ABSTRACT
Gut stem cells are accessible by biopsy and propagate robustly in culture, offering an invaluable resource for autologous cell therapies. Insulin-producing cells can be induced in mouse gut, but it has not been possible to generate abundant and durable insulin-secreting cells from human gut tissues to evaluate their potential as a cell therapy for diabetes. Here we describe a protocol to differentiate cultured human gastric stem cells into pancreatic islet-like organoids containing gastric insulin-secreting (GINS) cells that resemble ß-cells in molecular hallmarks and function. Sequential activation of the inducing factors NGN3 and PDX1-MAFA led human gastric stem cells onto a distinctive differentiation path, including a SOX4High endocrine and GalaninHigh GINS precursor, before adopting ß-cell identity, at efficiencies close to 70%. GINS organoids acquired glucose-stimulated insulin secretion in 10 days and restored glucose homeostasis for over 100 days in diabetic mice after transplantation, providing proof of concept for a promising approach to treat diabetes.
Subject(s)
Diabetes Mellitus, Experimental , Insulin-Secreting Cells , Humans , Cell Differentiation/physiology , Diabetes Mellitus, Experimental/therapy , Glucose , Homeostasis , Insulin , Organoids , SOXC Transcription Factors , StomachABSTRACT
OBJECTIVES: The purpose of this prospective study was to evaluate a possible clinical benefit of LLLT in endodontic surgery. STUDY DESIGN: Seventy-two endosurgery cases on incisors and premolars were included to the study and were split randomly into an LLLT test group, a placebo group, and a control group. In the LLLT group, irradiation was performed intraoperatively and postoperatively 1, 3, and 7 days after surgery. In the placebo group, irradiation was performed without laser activation. In the control group, neither LLLT nor placebo therapy was used. Swelling, wound healing, and pain were evaluated by a blinded investigator 1, 3, and 7 days postoperatively. RESULTS: No statistically relevant differences between the LLLT and the placebo groups were found. Patients in the control group reported on statistically relevant stronger pain. CONCLUSION: In routine endodontic surgery cases, LLLT does not achieve a significant clinical benefit. Further, the results indicate a prominent placebo effect of the soft laser therapy.
