Christ O, Kronenwett R, Haas R, Zöller M
Department of Tumor Progression and Immune Defense, German Cancer Research Center, Heidelberg, Germany.
Exp Hematol. 2001 Mar;29(3):380-90. doi: 10.1016/s0301-472x(00)00674-3.
Mobilization of hematopoietic progenitor cells is achieved mainly by application of growth factors and, more recently, by blockade of adhesion. In this report, we describe the advantages of a combined treatment with granulocyte colony-stimulating factor (G-CSF) and anti-VLA4 (CD49d)/anti-CD44 as compared to treatment with the individual components.
Mobilization by intravenous injection of anti-CD44, anti-VLA4, or G-CSF was controlled in spleen and bone marrow with regard to frequencies of multipotential colony-forming unit (C-CFU), marrow repopulating ability, long-term reconstitution, recovery of myelopoiesis, and regain of immunocompetence.
Mobilization by anti-CD44 had a strong effect on expansion of early progenitor cells in the bone marrow, while the recovery in the spleen was poor. In anti-CD49d-mobilized noncommitted and committed progenitors, progenitor expansion was less pronounced, but settlement in the spleen was quite efficient. Thus, anti-CD44 and anti-CD49d differently influenced mobilization. Accordingly, mobilization and recovery after transfer were improved by combining anti-CD44 with anti-CD49d treatment. Mobilization by G-CSF was most efficient with respect to recovery of progenitor cells in the spleen. However, when transferring G-CSF-mobilized cells, regain of immunocompetence was strongly delayed. This disadvantage could be overridden when progenitor cells were mobilized via blockade of adhesion and when expansion of these mobilized progenitor cells was supported by low-dose G-CSF only during the last 24 hours before transfer.
Mobilization of pluripotent progenitor cells via antibody blockade of CD44 or CD49d or via G-CSF relies on distinct mechanisms. Therefore, the reconstitutive capacity of a transplant can be significantly improved by mobilization regimens combining antibody with low-dose G-CSF treatment.
造血祖细胞的动员主要通过应用生长因子来实现，最近也通过阻断黏附作用来实现。在本报告中，我们描述了与单独使用各组分治疗相比，联合使用粒细胞集落刺激因子（G-CSF）和抗VLA4（CD49d）/抗CD44治疗的优势。
通过静脉注射抗CD44、抗VLA4或G-CSF进行动员，在脾脏和骨髓中对多能集落形成单位（C-CFU）的频率、骨髓重建能力、长期造血重建、髓系造血恢复以及免疫能力恢复进行监测。
抗CD44动员对骨髓中早期祖细胞的扩增有强烈作用，而脾脏中的恢复较差。在抗CD49d动员的未定向和定向祖细胞中，祖细胞扩增不太明显，但在脾脏中的定居相当有效。因此，抗CD44和抗CD49d对动员的影响不同。相应地，联合抗CD44与抗CD49d治疗可改善移植后的动员和恢复。就脾脏中祖细胞的恢复而言，G-CSF动员最为有效。然而，在移植G-CSF动员的细胞时，免疫能力的恢复会严重延迟。当通过阻断黏附作用动员祖细胞，且仅在移植前最后24小时用低剂量G-CSF支持这些动员的祖细胞扩增时，这一缺点可以被克服。
通过对CD44或CD49d进行抗体阻断或通过G-CSF来动员多能祖细胞依赖于不同的机制。因此，通过将抗体与低剂量G-CSF治疗相结合的动员方案，可显著提高移植的重建能力。
