Comparative Study of The Effects of Confounding Factors on Improving Rat Pancreatic Islet Isolation Yield and Quality.

OBJECTIVE: Isolated pancreatic islets are valuable resources for a wide range of research, including cell replacement studies and cell-based platforms for diabetes drug discovery and disease modeling. Islet isolation is a complex and stepwise procedure aiming to obtain pure, viable, and functional islets for in vitro and in vivo studies. It should be noted that differences in rodent strains, gender, weight, and density gradients may affect the isolated islet's properties. We evaluated the variables affecting the rat islet isolation procedure to reach the maximum islet yield and functionality, which would be critical for further studies on islet regenerative biology. MATERIALS AND METHODS: The present experimental study compared the yield and purity of isolated islets from nondiabetic rats of two different strains. Next, islet particle number (IPN) and islet equivalent (IEQ) were compared between males and females, and the weight range that yields the highest number of islets was investigated. Moreover, the influence of three different density gradients, namely Histopaque, Pancoll, and Lymphodex, on final isolated islets purity and yield were assessed. Finally, the viability and functionality of isolated islets were measured. RESULTS: The IEQ, IPN, and purity of isolated islets in 15 Lister hooded rats (LHRs) were significantly (P≤0.05) higher than those of the other strains. Male LHRs resulted in significantly higher IEQ compared to females (P≤0.05). Moreover, IPN and IEQ did not significantly vary among different weight groups. Also, the utilization of Histopaque and Pancoll leads to higher yield and purity. In vivo assessments of the isolated islets presented significantly reduced blood glucose percentage in the transplanted group on days 2-5 following transplantation. CONCLUSION: Based on these results, an optimal protocol for isolating high-quality rat islets with a constant yield, purity, and function has been established as an essential platform for developing diabetes research.

Mesenchymal stem cell transplantation in newly diagnosed type-1 diabetes patients: a phase I/II randomized placebo-controlled clinical trial.

BACKGROUND: Type-1 diabetes (T1D) occurs following autoimmune-induced pancreatic beta cells death. Among several treatment modalities, mesenchymal stem cells (MSCs) transplantation is promising for autoimmune disorders due to immunomodulation, regeneration, and migration to damaged tissue upon systemic injection. This study assessed the safety and efficacy of intravenous injection of autologous bone marrow-derived MSCs in newly diagnosed T1D patients. METHODS: After receiving informed consent, 21 patients who met the study criteria were enrolled and randomly assigned to receive either MSCs or placebo. Each patient in the experimental group received two doses of MSCs and was followed for at least one-year post-transplantation. RESULTS: The results have shown that this transplantation is safe and significantly reduces the number of hypoglycemic episodes. MSCs transplantation improved glycated hemoglobin (HbA1c), shifted serum cytokine patterns from pro-inflammatory to anti-inflammatory, increased the number of regulatory T-cells in the peripheral blood, and improved quality of life. Early transplantation of MSCs significantly improved HbA1c and C-peptide levels and shifted pro-inflammatory cytokines to anti-inflammatory cytokines. Also, exercise combined with MSCs transplantation improved glycemic and immunologic indices. CONCLUSIONS: Taken together, autologous MSC transplantation is safe and effective, and its early transplantation is a promising treatment in newly diagnosed T1D children suffering from hypoglycemic episodes. TRIAL REGISTRATION: This clinical trial was registered at the Iranian Registry of Clinical Trials (IRCT) with the identifier IRCT ID: IRCT2016070428786N1 registered on August 20, 2016 (Retrospectively registered) ( https://en.irct.ir/trial/23256 ) and at the U.S. National Institutes of Health (ClinicalTrials.gov) with the related identifier NCT04078308 registered on September 6, 2019 (Retrospectively registered). ( https://clinicaltrials.gov/ct2/show/NCT04078308 ).

THERAPY OF ENDOCRINE DISEASE: Islet transplantation for type 1 diabetes: so close and yet so far away.

Over the past decades, tremendous efforts have been made to establish pancreatic islet transplantation as a standard therapy for type 1 diabetes. Recent advances in islet transplantation have resulted in steady improvements in the 5-year insulin independence rates for diabetic patients. Here we review the key challenges encountered in the islet transplantation field which include islet source limitation, sub-optimal engraftment of islets, lack of oxygen and blood supply for transplanted islets, and immune rejection of islets. Additionally, we discuss possible solutions for these challenges.