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Clinical translation of pluripotent stem cell-based therapies: successes and challenges. 多能干细胞疗法的临床转化:成功与挑战。
Pub Date : 2024-04-01 DOI: 10.1242/dev.202067
Josefine Rågård Christiansen, A. Kirkeby
The translational stem cell research field has progressed immensely in the past decade. Development and refinement of differentiation protocols now allows the generation of a range of cell types, such as pancreatic β-cells and dopaminergic neurons, from human pluripotent stem cells (hPSCs) in an efficient and good manufacturing practice-compliant fashion. This has led to the initiation of several clinical trials using hPSC-derived cells to replace lost or dysfunctional cells, demonstrating evidence of both safety and efficacy. Here, we highlight successes from some of the hPSC-based trials reporting early signs of efficacy and discuss common challenges in clinical translation of cell therapies.
过去十年,转化干细胞研究领域取得了巨大进步。分化方案的开发和完善,使我们能够以高效和符合良好生产规范的方式,从人类多能干细胞(hPSC)中生成一系列细胞类型,如胰腺β细胞和多巴胺能神经元。因此,利用 hPSC 衍生细胞替代丢失或功能障碍细胞的几项临床试验已经启动,证明了其安全性和有效性。在此,我们将重点介绍一些基于 hPSC 的成功试验,这些试验报告了早期疗效迹象,并讨论了细胞疗法临床转化过程中常见的挑战。
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引用次数: 0
The Shot CH1 domain recognises a distinct form of F-actin during Drosophila oocyte determination. 在果蝇卵母细胞确定过程中,Shot CH1 结构域能识别不同形式的 F-肌动蛋白。
Pub Date : 2024-04-01 DOI: 10.1242/dev.202370
D. Nashchekin, I. Squires, A. Prokop, D. St Johnston
In Drosophila, only one cell in a multicellular female germline cyst is specified as an oocyte and a similar process occurs in mammals. The symmetry-breaking cue for oocyte selection is provided by the fusome, a tubular structure connecting all cells in the cyst. The Drosophila spectraplakin Shot localises to the fusome and translates its asymmetry into a polarised microtubule network that is essential for oocyte specification, but how Shot recognises the fusome is unclear. Here, we demonstrate that the actin-binding domain (ABD) of Shot is necessary and sufficient to localise Shot to the fusome and mediates Shot function in oocyte specification together with the microtubule-binding domains. The calponin homology domain 1 of the Shot ABD recognises fusomal F-actin and requires calponin homology domain 2 to distinguish it from other forms of F-actin in the cyst. By contrast, the ABDs of utrophin, Fimbrin, Filamin, Lifeact and F-tractin do not recognise fusomal F-actin. We therefore propose that Shot propagates fusome asymmetry by recognising a specific conformational state of F-actin on the fusome.
在果蝇中,多细胞雌性生殖细胞囊中只有一个细胞被指定为卵母细胞,哺乳动物也有类似的过程。连接囊中所有细胞的管状结构 "纺锤体 "为卵母细胞选择提供了打破对称的线索。果蝇的谱拉蛋白 Shot 定位于纺锤体,并将其不对称性转化为极化微管网络,这对卵母细胞的规格化至关重要,但 Shot 如何识别纺锤体尚不清楚。在这里,我们证明了 Shot 的肌动蛋白结合结构域(ABD)是将 Shot 定位于纺锤体的必要且充分条件,它与微管结合结构域一起介导 Shot 在卵母细胞规格化中的功能。Shot ABD 的钙调素同源结构域 1 能识别纺锤体 F-肌动蛋白,并需要钙调素同源结构域 2 将其与囊中其他形式的 F-肌动蛋白区分开来。相比之下,utrophin、Fimbrin、Filamin、Lifeact 和 F-tractin 的 ABD 不能识别纺锤体 F-肌动蛋白。因此,我们认为 Shot 是通过识别纺锤体上 F-actin 的特定构象状态来传播纺锤体不对称的。
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引用次数: 0
Editorial: One Health—Anatomy of a Fractured Vision 社论:一个健康--剖析破碎的愿景
Pub Date : 2024-01-10 DOI: 10.1057/s41301-023-00399-8
Nicoletta Dentico
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引用次数: 0
The Weaponization of Identity and Citizenship: The Case of Tanzania 身份和公民权的武器化:坦桑尼亚案例
Pub Date : 2020-02-11 DOI: 10.1057/s41301-020-00252-2
Aidan Eyakuze, Khalifa Said
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引用次数: 0
Archeology of Knowledge: An Interview with Heidi Grunebaum on Identities and Citizenship 知识考古学:就身份和公民权问题采访海蒂-格鲁内鲍姆
Pub Date : 2020-02-05 DOI: 10.1057/s41301-020-00250-4
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引用次数: 0
The Soldier, The Terrorist, and The Woman: A Gendered Analysis of Enforced Displacement in Northwestern Pakistan Post 2014 士兵、恐怖分子和妇女:2014 年后巴基斯坦西北部强迫流离失所问题的性别分析
Pub Date : 2020-01-27 DOI: 10.1057/s41301-020-00236-2
Zainab Najeeb
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引用次数: 0
Closing the Gap Between Legal and Social Citizenship for Roma People 缩小罗姆人法律公民身份与社会公民身份之间的差距
Pub Date : 2020-01-15 DOI: 10.1057/s41301-020-00242-4
C. Grigore
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引用次数: 0
The Haunting Specter of Hindu Ethnonationalist-Neocolonial Development in the Indian Occupied Kashmir 印占克什米尔地区印度教民族主义-殖民主义发展的幽灵
Pub Date : 2020-01-14 DOI: 10.1057/s41301-020-00234-4
A. Zia
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引用次数: 1
Finance’s New Avatar 金融业的新头像
Pub Date : 2020-01-14 DOI: 10.1057/s41301-020-00239-z
K. Jomo
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引用次数: 0
Climate Migration and Loss: Exploring the Conceptual Borders of Citizenship, Sovereign Authority, and the Deterritorialized State 气候移民与损失:探索公民身份、主权权威和威慑化国家的概念边界
Pub Date : 2019-12-05 DOI: 10.1057/s41301-019-00232-1
Nicole S. Marshall
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引用次数: 1
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