Our long term goal is to develop a cell-based therapy containing human myeloid progenitor cells to enhance resistance to pathogens and recovery from infections after hematopoietic cell transplantation or chemotherapy. In our preclinical models, a single infusion of Common Myeloid Progenitors and Granulocyte/Macrophage Progenitors, offers protection from lethal challenges of Aspergillus and Pseudomonas during hematopoietic cell transplantation induced neutropenia. We will test whether human myeloid progenitors isolated from mobilized peripheral blood, umbilical cord blood, and bone marrow have similar or dissimilar differentiation and especially proliferation capabilities. This will be important in determining the eventual source of progenitors for clinical use. It will be necessary to define the progenitor populations in mobilized peripheral blood, as the staining patterns differ. In addition, using preclinical models, we will determine whether in vitro expanded and differentiated myeloid progenitor cells, the targeted cell source for clinical use, provide similar protection and whether administration of G-CSF or GM-CSF can enhance protection. To define the test conditions, we will first determine the minimum effective dose of bone marrow-derived progenitors. The second phase of this SBIR will include optimizing ex vivo expansion conditions and testing whether human cells can provide protection from infection in an immunodeficient mouse model.
| Domen, Jos; Christensen, Julie L; Gille, Daphne et al. (2016) Cryopreserved Ex Vivo-Expanded Allogeneic Myeloid Progenitor Cell Product Protects Neutropenic Mice From a Lethal Fungal Infection. Cell Transplant 25:17-33 |
