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The kynurenine pathway (KP) of tryptophan metabolism is linked to antimicrobial activity and modulation of immune responses but its role in stem cell biology is unknown. We show that human and mouse mesenchymal and neural stem cells (MSCs and NSCs) express the complete KP, including indoleamine 2,3 dioxygenase 1 (IDO) and IDO2, that it is highly regulated by type I (IFN-β) and II interferons (IFN-γ), and that its transcriptional modulation depends on the type of interferon, cell type and species. IFN-γ inhibited proliferation and altered human and mouse MSC neural, adipocytic and osteocytic differentiation via the activation of IDO. A functional KP present in MSCs, NSCs and perhaps other stem cell types offers novel therapeutic opportunities for optimisation of stem cell proliferation and differentiation.

Background: Accumulating evidence has demonstrated that the NT2 embryonal carcinoma cell line and multipotential stem cells found in BM, mesenchymal stromal cells (MSC), have the ability to differentiate into a wide variety of cell types. This study was designed to explore the efficacy of these two human stem cell types as a graft source for the treatment of demyelinating disorders such as Krabbe's disease and multiple sclerosis (MS)., Methods: We examined the engraftment and in vivo differentiation of adult MSC and NT2 cells after transplantation into two demyelinating environments, the neonatal and postnatal twitcher mouse brain., Results: Both types of xenografts led to anatomical integration, without tumor formation, and remained viable in the normal and twitcher mouse brain, showing differentiation into neurons, astrocytes and oligodendrocytes., Discussion: This study represents a platform for further stem cell transplantation studies in the twitcher model and potentially has important therapeutic implications.