Sema4D as an inhibitory regulator in oligodendrocyte development.

The specific functions of intrinsic regulators of OL differentiation are poorly understood. Sema4D, originally found as a negative regulator of axon guidance, is mainly expressed by oligodendrocytes in the postnatal brain, and our previous study revealed that the lack of Sema4D induced an increase in the number of oligodendrocytes in the cerebral cortex, suggesting that Sema4D may function as an intrinsic regulator of oligodendrocyte development. In this study, we assessed the effects of Sema4D deficiency and of the exogenous addition of Sema4D on oligodendrocyte differentiation. Sema4D deficiency induced an increase in the number of oligodendrocytes in the cerebral cortex at postnatal day 14 and later, without increase in the number of oligodendrocyte progenitor cells. This increase was also observed in cultured oligodendrocytes obtained from Sema4D-deficient mice. Then we investigated whether Sema4D deficiency can increase the proliferation of the progenitor cells or influence the apoptosis. Apoptotic oligodendrocytes were markedly reduced in number in the developing cerebral cortex and in cultured oligodendrocytes obtained from Sema4D-deficient mice, although no significant change was found in proliferation of oligodendrocyte progenitor cells. Exogenous addition of Sema4D prevented the oligodendrocytes from this reduction of apoptosis, and further enhanced apoptosis in oligodendrocytes. Thus, Sema4D may act as an intrinsic inhibitory regulator of oligodendrocyte differentiation by promoting apoptosis.

Synthesis and Glycan-Protein Interaction Studies of Se-Sialosides by 77Se NMR.

To expand the potential of Se-carbohydrates for multifunctional mimicry of sugars, herein we addressed the synthesis of the highly challenging and biologically significant Se-glycosides of sialic acid (Se-sialosides). An α-sialyl selenolate anion generated in situ smoothly reacted with electrophiles to give α-Se-sialosides as single stereoisomers. A Se-sialoside was sequentially incorporated with selenium, producing a triseleno-sialoside. This molecule was used as a 77Se NMR-active handle for studying glycan-protein interaction, revealing different binding profiles of sialic acid binding proteins.

The in vivo evaluation of the therapeutic potential of human adipose tissue-derived mesenchymal stem cells for acute liver disease.

Mesenchymal stem cells (MSCs) have emerged as an attractive candidate for cell therapy applications. In the prior decade, many animal studies have demonstrated that MSCs are therapeutically beneficial for the treatment of liver disease. The carbon tetrachloride (CCl4)-induced acute hepatitis model has been the most widely used model in these studies. Our group has utilized the CCl4-induced mouse hepatitis model to study the therapeutic potential of human adipose tissue-derived MSCs (hADSCs). We have demonstrated that systemically administered hADSCs engrafted into the damaged liver and promoted tissue repair. This phenomenon likely reflected the paracrine effects of the administered hADSCs. In this chapter, we describe a method to evaluate the therapeutic efficacy of the systemic administration of hADSCs in the CCl4-induced mouse model of acute hepatitis.