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已发表论文
包封子宫内膜再生细胞来源外泌体的口服微胶囊促进肠上皮屏障修复并改善实验性结肠炎
Authors Yang GM, Jiang HY, Ren SH , Xu YN, Wang HD, Shao B , Chen Q, Xiao YY, Sun CL, Liu X, Ren YF, Wang H
Received 29 May 2025
Accepted for publication 8 January 2026
Published 2 February 2026 Volume 2026:21 540230
DOI https://doi.org/10.2147/IJN.S540230
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 4
Editor who approved publication: Professor Dong Wang
Guang-Mei Yang,1,2,* Hong-Yu Jiang,1,2,* Shao-Hua Ren,1– 3,* Yi-Ni Xu,1,2 Hong-Da Wang,1,2 Bo Shao,1,2 Qiang Chen,1,2 Yi-Yi Xiao,1,2 Cheng-Lu Sun,1,2 Xu Liu,1,2 Yu-Fan Ren,1,2 Hao Wang1,2,4
1Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2Tianjin General Surgery Institute, Tianjin, People’s Republic of China; 3Department of General Surgery, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, People’s Republic of China; 4Tianjin Key Laboratory of Precise Vascular Reconstruction and Organ Function Repair, Tianjin, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Hao Wang, Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, People’s Republic of China, Tel +86-22-60362502, Email hwangca272@hotmail.com; hwang1@tmu.edu.cn
Background: Endometrial regenerative cell-derived exosomes (ERC-Exos) exhibit tissue repair and anti-inflammatory properties for ulcerative colitis (UC) treatment, but oral administration is limited by gastrointestinal degradation. This study first developed chitosan-sodium alginate microcapsules (CSE) for ERC-Exos delivery and explored the role of milk fat globule-EGF factor 8 (MFGE8).
Methods: MFGE8-knockdown ERC-Exos (MFGE8−/−-ERC-Exos) were constructed via lentiviral transfection. Colitis-targeted exosomes (CSE) were prepared, and their in vivo stability and targeting ability were verified. A dextran sulfate sodium (DSS)-induced murine colitis model was used to evaluate the effects of CSE. Immunofluorescence staining was utilized to assess colon DC infiltration; Flow cytometry was employed to detect CD4⁺ T cell proliferation and dendritic cell (DC) maturation. EdU/TUNEL staining and Western blotting were performed to determine intestinal epithelial cell proliferation and apoptosis, as well as the activation level of the PI3K/AKT/mTOR pathway.
Results: CSE achieved 89.2%± 1.5% encapsulation efficiency and 78% colon-targeted release, resisting gastric degradation. Oral CSE significantly alleviated DSS-induced weight loss (P< 0.001), colon shortening (P< 0.0001), and histopathological damage, while restoring intestinal barrier function (reduced permeability, P< 0.0001; upregulated tight junction proteins ZO-1/Occludin/Claudin-1). It also inhibited DC maturation (MLN: P< 0.0001; LP: P< 0.0001) and CD4⁺T cell proliferation (MLN: P< 0.001; LP: P< 0.01), and normalized cytokine profiles (reduced IL-6/IL-1β/TNF-α, P< 0.001; increased IL-10, P< 0.0001). MFGE8 knockdown significantly attenuated these effects. Mechanistically, MFGE8 mediated ERC-Exos uptake by intestinal epithelial cells via αvβ 5 integrin, activating PI3K/AKT/mTOR to inhibit apoptosis (P< 0.0001) and promote proliferation (P< 0.0001).
Conclusion: This study is the first to confirm that the CSE carrier achieves colonic targeted release, overcoming the limitations of oral exosome delivery. MFGE8 mediates the intestinal epithelial repair effect of ERC-Exos via the PI3K/AKT/mTOR pathway.
Keywords: oral administration, ulcerative colitis, endometrial regenerative cells, exosomes, milk fat globule-EGF factor 8, intestinal barrier
1Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2Tianjin General Surgery Institute, Tianjin, People’s Republic of China; 3Department of General Surgery, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, People’s Republic of China; 4Tianjin Key Laboratory of Precise Vascular Reconstruction and Organ Function Repair, Tianjin, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Hao Wang, Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, People’s Republic of China, Tel +86-22-60362502, Email hwangca272@hotmail.com; hwang1@tmu.edu.cn
Background: Endometrial regenerative cell-derived exosomes (ERC-Exos) exhibit tissue repair and anti-inflammatory properties for ulcerative colitis (UC) treatment, but oral administration is limited by gastrointestinal degradation. This study first developed chitosan-sodium alginate microcapsules (CSE) for ERC-Exos delivery and explored the role of milk fat globule-EGF factor 8 (MFGE8).
Methods: MFGE8-knockdown ERC-Exos (MFGE8−/−-ERC-Exos) were constructed via lentiviral transfection. Colitis-targeted exosomes (CSE) were prepared, and their in vivo stability and targeting ability were verified. A dextran sulfate sodium (DSS)-induced murine colitis model was used to evaluate the effects of CSE. Immunofluorescence staining was utilized to assess colon DC infiltration; Flow cytometry was employed to detect CD4⁺ T cell proliferation and dendritic cell (DC) maturation. EdU/TUNEL staining and Western blotting were performed to determine intestinal epithelial cell proliferation and apoptosis, as well as the activation level of the PI3K/AKT/mTOR pathway.
Results: CSE achieved 89.2%± 1.5% encapsulation efficiency and 78% colon-targeted release, resisting gastric degradation. Oral CSE significantly alleviated DSS-induced weight loss (P< 0.001), colon shortening (P< 0.0001), and histopathological damage, while restoring intestinal barrier function (reduced permeability, P< 0.0001; upregulated tight junction proteins ZO-1/Occludin/Claudin-1). It also inhibited DC maturation (MLN: P< 0.0001; LP: P< 0.0001) and CD4⁺T cell proliferation (MLN: P< 0.001; LP: P< 0.01), and normalized cytokine profiles (reduced IL-6/IL-1β/TNF-α, P< 0.001; increased IL-10, P< 0.0001). MFGE8 knockdown significantly attenuated these effects. Mechanistically, MFGE8 mediated ERC-Exos uptake by intestinal epithelial cells via αvβ 5 integrin, activating PI3K/AKT/mTOR to inhibit apoptosis (P< 0.0001) and promote proliferation (P< 0.0001).
Conclusion: This study is the first to confirm that the CSE carrier achieves colonic targeted release, overcoming the limitations of oral exosome delivery. MFGE8 mediates the intestinal epithelial repair effect of ERC-Exos via the PI3K/AKT/mTOR pathway.
Keywords: oral administration, ulcerative colitis, endometrial regenerative cells, exosomes, milk fat globule-EGF factor 8, intestinal barrier