2012年9月28日 訊 /生物谷BIOON/ --來(lái)自美國(guó)梅奧診所(Mayo Clinic)的研究人員發(fā)現(xiàn)一種新方法能夠檢測(cè)和清除潛在危險(xiǎn)性的干細(xì)胞以便使得干細(xì)胞療法更加安全。誘導(dǎo)性多能干細(xì)胞(induced Pluripotent Stem cell, iPSC)是對(duì)來(lái)自成體組織的細(xì)胞進(jìn)行重編程而獲得的,，具有類似胚胎干細(xì)胞的性質(zhì),，即能夠無(wú)限制地分化為任何所需的細(xì)胞類型，如皮膚細(xì)胞,、腦細(xì)胞,、肺細(xì)胞和心臟細(xì)胞。然而,，在分化過(guò)程種,，一些殘留的多能性細(xì)胞或者胚胎細(xì)胞樣細(xì)胞(embryonic-like cell)可能繼續(xù)存在而導(dǎo)致腫瘤產(chǎn)生。相關(guān)研究論文于近期刊登Stem Cells Translational Medicine期刊上。
論文通訊作者Timothy Nelson博士說(shuō),，“多能性干細(xì)胞大有希望用于在再生醫(yī)學(xué)領(lǐng)域,，但是細(xì)胞不受控制生長(zhǎng)的風(fēng)險(xiǎn)將繼續(xù)阻止人們將它們作為治療方法進(jìn)行使用。”
利用小鼠模式動(dòng)物,，梅奧診所研究人員利用一種化療藥物預(yù)先處理干細(xì)胞,，其中這種藥物能夠選擇性地破壞這些干細(xì)胞的DNA，從而有效地殺死這些形成腫瘤的細(xì)胞,。Nelson博士說(shuō),，遭受損傷的細(xì)胞全部死亡，而且這種化療藥物不影響健康細(xì)胞,。
論文共同作者Alyson Smith博士說(shuō),，“構(gòu)建新療法的雙重目標(biāo)：基于干細(xì)胞的再生療法有助于改善疾病療效，同時(shí)也要確保安全,。這項(xiàng)研究勾畫出一種策略以便干細(xì)胞療法對(duì)我們的病人更加安全,，同時(shí)確保它們的治療效果，因而就能夠克服將這些治療方法應(yīng)用到診所時(shí)所面臨的障礙,。”
研究人員還在繼續(xù)優(yōu)化和改進(jìn)干細(xì)胞療法,。他們正發(fā)現(xiàn)干細(xì)胞可能具有比人們?cè)胂笾懈佣嗟墓δ埽@就意味著它們能夠被用來(lái)治療更加多樣性的疾病,、損傷和先天性異常,。
論文共同作者Andre Terzic博士說(shuō),，“通過(guò)利用再生醫(yī)學(xué)的潛力,，我們將能夠給病人提供更加明確的治療方法。”(生物谷Bioon.com)
doi: 10.5966/sctm.2012-0066
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Apoptotic Susceptibility to DNA Damage of Pluripotent Stem Cells Facilitates Pharmacologic Purging of Teratoma Risk
Alyson J. Smitha,b, Natalie G. Nelsonb, Saji Oommena,b, Katherine A. Hartjesb, Clifford D. Folmesc, Andre Terzica,b,c,d,e and Timothy J. Nelson
Pluripotent stem cells have been the focus of bioengineering efforts designed to generate regenerative products, yet harnessing therapeutic capacity while minimizing risk of dysregulated growth remains a challenge. The risk of residual undifferentiated stem cells within a differentiated progenitor population requires a targeted approach to eliminate contaminating cells prior to delivery. In this study we aimed to validate a toxicity strategy that could selectively purge pluripotent stem cells in response to DNA damage and avoid risk of uncontrolled cell growth upon transplantation. Compared with somatic cell types, embryonic stem cells and induced pluripotent stem cells displayed hypersensitivity to apoptotic induction by genotoxic agents. Notably, hypersensitivity in pluripotent stem cells was stage-specific and consistently lost upon in vitro differentiation, with the mean half-maximal inhibitory concentration increasing nearly 2 orders of magnitude with tissue specification. Quantitative polymerase chain reaction and Western blotting demonstrated that the innate response was mediated through upregulation of the BH3-only protein Puma in both natural and induced pluripotent stem cells. Pretreatment with genotoxic etoposide purged hypersensitive pluripotent stem cells to yield a progenitor population refractory to teratoma formation upon transplantation. Collectively, this study exploits a hypersensitive apoptotic response to DNA damage within pluripotent stem cells to decrease risk of dysregulated growth and augment the safety profile of transplant-ready, bioengineered progenitor cells.
