Pro-repair properties of a human embryonic stem cell-derived astrocyte cell therapy in demyelinating disorders.

Remyelination failure in demyelinating diseases is driven by inefficient myelin debris clearance, impaired oligodendrocyte progenitor cell (OPC) differentiation into mature oligodendrocytes, and the absence of a sustained pro-repair inflammatory environment. Effective remyelination requires a pro-repair inflammatory environment that supports myelin debris removal and promotes OPC maturation. We examined whether AstroRx, a clinical-grade human embryonic stem cell (hESC)-derived astrocyte therapy, addresses these barriers. In co-cultures in-vitro, AstroRx enhanced microglial phagocytosis of myelin debris, extended lymphocyte proliferation, and survival without excessive activation, and enhanced murine and hESC-derived OPC differentiation. In a lysolecithin-induced demyelination model in-vivo, intraventricular-delivered AstroRx promoted microglial-mediated myelin debris clearance and oligodendrogenesis in the peri-lesion white matter. These findings demonstrate that AstroRx sustains a pro-repair effect via a bystander mechanism, maintaining an inflammatory milieu, facilitating myelin debris removal, and oligodendrogenesis. With demonstrated clinical safety, scalability, and multi-targeted reparative effects, AstroRx offers a promising off-the-shelf cell therapy for chronic demyelination.