Tong J, Gordon M S, Srour E F, Cooper R J, Orazi A, McNiece I, Hoffman R
Hematology-Oncology Section, Indiana University School of Medicine, Indianapolis 46202-5121.
Blood. 1993 Aug 1;82(3):784-91.
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)
越来越多的体外研究表明，重组人干细胞因子（SCF）能够增强人类造血祖细胞（HPC）和干细胞（HSC）的增殖能力。我们通过分析8例局部晚期或转移性乳腺癌患者骨髓（BM）中的HPC和HSC对SCF给药的反应，进一步评估了这种生物学效应。这些患者参与了一项正在进行的I期研究。SCF通过每日皮下注射给药14天，剂量为10、25或50微克/千克/天。在第0天（预处理）和第15天（治疗后）采集BM样本，对BM中CD34+HLA-DR+细胞和CD34+HLA-DR-CD15-细胞进行定量分析，我们实验室先前已证明，这两类细胞分别富含不同类型的分化型和原始型HPC。然后通过细胞分选分离出这些CD34+HLA-DR+和CD34+HLA-DR-CD15-细胞，并对几类HPC进行检测，包括高增殖潜能集落形成细胞（HPP-CFC）、巨核细胞爆式集落形成单位（BFU-MK）和长期骨髓培养起始细胞（LTBMC-IC）。给予SCF后，CD34+细胞的绝对数量增加了3.3倍（范围为1.4至18.8倍；P = 0.018），CD34+HLA-DR+细胞的绝对数量增加了3.7倍（范围为1.2至8.2倍；P = 0.028），CD34+HLA-DR-CD-细胞的绝对数量增加了2.4倍（范围为1.1至29.3倍；P = 0.010）。输注SCF后，每毫升骨髓中HPP-CFC（P = 0.018）、BFU-MK（P = 0.046）、粒-红-单-巨核细胞集落形成单位（CFU-GEMM：P = 0.043）、红系爆式集落形成单位（BFU-E；P = 0.043）、粒-巨噬细胞集落形成单位（CFU-GM；P = 0.045）和巨核细胞集落形成单位（CFU-MK；P = 0.028）的绝对数量有统计学意义的增加。用第0天获得的CD34+HLA-DR-CD15-细胞起始培养、添加SCF和白细胞介素-3（IL-3）的无基质LTBMC可产生活细胞9.6周，而用第15天获得的CD34+HLA-DR-CD15-细胞起始培养的LTBMC可产生活细胞11.5周。用第15天的CD34+HLA-DR-CD15-细胞起始培养的LTBMC的累积细胞产量在统计学上高于用第0天的细胞起始培养的LTBMC（P = 0.031）。这些相同的培养物产生CFU-GM的时间为6.3周（第0天）对9周（第15天）。（摘要截断于400字）
