Anastasia Luigi, Sampaolesi Maurilio, Papini Nadia, Oleari Diego, Lamorte Giuseppe, Tringali Cristina, Monti Eugenio, Galli Daniela, Tettamanti Guido, Cossu Giulio, Venerando Bruno
Department of Medical Chemistry, Biochemistry and Biotechnology, University of Milan, L.I.T.A. via F.lli Cervi 93, 20090 Segrate, Milan, Italy.
Cell Death Differ. 2006 Dec;13(12):2042-51. doi: 10.1038/sj.cdd.4401958. Epub 2006 May 26.
Stem cells hold a great potential for the regeneration of damaged tissues in cardiovascular or musculoskeletal diseases. Unfortunately, problems such as limited availability, control of cell fate, and allograft rejection need to be addressed before therapeutic applications may become feasible. Generation of multipotent progenitors from adult differentiated cells could be a very attractive alternative to the limited in vitro self-renewal of several types of stem cells. In this direction, a recently synthesized unnatural purine, named reversine, has been proposed to induce reversion of adult cells to a multipotent state, which could be then converted into other cell types under appropriate stimuli. Our study suggests that reversine treatment transforms primary murine and human dermal fibroblasts into myogenic-competent cells both in vitro and in vivo. Moreover, this is the first study to demonstrate that plasticity changes arise in primary mouse and human cells following reversine exposure.
干细胞在心血管或肌肉骨骼疾病中受损组织的再生方面具有巨大潜力。不幸的是,在治疗应用可行之前,需要解决诸如可用性有限、细胞命运控制和同种异体移植排斥等问题。从成体分化细胞生成多能祖细胞可能是几种类型干细胞有限的体外自我更新的一种非常有吸引力的替代方法。在这个方向上,一种最近合成的名为reversine的非天然嘌呤已被提出可诱导成体细胞逆转为多能状态,然后在适当刺激下可将其转化为其他细胞类型。我们的研究表明,reversine处理在体外和体内均可将原代小鼠和人真皮成纤维细胞转化为具有成肌能力的细胞。此外,这是第一项证明reversine处理后原代小鼠和人细胞会出现可塑性变化的研究。