Cell：iPS走向临床的“临门一脚”

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Cell：iPS走向临床的“临门一脚”
! g% E+ O- @  L  G摘要： 自从iPS摆脱了慢病毒载体的依赖以来，iPS技术从理论到临床的距离又近了，本期的Cell子刊《Cell Stem Cell》又刊发一篇iPS技术的前沿报道，Generation of Human Induced Pluripotent Stem Cells by Direct Delivery of Reprogramming Proteins。  
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自从iPS摆脱了慢病毒载体的依赖以来，iPS技术从理论到临床的距离又近了，本期的Cell子刊《Cell Stem Cell》又刊发一篇iPS技术的前沿报道，Generation of Human Induced Pluripotent Stem Cells by Direct Delivery of Reprogramming Proteins。
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" Z8 i5 {8 J% n; X$ r# T前不久，斯克里普斯研究所（Scripps Research Institute）的丁盛用重组的蛋白就能诱导出多能干细胞。
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丁盛博士将这一重组蛋白诱导技术应用于小鼠细胞上，未来他将继续在人体细胞中研究重组蛋白诱导的效果。此外，哈佛大学医学院干细胞研究中心的科学家也开发出了这一新的重组蛋白诱导技术，并抢先一步，将这一技术应用于人体的人成纤维细胞上。哈佛大学干细胞研究中心的研究人员取得了胜利，首次成功地将人体成纤维细胞经四个重组蛋白诱导转化成iPS细胞。
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构成iPS重组蛋白诱导技术的主要成分是：4个重组蛋白（Oct4，Sox2，Klf4和c-Myc）以及促进重组蛋白穿透细胞的多肽（cell-penetrating peptide，CCP）。在CCP的帮助下，重组蛋白进入成纤维细胞内，促进细胞转化成iPS细胞。/ O' o! U9 d6 p; Q. j: r

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文章的通讯作者，干细胞和再生医学首席科学家Robert Lanza表示，这是一种安全的iPS技术，他们将尽快地从基础研究升级到细胞治疗的研究上。他们希望明年能将这一技术应用于临床试验中。8 @2 ]3 K3 T, O4 a6 u

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; \0 p. ^6 {# A" K& B; D目前，相比其他iPS技术，重组蛋白诱导iPS是一项健康风险最低的技术。尽管，目前这一技术的诱导效率比较低，Lanza表示，他们将纯化重组蛋白以提高蛋白传递的效率，进而提高iPS诱导效率。
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( D( P5 [( {: D1 c5 @6 g3 g. J推荐原文检索：Generation of Human Induced Pluripotent Stem Cells by Direct Delivery of Reprogramming Proteins
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  k* S; z1 D7 K* uDohoon Kim1,5,Chun-Hyung Kim1,5,Jung-Il Moon1,Young-Gie Chung3,Mi-Yoon Chang1,Baek-Soo Han1,Sanghyeok Ko1,Eungi Yang1,Kwang Yul Cha4,Robert Lanza3,,andKwang-Soo Kim1,2,4,,
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" K6 l4 E; h& Z1 Molecular Neurobiology Laboratory, Department of Psychiatry and McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA
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2 Harvard Stem Cell Institute, 115 Mill Street, Belmont, MA 02478, USA
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$ Y; b" k3 m2 y! C2 f; p* ~3 Stem Cell and Regenerative Medicine International, 381 Plantation Street, Worcester, MA 01605, USA# H7 F% i! o5 H: d$ u+ R
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4 CHA Stem Cell Institute, CHA University, 606-16 Yoeksam 1-dong, Gangnam-gu, Korea9 O" j9 \. G( _6 y( }' J
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5 These authors contributed equally to this work; F1 u% H. ^  |

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6 S' U% |$ k3 F+ t1 R* r/ `: jMain Text& W% _3 P( ^: s
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To date, all methods to generate induced pluripotent stem cells (iPSCs) require the use of genetic materials and/or potentially mutagenic molecules. Here we report the generation of stable iPSCs from human fibroblasts by directly delivering four reprogramming proteins (Oct4, Sox2, Klf4, and c-Myc) fused with a cell-penetrating peptide (CPP). These protein-induced human iPSCs (p-hiPSCs) exhibited similarity to human embryonic stem cells (hESCs) in morphology, proliferation, and expression of characteristic pluripotency markers. p-hiPSC lines produced with these recombinant proteins were successfully maintained for more than 35 passages and differentiated into derivatives of all three embryonic germ layers both invitro and in teratomas. This system eliminates the potential risks associated with the use of viruses, DNA transfection, and potentially harmful chemicals and in the future could potentially provide a safe source of patient-specific cells for regenerative medicine. ……

hermit

thanks

hualin840518

希望能多提供信息，多交流，共同进步！

刘实

From the perspective of Central Dogma, the genetic risk of exogenous genes may well be realized with their transcription into some mRNAs and then translation into some proteins.  Thus, merely avoiding the upstream oncogenes but nevertheless employing the downstream oncoproteins would not logically eliminate the risk on the end point of the same line of genetic-chemical flow.  - N: _/ ?2 F% i' [7 S0 E$ H# C
------This is an earlier PUBLISHED criticism towards Ding's Cell Stem Cell paper of protein iPS cells(piPSCs).  This criticism should be appliable to this new piPSC.

刘实

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Robert Lanza has made too many claims in the past but how many of them have been realized.  He was even criticized by the US senators for his false statements.