Clinical Use of Selected and Expanded Peripheral Blood CD34+ Cells: A Preliminary Report of Feasibility and Safety

Zimmerman, Todd; Williams, Stephanie; Bender, James; Lee, Wanda J.; Blake, Martin I.; Carreón, J; Swinney, P; Smith, Stephen J.; Schilling, Marta; Oldham, Fred B.; Epps, Dennis Van; Williams, Douglas E.

doi:10.1089/scd.1.1995.4.527

Cited by 8 publications

(2 citation statements)

References 2 publications

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“…A well‐controlled, closed, and reproducible culture environment, such as that offered by stirred bioreactors, will undoubtedly prove advantageous for clinical applications, especially considering the scale involved for clinical cultures. The culture volume employed for recent clinical trials averaged about 5 L (Zimmerman et al, 1995; Williams et al, 1996). Fifty T‐150 flasks each containing 100 mL of culture medium or 20 gas‐permeable 300‐cm 2 culture bags each containing 250 mL would be necessary to accommodate this volume.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Hematopoietic Cell Expansion, Oxygen Uptake, and Glycolysis in a Controlled, Stirred-Tank Bioreactor System

et al. 1998

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Cultures of umbilical cord blood and mobilized peripheral blood mononuclear cells were carried out in a stirred bioreactor with pH and dissolved oxygen control. Expansion of total cells and colony-forming units granulocyte-macrophage was greatly enhanced by the use of a cell-dilution feeding protocol (as compared to a cell-retention feeding protocol). The specific oxygen consumption rate (qO2) for these cultures ranged from 1.7 x 10(-8) to 1.2 x 10(-7) micromol/(cell.h). The maximum in qO2 for each culture closely corresponded with the maximum percentage of progenitor or colony-forming cells (CFCs) present in the culture. The maximum qO2 values are slightly less than those reported for hybridomas, while the lowest qO2 values are somewhat greater than those reported for mature granulocytes. Examination of the ratio of lactate production to oxygen consumption in these cultures suggests that post-progenitor cells of the granulomonocytic lineage obtain a greater portion of their energy from glycolysis than do CFCs. The different metabolic profiles of CFCs and more mature cells suggest that monitoring the uptake or production of oxygen, lactate, and other metabolites will allow estimation of the content of several cell types in culture.

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Section: Introductionmentioning

confidence: 99%

Characterization of Hematopoietic Cell Expansion, Oxygen Uptake, and Glycolysis in a Controlled, Stirred-Tank Bioreactor System

et al. 1998

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“…Previous studies from several groups have documented the safety of an ex vivo expanded BM or PBPC stem cell product for transplant. [29][30][31][32] We recently demonstrated the ability to expand small volume BM MNC separated from WBM aspirates (р40 ml) using a stromal-based perfusion culture to obtain sufficient cells for successful hematopoietic engraftment following myeloablative chemotherapy in advanced stage breast cancer patients. 33 While sustained clinical engraftment requires long-term follow-up, we are encouraged by these findings.…”

Section: Discussionmentioning

confidence: 99%

Ex vivo expansion of bone marrow from breast cancer patients: reduction in tumor cell content through passive purging

Lundell

Vredenburgh

Tyer

et al. 1998

Bone Marrow Transplant

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Summary:High-dose chemotherapy (HDC) with hematopoietic support appears promising in the treatment of breast cancer, although reinfusion of contaminating tumor cells may contribute to disease relapse. Ex vivo expansion may reduce tumor cell content through use of a small inoculum volume and by passive purging during culture. We assessed the ex vivo expansion potential of tumor cell positive bone marrow (BM) from breast cancer patients and the effect of ex vivo expansion on tumor cell content. Cryopreserved/thawed mononuclear cell (C/T MNC) BM harvests with known tumor cell contamination (n = 7) were assessed for tumor cells preand post-expansion using immunocytochemical (ICC) staining. Pre-expansion inoculum samples contained a range of 6-2128 tumor cells per 5.0 × 10 6 nucleated cells. Ex vivo expansion resulted in fold expansions of 6.67 and 11.37 for total cells and CFU-GM, respectively. Tumor cells were undetectable in four of the seven postexpansion samples and were reduced in the remaining three samples. The data demonstrate passive purging of breast cancer cells during ex vivo expansion, with hematopoietic progenitor cell expansion comparable to that of normal BM. Reduction in tumor cell number contained in the small volume culture inoculum combined with passive purging during the ex vivo expansion process suggest a potential 2-4+ log reduction in tumor cell content in the reinfused cell product. Keywords: bone marrow transplantation; ex vivo expansion; tumor cell contamination Immunologic techniques have revealed tumor cell infiltration of the BM in as many as 48% of early stage breast cancer patients at the time of diagnosis. [1][2][3][4] The presence of tumor cells in the BM has been shown to be predictive of relapse in early stage 5-7 and advanced stage 8,9 breast cancer patients. In addition, the number of tumor cells identified in the BM has been correlated with shorter disease-free and overall survival. 6 Although the prognostic significance of tumor cells in PBPC collections requires further evaluation,

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Flow cytometric characterization of perfused human bone marrow cultures: Identification of the major cell lineages and correlation with the CFU‐GM assay

et al. 2003

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Background: Prolific cultures of human bone marrow mononuclear cells (BM MNCs) were recently developed that include a full spectrum of hematopoietic and accessory cells, with the presence of autofluorescent cells indicating adequate cell expansion. However, phenotypic and functional clonogenic characterizations of the autofluorescent cells and the various other subpopulations present in these cultures have not been carried out. Methods: Cells from a continuously perfused bioreactor inoculated with BM MNCs and cultured for 12 days in serum-containing medium with PIXY321, erythropoietin, and with or without FLT3-L were evaluated by using flow cytometry. Results: Two antibodies, CD71 and CD13, allowed the separation of the autofluorescent cells into two distinct populations. The CD71 ϩ CD13 ϩϩ autofluorescent population contained the colony-forming unit (CFU) fibroblast, and the CD71 ϩϩ CD13 ϩϩ autofluorescent population contained macrophage/dendritic like cells. The CFU-granulo-

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Clinical Use of Selected and Expanded Peripheral Blood CD34+ Cells: A Preliminary Report of Feasibility and Safety

Cited by 8 publications

References 2 publications

Characterization of Hematopoietic Cell Expansion, Oxygen Uptake, and Glycolysis in a Controlled, Stirred-Tank Bioreactor System

Characterization of Hematopoietic Cell Expansion, Oxygen Uptake, and Glycolysis in a Controlled, Stirred-Tank Bioreactor System

Ex vivo expansion of bone marrow from breast cancer patients: reduction in tumor cell content through passive purging

Flow cytometric characterization of perfused human bone marrow cultures: Identification of the major cell lineages and correlation with the CFU‐GM assay

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