Lee Jungmin, Dykstra Brad, Sackstein Robert, Rossi Derrick J
aDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge bProgram in Cellular and Molecular Medicine, Division of Hematology/Oncology, Boston Children's Hospital cDepartment of Dermatology, and Program of Excellence in Glycosciences, Brigham & Women's Hospital, Harvard Medical School dDivision of Hematology, Department of Medicine, Brigham & Women's Hospital eDepartment of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston fHarvard Stem Cell Institute, Cambridge, Massachusetts, USA *Jungmin Lee and Brad Dykstra contributed equally to the writing of this manuscript.
Curr Opin Hematol. 2015 Jul;22(4):317-23. doi: 10.1097/MOH.0000000000000147.
Human pluripotent stem cells (PSCs) have the potential to provide an inexhaustible source of hematopoietic stem cells (HSCs) that could be used in disease modeling and in clinical applications such as transplantation. Although the goal of deriving definitive HSCs from PSCs has not been achieved, recent studies indicate that progress is being made. This review will provide information on the current status of deriving HSCs from PSCs, and will highlight existing challenges and obstacles.
Recent strides in HSC generation from PSCs has included derivation of developmental intermediates, identification of transcription factors and small molecules that support hematopoietic derivation, and the development of strategies to recapitulate niche-like conditions.
Despite considerable progress in defining the molecular events driving derivation of hematopoietic progenitor cells from PSCs, the generation of robust transplantable HSCs from PSCs remains elusive. We propose that this goal can be facilitated by better understanding of the regulatory pathways governing HSC identity, development of HSC supportive conditions, and examining the marrow homing properties of PSC-derived HSCs.
人类多能干细胞(PSC)有潜力提供源源不断的造血干细胞(HSC),可用于疾病建模以及移植等临床应用。尽管从PSC中获得确定性HSC的目标尚未实现,但最近的研究表明正在取得进展。本综述将提供有关从PSC中获得HSC的现状信息,并突出当前存在的挑战和障碍。
最近在从PSC生成HSC方面取得的进展包括发育中间体的衍生、支持造血衍生的转录因子和小分子的鉴定,以及重现类似龛位条件的策略的开发。
尽管在确定驱动从PSC中衍生造血祖细胞的分子事件方面取得了相当大的进展,但从PSC中生成强大的可移植HSC仍然难以实现。我们认为,通过更好地理解控制HSC特性的调控途径、开发支持HSC的条件以及研究PSC衍生的HSC的骨髓归巢特性,可以推动实现这一目标。