2012年9月28日 讯 /生物谷BIOON/ --来自美国梅奥诊所(Mayo Clinic)的研究人员发现一种新方法能够检测和清除潜在危险性的干细胞以便使得干细胞疗法更加安全。诱导性多能干细胞(induced Pluripotent Stem cell, iPSC)是对来自成体组织的细胞进行重编程而获得的，具有类似胚胎干细胞的性质，即能够无限制地分化为任何所需的细胞类型，如皮肤细胞、脑细胞、肺细胞和心脏细胞。然而，在分化过程种，一些残留的多能性细胞或者胚胎细胞样细胞(embryonic-like cell)可能继续存在而导致肿瘤产生。相关研究论文于近期刊登Stem Cells Translational Medicine期刊上。
论文通讯作者Timothy Nelson博士说，“多能性干细胞大有希望用于在再生医学领域，但是细胞不受控制生长的风险将继续阻止人们将它们作为治疗方法进行使用。”
利用小鼠模式动物，梅奥诊所研究人员利用一种化疗药物预先处理干细胞，其中这种药物能够选择性地破坏这些干细胞的DNA，从而有效地杀死这些形成肿瘤的细胞。Nelson博士说，遭受损伤的细胞全部死亡，而且这种化疗药物不影响健康细胞。
论文共同作者Alyson Smith博士说，“构建新疗法的双重目标：基于干细胞的再生疗法有助于改善疾病疗效，同时也要确保安全。这项研究勾画出一种策略以便干细胞疗法对我们的病人更加安全，同时确保它们的治疗效果，因而就能够克服将这些治疗方法应用到诊所时所面临的障碍。”
研究人员还在继续优化和改进干细胞疗法。他们正发现干细胞可能具有比人们原想象中更加多的功能，这就意味着它们能够被用来治疗更加多样性的疾病、损伤和先天性异常。
论文共同作者Andre Terzic博士说，“通过利用再生医学的潜力，我们将能够给病人提供更加明确的治疗方法。”(生物谷Bioon.com)
doi: 10.5966/sctm.2012-0066
PMC:
PMID:
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.
