Teratogenic potential in cultures optimized for oligodendrocyte development from mouse embryonic stem cells.

We describe a rapid and efficient 5-step program of defined factors for the genesis of brain myelin-forming oligodendrocytes (OLs) from embryonic stem cells (ESCs). The OLs emerge on the same time frame in vitro as seen in vivo. Factors promoting neural induction (retinoids, noggin) are required, while exogenous Sonic hedgehog is not.

Stem cell-derived therapeutic myelin repair requires 7% cell replacement.

Embryonic stem cells (ESCs) hold great potential for therapeutic regeneration and repair in many diseases. However, many challenges remain before this can be translated into effective therapy. A principal and significant limit for outcome evaluations of clinical trials is to define the minimal graft population necessary for functional repair.

From stem cells to oligodendrocytes: prospects for brain therapy.

Multiple sclerosis is an autoimmune disease that destroys myelin-forming oligodendrocytes of the CNS. While the damage can be partially controlled using anti-inflammatory cytokines and steroids, endogenous repair is insufficient to replace lost cells. Until now cell replenishment (transplant therapy) has been viewed as unlikely to succeed due to allograft rejection in this sensitized immune environment.

PDGF alpha-receptor signal strength controls an RTK rheostat that integrates phosphoinositol 3'-kinase and phospholipase Cgamma pathways during oligodendrocyte maturation.

Receptors with tyrosine kinase activity (RTKs) control tissue growth and development in metazoans. How they generate cell-specific responses remains essentially unknown; one model proposes that distinct RTKs activate different second-messenger pathways, whereas a second proposes that all RTKs deliver a generic "go" signal to these pathways that is uniquely interpreted by downstream, cell-specific response competence factors. We examine pathway activation and pathway-specific responses downstream of PDGFalpha receptors, whose expression in the developing CNS identifies oligodendrocyte progenitor cells (OPCs) and whose activation controls OPC proliferation, migration, survival, and maturation.