Pompe disease is caused by autosomal recessive mutations in the acid alpha-glucosidase (GAA) gene, which encodes GAA. Although enzyme replacement therapy has recently improved patient survival greatly, the results in skeletal muscles and for advanced disease are still not satisfactory. Here, we report the derivation of Pompe disease-induced pluripotent stem cells (PomD-iPSCs) from two patients with different GAA mutations and their potential for pathogenesis modeling, drug testing and disease marker identification. PomD-iPSCs maintained pluripotent features and had low GAA activity and high glycogen content. Cardiomyocyte-like cells (CMLCs) differentiated from PomD-iPSCs recapitulated the hallmark Pompe disease pathophysiological phenotypes, including high levels of glycogen and multiple ultrastructural aberrances. Drug rescue assessment showed that exposure of PomD-iPSC-derived CMLCs to recombinant human GAA reversed the major pathologic phenotypes. Furthermore, l-carnitine treatment reduced defective cellular respiration in the diseased cells. By comparative transcriptome analysis, we identified glycogen metabolism, lysosome and mitochondria-related marker genes whose expression robustly correlated with the therapeutic effect of drug treatment in PomD-iPSC-derived CMLCs. Collectively, these results demonstrate that PomD-iPSCs are a promising in vitro disease model for the development of novel therapeutic strategies for Pompe disease.
We examined the lymphocytes of peripheral blood (PB) and peritoneal fluid (PF) of women with or without endometriosis to investigate the alteration of cytotoxic activity of natural killer (NK) cells and activation of T cells in the peritoneal cavity of women with endometriosis. A total of 16 control women and 14 patients with stage III-IV endometriosis were selected on the basis of laparoscopic examination in National Taiwan University Hospital. The lymphocyte subpopulations (B cell, NK cell and T cell), including T-cell activation markers (CD69, CD25, HLA-DR), in PB and PF were analysed by dual-colour flow cytometry. The NK cytotoxicity of PB and PF mononuclear cells was evaluated by 51Cr release assay. There was a significant decrease of NK cytotoxicity and CD25+ CD3+ lymphocyte subpopulation in PF of women with endometriosis compared with those without endometriosis. However, there was no difference in the proportion of NK cells in both PB and PF between women with and without endometriosis. Therefore, the decreased NK cytotoxicity in PF of women with endometriosis was due to the functional defect, but not quantitative defect, of NK cells. The concomitant reduction of activated T cells in women with endometriosis might suggest its possible role in the defect of NK cytotoxicity.
DCV is highly efficient for cryopreservation of ovarian tissue. Using less concentrated cryoprotectants appears to reduce toxicity. Direct cover by liquid nitrogen maximizes cooling that could facilitate vitrification and prevent ice crystal injury.
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