据物理学家组织网近日报道,美国科学家采用一种新奇的方法,对诱导多能干细胞(iPS细胞)进行分化,在试管内制造出了无数的人类红血细胞和血小板。他们表示,得到的红血细胞有望用于诊查疟疾和镰状细胞血症,而血小板则可用来探查心血管病并治疗凝血障碍。研究发表在最新一期的《血液》杂志上。
科学家们一般通过对成人干细胞进行重组,让其回到初始的干细胞状态,从而获得iPS细胞。iPS细胞可以利用皮肤细胞、血液细胞等成熟的身体细胞生成,并可进一步分化成各种其他类型的细胞。由于其源于病人体内,不会引发免疫排斥反应,从而成为生物研究领域的一个强大工具以及再生医疗的重要来源。
最新研究中用到的iPS细胞来自波士顿大学再生医学中心的诱导多能干细胞库。该中心联合负责人兼波士顿大学医学院助理教授乔治·墨菲与波士顿大学公共健康学院环境健康教授戴维·希尔携手领导的研究团队首先让这些iPS细胞接触生长因子,随后用一种专利技术诱导它们分化成了红血细胞和血小板。科学家们也对iPS细胞进行了深入诊查,以研究血液细胞如何形成以及这一过程在身体内如何被调节。
该研究的新奇之处是研究人员在其中添加了用来调节芳香烃受体(AhR)通路的化合物。以前的研究表明,这一通路会通过芳香烃受体同环境中的有毒物质相互作用来促进癌细胞发育。然而,在最新研究中,功能性红血细胞和血小板的产量在短时间内呈指数增加,这表明,AhR在正常的血液细胞的发育过程中也起重要作用。
墨菲说:“最新发现使我们获得了大量的红血细胞和血小板,可以满足治疗所需。而且最新研究也表明,AhR在血液细胞如何形成方面具有非常重要的生物学功能。”
输血是一种不可缺少的细胞疗法,血供应的安全性和充足性也一直备受关注。去年,美国马里兰州负责统计血液供应和需求的国家血液资源中心报告称,美国的血液供应因需求大大超过供给而趋于干涸,许多州已严重缺血。一些地区的红十字会官员说,血液严重短缺迫使非急诊手术延期。墨菲表示:“用病人自己的iPS细胞生成的红血细胞和血小板有望解决与免疫排斥和污染有关的问题,也有望减少可预见的血液短缺和献血需求。”(生物谷 Bioon.com)
生物谷推荐的英文摘要
Blood doi: 10.1182/blood-2012-11-466722
The aryl hydrocarbon receptor directs hematopoietic progenitor cell expansion and differentiation
Brenden W. Smith1, Sarah S. Rozelle, Amy Leung, Jessalyn Ubellacker, Ashley Parks, Shirley K. Nah, Deborah French, Paul Gadue, Stefano Monti, David H.K. Chui, Martin H. Steinberg, Andrew L. Frelinger, Alan D. Michelson6, Roger Theberge, Mark E. McComb, Catherine E. Costello, Darrell N. Kotton, Gustavo Mostoslavsky, David H. Sherr, and George J. Murphy,*
The evolutionarily conserved aryl hydrocarbon receptor (AhR) has been studied for its role in environmental chemical-induced toxicity. However, recent studies demonstrate that the AhR may regulate the hematopoietic and immune systems during development in a cell-specific manner. These results, together with the absence of an in vitro model system enabling production of large numbers of primary human hematopoietic progenitor cells (HPs) capable of differentiating into megakaryocyte- and erythroid-lineage cells, motivated us to determine if AhR modulation could facilitate both progenitor cell expansion and megakaryocyte and erythroid cell differentiation. Using a novel, iPSC-based, chemically-defined, serum and feeder cell-free culture system, we show that a functional AhR is expressed in HPs, and that remarkably, AhR activation in these HPs drives an unprecedented expansion of HPs, megakaryocyte- and erythroid-lineage cells. Further AhR modulation within rapidly expanding progenitor cell populations directs cell fate, with chronic AhR agonism permissive to erythroid differentiation and acute antagonism favoring megakaryocyte specification. These results highlight the development of a new, GMP-compliant platform for generating virtually unlimited numbers of human HPs with which to scrutinize red blood cell and platelet development, including the assessment of the role of this environmental chemical receptor in critical cell fate decisions during hematopoiesis.