多能干细胞向造血细胞定向诱导分化的研究进展

Advances in the Research on Induced Differentiation of Pluripotent Stem Cells into Hematopoietic Stem Progenitor Cells

造血干细胞(HSC)移植是血液系统疾病最有效的治疗手段。现阶段,同种异体HSC移植和同种自体HSC移植已在临床被广泛采用,但仍存在不少难题,如:异基因移植物抗宿主发病(GVHD)难题,以及自体HSC移植数量限制等。多能干细胞(PSC)具备在体外自主更新的潜力,多向分化和形成人体所必需的HSC,PSC包含诱导多能干细胞(iPSC)和胚胎干细胞(ESC)。由于不清楚PSC向HSC分化的内在调节机制和外在调节机制,导致PSC向HSC诱导分化的效率低下,且难以获得机体自身造血功能的HSC等。为此,综述PSC造血分化过程的研究进展。以小鼠体内胚胎造血发生为切入点,利用体外PSC造血分化研究平台,阐述PSC向HSC的内源性分子调控事件,包括转录因子和信号通路介导的造血调控;外源性分子调控事件,包括基质细胞、细胞因子以及新型生物材料等参与的造血调控。同时指出PSC向HSC/HSPC功能移植应用存在问题,为PSC向HSC体外分化研究,为实现PSC来源的HSC以及下游血液细胞的临床转化应用提供依据。

Hematopoietic stem cells(HSC)transplantation is an effective means for the treatment of various hematological diseases.At present,allograft and autologous HSC transplantation are widely used in clinical practice,but there are still many problems,such as graft-versus-host disease caused by allogeneic transplantation,the limited number of HSC for autologous HSC transplantation.Pluripotent stem cells(PSC)including embryonic stem cells(ESCs)and induced pluripotent stem cells(iPSCs)have the ability of self-renewal and multidirectional differentiation in vitro,which theoretically continuously produce HSC.However,there are still key scientific problems to be solved in the study of PSC hematopoietic differentiation,such as low efficiency in hematopoietic differentiation and difficulties to obtain PSC derived HSC that has long-term hematopoiesis potential in vivo.The reasons are that the internal regulation mechanism and external environment for PSC hematopoietic differentiation has not clear yet.This article reviewed the role of internal regulatory elements including transcription factors and signaling pathways,and external microenvironmental factors including stromal cells,cytokines and novel biomaterials in regulating PSC hematopoietic differentiation during in vitro and in vivo embryonic hematopoietic development,providing a theoretical basis for the study of PSC hematopoietic differentiation in vitro and clinical transformation of PSC-derived HSC.