論文

The Musashi family is an evolutionarily conserved group of RNA-binding proteins. In mammal, two members of the group, Msi1 and Msi2, have been identified to date. Msi1 is considered to play roles in maintaining the stem cell status (stemness) of neural stem/progenitor cells in adults and in the development of central nervous system through translational regulation of its target mRNAs, which encode regulators of signal transduction and the cell cycle. Recently, strong expression of Msi1 in various somatic stem/progenitor cells of adult tissues, such as eye, gut, stomach, breast, and hair follicle, has been reported. The protein is also expressed in various cancer cells, and ectopically emerging cells have been found in neural tissues of patients with diseases involving neural disorder, including epilepsy. Many novel target mRNAs and regulatory pathways of Msi1 have been reported in recent years. Here, we present a review of the functions and action mechanisms of Msi1 protein and discuss possible directions for further study.

Embryonic stem cells (ES cells) differentiate into multiple cell lineages including neural cells. The present study optimized the method to induce differentiation of gamma-aminobutyric acid-producing neurons (GABAergic neurons) from ES cell-derived neural stem/progenitor cells (NS/PCs), and transplanted these ES cell-derived GABAergic neurons producing neural progenitors into kindled epileptic mice, and analyzed the morphological and functional recovery from epilepsy. The response of kindling was evaluated by the modified Racine scale. Following stage 5 kindling, the mice were divided into two groups. Group 1 received NS/PCs derived from the ES cells ubiquitously expressing green fluorescent protein transplanted into the dorsal hippocampal area. Group 2 received microinjections of only the medium. After transplantation, the recovery of seizures was evaluated by the modified Racine scale again. All mice were perfused and fixed for immunohistochemical analysis after finishing the kindling experiment. In Group 1, one mouse was classified as stage 0, five as stage 3, and one as stage 4 recovering from stage 5 at 6 weeks after transplantation. In Group 2, all mice remained in stage 5. The transplanted cells were examined immunohistochemically using neuronal and GABAergic markers. In the transplanted mice, substantial hippocampal GABAergic re-innervation and seizure-suppressing effects were observed. NS/PCs derived from ES cells have high potential for use in transplantation therapy for clinically intractable epilepsies.