title: Therapeutic potential of motor neurons differentiated from embryonic stem cells and induced pluripotent stem cells.
abstract: Degeneration of motor neurons (MN) caused by disease or injury leads to paralysis and is fatal in some conditions. To date, there are no effective treatments for MN disorders; therefore, cell therapy is a promising strategy to replace lost MN. Embryonic stem (ES) cells isolated from the inner cell mass of mammalian blastocysts self-renew and are pluripotent because they differentiate into cell types of the three germinal layers. Reprogramming of adult cells to a state similar to ES cells, termed induced pluripotent stem (iPS) cells, has been recently reported. It is well established that pluripotent cell types can give rise to specialized phenotypes, including neurons. Mouse, monkey and human MN can be differentiated from ES and iPS cells using procedures generally involving embryoid bodies formation and stimulation with retinoic acid and Sonic hedgehog. Differentiated MN express characteristic molecular markers such as Islet1, HB9 and Choline acetyltransferase, exhibit electrophysiological maturity and are able to form synaptic contacts similar to neuromuscular junctions in vitro. Furthermore, transplanted MN promote functional recovery in animal models of neurodegenerative diseases and MN injury. The potential clinical applications of stem cell-derived MN was enhanced after iPS cell derivation, which makes possible the generation of patient-specific pluripotent cells for autologous cell replacement therapies and may be used for drug development and disease modeling. This review summarizes MN differentiation protocols from ES and iPS cells in regard to neuronal differentiation efficiency, expression of MN markers and functional properties in vitro, as well as their therapeutic effects after grafting.
authors.affiliation: Instituto de Fisiología Celular-Neurociencias, Universidad Nacional Autónoma de México, DF, Mexico.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: López-González
authors.forename: Iván
authors.initials: I
authors.lastname: Velasco
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000502:physiology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000502:physiology*; D009046:Motor Neurons / Q000637:transplantation*; D019636:Neurodegenerative Diseases / Q000628:therapy*; D044968:Regenerative Medicine; D013118:Spinal Cord Diseases / Q000628:therapy; D014157:Transcription Factors / Q000494:pharmacology / Q000502:physiology
chemical_list: D014157:Transcription Factors