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通过R-spondin 1和Slit2诱导肠道干细胞可以增加化学辐射保护
Wei-Jie Zhou1, Zhen H Geng, Jason R Spence
1Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, Michigan 48109, USA.
Nature
|August 2, 2013
概括
用R-spondin 1和Slit2诱导成年干细胞可以修复化学辐射造成的组织损伤. 这种方法可以保护小鼠免受致命剂量的影响,提高对癌症治疗的耐受性,而不会降低瘤的敏感性.
科学领域:
- 在瘤学瘤学.
- 干细胞生物学 干细胞生物学
- 胃肠病学 胃肠病学
背景情况:
- 癌症研究侧重于预防和向治疗,但在晚期癌症中减轻化学辐射诱导的组织损伤仍然是一个挑战.
- 肠道干细胞 (ISC) 在肠道组织的修复和再生中起着至关重要的作用.
- 了解ISC调节对于开发癌症治疗期间的支持性疗法至关重要.
研究的目的:
- 调查诱导成年干细胞是否可以修复化学辐射诱导的组织损伤并改善小鼠的存活率.
- 探索Slit2及其受体Robo1在调节肠干细胞数量和功能的作用.
- 确定R-spondin 1 (Rspo1) 和Slit2是否可以作为治疗辅助剂,以提高宿主对化疗和放射治疗的耐受性.
主要方法:
- 研究了Slit2和Robo1在肠道干细胞中的表达.
- 利用基因操纵 (Robo1,Slit2转基因的部分删除) 来评估ISC反应.
- 在小鼠模型中,在致命的化疗辐射过程中给予R-spondin 1 (Rspo1) 和Slit2.
- 评估ISC损失,肠道完整性,动物生存率和瘤对化疗的敏感性.
主要成果:
- Slit2和Robo1以ISC表达,调节它们的数量和形态.
- 部分Robo1删除降低了ISC数量,并导致小腺缩.
- Slit2转基因增加了ISC数量,并导致了状缩.
- 结合Rspo1和Slit2治疗可以减少致命化学辐射期间的ISC损失和肠道损伤.
- 这种治疗可以保护小鼠免于死亡,而不会影响瘤对化疗的敏感性.
结论:
- 通过调节ISC行为,R-spondin 1和Slit2可以防止化学辐射诱导的肠损伤.
- 这些因素可以作为治疗辅助剂,以改善患者对转移性癌症激烈化疗和放射治疗的耐受性.
- 这一策略提供了一种潜在的方法,通过支持宿主的弹性来提高癌症治疗的有效性.
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