Generation of Transplantable Retinal Photoreceptors from a Current Good Manufacturing Practice-Manufactured Human Induced Pluripotent Stem Cell Line.

Retinal degeneration often results in the loss of light-sensing photoreceptors, which leads to permanent vision loss. Generating transplantable retinal photoreceptors using human somatic cell-derived induced pluripotent stem cells (iPSCs) holds promise to treat a variety of retinal degenerative diseases by replacing the damaged or dysfunctional native photoreceptors with healthy and functional ones. Establishment of effective methods to produce retinal cells including photoreceptors in chemically defined conditions using current Good Manufacturing Practice (cGMP)-manufactured human iPSC lines is critical for advancing cell replacement therapy to the clinic. In this study, we used a human iPSC line (NCL-1) derived under cGMP-compliant conditions from CD34+ cord blood cells. The cells were differentiated into retinal cells using a small molecule-based retinal induction protocol. We show that retinal cells including photoreceptors, retinal pigmented epithelial cells and optic cup-like retinal organoids can be generated from the NCL-1 iPSC line. Additionally, we show that following subretinal transplantation into immunodeficient host mouse eyes, retinal cells successfully integrated into the photoreceptor layer and developed into mature photoreceptors. This study provides strong evidence that transplantable photoreceptors can be generated from a cGMP-manufactured human iPSC line for clinical applications. Stem Cells Translational Medicine 2018;7:210-219

Ferromagnetism of anderson localized electrons: application to cluster compounds

A study of the electrical transport and magnetic properties of a series of cluster compounds with the generic formula A<SUB>0.5</SUB>M<SUB>2</SUB>X<SUB>4</SUB> suggests that the electrons at the Fermi surface are localized, and the ferromagnetism seen in these compounds arises from these electrons. The magnetism of these compounds shows some features characteristic of itinerant models and others which are characteristic of localized models. We construct a model which has a nondegenerate band of localized states with on-site repulsion. Further, the singly occupied states interact via direct exchange interaction which is ferromagnetic. Using a mean-field approximation we calculate the various magnetic properties, which are in qualitative accord with the observed behavior. In particular, we find that the single-particle excitations play a dominant role in the magnetism of these compounds, even though the electrons are localized. We also analyze the spin-wave excitations in this model and discuss their effect on low-temperature thermodynamics