2012年8月24日 訊 /生物谷BIOON/ --約翰霍普金斯大學(xué)科學(xué)家已經(jīng)開發(fā)出一種可靠的方法來把血細(xì)胞恢復(fù)到原始的干細(xì)胞狀態(tài),，一旦獲得干細(xì)胞樣特性后就可以發(fā)展成體內(nèi)任何其他類型的細(xì)胞,。這項研究工作結(jié)果發(fā)表在8月8日的PLoS One雜志上，約翰霍普金斯大學(xué)細(xì)胞工程和Kimmel癌癥中心腫瘤科及兒科助理教授Elias Zambidis醫(yī)學(xué)博士,、哲學(xué)博士說：研究人員能有效地將血細(xì)胞轉(zhuǎn)化為干細(xì)胞。
去年春天在PLoS ONE雜志上,，Zambidis和他的同事講述了成功將心臟細(xì)胞安全轉(zhuǎn)化成成血細(xì)胞的方法,。在最新的實驗中，他和他的同事們描述將血細(xì)胞轉(zhuǎn)化成為所謂的誘導(dǎo)多能干細(xì)胞（iPS）的方法,。Zambidis說,，他的團隊已經(jīng)成功開發(fā)一種超級高效、無病毒的方法來制造iPS細(xì)胞,。一般來說,，數(shù)百個血細(xì)胞中，只有一個或兩個可能變成iPS細(xì)胞,。而使用Zambidis的方法,，50％至60％的血細(xì)胞將會轉(zhuǎn)變成iPS細(xì)胞,。
Zambidis的團隊還發(fā)現(xiàn)，利用病毒將細(xì)胞轉(zhuǎn)換成干細(xì)胞狀態(tài)的方法,，科學(xué)家使用病毒去遞送目的基因到細(xì)胞中去,，以開啟轉(zhuǎn)換來自某種類型（例如皮膚或血液）的細(xì)胞回到干細(xì)胞狀態(tài)的過程。然而,，這種方式使用的病毒會導(dǎo)致基因變異,，導(dǎo)致轉(zhuǎn)化后的細(xì)胞演變成癌癥細(xì)胞。為了不使用病毒就將基因插入,，Zambidis團隊使用了載體質(zhì)粒,。在新的研究中，美國約翰霍普金斯大學(xué)研究小組用生長因子處理臍帶血細(xì)胞,，打算用質(zhì)粒轉(zhuǎn)染四個基因到細(xì)胞中,。他們用電脈沖刺激細(xì)胞，使得該質(zhì)?？梢酝ㄟ^細(xì)胞表面微小的孔已滑動進入細(xì)胞內(nèi),。一旦進入，質(zhì)粒引發(fā)細(xì)胞恢復(fù)到原始細(xì)胞狀態(tài),。
當(dāng)科學(xué)家比較使用血細(xì)胞方法生長的細(xì)胞與從毛細(xì)胞和皮膚細(xì)胞來源的iPS細(xì)胞轉(zhuǎn)化成的細(xì)胞時,，他們發(fā)現(xiàn)，最優(yōu)越的iPS細(xì)胞來自只用四種基因改造并與骨髓細(xì)胞培養(yǎng)過的造血干細(xì)胞,。這些細(xì)胞在7至14天之內(nèi)轉(zhuǎn)換為一個原始的干細(xì)胞狀態(tài),。在正在進行的研究中，Zambidis和他的同事正在測試新制造的iPS細(xì)胞的質(zhì)量和轉(zhuǎn)換為其他類型的細(xì)胞的能力,。生產(chǎn)無病毒iPS細(xì)胞的有效方法來可能會加速干細(xì)胞療法的開發(fā),。（生物谷：Bioon.com）
編譯自：Researchers return blood cells to stem cell state
doi:10.1371/journal.pone.0042838
PMC:
PMID:
Growth Factor-Activated Stem Cell Circuits and Stromal Signals Cooperatively Accelerate Non-Integrated iPSC Reprogramming of Human Myeloid Progenitors
Tea Soon Park1,2, Jeffrey S. Huo1,2, Ann Peters1,2, C. Conover Talbot Jr.3, Karan Verma1,2, Ludovic Zimmerlin1,2, Ian M. Kaplan1,2, Elias T. Zambidis1,2*
Nonviral conversion of skin or blood cells into clinically useful human induced pluripotent stem cells (hiPSC) occurs in only rare fractions (~0.001%–0.5%) of donor cells transfected with non-integrating reprogramming factors. Pluripotency induction of developmentally immature stem-progenitors is generally more efficient than differentiated somatic cell targets. However, the nature of augmented progenitor reprogramming remains obscure, and its potential has not been fully explored for improving the extremely slow pace of non-integrated reprogramming. Here, we report highly optimized four-factor reprogramming of lineage-committed cord blood (CB) myeloid progenitors with bulk efficiencies of ~50% in purified episome-expressing cells. Lineage-committed CD33+CD45+CD34? myeloid cells and not primitive hematopoietic stem-progenitors were the main targets of a rapid and nearly complete non-integrated reprogramming. The efficient conversion of mature myeloid populations into NANOG+TRA-1-81+ hiPSC was mediated by synergies between hematopoietic growth factor (GF), stromal activation signals, and episomal Yamanaka factor expression. Using a modular bioinformatics approach, we demonstrated that efficient myeloid reprogramming correlated not to increased proliferation or endogenous Core factor expressions, but to poised expression of GF-activated transcriptional circuits that commonly regulate plasticity in both hematopoietic progenitors and embryonic stem cells (ESC). Factor-driven conversion of myeloid progenitors to a high-fidelity pluripotent state was further accelerated by soluble and contact-dependent stromal signals that included an implied and unexpected role for Toll receptor-NFκB signaling. These data provide a paradigm for understanding the augmented reprogramming capacity of somatic progenitors, and reveal that efficient induced pluripotency in other cell types may also require extrinsic activation of a molecular framework that commonly regulates self-renewal and differentiation in both hematopoietic progenitors and ESC.
