Human CD34 ⁺ cells differentiate into microglia and express recombinant therapeutic protein

In rodents, bone marrow-derived cells enter the brain during adult life. Allogeneic bone marrow transplantation is used to treat genetic CNS diseases, but the fate of human bone marrow and CD34(+) cells within the brain remains to be elucidated. The present study demonstrates that cells derived from human CD34(+) cells, isolated from either cord blood or peripheral blood, migrate into the brain after infusion into nonobese diabetic/severe combined immunodeficient mice. Both types of CD34(+)-derived cells differentiate into perivascular and ramified microglia. The lentiviral transfer of genes into CD34(+) cells before infusion does not modify the differentiation of human CD34(+) cells into microglia, allowing new transgenic proteins to be expressed in these cells. The transplantation of CD34(+) cells could thus be used for the treatment of CNS diseases.