MSCs derived from amniotic fluid and umbilical cord require different administration schemes and exert different curative effects on different tissues in rats with CLP-induced sepsis

Rui Chen; Yingjun Xie; Xuan Zhong; Fei Chen; Yu Gong; Na Wang; Ding Wang

doi:10.1186/s13287-021-02218-8

MSCs derived from amniotic fluid and umbilical cord require different administration schemes and exert different curative effects on different tissues in rats with CLP-induced sepsis

Stem Cell Res Ther. 2021 Mar 6;12(1):164. doi: 10.1186/s13287-021-02218-8.

Authors

Rui Chen^#^{1

2}, Yingjun Xie^#^{1

2}, Xuan Zhong^#³, Fei Chen^{1

2}, Yu Gong⁴, Na Wang⁵, Ding Wang^{6

7}

Affiliations

¹ Department of Obstetrics and Gynecology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, Guangdong, China.
² Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, Guangdong, China.
³ Medical Intensive Care Unit, Guangdong Women and Children Hospital, Guangzhou, 510150, Guangdong, China.
⁴ Central Laboratory, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, Guangdong, China.
⁵ Department of Pathology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, Guangdong, China.
⁶ Department of Obstetrics and Gynecology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, Guangdong, China. largestone_1984@163.com.
⁷ Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, Guangdong, China. largestone_1984@163.com.

^# Contributed equally.

Abstract

Background: Mesenchymal stem cells (MSCs) are derived from multiple tissues, including amniotic fluid (AF-MSCs) and the umbilical cord (UC-MSCs). Although the therapeutic effect of MSCs on sepsis is already known, researchers have not determined whether the cells from different sources require different therapeutic schedules or exert different curative effects. We assessed the biofunction of the administration of AF-MSCs and UC-MSCs in rats with caecal ligation and puncture (CLP)-induced sepsis.

Methods: CLP was used to establish a disease model of sepsis in rats, and intravenous tail vein administration of AF-MSCs and UC-MSCs was performed to treat sepsis at 6 h after CLP. Two phases of animal experiments were implemented using MSCs harvested in saline with or without filtration. The curative effect was measured by determining the survival rate. Further effects were assessed by measuring proinflammatory cytokine levels, the plasma coagulation index, tissue histology and the pathology of the lung, liver and kidney.

Results: We generated rats with medium-grade sepsis with a 30-40% survival rate to study the curative effects of AF-MSCs and UC-MSCs. MSCs reversed CLP-induced changes in proinflammatory cytokine levels and coagulation activation. MSCs ameliorated CLP-induced histological and pathological changes in the lung, liver and kidney. AF-MSCs and UC-MSCs functioned differently in different tissues; UC-MSCs performed well in reducing the upregulation of inflammatory cytokine levels in the lungs and inhibiting the inflammatory cell infiltration into the liver capsule, while AF-MSCs performed well in inhibiting cell death in the kidneys and reducing the plasma blood urea nitrogen (BUN) level, an indicator of renal function.

Conclusions: Our studies suggest the safety and efficacy of AF-MSCs and UC-MSCs in the treatment of CLP-induced sepsis in rats and show that the cells potentially exert different curative effects on the main sepsis-affected tissues.

Keywords: Amniotic fluid; Curative effect; Mesenchymal stem cells; Sepsis; Umbilical cord.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amniotic Fluid
Animals
Mesenchymal Stem Cell Transplantation*
Mesenchymal Stem Cells*
Punctures
Rats
Sepsis* / therapy
Umbilical Cord