In Vivo Growing of New Cell Colonies in a Portion of Bone Marrow: Potential Use for Indirect Cell Therapy

The ability of bone marrow cells (BMCs) to migrate to different organs can be used for indirect cell therapy, a procedure based on the engraftment of therapeutic cells in a different place from where they will finally move to and perform their action and which could be particularly useful for chronic illness where a persistent and long-lasting therapeutic action is required. Thus, establishing a stable colony of engineered BMCs is a requisite for the chronic provision of damaged tissues with engineered cells. Reported here is a procedure for creating such a cell colony in a portion of the bone marrow (BM). The study was performed in C57BL/6j mice and consisted of developing a focal niche in a portion of the bone marrow with focal irradiation so that it could be selectively colonized by BM cells (C57BL/6-FG-VC-GFP mice) injected in the blood stream. Both the arrival of cells coming from the nonirradiated BM (week 1 after irradiation) and the proliferation of cells in the irradiated BM (week 2) prevented the homing of injected cells in the BM niche. However, when BMCs were injected in a time window about 48 h after irradiation they migrated to the BM niche where they established a cell colony able to: 1) survive for a long period of time [the percentage of injected cells increased in the BM from day 30 postinjection (15%) to day 110 postinjection 28%)]; 2) express cell differentiation markers (90% of them were lineage committed 4 weeks after engraftment); and 3) colonize to the blood stream (with 5% and 9% of all blood cells being computed 1 and 3 months after engraftment, respectively). The intravenous injection of BMCs in combination with a previous transitory focal myeloablation is a safe and easy method for creating the long-lasting colony of modified BMCs needed for treating chronic and progressive illness with indirect cell therapy.