Cell and Organ Transplantology. 2024; 12(2):102-109 (e2024122170)
DOI: 10.22494/cot.v12i2.170

Changes in the macrophage polarization in the kidneys of rats with acute respiratory distress syndrome after transplantation of human umbilical cord-derived mesenchymal stem cell

Palii I., Dovgalyuk A., Kramar S., Korda M.

• I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine

Abstract

Acute respiratory distress syndrome (ARDS) is a critical state of the body characterized by severe hypoxemia and multiple organ failure. One of the organs that is most often additionally affected due to the systemic inflammatory reaction that occurs in the lungs during ARDS is the kidney. It is known that mesenchymal stem cells (MSCs) can exhibit nephroprotective effects due to their anti-inflammatory and immunomodulatory abilities, but the mechanisms of such therapeutic effects require further elucidation.
The purpose is to analyze macrophage polarization in the damaged kidneys of rats with modeled ARDS following the transplantation of human umbilical cord-derived MSCs.
Materials and methods. Seventy-two sexually mature male Wistar rats were randomly divided into nine groups: intact animals, 3 days, 7 days and 28 days after ARDS modeling, control-MSC and four correction groups: 24 h ARDS + 2 days MSCs, 4 days of ARDS + 3 days of MSCs, 14 days of ARDS + 14 days of MSCs, 21 days of ARDS + 7 days of MSCs. ARDS was modeled by intranasal administration of lipopolysaccharide (LPS) at a dose of 5 mg/kg. A suspension of MSCs was obtained from the umbilical cord of a healthy donor after a normal delivery by an enzymatic method and administered intraperitoneally at a dose of 1 million cells/kg of body weight. For immunohistochemical determination of the total number of macrophages, pro-inflammatory M1 and anti-inflammatory M2 cells, monoclonal antibodies to CD68, CD86 and CD163 were used, respectively, and the percentage of visual fields occupied by the immunoprecipitate was calculated.
Results. Comparative analysis of the percentage of areas occupied by the immunoprecipitate with the corresponding antibodies showed a statistically significant increase in the total number of macrophages (3.8-fold on day 3 of ARDS, 2.8-fold on day 7 of ARDS and 2.4-fold on day 28 of ARDS, respectively), as well as a sharp increase in pro-inflammatory M1 (8.8-fold on day 3 of ARDS, 4.9-fold on day 7 of ARDS, and 4.8-fold on day 28 of ARDS, respectively) and a moderate increase in the percentage of anti-inflammatory M2 cells (1.9-fold on day 3 of ARDS, 2-fold on day 7 of ARDS, and 1.6-fold on day 28 of ARDS, respectively) in modeled ARDS compared to intact animals. This indicates the activation of the inflammatory cascade in the kidneys caused by the development of ARDS. On the other hand, in groups of animals that received MSC correction, a significant decrease, compared to untreated animals, in the total number of macrophages was detected (at 24 h of ARDS + 2 days of MSCs, it was 3.2 times lower than on day 3 of ARDS and ≥ 2 times at later times of the experiment), among which anti-inflammatory cells of the M2 phenotype predominated.
Conclusion. Transplanted human umbilical cord-derived MSCs have a pronounced immunomodulatory effect in the affected kidneys of rats with acute respiratory distress syndrome, which is manifested in their ability to change the polarization of macrophages in the anti-inflammatory direction.

Keywords: acute respiratory distress syndrome; kidney damage; mesenchymal stem cells; M1 and M2 macrophages

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