Regeneration of Brain and Dopaminergic Neurons Utilizing Pluripotent Stem Cells: Lessons from Planarians

Abstract

Cell-transplantation therapy for Parkinson’s disease is close to becoming a reality thanks to the recent development of methods for the differentiation of dopaminergic neurons and/or dopaminergic progenitor cells from embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) under in vitro conditions (Kawasaki et al., 2000, Perrier et al., 2004). There have been several reports concerning pre-clinical trial research for cell-transplantation therapy for Parkinson’s disease with dopaminergic progenitor cells derived from either ESCs or iPSCs using rodent and non-human primate disease models before clinical trial (Bjorklund et al., 2002; Takagi et al., 2005; Wernig et al., 2008). Many researchers have contributed to improve the technology to create more efficient differentiation methods of donor cells for clinical applications (Chambers et al., 2009; Morizane et al., 2011). However, we still need to overcome many problems before such technology can be used in clinical settings. Even if we succeed in obtaining an optimized donor cell population for celltransplantation, the rate of success of the transplantation may depend not only on the quality of donor cells but also on the host brain environment. One important issue is how to integrate dopaminergic neurons or dopaminergic progenitor cells into target regions after transplantation. However, we do not know what kind of donor cells will be efficiently integrated into the neural networks of the host brain. Also, we do not know whether fully differentiated neurons will really survive in the host brain. In addition, we need to know what state of the host brain environment will allow the participation of donor cells in the neural networks of the host brain. In order to solve such problems, planarians provide unique opportunities because they show robust regenerative ability based on their pluripotent stem cell system.