造血干/祖细胞体外扩增和临床应用

Expansion ex vivo and clinical applications of hematopoietic stem/progenitor cells

造血干细胞(HSC)处于血细胞谱系顶端,维持机体正常造血稳态与免疫功能。HSC移植(HSCT)的临床应用为恶性血液系统疾病提供治愈可能,也是未来基因疗法的理想靶细胞。HSCT部分供者动员不良、脐带血来源HSC多向分化能力良好但数量少等问题是HSC治疗发展的瓶颈。真正意义的HSC体外分离仍存在技术瓶颈,目前仅能高效分离出造血干/祖细胞(HSPC),通过添加细胞因子、小分子化合物和模拟HSC生存环境(骨髓生态位)以及基因编辑干预进行HSPC体外培养扩增,进而实现HSC的数量增加满足临床需求。高效安全的HSPC体外扩增将推进临床移植应用发展,对治愈血液疾病和提供足够数量HSC用于基因治疗具有重要意义。

Hematopoietic stem cells(HSC)are at the top of the blood cell lineage and maintain normal hematopoietic homeostasis and immune function.The clinical application of hematopoietic stem cell transplantation(HSCT)provides the possibility of curing malignant hematological diseases,and it is also an ideal target cell for future gene therapy.There are many challenges with the development of HSC therapy,including poor mobilization of HSCT donors and a limited number of cord blood-derived HSCs.At present,there are still technical challenges in the isolation of HSC ex vivo.Only hematopoietic stem/progenitor cells(HSPC)can be efficiently isolated.HSPC can be expanded ex vivo by adding cytokines,small molecular compounds,simulating HSC survival environment(bone marrow niche)and gene editing intervention,so as to increase the number of HSC to meet clinical needs.Efficient and safe expansion of HSPC ex vivo will promote the development of clinical transplantation applications,which is of great significance for curing blood diseases and providing sufficient number of HSC for gene therapy.