An immunomodulatory encapsulation system to deliver human iPSC-derived dopaminergic neuron progenitors for Parkinson's disease treatment†

Abstract

Parkinson's disease is a neurodegenerative condition associated with the progressive loss of dopaminergic neurons. This leads to neurological impairments with heightening severity and is globally increasing in prevalence due to population ageing. Cell transplantation has demonstrated significant promise in altering the disease course in the clinic, and stem cell-derived grafts are being investigated. Current clinical protocols involve systemic immunosuppression to prevent graft rejection, which could potentially be avoided by encapsulating the therapeutic cells in a locally immunosuppressive biomaterial matrix before delivery. Here we report the progression of an immunomodulatory encapsulation system employing ultrapure alginate hydrogel beads alongside tacrolimus-loaded microparticles in the encapsulation of dopaminergic neuron progenitors derived from human induced pluripotent stem cells (hiPSCs). The hiPSC-derived progenitors were characterised and displayed robust viability after encapsulation within alginate beads, producing dopamine as they matured in vitro. The encapsulation system effectively reduced T cell activation (3-fold) and protected progenitors from cytotoxicity in vitro. The alginate bead diameter was optimised using microfluidics to yield spherical and monodisperse hydrogels with a median size of 215.6 ± 0.5 μm, suitable for delivery to the brain through a surgical cannula. This technology has the potential to advance cell transplantation by locally protecting grafts from the host immune system.