In vivo administration of recombinant methionyl human stem cell factor expands the number of human marrow hematopoietic stem cells.
In vivo administration of recombinant methionyl human stem cell factor expands the number of human marrow hematopoietic stem cells.
复制标题
DOI：
10.1182/blood.v82.3.784.784
复制
发表时间：
1993-08
期刊：
影响因子：
20.3
通讯作者：
Jay Tong;M. Gordon;E. Srour;R. Cooper;A. Orazi;I. Mcniece;R. Hoffman
中科院分区：
文献类型：
--
作者：
Jay Tong;M. Gordon;E. Srour;R. Cooper;A. Orazi;I. Mcniece;R. Hoffman
越来越多的体外研究表明，重组人干细胞因子（SCF）能够增强人造血祖细胞（HPC）和干细胞（HSC）的增殖能力。我们进一步评估了这种生物学效应，通过分析骨髓（BM）HPC和HSC对8例局部晚期或转移性乳腺癌患者SCF给药的反应，这些患者入选了正在进行的I期研究。SCF以10、25或50 μ g/kg/d的剂量通过每日皮下注射给药14天。在第0天（治疗前）和第15天（治疗后）对BM样品中的BM CD 34 + HLA-DR+和CD 34 + HLA-DR-CD 15-细胞进行定量，这些细胞先前由我们的实验室显示为分别富集各种类型的分化和原始HPC。这些CD 34 + HLA-DR+和CD 34 + HLA-DR-CD 15-细胞然后通过细胞分选分离并分析几种类型的HPC，包括高增殖潜能集落形成细胞（HPP-CFC）、爆发形成单位巨核细胞（BFU-MK）和长期BM培养起始细胞（LTBMC-IC）。SCF给药导致3.3倍的（范围，1.4- 18.8倍; P = 0.018）CD 34+细胞的绝对数量增加，3.7倍CD 34 + HLA-DR+细胞的绝对数量增加（范围，1.2- 8.2倍; P = 0.028），（范围，1.1- 29.3倍; P = 0.010）CD 34 + HLA-DR-CD 15-细胞的绝对数量增加。SCF输注后，HPP-CFC的绝对数量在统计学上显著增加，（P = .018），BFU-MK（P = 0.046），CFU-粒细胞、红细胞、单核细胞、巨核细胞（CFU-GEMM：P = .043），BFU-红细胞观察到每毫升骨髓中的CFU-粒细胞、巨噬细胞（CFU-GM; P = .045）和CFU-巨核细胞（CFU-MK; P = .028）。补充有SCF和白细胞介素-3（IL-3）的无基质细胞的LTBMCs，用第0天获得的CD 34 + HLA-DR-CD 15-细胞起始，产生活细胞9.6周，而用第15天获得的CD 34 + HLA-DR-CD 15-细胞起始的LTBMCs产生活细胞11.5周。用第15天的CD 34 + HLA-DR-CD 15-细胞启动的LTBMC的累积细胞产量在统计学上大于第0天的LTBMC（P = 0.031）。这些相同的培养物产生CFU-GM持续6.3周（第0天）对9周（第15天）。（400字处截断摘要）
A growing number of in vitro studies suggest that recombinant human stem cell factor (SCF) is capable of augmenting the proliferative capacity of human hematopoietic progenitor cells (HPC) and stem cells (HSC). We further evaluated this biologic effect by analyzing the response of bone marrow (BM) HPCs and HSCs to the administration of SCF in eight patients with locally advanced or metastatic breast cancer who were enrolled in an ongoing phase I study. SCF was administered for 14 days by daily subcutaneous injection at dosages of 10, 25, or 50 micrograms/kg/d. BM CD34+ HLA-DR+ and CD34+ HLA-DR- CD15- cells, previously shown by our laboratory to be enriched for various classes of differentiated and primitive HPCs, respectively, were quantitated in BM samples on day 0 (pretreatment) and day 15 (posttreatment). These CD34+ HLA-DR+ and CD34+ HLA-DR- CD15- cells were then isolated by cell-sorting and assayed for several classes of HPCs, including the high--proliferative potential colony-forming cell (HPP-CFC), the burst-forming unit--megakaryocyte (BFU-MK), and the long-term BM culture--initiating cell (LTBMC-IC). SCF administration resulted in a 3.3-fold (range, 1.4- to 18.8-fold; P = .018) increase in the absolute numbers of CD34+ cells, a 3.7-fold (range, 1.2- to 8.2-fold; P = .028) increase in the absolute numbers of CD34+ HLA-DR+ cells, and a 2.4-fold (range, 1.1- to 29.3-fold; P = .010) increase in the absolute numbers of CD34+ HLA-DR- CD15- cells. Following the infusion of SCF, a statistically significant increase in the absolute numbers of HPP-CFC (P = .018), BFU-MK (P = .046), CFU-granulocyte, erythrocyte, monocyte, megakaryocyte (CFU-GEMM: P = .043), BFU-erythrocyte (BFU-E; P = .043), CFU-granulocyte, macrophage (CFU-GM; P = .045), and CFU-megakaryocyte (CFU-MK; P = .028) per milliliter of marrow was observed. Stromal cell-free LTBMCs supplemented with SCF and interleukin-3 (IL-3), initiated with CD34+ HLA-DR- CD15- cells obtained on day 0, produced viable cells for 9.6 weeks, compared with 11.5 weeks for LTBMCs initiated with CD34+ HLA-DR- CD15- cells obtained on day 15. Cumulative cellular production by LTBMCs initiated with day 15 CD34+ HLA-DR- CD15- cells was statistically greater than that by day 0 LTBMCs (P = .031). These same cultures produced CFU-GM for 6.3 weeks (day 0) versus 9 weeks (day 15).(ABSTRACT TRUNCATED AT 400 WORDS)