Derivation of midbrain dopamine neurons from human embryonic stem cells

• DOI: 10.1073/pnas.0404700101
• Publication Date: 2004-08-14T01:32:56Z
• Authors: Anselme L. Perrier; Viviane Tabar; Tiziano Barberi; Maria E. Rubio; Juan Bruses; Norbert Topf; Neil L. Harrison; Lorenz Studer
• Keywords: Directed differentiation

Human embryonic stem (hES) cells are defined by their extensive self-renewal capacity and potential to differentiate into any cell type of the human body. The challenge in using hES for developmental biology regenerative medicine has been direct wide differentiation toward derivation a specific fate. Within nervous system, have shown vitro neural progenitor cells, neurons, astrocytes. However, our knowledge, selective given neuron subtype not yet demonstrated. Here, we describe conditions neurons midbrain dopaminergic identity. Neuroectodermal was triggered on stromal feeder followed regional specification means sequential application patterning molecules that vivo development. Progression dopamine (DA) fate monitored expression key transcription factors, including Pax2, Pax5, engrailed-1 (En1), measurements DA release, presence tetrodotoxin-sensitive action potentials, electron-microscopic visualization tyrosinehydroxylase-positive synaptic terminals. High-yield confirmed from three independent two monkey lines. availability unlimited numbers is first step exploring preclinical models Parkinson's disease. This experimental system also provides powerful tool probe molecular mechanisms control development function neurons.