HIV RESISTANT AND FUNCTIONAL HEMATOPOIETIC STEM/PROGENITOR CELLS AND MACROPHAGES FROM INDUCED PLURIPOTENT STEM CELLS

摘要

Hematopoietic stem cells (HSCs) are programmed to generate induced pluripotent stem cells (iPSCs) that express anti-HIV polynucleotides including a CCR5 shRNA and a human/rhesus chimeric TRIM5? gene and optionally a Tar decoy. Upon directed differentiation of the anti-HIV iPSCs towards the hematopoietic lineage, colonies forming CD133+ HSCs were obtained. These cells were further differentiated into functional end stage macrophages which displayed a normal phenotypic profile. Upon viral challenge in vitro and in vivo, the anti-HIV iPSC derived macrophages exhibited strong protection from HIV-1 infection and can be used for the prevention or treatment of HIV infection in patients.