Generation of Human iPSC-derived Neural Progenitor Cells (NPCs) as Drug Discovery Model for Neurological and Mitochondrial Disorders
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Author:
Date:
2021-03-05
[Abstract] The high attrition rate in drug development processes calls for additional human-based model systems. However, in the context of brain disorders, sampling live neuronal cells for compound testing is not applicable. The use of human induced pluripotent stem cells (iPSCs) has revolutionized the field of neuronal disease modeling and drug discovery. Thanks to the development of iPSC-based neuronal differentiation protocols, including tridimensional cerebral organoids, it is now possible to molecularly dissect human neuronal development and human brain disease pathogenesis in a dish. These approaches may allow dissecting patient-specific treatment efficacy in a disease-relevant cellular context. For drug discovery approaches, however, a highly reproducible and cost-effective cell model is ...
[摘要] [摘要]药物开发过程中的高流失率要求使用其他基于人的模型系统。但是,在脑部疾病的情况下,不适合对活的神经元细胞进行采样以进行化合物测试。人类诱导的多能干细胞(iPSC )的使用彻底改变了神经元疾病建模和药物发现领域。由于基于iPSC的神经元分化方案(包括三维脑类器官)的发展,现在可以在一个碟子中分子解剖人神经元发育和人脑疾病的发病机理。这些方法可以允许在与疾病相关的细胞环境中解剖患者特异性的治疗功效。但是,对于药物发现方法,需要高度可复制且具有成本效益的细胞模型。在这里,我们描述了一种一步-步骤,用于从人产生健壮和可膨胀的神经祖细胞(NPC)工艺的iPSC 。用此协议生成的NPC是同质的且高度增殖。这些功能使NPC适合开发用于药物发现的高通量化合物筛选。人iPSC衍生的NPC示出了代谢依赖于线粒体活性,因此可也用于研究神经病症,其中线粒体功能受到影响。该协议涵盖了制备,培养和表征人iPSC来源的NPC所需的所有步骤。
图形摘要:
示意性的协议的所述发电机密封的离子人类源自iPSC的的NPC
[背景技术]近年来,目标为中心的药物发现的缺点已经用于寻址的神经系统疾病的方案变得明显,特别是(保罗等人,2010) ...
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Isolation and Establishment of Mesenchymal Stem Cells from Wharton’s Jelly of Human Umbilical Cord
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Author:
Date:
2018-02-20
[Abstract] Mesenchymal stem cells (MSCs) are currently considered as ‘medicinal signaling cells’ and a promising resource in regard to cell-based regenerative therapy. Umbilical cord is a human term perinatal tissue which is easily attainable, and a promising source of stem cells with no associated ethical concerns. MSCs have been isolated from different regions of the umbilical cord and Wharton’s jelly (WJ) is the gelatinous matrix that surrounds and provides protection to the umbilical cord blood vessels. Being more primitive, MSCs from human umbilical cord exhibit greater proliferative capacity and immunosuppressive ability as compared to adult stem cells which gives them a therapeutic advantage. To meet the requirements for cell therapy, it is important to generate MSCs at a clinical scale by ...
[摘要] 间充质干细胞(mesenchymal stem cells,MSCs)目前被认为是“医药信号传导细胞”,在基于细胞的再生治疗方面是一种很有前景的资源。脐带是人类的围产期组织,很容易实现,是一种有前途的干细胞来源,没有相关的伦理问题。 MSC已经从脐带的不同区域分离出来,而Wharton's果冻(WJ)是包围并提供对脐带血管的保护的凝胶状基质。更原始的是,与成人干细胞相比,来自人脐带的MSC表现出更大的增殖能力和免疫抑制能力,这使其具有治疗优势。为了满足细胞疗法的要求,通过遵循不耗时或劳动强度的步骤来产生临床规模的MSC是重要的。在此我们提出了一种简单,高效的方法,通过外植体培养方法从人脐带WJ中分离出MSC,这种方法具有重现性和成本效益。
【背景】间充质干细胞(MSC)具有显着的临床潜力来治疗各种衰弱性疾病,主要是由于其独特的免疫调节作用和再生能力(Caplan and Sorrell,2015)。它们存在于许多组织中(Hass et al。,2011),并被观察到是血管周围的体内(Caplan和Correa,2011)。来源或来源本身的小生境可能导致各种MSC类型之间的重要功能差异(Kwon等人,2016年)。虽然骨髓是研究得最充分和最好的MSCs来源,但也有一定的局限性(Liu et al。,2016)。 ...
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Differentiation of Human Induced Pluripotent Stem Cells (iPS Cells) and Embryonic Stem Cells (ES Cells) into Dendritic Cell (DC) Subsets
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Author:
Date:
2017-08-05
[Abstract] Induced pluripotent stem cells (iPS cells) are engineered stem cells, which exhibit properties very similar to embryonic stem cells (ES cells; Takahashi and Yamanaka, 2016). Both iPS cells and ES cells have an extraordinary self-renewal capacity and can differentiate into all cell types of our body, including hematopoietic stem/progenitor cells and dendritic cells (DC) derived thereof. This makes iPS cells particularly well suited for studying molecular mechanisms of diseases, drug discovery and regenerative therapy (Grskovic et al., 2011; Bellin et al., 2012; Robinton and Daley, 2012).
DC are the major antigen presenting cells of the immune system and thus they are key players in modulating and directing immune responses (Merad et al., 2013). DC ...
[摘要] 诱导的多能干细胞(iPS细胞)是工程干细胞,其表现出与胚胎干细胞(ES细胞,Takahashi和Yamanaka,2016)非常相似的性质。 iPS细胞和ES细胞都具有非凡的自我更新能力,可以分化成我们身体的所有细胞类型,包括造血干细胞/祖细胞和源自其的树突状细胞(DC)。这使得iPS细胞特别适用于研究疾病,药物发现和再生治疗的分子机制(Grskovic等人,2011; Bellin等人,2012; Robinton和Daley,2012)。   DC是免疫系统的主要抗原呈递细胞,因此它们是调节和引导免疫应答的关键参与者(Merad等人,2013)。 DC巡逻外周和界面组织(例如,肺,肠和皮肤)以检测入侵的病原体,并且在激活时,它们迁移到淋巴结以激活和引发淋巴细胞。   DC包含具有功能专门子集的表型异质家族(Schlitzer和Ginhoux,2014)。通常,经典DC(cDC)和浆细胞样DC(pDC)是分别表现出典型的和等离子体细胞样的DC形态。 cDC识别许多病原体并在激活后分泌促炎细胞因子,而pDC专门检测细胞内病原体并分泌I型干扰素(Merad等,2013; Schlitzer和Ginhoux,2014)。在被称为CD141 Clec9a + cDC1和CD1c + ...
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