Timeus F, Crescenzio N, Basso G, Ramenghi U, Saracco P, Gabutti V
Department of Pediatric Hematology-Oncology, University of Torino, Italy.
Stem Cells. 1998;16(2):120-6. doi: 10.1002/stem.160120.
Self-renewal, proliferation, differentiation, homing, and mobilization of hematopoietic progenitor cells (HPCs) are regulated by a complex mechanism that involves the bone marrow (BM) microenvironment. Cell adhesion molecules (CAMs) expressed on HPCs and on endothelial and stromal cells play a pivotal role in this process. In this study, we have used three-color cytofluorometric analysis to compare CAM expression in the subsets of cord blood (CB) and BM HPCs and examined the effect of a short exposure to various cytokines on L-selectin expression. The study was carried out on unseparated samples to avoid any possible bias from positive CD34 selection. CAMs were highly expressed in both CB and BM CD34+CD38+ cells. In this population, L-selectin, H-CAM, and LFA-1 were significantly more expressed in BM than in CB. With regard to the more immature progenitors, the subsets of CD34+/CD38-/L-selectin+ and CD34+/CD38-/LFA1+ cells were significantly larger in CB than in BM. Since the expression of such CAMs has been related to the repopulating capacity of HPCs, our results suggest a possible advantage in homing and engraftment of more undifferentiated CB as opposed to BM HPCs. A 4/24-h exposure to various cytokines significantly increased the percentage of CB CD34+/CD38+/L-selectin+ cells, while HPCs were differentiated since the percentage of CD34+/CD38-/L-selectin+ cells was reduced. These data show that a short exposure to cytokines increases L-selectin expression in the more differentiated CB HPCs. This could improve their homing in a transplant setting.
造血祖细胞(HPC)的自我更新、增殖、分化、归巢及动员受涉及骨髓(BM)微环境的复杂机制调控。HPC以及内皮细胞和基质细胞上表达的细胞黏附分子(CAM)在此过程中起关键作用。在本研究中,我们采用三色细胞荧光分析比较脐血(CB)和BM HPC亚群中CAM的表达,并检测短期暴露于各种细胞因子对L-选择素表达的影响。该研究在未分离的样本上进行,以避免阳性CD34选择带来的任何可能偏差。CAM在CB和BM CD34+CD38+细胞中均高表达。在该群体中,L-选择素、H-CAM和LFA-1在BM中的表达明显高于CB。对于更不成熟的祖细胞,CB中CD34+/CD38-/L-选择素+和CD34+/CD38-/LFA1+细胞亚群明显大于BM。由于此类CAM的表达与HPC的再增殖能力相关,我们的结果表明,与BM HPC相比,更未分化的CB在归巢和植入方面可能具有优势。短期暴露于各种细胞因子4/24小时可显著增加CB CD34+/CD38+/L-选择素+细胞的百分比,而HPC发生分化,因为CD34+/CD38-/L-选择素+细胞的百分比降低。这些数据表明,短期暴露于细胞因子可增加更分化的CB HPC中L-选择素的表达。这可能会改善它们在移植环境中的归巢。