近日，英國(guó)研究人員利用皮膚細(xì)胞培育出了部分誘導(dǎo)多功能干細(xì)胞（piPS細(xì)胞）,，它與曾引起科學(xué)界轟動(dòng)的誘導(dǎo)多功能干細(xì)胞（iPS細(xì)胞）功能類似,，但出現(xiàn)腫瘤的風(fēng)險(xiǎn)大大降低。實(shí)驗(yàn)證實(shí)它可進(jìn)一步培育為血管細(xì)胞,，將來(lái)有望用于治療相關(guān)疾病,。相關(guān)論文發(fā)表在在新一期美國(guó)《國(guó)家科學(xué)院院刊》（PNAS）上。
這項(xiàng)研究的意義要從胚胎干細(xì)胞說(shuō)起,，小小的胚胎能夠長(zhǎng)大成人,，是因?yàn)槠渲械母杉?xì)胞能夠分化變成各種器官組織。前幾年日美研究人員報(bào)告說(shuō)可以使已經(jīng)分化完成的皮膚細(xì)胞“時(shí)光倒轉(zhuǎn)”回到干細(xì)胞狀態(tài),，再利用它培育出其他組織,，引起科學(xué)界轟動(dòng)。這樣得到的細(xì)胞稱為誘導(dǎo)多功能干細(xì)胞,，但有一個(gè)問(wèn)題是其培育出的組織出現(xiàn)腫瘤的風(fēng)險(xiǎn)較大,。
英國(guó)倫敦大學(xué)國(guó)王學(xué)院的徐清波等人報(bào)告說(shuō)，他們將4個(gè)基因OCT4,、SOX2,、KLF4和c-MYC引入人類皮膚細(xì)胞中，就可以使其回到干細(xì)胞狀態(tài),。此前研究需要用28天培育出iPS細(xì)胞,，而這次研究只用了4天時(shí)間就可以讓皮膚細(xì)胞回到干細(xì)胞狀態(tài)，研究人員將其新培育出的種類稱為PiPS細(xì)胞,。
“名稱前加的字母‘P’是‘部分’的意思,，這一方面是因?yàn)樗蛔吡薸PS細(xì)胞的部分歷程，另一方面也是因?yàn)樗谛阅苌吓ciPS細(xì)胞部分相似”,，徐清波向新華社記者介紹說(shuō),，“它保留了iPS細(xì)胞性能中好的部分,，即仍然可在此基礎(chǔ)上培育出其他組織，但沒(méi)有了壞的部分,，即減少了所培育出的組織出現(xiàn)腫瘤的風(fēng)險(xiǎn),。”
研究人員利用部分誘導(dǎo)多功能干細(xì)胞培育出了血管細(xì)胞，這種細(xì)胞可以在試管中進(jìn)一步生長(zhǎng)為成形的血管,。如果給肢體缺血的實(shí)驗(yàn)鼠注入由部分誘導(dǎo)多功能干細(xì)胞培育出的血管細(xì)胞,，它能夠在小鼠體內(nèi)形成新血管，幫助其改善缺血癥狀,。
這說(shuō)明將來(lái)有望用部分誘導(dǎo)多功能干細(xì)胞治療一些疾病,，比如有些糖尿病患者會(huì)出現(xiàn)下肢血管壞死的現(xiàn)象，用部分誘導(dǎo)多功能干細(xì)胞就可以幫助他們形成新的血管,，還有心血管系統(tǒng)出現(xiàn)問(wèn)題的患者也可能從中受益,。（生物谷Bioon.com）
doi:10.1073/pnas.1205526109
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Direct reprogramming of fibroblasts into endothelial cells capable of angiogenesis and reendothelialization in tissue-engineered vessels
Andriana Margaritia, Bernhard Winklera, Eirini Karamaritia, Anna Zampetakia, Tsung-neng Tsaia, Dilair Babanb, Jiannis Ragoussisb, Yi Huangc, Jing-Dong J. Hanc, Lingfang Zenga, Yanhua Hua, and Qingbo Xua,1
The generation of induced pluripotent stem (iPS) cells is an important tool for regenerative medicine. However, the main restriction is the risk of tumor development. In this study we found that during the early stages of somatic cell reprogramming toward a pluripotent state, specific gene expression patterns are altered. Therefore, we developed a method to generate partial-iPS (PiPS) cells by transferring four reprogramming factors (OCT4, SOX2, KLF4, and c-MYC) to human fibroblasts for 4 d. PiPS cells did not form tumors in vivo and clearly displayed the potential to differentiate into endothelial cells (ECs) in response to defined media and culture conditions. To clarify the mechanism of PiPS cell differentiation into ECs, SET translocation (myeloid leukemia-associated) (SET) similar protein (SETSIP) was indentified to be induced during somatic cell reprogramming. Importantly, when PiPS cells were treated with VEGF, SETSIP was translocated to the cell nucleus, directly bound to the VE-cadherin promoter, increasing vascular endothelial-cadherin (VE-cadherin) expression levels and EC differentiation. Functionally, PiPS-ECs improved neovascularization and blood flow recovery in a hindlimb ischemic model. Furthermore, PiPS-ECs displayed good attachment, stabilization, patency, and typical vascular structure when seeded on decellularized vessel scaffolds. These findings indicate that reprogramming of fibroblasts into ECs via SETSIP and VEGF has a potential clinical application.
