Mesenchymal stromal cells modulate unfolded protein response and preserve β-cell mass in type 1 diabetes

Abstract

Introduction: Transplantation of mesenchymal stromal cells (MSCs) is a promising therapy for type 1 diabetes (T1D). However, whether the infused MSCs affect the endoplasmic reticulum stress or subsequent unfolded protein response in β cells remains unclear. Methods: To investigate this, we induced early-onset T1D in non-obese diabetic mice using streptozotocin. Subsequently, T1D mice were randomly assigned to receive either MSCs or phosphatebuffered saline. We observed the in vivo homing of MSCs and assessed their effectiveness by analyzing blood glucose levels, body weight, histopathology, pancreatic protein expression, and serum levels of cytokines, proinsulin, and Cpeptide. Results: Infused MSCs were found in the lungs, liver, spleen, and pancreas of T1D mice. They exhibited various effects, including reducing blood glucose levels, regulating immunity, inhibiting inflammation, increasing βcell areas, and reducing the expression of key proteins in the unfolded protein response pathway. Fasting serum proinsulin and C-peptide levels were significantly higher in the MSCs treatment group than in the T1D model group.However, there was no significant difference in the biomarker of β-cell endoplasmic reticulum stress, the ratio of fasting serum proinsulin to C-peptide, between the two groups. Conclusion: Our findings reveal that MSCs infusion does not alleviate endoplasmic reticulum stress in β cells directly but modulates the unfolded protein response pathway to preserve β-cell mass and function in T1D mice.