方法存在各种问题,而作为一种糖尿病治疗的有效方法,糖尿病细胞治疗与以往方法相比具有不可替代的优势。本着重介绍几种通过细胞水平治疗糖尿病的方法,分析了各种方法存在的优势与不足。     

Application of methods for viral clearance in stem cell production

Regenerative medicine therapies will allow in the future the transplant of cells of human origin in some diseases that until now have been incurable. The assurance of the safety and quality, especially from a microbiological point of view, is very important for these therapeutic products. Depending on the starting material, there are several sources of pathogen presence, mainly human viruses. Also, the use of feeders of animal origin as layers in which the stem cells can grow may permit the transmission of animal pathogens to these cells. However, cell sources are limited due to the low availability of spare in vitro fecundation human embryos and the low rate of success in the derivation of human stem cell lines. Thus, in several cases, it will be necessary to evaluate the possibility of removing or inactivating these microorganisms. In this paper, we summarize the main methods of viral clearance and we have provided an overview of the main features taking into account in the viral clearance techniques.     

Expression of the Argonaute protein PiwiL2 and piRNAs in adult mouse mesenchymal stem cells

Piwi (P-element-induced wimpy testis) first discovered in Drosophila is a member of the Argonaute family of micro-RNA binding proteins with essential roles in germ-cell development. The murine homologue of PiwiL2, also known as Mili is selectively expressed in the testes, and mice bearing targeted mutations of the PiwiL2 gene are male-sterile. PiwiL2 proteins are thought to protect the germ line genome by suppressing retrotransposons, stabilizing heterochromatin structure, and regulating target genes during meiosis and mitosis. Here, we report that PiwiL2 and associated piRNAs (piRs) may play similar roles in adult mouse mesenchymal stem cells. We found that PiwiL2 is expressed in the cytoplasm of metaphase mesenchymal stem cells from the bone marrow of adult and aged mice. Knockdown of PiwiL2 with a specific siRNA enhanced cell proliferation, significantly increased the number of cells in G1/S and G2/M cell cycle phases and was associated with increased expression of cell cycle genes CCND1, CDK8, microtubule regulation genes, and decreased expression of tumor suppressors Cables 1, LATS, and Cxxc4. The results suggest broader roles for Piwi in genome surveillance beyond the germ line and a possible role in regulating the cell cycle of mesenchymal stem cells.     

小鼠角膜上皮祖细胞系TKE2的表型研究

目的：观察小鼠角膜上皮祖细胞系TKE2在扩增以及分化状态下的角蛋白及干细胞标志物的表达情况。方法小鼠角膜上皮祖细胞系TKE2在无血清培养基Keratinocyte-SFM （KSFM）以及含10﹪胎牛血清（FBS）的DMEM培养基中培养,约70﹪融合时进行角蛋白10、12、14、15、16（K10、K12、K14、K15、K16）以及Connexin43、ABCG2的免疫荧光染色,以及Ki67、P63、PCNA的免疫细胞化学染色。结果无血清培养状态下的TKE2细胞呈克隆样生长,克隆内所有细胞呈ABCG2、K14、Ki67、PCNA以及P63阳性,K15阳性细胞散在分布,K16阳性细胞呈片状分布于克隆中央区,K10、K12以及Connexin43染色为阴性。在含有10﹪胎牛血清的DMEM中培养2 d后,细胞明显增大, ABCG2、K15、P63、Ki67以及PCNA转为阴性,克隆内只有少量细胞呈K16、K14阳性染色, K10、K12、Connexin43仍为阴性。结论 TKE2细胞具有角膜上皮干细胞特性,可以作为角膜缘上皮干细胞表型维持和分化诱导研究的良好工具。     

The multiple functions of Numb

Numb is an evolutionary conserved protein that plays critical roles in cell fate determination. Mammalian Numb displays a higher degree of structural complexity compared to the Drosophila homolog based on the number of encoding genes (Numb and Numb-like) and of alternative spliced isoforms. Accordingly, Numb proteins display a complex pattern of functions such as the control of asymmetric cell division and cell fate choice, endocytosis, cell adhesion, cell migration, ubiquitination of specific substrates and a number of signaling pathways (i.e. Notch, Hedgehog, p53). Recent findings indicate that, besides controlling such physiologic developmental processes, subversion of the above Numb-dependent events plays a critical role in disease (e.g. cancer). We will review here the multiple functions of mNumb and their underlying molecular mechanisms in development and disease.     

细胞药物的研发现状——细胞药物连载之三

近年来,细胞药物的研究受到了国内外重视。特别是干细胞药物,已成为世界各国竞相研究的热点领域,但各国的干细胞药物绝大多数仍处于研究阶段,全球真正上市的干细胞药物很少。目前正在研发的干细胞药物主要集中在治疗慢性疾病（关节炎、糖尿病和癌症等）和心脏相关疾病（心肌梗死、心脏衰竭等）。一些传统体细胞药物（软骨细胞、心肌细胞、胰岛细胞等）和免疫细胞药物已在临床应用。     

The Patchwork Mouse Phenotype: Implication for Melanocyte Replacement in the Hair Follicle

Mice homozygous for the recessive patchwork (pwk) mutation are characterized by a variegated pigment pattern with a mixture of unpigmented and normally pigmented hairs. The pigmented hair bulbs contain functional melanocytes. By contrast, the unpigmented hair bulbs contain no melanocytes. This lack results from the death of melanoblasts in the hair follicle at the end of embryogenesis. Here, we report that melanoblasts and melanocytes are found in the epidermis of pwk/pwk mice. Furthermore, these epidermal pigment cells are able to colonize new hair follicles after skin wounding. Despite the presence of epidermal pigment cells with a colonization potential, a follicle that had produced an unpigmented hair produces a new unpigmented hair during the successive hair growth cycles. This hair color continuity is also true for the pigmented hair follicles. Thus, in normal conditions, the hair acts as an independent functional unit as regards its pigment cells population.     

细胞药物的临床应用——细胞药物连载之五

近年来,细胞药物在基础研究领域的成果促进了临床应用。现在细胞药物治疗的疾病种类很多,包括神经系统疾病、自身免疫系统疾病、心血管系统疾病、血液系统疾病、消化系统疾病、下肢缺血、整形美容、抗衰老及抗肿瘤等,涉及的细胞主要有各种干细胞、软骨细胞、肝细胞、DC及CIK细胞等。国内外越来越多的机构和组织开展了细胞治疗的临床研究及应用。     

角膜内皮细胞再生研究新进展

人角膜内皮细胞的主要功能是维持角膜透明性,角膜内皮单层发育成熟形成细胞接触后,内皮细胞会停止分裂增殖,但并没有退出细胞周期。角膜内皮细胞的增殖有多种因素的参与和影响,接触抑制和G1期抑制使细胞增殖暂时停止;细胞因子TGF-β2抑制人角膜内皮细胞进入细胞周期S期,而EGF、FGF、NGF则能够促进细胞的增殖;ROCK抑制剂Y-27632能够促进角膜内皮细胞的粘连,有助于内皮细胞的损伤修复。体外培养角膜内皮前体细胞、诱导多潜能干细胞向角膜内皮细胞分化,为今后治疗角膜内皮失代偿提供了新方向。