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诱导多能干细胞促进糖尿病足溃疡愈合的研究进展
编辑人员丨3天前
糖尿病足溃疡等慢性创伤在人群中广泛流行,给患者和社会都带来了巨大的负担。而在现有的治疗方式下,糖尿病足溃疡往往愈合不良且容易复发,因此找寻新型疗法显得尤为迫切和重要。干细胞疗法作为一种新兴的治疗方式,其在糖尿病足溃疡愈合中的作用已得到大量基础和临床研究的证实。然而,由于获取干细胞往往依赖于侵入性手段,免疫排斥和移植后的细胞存活率低等问题也限制了干细胞疗法的大规模应用和推广。近年来,随着诱导多能干细胞(iPSC)技术的发展和进步,其在糖尿病足溃疡的治疗中表现出很强的转化潜能。该文将围绕iPSC在包括糖尿病溃疡和肢体缺血在内的创伤愈合动物模型中的应用及前景、临床应用的局限性和改善安全性的方法展开综述。
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编辑人员丨3天前
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诱导多能干细胞在遗传性疾病研究中的应用
编辑人员丨3天前
疾病细胞模型是了解疾病发病机制以及筛选治疗药物的重要工具之一。从活体组织或者体液分离获取的原代细胞与患者基因型相同,是构建疾病细胞模型的重要细胞来源之一。尽管原代细胞具有诸多的优点,但是原代细胞分离费时费力且难以在体外培养扩增。干细胞具有持续增殖以及分化成其他细胞类群的潜能,相比于原代细胞,其在疾病细胞模型的构建更具有潜力。根据干细胞的来源不同,可将其分为成体干细胞和胚胎干细胞。目前已有胚胎干细胞用于构建疾病细胞模型的相关报道,但是该项技术涉及的伦理道德问题相对复杂,其发展前景并不理想。诱导多能干细胞(induced pluripotent stem cells,iPSCs)技术的出现解决了胚胎干细胞引起的人伦道德问题,为疾病细胞模型的构建提供了新方法。本文主要对诱导多能干细胞在神经退行性疾病、心律失常以及石骨症等人类遗传性疾病研究中的应用进展进行综述。
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编辑人员丨3天前
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诱导性多能干细胞技术探索双相障碍发病机制的研究进展
编辑人员丨3天前
双相障碍目前已成为全球性的公共健康问题之一,由于缺乏准确可靠的研究手段,其发病机制尚未完全清楚。近年来,诱导性多能干细胞(induced pluripotent stem cells,iPSCs)技术已被用于双相障碍等精神疾病的发病机制探索,通过建立与双相障碍患者具有相同遗传信息的体外神经细胞模型,研究者们在神经发育、离子通道、线粒体功能、坍塌反应调节蛋白磷酰化、微小核糖核酸表达及免疫炎症反应等方面寻找到了双相障碍发病机制的线索。目前iPSCs技术尽管仍有诸多问题需要改善和解决,但因其可立足于临床样本,建立双相障碍神经细胞体外模型,因此具有巨大的基础研究及临床应用价值。期待基于iPSCs技术建立的双相障碍体外细胞模型能够早日突破各方面瓶颈,为精神疾病的病因研究和治疗带来曙光。
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编辑人员丨3天前
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特纳综合征临床研究进展
编辑人员丨3天前
特纳综合征(Turner syndrome,TS)是一种相对常见的染色体病,与一条X染色体部分或完全丢失相关。患者通常表现为多系统疾病,该疾病虽然有明显的核型,但由于早期没有特征性病理改变,故延迟诊断的可能性很大,平均诊断年龄在15岁。虽然生长激素及性激素替代疗法已广泛应用于临床,但目前仍未有治愈该病的治疗方案。因此,早期筛查、及早干预、联合多系统进行治疗及长期定期复查尤为重要。本文就TS的常用诊断手段、常见并发症、治疗方法及展望进行综述。
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编辑人员丨3天前
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诱导多能干细胞源性胰岛类器官的研究及临床试验进展
编辑人员丨3天前
胰岛细胞移植(ICT)受到供体来源和免疫抑制的限制,未广泛应用于临床。诱导多能干细胞(iPSC)作为胰岛细胞替代来源有望解决ICT供源短缺和免疫抑制的问题,已经开展的临床试验证实了胰岛素分泌细胞(IPC)植入后的安全性和有效性。该文重点论述iPSC来源的胰岛类器官涉及的有关问题和未来需要解决的困难,并提出最优化的诱导方案,旨在为iPSC诱导提供参考。此外,该文还阐述iPSC诱导的IPC在1型糖尿病治疗中的临床试验现状。
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编辑人员丨3天前
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不同类型的人诱导多能干细胞异种嵌合能力的比较研究
编辑人员丨3天前
目的:比较不同培养方法建立不同类型的人诱导多能干细胞(hiPSC)的嵌合情况,筛选高异种嵌合能力的hiPSC。方法:2022年9月至2023年10月,中山大学附属第一医院显微创伤手外科根据文献报道的方法,使用100只雌性C57小鼠、20只雄性C57小鼠和10只多重免疫缺陷鼠(NOD/SCID),通过不同的化学小分子诱导培养方法建立8细胞期胚胎样细胞(8CLC)、潜能扩展多能干细胞(EPS)、原始态多能干细胞(Na?ve iPSC)、形成态多能干细胞(Formative iPSC)和始发态多能干细胞(Primed iPSC)。利用形态学观察、细胞免疫荧光、实时荧光定量PCR和畸胎瘤形成进行细胞系鉴定。将各种不同的细胞系使用CRISRR/CAS 9基因编辑技术标记GFP,筛选并扩增阳性细胞后,进行小鼠囊胚期注射,每次注射10个细胞形成嵌合胚胎,并将嵌合胚胎进行体外胚胎培养,观察评估嵌合情况。所有计量资料以均值±标准差(Mean±SD)表示,各亚组间的比较均先采用ANOVA单因素方差分析,再通过Bonferroni法进行两两比较, P<0.05表示差异有统计学意义。 结果:依据形态学、细胞免疫荧光、实时荧光定量PCR、畸胎瘤形成实验的鉴定与验证,成功培养出了8CLC、EPS、Na?ve、Formative、Primed这5种代表胚胎发育不同阶段的iPSC细胞系。小鼠囊胚期注射后进行体外培养,发现8CLC和Na?ve iPSC相比其他细胞系,第3天(两细胞系分别为74.28%和56.00%)和第5天(分别为62.85%和40.00%)的GFP阳性率更高,差异有统计学意义( P<0.05)。 结论:8CLC和Na?ve iPSC作为供体细胞更有利于人-鼠异种嵌合胚胎的体外培养,有益于提高人-鼠异种嵌合后胚胎的嵌合率。
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编辑人员丨3天前
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Generating universal chimeric antigen receptor expressing cell products from induced pluripotent stem cells: beyond the autologous CAR-T cells
编辑人员丨3天前
Adoptive therapeutic immune cells, such as chimeric antigen receptor (CAR)-T cells and natural killer cells, have established a new generation of precision medicine based on which dramatic breakthroughs have been achieved in intractable lymphoma treatments. Currently, well-explored approaches focus on autologous cells due to their low immunogenicity, but they are highly restricted by the high costs, time consumption of processing, and the insufficiency of primary cells in some patients. Induced pluripotent stem cells (iPSCs) are cell sources that can theoretically produce indefinite well-differentiated immune cells. Based on the above facts, it may be reasonable to combine the iPSC technology and the CAR design to produce a series of highly controllable and economical "live" drugs. Manufacturing hypoimmunogenic iPSCs by inactivation or over-expression at the genetic level and then arming the derived cells with CAR have emerged as a form of "off-the-shelf" strategy to eliminate tumor cells efficiently and safely in a broader range of patients. This review describes the reasonability, feasibility, superiority, and drawbacks of such approaches, summarizes the current practices and relevant research progress, and provides insights into the possible new paths for personalized cell-based therapies.
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编辑人员丨3天前
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Semaphorin 3A-hypoxia inducible factor 1 subunit alpha co-overexpression enhances the osteogenic differentiation of induced pluripotent stem cells-derived mesenchymal stem cells in vitro
编辑人员丨3天前
Background::Mesenchymal stem or stromal cells (MSCs) derived from the induced pluripotent stem cells (iPSCs) have uniform biological activity, which makes the clinical application of MSCs in bone repair possible. Culturing the iPSC-MSCs onto osteoconductive materials is a promising tissue engineering-based strategy in bone regeneration. The aim of this work was to evaluate the effects of semaphorin 3A (Sema3A) and hypoxia inducible factor 1 subunit alpha (HIF1α) co-overexpression on the survival and osteogenic differentiation of iPSC-MSCs.Methods::Sema3A and HIF1α were linked together with the three (GGGGS; G, glycine; S, serine) peptide fragment, and their co-expression in iPSC-MSCs was mediated by a lentiviral vector. The fusion protein retained the immune reactivity for both Sema3A and HIF1α as determined with Western blotting. iPSC-MSCs were infected with overexpression lentivirus (oeLenti) as negative control, oeLenti-Sema3A, oeLenti-HIF1α or oeLenti-Sema3A-HIF1α lentiviruses.Results::Sema3A overexpression alone promoted the osteogenic differentiation of iPSC-MSCs (the activity and/or expression of osteoblast markers, such as alkaline phosphatase, osteopontin, and osteocalcin, were upregulated), and suppressed cell survival. The Sema3A-HIF1α fusion protein showed a comparable osteoconductive effect to that of Sema3A without reducing cell survival. We further seeded iPSC-MSCs modified by SemaA-HIF1α overexpression onto hydroxyapatite (HA) scaffolds, and evaluated their growth and differentiation on this three-dimensional material. Additional data indicated that, as compared to iPSC-MSCs cultured in ordinary two-dimensional dishes, cells cultured in HA scaffolds grew (blank vs. HA scaffolds: 0.83 vs. 1.39 for survival) and differentiated better (blank vs. HA scaffolds: 11.29 vs. 16.62 for alkaline phosphatase activity). Conclusion::Modifying iPSC-MSCs with pro-osteogenic (Sema3A) and pro-survival (HIF1α) factors may represent a promising strategy to optimize tissue engineering-based strategy in bone repair.
Semaphorin 3A Hypoxia inducible factor 1 subunit alpha Induced pluripotent stem cells Mesenchymal stems...不再出现此类内容
编辑人员丨3天前
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嵌合抗原受体自然杀伤细胞在血液系统恶性肿瘤中的研究进展
编辑人员丨3天前
嵌合抗原受体自然杀伤细胞(CAR-NK)免疫治疗技术是一种新型抗肿瘤免疫方法。NK细胞可来源于外周血、脐带血、NK-92细胞系及诱导多能干细胞。CAR-NK细胞可非特异性识别靶抗原且无人类白细胞抗原限制性,异体输注不会引起移植物抗宿主病,对白血病、淋巴瘤及多发性骨髓瘤的原代细胞及动物模型具有较强的抗肿瘤效应,作为现货型产品在临床中具有广泛的应用前景。对CAR-NK载体构建及其在血液肿瘤中的临床初步应用和面临的挑战进行综述。
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编辑人员丨3天前
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Induced pluripotent stem cell-derived motor neurons from amyotrophic lateral sclerosis (ALS) patients carrying different superoxide dismutase 1 mutations recapitulate pathological features of ALS
编辑人员丨3天前
Background::Investigations of the pathogenic mechanisms in motor neurons (MNs) derived from amyotrophic lateral sclerosis (ALS) disease-specific induced pluripotent stem (iPS) cell lines could improve understanding of the issues affecting MNs. Therefore, in this study we explored mutant superoxide dismutase 1 (SOD1) protein expression in MNs derived from the iPS cell lines of ALS patients carrying different SOD1 mutations.Methods::We generated induced pluripotent stem cell (iPSC) lines from two familial ALS (FALS) patients with SOD1-V14M and SOD1-C111Y mutations, and then differentiated them into MNs. We investigated levels of the SOD1 protein in iPSCs and MNs, the intracellular Ca 2+ levels in MNs, and the lactate dehydrogenase (LDH) activity in the process of differentiation into the MNs derived from the controls and ALS patients’ iPSCs. Results::The iPSCs from the two FALS patients were capable of differentiation into MNs carrying different SOD1 mutations and differentially expressed MN markers. We detected high SOD1 protein expression and high intracellular calcium levels in both the MN and iPSCs that were derived from the two SOD1 mutant patients. However, at no time did we observe stronger LDH activity in the patient lines compared with the control lines. Conclusions::MNs derived from patient-specific iPSC lines can recapitulate key aspects of ALS pathogenesis, providing a cell-based disease model to further elucidate disease pathogenesis and explore gene repair coupled with cell-replacement therapy. Incremental mutant expressions of SOD1 in MNs may have disrupted MN function, either causing or contributing to the intracellular calcium disturbances, which could lead to the occurrence and development of the disease.
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编辑人员丨3天前
