Maintenance of transplantation potential in ex vivo expanded CD34(+)- selected human peripheral blood progenitor cells

作者: R Henschler , W Brugger , T Luft , T Frey , R Mertelsmann

DOI: 10.1182/BLOOD.V84.9.2898.2898

关键词:

摘要: CD34(+)-selected hematopoietic progenitor cells are being increasingly used for autotransplantation, and recent evidence indicates that these can be expanded ex vivo. Of 15 patients with solid tumors undergoing a phase I/II clinical trial using peripheral blood (PBPCs) after high-dose chemotherapy, we analyzed the frequency of long-term culture-initiating (LTCIC) as measure transplantation potential before vivo expansion CD34+ cells. PBPCs were mobilized by combination chemotherapy granulocyte colony-stimulating factor (G-CSF). The original unseparated leukapheresis preparations, CD34(+)-enriched transplants, well nonabsorbed fractions eluting from CD34 immunoaffinity columns (Ceprate; CellPro, Bothell, WA) monitored their capacity to repopulate irradiated allogeneic stroma in human bone marrow cultures. We found preservation more than three quarters fully functional LTCIC fractions. Quantitation limiting dilution analysis showed 53-fold enrichment 1/9,075 an incidence 1/169 Thus, single apheresis, it was possible harvest median 1.65 x 10(4) per kg body weight (range, 0.71 3.72). In addition, six patients, large-scale expansions performed five-factor cytokine consisting stem cell (SCF), interleukin-1 (IL-1), IL-3, IL-6, erythropoietin (EPO), previously shown expand committed preserved, but not during culture period. Optimization growth requirements assays estimation indicated SCF, IL-1, EPO together autologous plasma most reliable securing both high yield and, at same time, optimal LTCIC. Our data suggest vivo-expanded might able allow reconstitution hematopoiesis.

参考文章(26)
AA Ross, BW Cooper, HM Lazarus, W Mackay, TJ Moss, N Ciobanu, MS Tallman, MJ Kennedy, NE Davidson, D Sweet, Detection and Viability of Tumor Cells in Peripheral Blood Stem Cell Collections From Breast Cancer Patients Using Immunocytochemical and Clonogenic Assay Techniques Blood. ,vol. 82, pp. 2605- 2610 ,(1993) , 10.1182/BLOOD.V82.9.2605.BLOODJOURNAL8292605
HJ Sutherland, CJ Eaves, AC Eaves, W Dragowska, PM Lansdorp, Characterization and Partial Purification of Human Marrow Cells Capable of Initiating Long-Term Hematopoiesis In Vitro Blood. ,vol. 74, pp. 1563- 1570 ,(1989) , 10.1182/BLOOD.V74.5.1563.1563
E J Shpall, R B Jones, S I Bearman, W A Franklin, P G Archer, T Curiel, M Bitter, H N Claman, S M Stemmer, M Purdy, Transplantation of enriched CD34-positive autologous marrow into breast cancer patients following high-dose chemotherapy: influence of CD34-positive peripheral-blood progenitors and growth factors on engraftment. Journal of Clinical Oncology. ,vol. 12, pp. 28- 36 ,(1994) , 10.1200/JCO.1994.12.1.28
G. Spangrude, S Heimfeld, I. Weissman, Purification and Characterization of Mouse Hematopoietic Stem Cells Science. ,vol. 241, pp. 58- 62 ,(1988) , 10.1126/SCIENCE.2898810
H. J. Sutherland, P. M. Lansdorp, D. H. Henkelman, A. C. Eaves, C. J. Eaves, Functional characterization of individual human hematopoietic stem cells cultured at limiting dilution on supportive marrow stromal layers. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 87, pp. 3584- 3588 ,(1990) , 10.1073/PNAS.87.9.3584