Neutropenic Mice Can Be Protected from Fungus Infection by Ex Vivo Expanded Allogeneic Myeloid Progenitors.

Neutropenia induced by chemotherapy, hematopoietic cell transplantation, as well as radiation-induced neutropenia is accompanied by a significant morbidity and mortality due to increased susceptibility to a variety of pathogens. Despite clinical advances, such as the availability of growth factors that can stimulate granulopoiesis, like G-CSF, and new generations of antibiotics and antifungal agents, the problem persists. Direct cellular therapy with mature granulocytes has met with limited success, and would be difficult to implement due to the large number of cells needed, their very short lifespan and the inability to store the cells between harvesting and use. Our long-term goal is to develop a non-HLA-restricted cell-based short-term bridging therapy to reduce susceptibility to infection and enhance recovery from infections in the setting of neutropenia. The recent characterization of surface marker profiles of early myeloid progenitors has allowed the prospective testing of these cells. It has been clearly shown that the use of limited numbers of a combination of Common Myeloid Progenitors (CMP) and Granulocyte-Macrophage-Progenitors (GMP), purified from bone marrow, can protect mice from a normally lethal challenge with fungus or bacteria [