The Preventive Role Of Human Amniotic Mesenchymal Stem Cells (hAMSCs) In Insulitis Of Nonobese Diabetic (NOD) Mice

Objective Multipotent mesenchymal stromal cells(MSCs)exhibit migratory capacity to injured areas and may contribute to tissue regeneration by the secretion of bioactivefactors and immunomodulatory potential.Therefore,MSCs are considered as a promising approach to treat patients with different autoimmune diseases(AID),including T1D patients.Phenotypical and functional alterations of other MSCs in treatment autoimmune diabetes have been reported.However,little is known about the properties and role of MSCs derived from amnion in preventing autoimmune diabetes.Thus,the aim of the present study was to investigate the in vitro properties and the in vivo protective efficacy of MSCs isolated from human amnion in T cell-mediated autoimmune diabetes in NOD mice.Methods hAMSCs were isolated from term placenta and cultured until fourth passage.Then,morphology,expression of surface markers,differentiation potential were in vitro analyzed.Tumor formation of hAMSCs was performed in nude mice.hAMSCs protective potential was evaluated using NOD mice.Six-week-old NOD mice were randomly divided into two groups.1×10^6 hAMSCs were suspended in 0.2 mL PBS and administrated by tail vein in the preventive group,once a week for three weeks.At the same time the control group of prediabetic mice were injected with same volume PBS.Oral glucose tollerance test,islets,regulatory T cells and helper T cells were assessed at 12 week and 28 week respectively.Results hAMSCs presented similar morphology,immunophenotype,differentiation potential as other MSCs.When administered into nude mice,no neoplasm was observed.Systemic infusion of hAMCs significantly reduced the severity of insulitis of NOD mice and improved oral glucose tolerance test at 28 week.hAMSC treatment increased the pecentage of CD4+CD25+Foxp3+Tregs in pacreatic lymph node(13.93±0.35 vs 11.17±0.35,14.45±0.55 vs 11.95±0.65,p=0.026,p=0.0025)both at 12week and 28 week.Conclusions MSCs isolated from human amnion were able to alleviate insulitis of prediabtetic NOD mice,which maybe related to higher percentage of CD4+CD25+Foxp3+Tregs in pacreatic lymph node.Our results provide support for the use of hAMSCs for preventing prediabetic autoimmnue diabetes.