The future of cell therapy

Peripheral blood has replaced bone marrow as a source of hematopoietic stem cells for autologous rescue after high-dose chemotherapy. Patients who receive peripheral blood stem cell (PBSC) transplants experience rapid and sustained hematopoietic reconstitution. As a result, transplant-related mortality is now less than 5% at many centers, and the cost of high-dose chemotherapy has decreased considerably. However, the relapse rate continues to be unacceptably high, and the collection of hematopoietic stem cells from peripheral blood is inconvenient, time consuming, and expensive. This article discusses the current status of novel technologies such as positive selection of hematopoietic stem cells, ex vivo expansion of hematopoietic progenitor cells, allogeneic PBSC transplants, and umbilical cord blood transplants. Several companies are actively developing devices that positively select hematopoietic stem cells. Because positive selection reduces the volume of infused cells, patients experience fewer adverse effects related to dimethylsulfoxide (DMSO) or lysed cells. These devices may also serve as an ex vivo method to remove ("purge") residual tumor cells. Positively selected hematopoietic stem cells may be expanded ex vivo to produce a large number of a specific population of hematopoietic cells. By adding cytokines that stimulate and activate lymphocytes, natural killer cells, and other immune effector cells, investigators could expand the number of immune effector cells with antitumor activity and then infuse them into patients as a form of adoptive immunotherapy. Finally, peripheral blood and umbilical cord blood are promising new sources of hematopoietic stem cells for allogeneic transplants.