2012年11月25日 訊 /生物谷BIOON/ --近日,，加州大學(xué)歐文分校研究人員已經(jīng)創(chuàng)建了一個新的干細(xì)胞來源的細(xì)胞類型,，新類型細(xì)胞具有治療神經(jīng)退行性疾病如阿爾茨海默氏癥的潛在能力。
這種新類型細(xì)胞為脈絡(luò)叢上皮細(xì)胞CPECs,，可從現(xiàn)有的小鼠和人類胚胎干細(xì)胞系中獲得,。
CPECs對脈絡(luò)叢正常運作是至關(guān)重要的，脈絡(luò)叢在大腦中的作用主要是產(chǎn)生腦脊液,，CPECs的作用是清除大腦代謝廢物,。在神經(jīng)退行性疾病中，脈絡(luò)叢和CPECs過早老化,，從而減少腦脊液的形成,，斑塊蛋白堆積誘發(fā)老年癡呆癥。
現(xiàn)在,，研究人員第一次可以利用干細(xì)胞來創(chuàng)建大量上皮細(xì)胞,，來治療神經(jīng)退行性疾病。這項研究發(fā)表在11月7日出版的The Journal of Neuroscience雜志上,。
要創(chuàng)建新的細(xì)胞,， Monuki和他的同事們使得胚胎干細(xì)胞分化為不成熟的神經(jīng)干細(xì)胞。然后,，他們使這些未成熟細(xì)胞轉(zhuǎn)換成CPECs,，后者能夠被傳遞到患者的脈絡(luò)叢中。
Monuki說這些細(xì)胞可能至少從三方面來治療神經(jīng)退行性疾病,。首先,，他們能夠增加腦脊液的生成，可以幫助清除腦組織中斑塊物質(zhì),，限制疾病進(jìn)展,；其次，CPECs可以設(shè)計載體遞送高水平治療化合物進(jìn)入腦脊液中,；第三,，這些細(xì)胞可用于篩選和優(yōu)化能改善脈絡(luò)膜叢功能的藥物。
Monuki說,，接下來的步驟是建立一個有效的藥物篩選系統(tǒng),，并進(jìn)行驗證研究分析CPECs對亨廷頓氏,、阿爾茨海默氏病小鼠模型大腦的影響。（生物谷：Bioon.com）
doi:10.1523/JNEUROSCI.3227-12.2012
PMC:
PMID:
BMP4 Sufficiency to Induce Choroid Plexus Epithelial Fate from Embryonic Stem Cell-Derived Neuroepithelial Progenitors
M. Watanabe, Y.-J. Kang, L. M. Davies, S. Meghpara, K. Lau, C.-Y. Chung, J. Kathiriya, A.-K. Hadjantonakis, E. S. Monuki.
Choroid 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.
