Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Dec 30;25(1):520.
doi: 10.3390/ijms25010520.

Study of the Effect of Wild-Type and Transiently Expressing CXCR4 and IL-10 Mesenchymal Stromal Cells in a Mouse Model of Peritonitis

Soledad Garcia Gómez-Heras  1 , Mariano Garcia-Arranz  2   3 , Luz Vega-Clemente  2 , Rocio Olivera-Salazar  2 , Juan Felipe Vélez Pinto  3 , María Fernández-García  4 , Héctor Guadalajara  2   5 , Rosa Yáñez  4 , Damian Garcia-Olmo  2   3   5
Affiliations

Study of the Effect of Wild-Type and Transiently Expressing CXCR4 and IL-10 Mesenchymal Stromal Cells in a Mouse Model of Peritonitis

Soledad Garcia Gómez-Heras et al. Int J Mol Sci. .

Abstract

Sepsis due to peritonitis is a process associated with an inflammatory state. Mesenchymal stromal cells (MSCs) modulate the immune system due to the paracrine factors released and may be a therapeutic alternative. Three treatment groups were developed in a murine model of peritonitis to verify the effect of human adipose mesenchymal stem cell (hASCs). Additionally, a temporary modification was carried out on them to improve their arrival in inflamed tissues (CXCR4), as well as their anti-inflammatory activity (IL-10). The capacity to reduce systemic inflammation was studied using a local application (peritoneal injection) as a treatment route. Comparisons involving the therapeutic effect of wild-type ASCs and ASCs transiently expressing CXCR4 and IL-10 were carried out with the aim of generating an improved anti-inflammatory response for sepsis in addition to standard antibiotic treatment. However, under the experimental conditions used in these studies, no differences were found between both groups with ASCs. The peritoneal administration of hASCs or genetically modified hASCs constitutes an efficient and safe therapy in our model of mouse peritonitis.

Keywords: CXCR4; IL-10; mesenchymal stromal cells; sepsis; stem cell therapy.

PubMed Disclaimer

Conflict of interest statement

Mariano García-Arranz and Damián García-Olmo are inventors of one patent related with this study titled “Identification and isolation of multipotent cells from no osteochondral mesenchymal tissue” (WO 2006/057649). Rosa Yáñez, Maria Fernández-García, Mariano García-Arranz and Damián García-Olmo are inventors of a patent titled “Mesenchymal Stem Cells co-expressing CXCR4 and IL-10 and uses thereof”. The rest of the authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Follow-up of the animals. (A) Daily follow-up table. All columns include data at 5 and 11 days of follow-up. The minor value indicates better status in all parameters. (B) Weight evolution. (mean ± SD).
Figure 2
Figure 2
Tissue damage in the intestinal loops. (A) Macrophage population in the cecum. Percentage of macrophages M2(CD163+) with respect to the total number of macrophages(CD68+) found in the different study groups. (B) Tissue damage in the cecum layers observed in the three studied groups. (C) Tissue damage in the colon and small intestine layers. (D) Microphotographs of intestinal loops after 5 days of evolution. Hematoxylin-eosin, 400×. In the cecum of the control group, inflammatory infiltration is rather abundant, while it is milder in the cell-treated groups. In the colon and small intestine of the control group, all tissue layers are very damaged. On the other hand, in the hASCs and hASCs-MOD groups, the inflammatory infiltrate is reduced and only the outer layers (serosa and outer muscular) are affected. Yellow arrows: inflammatory infiltration.
Figure 3
Figure 3
Spleen reaction. (A) Microphotographs of spleen at day 11, hematoxylin-eosin, 100×. (1) Control group. The area of periarterial lymphatic sheath (PALS) is significantly increased. (2) In the hASCs group, there is a minimal increase in PALS dimension. (3) In the hASCs-MOD group, there is is mild increase in the size of PALS. (B) Percentage of macrophages M2 (CD163+) with respect to total macrophages (CD68+) found in the spleen in the different study groups. Yellow asterisk: PALS zone.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Chiarello M.M., Fransvea P., Cariati M., Adams N.J., Bianchi V., Brisinda G. Anastomoticleakage in colorectal cancer surgery. Surg Oncol. 2022;40:101708. doi: 10.1016/j.suronc.2022.101708. - DOI - PubMed
    1. Chiu C., Legrand M. Epidemiology of sepsis and septic shock. Curr. Opin. Anaesthesiol. 2021;34:71–76. doi: 10.1097/ACO.0000000000000958. - DOI - PubMed
    1. Griffin G., Smalley C.M., Fertel B.S., Mo K., Krizo J., Mangira C., Simon E. Reduced mortality and faster treatment in sepsis seen at freestanding vs. hospital-based emergency departments. Am. J. Emerg. Med. 2022;54:249–252. doi: 10.1016/j.ajem.2022.02.005. - DOI - PubMed
    1. Van Helsdingen C., Wildeboer A., Zafeiropoulou K., Jongen A., Bosmans J., Gallé C., Hakvoort T., Gijbels M., de Jonge W., Bouvy N., et al. Histology and transcriptome insights into the early processes of intestinal anastomotic healing: A rat model. BJS Open. 2023;7:zrad099. doi: 10.1093/bjsopen/zrad099. - DOI - PMC - PubMed
    1. Simon E., Truss K., Smalley C., Mo K., Mangira C., Krizo J., Fertel B. Improved hospital mortality rates after the implementation of emergency department sepsis teams. Am. J. Emerg. Med. 2022;51:218–222. doi: 10.1016/j.ajem.2021.10.035. - DOI - PubMed