Megakaryocytopoiesis in Stem Cell Transplantation

摘要

Mobilized peripheral blood progenitor cell transplant, used to reconstitute hematopoiesis following high-dose chemotherapy in breast cancer patients, is associated with a requisite period of profound thrombocytopenia. To prevent or reduce the need for repeated platelet transfusions, we designed a preclinical study to expand sufficient numbers of megakaryocyte progenitors and differentiated MK to be used as an autologous supplement to the conventional peripheral blood autograft. Our previous results have shown that IL-3 added to thrombopoietin produced over three-fold more megakaryocytes than with TPO alone. In view of the unavailability of interleukin-3 (IL-3) for clinical use in the U. S., the use of Promegapoietin, a chimeric cytokine with dual activation of thrombopoietin and IL-3 receptors, in our earlier study appeared promising. We were able to confirm that Promegapoietin is indeed the cytokine of choice for megakaryocyte production. Using it at a concentration of 200 ng/ml in a serum- free medium enabled us to harvest 6.4 megakaryocytes per peripheral blood CD 34+ cell seeded. Bone marrow cells were twice as productive, and umbilical cord blood 8.5-fold more productive as peripheral blood. These results will enable us in a short interval of time to start a clinical trial for testing the effectiveness of autologous megakaryocyte transplants for suppertive care of breast cancer patients.