Introduction Globoid cell leukodystrophy (GLD) is a severe disorder of the central and peripheral nervous system caused by the absence of galactocerebrosidase (GALC) activity. and real-time PCR. The physiological effects of twitcher mice were assessed. Results Oligodendrocyte markers were expressed in OPCs and 76%?±?5.76% of the OPCs were enhanced green fluorescent protein (eGFP)-positive eGFP was driven by the Avatrombopag Olig2 promoter. The effect of psychosine on cell viability indicated that OPCs were more resistant to psychosine toxicity. The GALC level of OPCs was 10.0?±?1.23?nmol/hour per mg protein which was significantly higher than other cells. Dir-labeled OPCs were injected into the forebrain of post-natal day 10 twitcher mice. The transplanted OPCs were myelin basic protein (MBP)-positive and remained along the injection tract as observed by fluorescent microscopy. The level of the Dir fluorescent signal and eGFP mRNA significantly decreased at days Avatrombopag 10 and 20 after injection as indicated by in-Vivo Multispectral Imaging System and real-time PCR. Because of poor cell survival and limited migration ability there was no significant improvement in brain GALC activity MBP level life span body weight and behavioral deficits of twitcher mice. Conclusions ESC-derived OPC transplantation was not sufficient to reverse the clinical course of GLD in twitcher mice. Introduction Globoid cell leukodystrophy (GLD) or Krabbe disease is an autosomal recessive disease caused by the deficiency of galactocerebrosidase (GALC) activity which is usually involved in the metabolism of galactosylceramide and psychosine [1 2 Psychosine is usually a toxic metabolite that accumulates in GLD and results in degeneration and apoptosis of oligodendrocytes causing demyelination of the central nervous system (CNS) and peripheral nervous system [3]. Cell-based therapies are highly promising strategies for neurodegenerative diseases. In addition to oligodendrocyte progenitors (OPCs) Schwann cells and olfactory ensheathing cells (OECs) have been explored as donor sources for cell transplantation therapy [4-6]. The clinical application of OPCs and OECs is usually hampered by the limited access to primary cells derived from the CNS. Neural stem cells (NSCs) and oligodendroglial cell lines have been considered as option therapeutic avenues [7-9]. The isolation of these cells also requires obtaining CNS tissue. The oligodendroglial differentiation of bone marrow-derived adult stem cells has been described and by Rabbit Polyclonal to LDLRAD3. many investigators; however an unambiguous demonstration of adult stem cell differentiation into functional oligodendroglial cells has still not been established [10-12]. Embryonic stem Avatrombopag cells (ESCs) have the potential to generate cells of all three embryonic germ layers [13 14 and many studies have shown the differentiation of ESCs into various cell types [15-18] including neural lineage cells [19-22]. Because of their self-renewal capacity and pluripotency ESCs provide novel prospects for cellular alternative strategies for neural degenerative diseases including GLD. The twitcher mouse is an animal model for human GLD (Krabbe disease). Twitcher mice have a spontaneous recessive mutation of the lysosomal enzyme galactocerebroside beta-galactosidase (GALC) which blocks the catabolism of galactosylceramide (or galactocerebroside) and results in an accumulation of the cytotoxic substrate of the enzyme GALC and psychosine which causes the death of myelin-forming cells (oligodendrocytes and Schwann cells) and demyelination [23]. The twitcher mouse is considered to be a useful model for clinical trials for the treatment of Krabbe disease. In twitcher mice bone marrow transplantation has been the only therapeutic approach that significantly delays disease onset and progression and can potentially deliver the functional enzyme GALC to the CNS by macrophage/microglia replacement with donor-derived cells [24]. Previous studies have indicated that NSC/progenitor cell types engrafted in the twitcher mouse brain have therapeutic benefit in which the engrafted cells secrete the GALC enzyme. However important issues such as the long-term survival of NSCs in the toxic environment and the efficacy of NSC transplants remain controversial [25 26 In this study mice ESCs Avatrombopag were.