The Function And Mechanism Of GC-MSC On The Induction Of Treg/Th17 Cell

Objective : To explore the immunomodulatory effect of GC-MSC in gastric cancer microenvironment, the influence of GC-MSC on the balance between Treg and Th17 cell in PBMC of healthy subject was tested which will provide important basis for further experimental studies about how GC-MSC promote the occurrence and the development of gastric cancer. Methods: GC-MSC, GCN-MSC of gastric cancer tissues and gastric cancer adjacent normal tissues of clinical patients were isolated by attachment culture and GC-MSC was authenticated by adipogenic inducing experiment, osteogenic inducing experiment and surface marker detection. To explore the influence of GC-MSC on Treg and Th17 cell in PBMC of healthy subject, ratios of Treg and Th17 cell in PBMC of healthy subject stimulated by GC-MSC-CM and cocultured with GC-MSC for 3 and 6 days were tested by flow cytometry. To test the influence of GCMSC-CM on the differentiation of Treg and Th17 cell in PBMC of healthy subject, ratios of Treg and Th17 cell in CD4~+ Na?ve T cell of healthy subject stimulated by GC-MSC-CM for 6 days were tested by flow cytometry. To explore the influence of GC-MSC on the proliferation of Treg and Th17 cell in PBMC of healthy subject, ratios of Treg and Th17 cell marked by CFSE stimulated by GC-MSC-CM for 3 and 6 days were tested by flow cytometry. Results: We successfully separated high purity GC-MSC from clinical gastric cancer tissues. After stimulared by GC-MSC-CM, the ratio of Treg cell in PBMC of healthy subject was increased and Th17 cell was reduced. After cocultured with GC-MSC the ratio of Th17 cell was significantly reduced but Treg cell was unchanged. Treg cell cloud be induced from CD4~+Na?ve T cell by GC-MSC-CM but Th17 cell cloud not. After stimulated by GC-MSC-CM, the profileration of Th17 cell in PBMC of healthy subject was reduced but Treg cell was unchanged. Conclusion:We find that GC-MSC could let the balance between Treg and Th17 in PBMC of healthy subject turn to Treg by increasing the differentiation of Treg cell and decreasing the proliferation of Th17 cell. What we find would supply important experimental evidence for futher studies of screening the key factor in the regulation of GC-MSC on Treg/Th17 cells, discussing the molecular mechanism of the regulation of GC-MSC on Treg/Th17 cells and evaluating the clinical significance of the key factor on diagnosis and prognosis of clinical gastric cancer patients.