Production of human hematopoietic progenitors in a clinical-scale stirred suspension bioreactor

Abstract

Ex vivo expanded primitive hematopoietic cells can be utilized in bone marrow transplantation therapies to treat patients suffering from various cancers and hematopoietic malignancies. A high initial cell density (10(6) cells/mL) and the supplement of soluble factors secreted by stromal feeders in combination with growth-promoting (interleukin-3 and stem cell factor) and growth-inhibiting (macrophage-inflammatory protein-1 alpha) cytokines resulted in high, long-term expansions (17-fold over a 14-day culture period) of human hematopoietic progenitors in a stirred suspension bioreactor. This study demonstrated that a transplantable dosage of human hematopoietic progenitor cells (8.1 +/- 1.3 x 10(6) colony forming unit-granulocyte/macrophage) can be generated from approximately 10 mL of bone marrow aspirate in a 14-day culture using a 250 mL suspension bioreactor system.