Project description:<p>The Starting Treatment with Agonist Replacement Therapy (START) study was a 24-week, open-label, randomized trial of methadone <i>versus</i> Suboxone (buprenorphine/naloxone) for the treatment of opioid dependence. Patients were over the age of 18 and met DSM-IV qualifications for opioid dependence. The primary goal of the study was to determine if either medicine was associated with liver toxicity issues in this vulnerable patient population. Liver enzymes were measured at four time points. Urinalysis for opioids, cocaine, cannabis, benzodiazepines, and methamphetamine were performed on a weekly basis. A flexible dosing scheme was used during which physicians could alter medication dose based on withdrawal symptoms and urinalysis results. Neither medication was found to be associated with liver enzyme levels.</p>
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
Project description:The generation of pancreatic organoids from human pluripotent stem cells represents a major breakthrough for regenerative medicine and the modeling of diseases such as diabetes. However, current approaches remain inefficient due to lengthy multi-step differentiation protocols and limited functional maturity in the organoids. In this study, we overcome these challenges using multi-phase optimization screens to achieve rapid generation of functionally mature pancreatic organoids from a stable endocrine progenitor culture. We conducted stepwise culture condition screens that enabled the stable culture of multiple pancreatic progenitor cell states, including the unprecedented stable propagation of NEUROD1-expressing endocrine progenitor-like cells (EpSCs). Further transcriptomic profiling of EpSC confirmed similarity of that to previously reported endocrine progenitor populations. Using EpSCs, we significantly reduced the number of steps and timing required to generate pancreatic organoids, enabling rapid testing of conditions for organoid maturation. Utilizing this optimized protocol, we further tested conditions to promote pancreatic organoid maturation. We identified that exosome-delivered WNT5B, in combination with RSPO1 (exoW/R), could strongly induce non-canonical WNT/JNK signaling, promoting pancreatic organoid maturation. This combinatorial exosome treatment enhances epithelial organization, reduces immature cell states, and significantly improves glucose responsiveness and insulin secretion. Collectively, our work establishes a robust pancreatic differentiation platform that integrates long-term progenitor expansion with optimized organoid maturation. This system provides a reproducible experimental framework for studying pancreatic development, investigating disease mechanisms, and facilitating future translational applications involving pancreatic organoids.
