Increase in the Expression of Glucose Transporter 2 (GLUT2) on the Peripheral Blood Insulin-Producing Cells (PB-IPC) in Type 1 Diabetic Patients after Receiving Stem Cell Educator Therapy.

Multicenter international clinical trials demonstrated the clinical safety and efficacy by using stem cell educator therapy to treat type 1 diabetes (T1D) and other autoimmune diseases. Previous studies characterized the peripheral blood insulin-producing cells (PB-IPC) from healthy donors with high potential to give rise to insulin-producing cells. PB-IPC displayed the molecular marker glucose transporter 2 (GLUT2), contributing to the glucose transport and sensing. To improve the clinical efficacy of stem cell educator therapy in the restoration of islet ß-cell function, we explored the GLUT2 expression on PB-IPC in recent onset and longstanding T1D patients. In the Food and Drug Administration (FDA)-approved phase 2 clinical studies, patients received one treatment with the stem cell educator therapy. Peripheral blood mononuclear cells (PBMC) were isolated for flow cytometry analysis of PB-IPC and other immune markers before and after the treatment with stem cell educator therapy. Flow cytometry revealed that both recent onset and longstanding T1D patients displayed very low levels of GLUT2 on PB-IPC. After the treatment with stem cell educator therapy, the percentages of GLUT2+CD45RO+ PB-IPC were markedly increased in these T1D subjects. Notably, we found that T1D patients shared common clinical features with patients with other autoimmune and inflammation-associated diseases, such as displaying low or no expression of GLUT2 on PB-IPC at baseline and exhibiting a high profile of the inflammatory cytokine interleukin (IL)-1ß. Flow cytometry demonstrated that their GLUT2 expressions on PB-IPC were also markedly upregulated, and the levels of IL-1ß-positive cells were significantly downregulated after the treatment with stem cell educator therapy. Stem cell educator therapy could upregulate the GLUT2 expression on PB-IPC and restore their function in T1D patients, leading to the improvement of clinical outcomes. The clinical data advances current understanding about the molecular mechanisms underlying the stem cell educator therapy, which can be expanded to treat patients with other autoimmune and inflammation-associated diseases.

Demographic Factors Associated with Presenting for Eye Evaluation in the Partnership for Research on Vaccines and Infectious Diseases in Liberia III Natural History Study of Ebola Virus Disease.

PURPOSE: Survivors of Ebola virus disease (EVD) are at risk for ocular complications after infection. We sought to identify demographic factors associated with the likelihood to present for eye examination among Ebola survivors enrolled in a longitudinal natural history study of EVD. METHODS: The Partnership for Research on Vaccines and Infectious Diseases in Liberia (PREVAIL) III Ebola natural history study is a 5-year study that seeks to identify long-term sequelae of EVD, including ocular sequelae. All survivors enrolled in the PREVAIL parent study from June 2015 to March 2016 were asked to return for comprehensive eye examination through June 2016. Logistic regression was conducted using self-reported survivor status, age, gender, and distance from the hospital as covariates. RESULTS: A total of 1448 subjects enrolled in the parent PREVAIL III longitudinal cohort during the defined window, of which 1375 (95.0%) followed up for baseline eye examination. Ebola survivors (635/661, 96.1%) and adult close contacts (727/767, 94.8%) demonstrated a comparable likelihood for presenting for eye examination (odds ratio [OR] 0.68, 95% confidence interval [CI] 0.36-1.28). In an adjusted model, age over 50 (OR 10.2, 95% CI 1.35-77.3) and living outside Montserrado County (OR 0.18, 95% CI 0.10-0.33) were associated with the likelihood of presenting for a baseline comprehensive eye examination. CONCLUSION: Most EVD survivors and their close contacts who enrolled during the study window presented for eye examinations. Older participants and those who lived closer to clinical facilities were most likely to present. Focused strategies accounting for these factors may assist with organizations planning survivor care in the setting of EVD.