Oligodendrocytes in human induced pluripotent stem cell-derived cortical grafts remyelinate adult rat and human cortical neurons

Neuronal loss and axonal demyelination underlie long-term functional impairments in patients affected by brain disorders such as ischemic stroke. Stem cell-based approaches reconstructing and remyelinating brain neural circuitry, leading to recovery, are highly warranted. Here, we demonstrate the in vitro and in vivo production of myelinating oligodendrocytes from a human induced pluripotent stem cell (iPSC)-derived long-term neuroepithelial stem (lt-NES) cell line, which also gives rise to neurons with the capacity to integrate into stroke-injured, adult rat cortical networks. Most importantly, the generated oligodendrocytes survive and form myelin-ensheathing human axons in the host tissue after grafting onto adult human cortical organotypic cultures. This lt-NES cell line is the first human stem cell source that, after intracerebral delivery, can repair both injured neural circuitries and demyelinated axons. Our findings provide supportive evidence for the potential future use of human iPSC-derived cell lines to promote effective clinical recovery following brain injuries.