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多能干细胞培育出脂肪细胞

近日,美国与德国科学家宣布成功利用人体多功能干细胞高效地培育出白色脂肪细胞和褐色脂肪细胞这两种人体脂肪生成细胞,相关报告在线发表于本周的《自然—细胞生物学》(Nature Cell Biology)上。这项研究为褐色脂肪组织活性相关治疗提供了潜在可能,从而降低体质指数(BMI)。

目前,疾病研究所需的人体多功能干细胞的来源有两种:人体胚胎和直接用成体细胞重编程。科学家需要一种高效实现多功能干细胞各种分化的方法。此外,要从其他来源获取上述两种脂肪细胞,现有的方法也并不理想。在这项研究中,Chad Cowan和同事以多功能干细胞为来源,通过表达脂肪诱导相关因子,将近90%的多功能干细胞分化成为白色和褐色脂肪细胞。所获得的细胞具有脂类代谢、胰岛素反应性等成熟功能,将这些细胞植入小鼠体内后,其会发生异位脂肪沉积,从而形成白色与褐色脂肪组织。

该项研究成果将直接有助于针对肥胖以及其他脂肪细胞相关症状的研究。

Programming human pluripotent stem cells into white and brown adipocytes

Tim Ahfeldt, Robert T. Schinzel, Youn-Kyoung Lee,David Hendrickson, Adam Kaplan, David H. Lum, Raymond Camahort, Fang Xia, Jennifer Shay, Eugene P. Rhee, Clary B. Clish, Rahul C. Deo,Tony Shen, Frank H. Lau, Alicia Cowley, Greg Mowrer, Heba Al-Siddiqi, Matthias Nahrendorf, Kiran Musunuru, Robert E. Gerszten, John L. Rinn1, & Chad A. Cowan

The utility of human pluripotent stem cells is dependent on efficient differentiation protocols that convert these cells into relevant adult cell types. Here we report the robust and efficient differentiation of human pluripotent stem cells into white or brown adipocytes. We found that inducible expression of PPARG2 alone or combined with CEBPB and/or PRDM16 in mesenchymal progenitor cells derived from pluripotent stem cells programmed their development towards a white or brown adipocyte cell fate with efficiencies of 85%–90%. These adipocytes retained their identity independent of transgene expression, could be maintained in culture for several weeks, expressed mature markers and had mature functional properties such as lipid catabolism and insulin-responsiveness. When transplanted into mice, the programmed cells gave rise to ectopic fat pads with the morphological and functional characteristics of white or brown adipose tissue. These results indicate that the cells could be used to faithfully model human disease.