Purging myeloma cell contaminants and simultaneous expansion of peripheral blood mobilised stem cells

Human hematopoietic stem cells (HSCs) are widely used as a cellular source for hematopoietic stem cell transplantation (HSCT) in the clinical treatment of hematological malignancies. After transplantation therapy, delays in hematopoietic recovery due to insufficient donor-derived HSCs can lead to increased risks of life-threatening infections and bleeding. Our previous studies developed an efficient ex vivo expansion culture medium (3a medium) for umbilical cord blood-derived HSCs (CBSCs), offering a potential solution to this problem. Nevertheless, the broader applicability of our culture method to alternative cell sources, and, of greater significance, its efficacy in eliminating potentially disease-associated contaminated tumor cells, especially in autologous transplantation, raises critical clinical questions. In this study, we modified the 3a medium by incorporating UM729 to replace UM171, added FLT3 ligand, and adjusted the concentrations of butyzamide, 740Y-P, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (PCL-PVAc-PEG, Soluplus^®ฎ) to create the modified 3a medium. This sophistication allowed efficient expansion of not only CBSCs but also peripheral blood mobilized HSCs (PBSCs). Additionally, we successfully removed contaminated myeloma cells by adding bortezomib and TNF-related Apoptosis inducing ligand (TRAIL) at appropriate concentrations, while maintaining HSCs through the addition of lenalidomide. Our research findings present the potential for widespread clinical application of the modified 3a medium and suggest a safe ex vivo culture technique for expanding human HSCs within peripheral blood derived donor grafts used for autologous HSCT.

Hematopoietic stem cell; expanding peripheral blood mobilized stem cells.