Improving the safety and function of pluripotent stem cell-derived neural transplants for the treatment of Parkinson's disease

© 2020 Isabelle Rose De LuzyClinical trials using fetal tissue have provided the necessary proof-of-principle evidence that transplanted dopamine neurons can appropriately integrate into the brain and alleviate motor symptoms in Parkinson’s disease patients for > 20 years. Pluripotent stem cells (PSCs), are now being pursued as an alternative cell source, circumventing ethical and availability issues, given their competent self-renewal and differentiation capabilities. Despite rapid progress in the field over the past decade, and recent advancement of these cells into clinical trials (Japan October 2018), we recognise a number of short-comings that require further attention. Despite the existence of efficient protocols for the directed differentiation of human PSC into ventral midbrain (VM) progenitors (i.e. cells capable of maturing into dopamine neurons and amenable to transplantation), a small proportion (10%) of cells in culture remain incorrectly specified. These cells are capable of significant expansion after transplantation, such that grafts commonly contain