An in vivo competitive repopulation assay for various sources of human hematopoietic stem cells

作     者：Rosler, ES Brandt, JE Chute, J Hoffman, R 

作者机构：Univ Illinois Coll Med Hematol Oncol Sect Chicago IL 60607 USA USN NIDDK Transplantat & Autoimmun Branch Bethesda MD 20084 USA 

出 版 物：《BLOOD》 (血液)

年 卷 期：2000年第96卷第10期

页      面：3414-3421页

核心收录：

学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

主　　题：抗原 CD34/代谢 骨髓细胞/免疫学 骨髓移植 细胞谱系/免疫学 胎血 流式细胞术 移植物存活/免疫学 HLA抗原 血细胞生成/免疫学 造血干细胞移植/方法 造血干细胞/免疫学 造血干细胞/生理学 小鼠 SCID 猪 动物 人类 小鼠 

摘      要：The marrow repopulating potential (MRP) of different sources of human hematopoietic stem cells (HSCs) was directly compared using an in vivo assay in which severe combined immunodeficient disease (SCID) mice were implanted with human fetal bones. HSCs from 2 human lymphocyte antigen (HLA)-mismatched donors were injected individually or simultaneously into the fetal bones of a 3rd distinct HLA type and donor and recipient myeloid and lymphoid cells were identified after 8 to 10 weeks. The study compared the MRP of umbilical cord blood (CB) and adult bone marrow (ABM) CD34(+) cells as well as grafts of each type expanded ex vivo. Equal numbers of CB and ABM CD34(+) cells injected individually demonstrated similar abilities to establish multilineage hematopoiesis. However, when CB and ABM cells were transplanted simultaneously, the engraftment of CB cells was markedly superior to ABM. CB and ABM CD34(+) cells were expanded ex vivo using either a porcine microvascular endothelial cell (PMVEC)based coculture system or a stroma-free expansion system. Primary CB CD34(+) cells or CD34(+) cells expanded in either culture system demonstrated a similar ability to engraft. However, the MRP of expanded grafts simultaneously injected with primary CB cells was uniformly inferior to primary CB cells. CD34(+) cell grafts expanded in the stroma-free system, furthermore, outcompeted CD34(+) cells expanded using the PMVEC coculture system. The triple HLA-mismatched SCID-hu model represents a novel in vivo stem cell assay system that permits the direct demonstration of the functional consequences of ex vivo HSC expansion and ontogeny-related differences in HSCs. (C) 2000 by The American Society of Hematology.