Ex vivo expansion of hematopoietic stem cells  

作　　者：XIE JingJing ZHANG ChengCheng 

机构地区：[1]Taishan Scholar Immunology Program, Binzhou Medical University [2]Departments of Physiology and Developmental Biology, University of Texas Southwestern Medical Center

出　　处：《Science China(Life Sciences)》2015年第9期839-853,共15页中国科学（生命科学英文版）

基　　金：supported by the National Institutes of Health(1R01CA172268);the Leukemia & Lymphoma Society(1024-14 and TRP-6024-14);the March of Dimes Foundation(1-FY14-201);the Cancer Prevention and Research Institute of Texas(RP140402);the Taishan Scholar Program

摘　　要：Ex vivo expansion of hematopoietic stem cells(HSCs) would benefit clinical applications in several aspects, to improve patient survival, utilize cord blood stem cells for adult applications, and selectively propagate stem cell populations after genetic manipulation. In this review we summarize and discuss recent advances in the culture systems of mouse and human HSCs, which include stroma/HSC co-culture, continuous perfusion and fed-batch cultures, and those supplemented with extrinsic ligands, membrane transportable transcription factors, complement components, protein modification enzymes, metabolites, or small molecule chemicals. Some of the expansion systems have been tested in clinical trials. The optimal condition for ex vivo expansion of the primitive and functional human HSCs is still under development. An improved understanding of the mechanisms for HSC cell fate determination and the HSC culture characteristics will guide development of new strategies to overcome difficulties. In the future, development of a combination treatment regimen with agents that enhance self-renewal, block differentiation, and improve homing will be critical. Methods to enhance yields and lower cost during collection and processing should be employed. The employment of an efficient system for ex vivo expansion of HSCs will facilitate the further development of novel strategies for cell and gene therapies including genome editing.Ex vivo expansion of hematopoietic stem cells （HSCs） would benefit clinical applications in several aspects, to improve patient survival, utilize cord blood stem cells for adult applications, and selectively propagate stem cell populations after genetic ma- nipulation. In this review we summarize and discuss recent advances in the culture systems of mouse and human HSCs, which include stroma/HSC co-culture, continuous perfusion and fed-batch cultures, and those supplemented with extrinsic ligands, membrane transportable transcription factors, complement components, protein modification enzymes, metabolites, or small molecule chemicals. Some of the expansion systems have been tested in clinical trials. The optimal condition for ex vivo ex- pansion of the primitive and functional human HSCs is still under development. An improved understanding of the mecha- nisms for HSC cell fate determination and the HSC culture characteristics will guide development of new strategies to over- come difficulties. In the future, development of a combination treatment regimen with agents that enhance self-renewal, block differentiation, and improve homing will be critical. Methods to enhance yields and lower cost during collection and pro- cessing should be employed. The employment of an efficient system for ex vivo expansion of HSCs will facilitate the further development of novel strategies for cell and gene therapies including genome editing.

关 键 词：ex vivo expansion hematopoietic stem cells NICHE signal transduction cord blood TRANSPLANTATION SCID-repopulating cell genome ed 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]