Glucose and Serum Deprivation Led to Altered Proliferation, Differentiation Potential and AMPK Activation in Stem Cells from Human Deciduous Tooth

Stem cell therapy is an evolving treatment strategy in regenerative medicine. Recent studies report stem cells from human exfoliated deciduous teeth could complement the traditional mesenchymal stem cell sources. Stem cells from human exfoliated deciduous teeth exhibit mesenchymal characteristics with multilineage differentiation potential. Mesenchymal stem cells are widely investigated for cell therapy and disease modeling. Although many research are being conducted to address the challenges of mesenchymal stem cell therapy in clinics, most of the studies are still in infancy. Host cell microenvironment is one of the major factors affecting the homing of transplanted stem cell and understanding the factors affecting the fate of stem cells of prime important. In this study we aimed to understand the effects of serum deprivation in stem cells derived from human deciduous tooth. Our study aimed to understand the morphological, transcriptional, cell cycle and stemness based changes of stem cells in nutrient deprived medium. Our results suggest that stem cells in nutrient deprived media undergo low proliferation, high apoptosis and changed the differentiation potential of the stem cells. Serum deprived mesenchymal stem cells exhibited enhanced chondrogenic differentiation potential and reduced osteogenic differentiation potential. Moreover, the activation of key metabolic sensor AMP-activated kinase (AMPK) leads to activation of transcription factors such as FOXO3, which leads to an S phase quiescence. Serum deprivation also enhanced the expression of stemness related genes Sox2 and c-Myc.

Serum deprivation-response protein induces apoptosis in hepatocellular carcinoma through ASK1-JNK/p38 MAPK pathways

Serum deprivation-response protein (SDPR), a phosphatidylserine-binding protein, which is known to have a promising role in caveolar biogenesis and morphology. However, its function in hepatocellular carcinoma (HCC) was still largely unknown. In this study, we discussed the characterization and identification of SDPR, and to present it as a novel apoptosis candidate in the incidence of HCC. We identified 81 HCC cases with lower SDPR expression in the tumor tissues with the help of qRT-PCR assay, and lower SDPR expression was potentially associated with poor prognostication. The phenotypic assays revealed that cell proliferation, invasion, and migration were profoundly connected with SDPR, both in vivo and in vitro. The data obtained from the gene set enrichment analysis (GSEA) carried out on the liver hepatocellular carcinoma (LIHC), and also The Cancer Genome Atlas (TCGA) findings indicated that SDPR was involved in apoptosis and flow cytometry experiments further confirmed this. Furthermore, we identified the interaction between SDPR and apoptosis signal-regulating kinase 1 (ASK1), which facilitated the ASK1 N-terminus-mediated dimerization and increased ASK1-mediated signaling, thereby activating the JNK/p38 mitogen-activated protein kinases (MAPKs) and finally enhanced cell apoptosis. Overall, this work identified SDPR as a tumor suppressor, because it promoted apoptosis by activating ASK1-JNK/p38 MAPK pathways in HCC.

Amniotic Membrane Extract Protects Islets From Serum-Deprivation Induced Impairments and Improves Islet Transplantation Outcome

Islet culture prior to transplantation is a standard practice in many transplantation centers. Nevertheless, the abundant islet mass loss and function impairment during this serum-deprivation culture period restrain the success of islet transplantation. In the present study, we used a natural biomaterial derived product, amniotic membrane extract (AME), as medium supplementation of islet pretransplant cultivation to investigate its protective effect on islet survival and function and its underlying mechanisms, as well as the engraftment outcome of islets following AME treatment. Results showed that AME supplementation improved islet viability and function, and decreased islet apoptosis and islet loss during serum-deprived culture. This was associated with the increased phosphorylation of PI3K/Akt and MAPK/ERK signaling pathway. Moreover, transplantation of serum-deprivation stressed islets that were pre-treated with AME into diabetic mice revealed better blood glucose control and improved islet graft survival. In conclusion, AME could improve islet survival and function in vivo and in vitro, and was at least partially through increasing phosphorylation of PI3K/Akt and MAPK/ERK signaling pathway.