J Neurosci：脉络丛上皮细胞治疗阿尔茨海默氏症

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作者：Beyond 来源：生物谷 2012-11-26 20:33:03: b& A+ |/ F! G! {
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2012年11月25日 讯 /生物谷BIOON/ --近日，加州大学欧文分校研究人员已经创建了一个新的干细胞来源的细胞类型，新类型细胞具有治疗神经退行性疾病如阿尔茨海默氏症的潜在能力。7 K+ @# f9 e* l3 {& z3 \6 ?
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这种新类型细胞为脉络丛上皮细胞CPECs，可从现有的小鼠和人类胚胎干细胞系中获得。2 C" p; ^1 x6 d
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CPECs对脉络丛正常运作是至关重要的，脉络丛在大脑中的作用主要是产生脑脊液，CPECs的作用是清除大脑代谢废物。在神经退行性疾病中，脉络丛和CPECs过早老化，从而减少脑脊液的形成，斑块蛋白堆积诱发老年痴呆症。9 |( U' a2 }- y; v

+ _! G4 ^. p1 s! C* U现在，研究人员第一次可以利用干细胞来创建大量上皮细胞，来治疗神经退行性疾病。这项研究发表在11月7日出版的The Journal of Neuroscience杂志上。
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5 Z6 _& P% |, m0 L要创建新的细胞， Monuki和他的同事们使得胚胎干细胞分化为不成熟的神经干细胞。然后，他们使这些未成熟细胞转换成CPECs，后者能够被传递到患者的脉络丛中。/ |. I% F: R  m  u4 G  `

  a1 r- }  E7 U0 {1 d& N) xMonuki说这些细胞可能至少从三方面来治疗神经退行性疾病。首先，他们能够增加脑脊液的生成，可以帮助清除脑组织中斑块物质，限制疾病进展；其次，CPECs可以设计载体递送高水平治疗化合物进入脑脊液中；第三，这些细胞可用于筛选和优化能改善脉络膜丛功能的药物。; F5 b2 K6 K7 a. l

: ]) k5 b  l) p4 V3 C: Y% j' B. iMonuki说，接下来的步骤是建立一个有效的药物筛选系统，并进行验证研究分析CPECs对亨廷顿氏、阿尔茨海默氏病小鼠模型大脑的影响。（生物谷：Bioon.com）6 E- Q, n  ~# |6 f; I

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坤明

BMP4 Sufficiency to Induce Choroid Plexus Epithelial Fate from Embryonic Stem Cell-Derived Neuroepithelial Progenitors$ D" f1 j: k+ Y% x( t
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M. Watanabe, Y.-J. Kang, L. M. Davies, S. Meghpara, K. Lau, C.-Y. Chung, J. Kathiriya, A.-K. Hadjantonakis, E. S. Monuki.
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# O$ [+ P1 K& O  d' V6 z8 V0 T9 OChoroid plexus epithelial cells (CPECs) have essential developmental and homeostatic roles related to the CSF and blood–CSF barrier they produce. Accordingly, CPEC dysfunction has been implicated in many neurological disorders, such as Alzheimer's disease, and transplant studies have provided proof-of-concept for CPEC-based therapies. However, such therapies have been hindered by the inability to expand or generate CPECs in culture. During development, CPECs differentiate from preneurogenic neuroepithelial cells and require bone morphogenetic protein (BMP) signaling, but whether BMPs suffice for CPEC induction is unknown. Here we provide evidence for BMP4 sufficiency to induce CPEC fate from neural progenitors derived from mouse embryonic stem cells (ESCs). CPEC specification by BMP4 was restricted to an early time period after neural induction in culture, with peak CPEC competency correlating to neuroepithelial cells rather than radial glia. In addition to molecular, cellular, and ultrastructural criteria, derived CPECs (dCPECs) had functions that were indistinguishable from primary CPECs, including self-assembly into secretory vesicles and integration into endogenous choroid plexus epithelium following intraventricular injection. We then used BMP4 to generate dCPECs from human ESC-derived neuroepithelial cells. These findings demonstrate BMP4 sufficiency to instruct CPEC fate, expand the repertoire of stem cell-derived neural derivatives in culture, and herald dCPEC-based therapeutic applications aimed at the unique interface between blood, CSF, and brain governed by CPECs. 4 }+ U6 e! |" P* a9 U
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