Alpl gene affects the therapeutic effect of bone marrow mesenchymal stem cells on ulcerative colitis

doi:10.12307/2021.006

Abstract

Abstract: BACKGROUND: Transplantation of bone marrow mesenchymal stem cells in the treatment of ulcerative colitis has achieved remarkable results, but the specific mechanism remains elusive.
OBJECTIVE: To observe and explore the role of Alpl gene in bone marrow mesenchymal stem cells on the treatment of ulcerative colitis.
METHODS: (1) Alpl+/- mice and wild-type mice were raised and bred for genotyping. (2) Bone marrow mesenchymal stem cells Alpl+/- mice and wild-type mice were cultured in vitro, and cell growth was observed. Osteoblasts induction and flow cytometry assay were performed for stem cell characterization by detecting cell surface markers. (3) Twenty-four C57BL/6 mice were randomly divided into normal group, model control group, wild-type mouse bone marrow mesenchymal stem cell treatment group, and Alpl+/- mouse bone marrow mesenchymal stem cell treatment group. The latter three groups were fed with 3% dextran sulfate sodium solution for 7 days to induce ulcerative colitis in mice. Bone marrow mesenchymal stem cells from wild-type mice and Alpl+/- mice were injected via tail vein on day 3 and day 5 after administration of dextran sulfate sodium solution. On day 10, the colon tissue was collected. (4) Daily body weight changes were recorded and disease activity index was calculated. Colon length was compared. Hematoxylin-eosin staining was used to observe and compare the histological changes of colonic mucosa.
RESULTS AND CONCLUSION: (1) The genotype identification showed that the heterozygotes were double bands, which was consistent with the prediction results provided by The Jackson Laboratory, indicating the Alpl+/- mice were successfully obtained. (2) Both groups of cells could form reddish brown osteogenic nodules, and both expressed classical mesenchymal stem cells markers CD146 and CD73. However, compared with wild-type bone marrow mesenchymal stem cells, Alpl+/- mouse bone marrow mesenchymal stem cells had various morphology and lack of long spindle cells with clear boundary. (3) Compared with the model control group, the enteritis symptoms and pathological changes of the two treatment groups were reduced, but the treatment effect of wild-type mouse bone marrow mesenchymal stem cell group was significantly better than that of Alpl+/- mouse bone marrow mesenchymal stem cell group. (4) The results suggest that bone marrow mesenchymal stem cell transplantation can treat ulcerative colitis induced by dextran sulfate sodium, and Alpl gene mutation inhibits the therapeutic effect of bone marrow mesenchymal stem cells on ulcerative colitis.

Key words: stem cells, bone marrow mesenchymal stem cells, ulcerative colitis, gene knockout, alkaline phosphatase, treatment, mice

CLC Number:

Zhang Lishu, Liu Anqi, He Xiaoning, Jin Yan, Li Bei, Jin Fang. Alpl gene affects the therapeutic effect of bone marrow mesenchymal stem cells on ulcerative colitis[J]. Chinese Journal of Tissue Engineering Research, 2021, 25(25): 3970-3975.

Figures/Tables 7

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