Mesenchymal stem cell secretome-loaded fibrin glue improves the healing of intestinal anastomosis

Wenwen Yu; Haicun Zhou; Xueliang Feng; Xiaoqin Liang; Dengwen Wei; Tianhong Xia; Bin Yang; Long Yan; Xiaochen Zhao; Hongbin Liu

doi:10.3389/fbioe.2023.1103709

Mesenchymal stem cell secretome-loaded fibrin glue improves the healing of intestinal anastomosis

Front Bioeng Biotechnol. 2023 Mar 31:11:1103709. doi: 10.3389/fbioe.2023.1103709. eCollection 2023.

Authors

Wenwen Yu¹, Haicun Zhou², Xueliang Feng¹, Xiaoqin Liang¹, Dengwen Wei³, Tianhong Xia⁴, Bin Yang⁴, Long Yan⁴, Xiaochen Zhao⁴, Hongbin Liu¹

Affiliations

¹ The Second Clinical Medical College, Lanzhou University, Lanzhou, China.
² Department of Breast Surgery, Gansu Maternal and Child Healthcare Hospital, Lanzhou, China.
³ Department of Abdominal Surgery, Gansu Provincial Cancer Hospital, Gansu Provincial Academic Institute for Medical Research, Lanzhou, China.
⁴ Key Laboratory of Stem Cells and Gene Drugs of Gansu Province, The 940th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Lanzhou, China.

Abstract

Anastomotic leakage is a serious complication following gastrointestinal surgery and one of the leading causes of patient mortality. Despite the significant clinical and economic burden, there are currently no reliable treatment options to improve the healing of intestinal anastomosis and subsequently prevent anastomotic leakage. Recently, the development of regenerative medicine has shown promise for improving anastomotic healing. Recent studies have illustrated that stem cell-derived secretome can enhance tissue regeneration without the safety and ethical limitations of stem cell transplantation. Herein, we developed a fibrin glue topical delivery system loaded with mesenchymal stem cells (MSCs)-derived secretome for controlled delivery of bioactive factors, and evaluated its application potential in improving the healing of intestinal anastomosis. Under in vitro conditions, the MSCs secretome significantly promoted cell proliferation viability in a dose-dependent manner and resulted in the controlled release of growth factors via fibrin glue delivery. We established a rat surgical anastomotic model and experimentally found that MSCs secretome-loaded fibrin glue enhanced anastomotic bursting pressure, increased granulation tissue formation and collagen deposition, and significantly promoted anastomotic healing. Mechanistically, fibrin glue accelerated cell proliferation, angiogenesis, and macrophage M2 polarization at the surgical anastomotic site by releasing bioactive factors in the secretome, and it also alleviated the inflammatory response and cell apoptosis at the anastomotic site. Our results demonstrated for the first time that MSCs-derived secretome could promote the healing of intestinal anastomosis. Considering the accessibility and safety of the cell-free secretome, we believed that secretome-loaded fibrin glue would be a cell-free therapy to accelerate the healing of intestinal anastomosis with great potential for clinical translation.

Keywords: anastomotic healing; cell-free therapy; drug delivery system; fibrin glue; regenerative medicine; stem cell secretome.

Grants and funding

This research was supported by the National Natural Science Foundation of China (No. 21772080), the Natural Science Foundation of Gansu Province (21JR1RA186, 21JR11RA173, 21JR11RA193), the Youth Science and Technology Fund Program of Gansu Province (22JR5RA1014), and the Health Industry Research Program of Gansu Province (GSWSKY 2021-043).