Chinese Journal of Tissue Engineering Research ›› 2019, Vol. 23 ›› Issue (13): 1969-1974.doi: 10.3969/j.issn.2095-4344.1658

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Conditioned medium derived from bone marrow mesenchymal stem cells with inflammatory activation regulates inflammatory response to acute radiation-induced intestinal injury

Zheng Yue1, 2, Ma Faxin2, Li Jinliang2, Lu Quan2, Luo Yujun2, Sha Weihong1, 2, Chen Hao2   

  1. 1Second Clinical Medical College of Southern Medical University, Guangzhou 510280, Guangdong Province, China; 2Department of Gastroenterology, Guangdong General Hospital (Guangdong Academy of Medical Sciences), Guangzhou 510080, Guangdong Province, China
  • Revised:2018-12-22 Online:2019-05-08 Published:2019-05-08
  • Contact: Sha Weihong, Professor, Doctoral supervisor, Chief physician, Second Clinical Medical College of Southern Medical University, Guangzhou 510280, Guangdong Province, China; Department of Gastroenterology, Guangdong General Hospital (Guangdong Academy of Medical Sciences), Guangzhou 510080, Guangdong Province, China; Chen Hao, MD, Physician, Department of Gastroenterology, Guangdong General Hospital (Guangdong Academy of Medical Sciences), Guangzhou 510080, Guangdong Province, China
  • About author:Zheng Yue, Master candidate, Attending physician, Second Clinical Medical College of Southern Medical University, Guangzhou 510280, Guangdong Province, China; Department of Gastroenterology, Guangdong General Hospital (Guangdong Academy of Medical Sciences), Guangzhou 510080, Guangdong Province, China
  • Supported by:

    the National Natural Science Foundation of China, No. 81300279 and 81741067 (both to CH); the Natural Science Foundation of Guangdong Province, No. 2016A030313815 (to SWH) and 2017A030313464 (to CH); the Scientific Research Plan Project of Guangdong Province, No. 2015A020212029 (to CH); the Scientific Research Plan Project of Guangzhou, No. 201707010419 (to SWH) and 201804010050 (to CH)

Abstract:

BACKGROUND: Bone marrow mesenchymal stem cells (MSCs) have powerful anti-inflammatory and immunomodulatory properties. Our previous experiments have demonstrated that conditioned medium from bone marrow MSCs with inflammatory activation (MSC-CMIEC-6(IR)) could improve the structural and functional repair of the small intestine after acute radiation-induced intestinal injury, but its effects on the inflammatory response to acute radiation-induced intestinal injury have not been elucidated.
OBJECTIVE: To investigate the effects of MSC-CM on the inflammatory response to acute radiation-induced intestinal injury.
METHODS: Eighty Sprague-Dawley rats (provided by the experimental center of the North Campus of Sun Yat-Sen University in China) were randomly divided into four groups (n=20/group): control group, irradiation (IR) group, irradiation+MSC-CMIEC-6(NOR) group (IR+MSC-CMIEC-6(NOR) group) and irradiation+MSC-CMIEC-6(IR) group (IR+MSC-CMIEC-6(IR) group), followed by continuous administration via the tail vein and abdominal cavity. Intestinal tissue and serum samples were collected 1, 3, 5, 7 days after radiation for hematoxylin-eosin staining and analysis of the concentrations of inflammatory factors usingELISA. Mesenteric lymph nodes were collected 3 days after radiation for analysis of the percentage of CD4+Foxp3+Treg cells using flow cytometry.
RESULTS AND CONCLUSION: Compared with the IR group and IR+MSC-CMIEC-6(NOR) group, the intestinal structure (small intestine epithelial villi and crypt) was significantly improved and the pro-inflammatory factors such as interleukin-1β, interleukin-6 and tumor necrosis factor-α in the small intestine were significantly decreased in the IR+MSC-CMIEC-6(IR) group, whereas the level of anti-inflammatory factor interleukin-10 was significantly increased. Similarly, the levels of pro-inflammatory factors such as Activin A, interleukin-1β, interleukin-6 and tumor necrosis factor-α in the serum samples were significantly decreased and the level of anti-inflammatory factor IL-10 was significantly increased. The levels of inflammatory factors changed most significantly at 3 days after irradiation. The number of CD4+Foxp3+ Treg cells in mesenteric lymph nodes in the IR+MSC-CMIEC-6(IR) group was significantly higher than that in the control group and IR+MSC-CMIEC-6(NOR) group. These results suggest that MSC-CMIEC-6(IR) can regulate the balance of pro-inflammatory factors and anti-inflammatory factors, and increase the number of CD4+Foxp3+ Treg cells in mesenteric lymph nodes, thus inhibiting the inflammatory response at systemic and mucosal levels in acute radiation-induced intestinal injury and promoting the repair of small intestinal mucosal injury.


中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

Key words: Bone Marrow, Mesenchymal Stem Cells, Culture Media, Conditioned, Radioactivity, Intestine, Small, Inflammation, Tissue Engineering

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