Ex-vivo expanded human blood-derived CD133+ cells promote repair of injured spinal cord

Abstract

Human blood-derived CD133+ cell populations, which are believed to represent a hematopoietic/endothelial progenitor fraction, have the ability to promote the repair of injured spinal cord in animal models. However, the mechanisms by which CD133+ cell transplantation promotes spinal cord regeneration remain to be clarified. Another possible hurdle on the way to clinical applicability of these cells is their scarce representation in the overall population of mononuclear cells. We therefore analyzed and compared ex-vivo expanded human cord blood derived CD133+ cells with freshly isolated CD133+ cells as well as corresponding CD133− control mononuclear cells in respect to their ability to promote spinal cord repair using in vitro assays and cell transplantation into a mouse spinal cord injury model. In vitro, expanded cells as well as fresh CD133+ cells formed endothelial progenitor cell (EPC) colonies, whereas CD133− cells formed no EPC colonies. In vivo, the administration of fresh CD133+ and expanded cells enhanced angiogenesis, astrogliosis, axon growth and functional recovery after injury. In contrast, the administration of CD133− cells failed to promote axon growth and functional recovery, but moderately enhanced angiogenesis and astrogliosis. In addition, high-dose administration of expanded cells was highly effective in the induction of regenerative processes at the injured spinal cord.