Graft protection by myeloid progenitor cells using lethal or non-lethal preconditioning

Myeloid progenitor cell (MPC) therapy can protect against infection and can be used as an irradiation countermeasure, but can also prevent rejection of matched grafts. Here we report on the matching requirements between MPCs and skin grafts, and on the development of a non-lethal preconditioning model that supports MPC-induced protection of skin grafts. Mouse MPCs (mMPC) were obtained from HSC following 10-day ex vivo expansion. Skin grafts were tested in host mice that either received a lethal dose of irradiation and reconstitution with allogeneic mMPC and third party HSCs or were given injections with depleting antibodies and chemotherapeutics followed by transplantation of mMPC without HSC. mMPC-matched grafts were protected and no significant difference was observed between mice receiving irradiation and fully matched grafts (major and minor transplantation antigens), partially matched grafts (major only), and fully matched grafts in mice that received sublethal irradiation. Haploidentical grafts (half of the MHC alleles not matched at all) are not protected. We conclude that closely matched mMPCs are sufficient to prevent rejection. We also show that mMPCs are effective in a trachea transplant model. Graft protection does not require either lethal preconditioning or an accompanying HSC transplantation, and affects both T- and B-cell responses.