<abstract xmlns="http://www.w3.org/1999/xhtml">

Mesenchymal stromal cells (MSC) are nonhematopoietic cells with fibroblast-like morphology and multipotent capacity that are widely used in pre-clinical and clinical investigations. Unfortunately, the efficiency of MSC treatment is hindered by the poor survival rate after transplantation at the damaged tissue.
The goal of this study was to investigate the fate of MSC exposed to various stimuli mimicking the <italic>in vivo</italic> microenvironment post transplantation. To this aim, murine bone marrow–derived MSC were stimulated with IFNγ and TNFα under low oxygen (hypoxia) or atmospheric (normoxia) conditions for 24 to 72 hours, in order to better mimic an ischemic injury.
The results showed that MSC pre-stimulation with TNFα and IFNγ enhanced immunosuppressive pathways by over-expression of NOS2, IDO, COX2 and production of NO. However, MSC viability was affected by these two cytokines in dose-dependent and time-dependent manners. Besides, priming with TNFα and/or IFNγ under low oxygen concentrations revealed that significantly increased cell mortality rate and decreased NO production.
Our data suggest that both hypoxia and inflammation could impact the cell survival after transplantation and reinforces the necessity of further investigations to better understand MSC behavior after transplantation in order to identify the MSC-based strategies with the highest therapeutic potential.
</abstract>

Mesenchymal stromal cells (MSC) are nonhematopoietic cells with fibroblast-like morphology and multipotent capacity that are widely used in pre-clinical and clinical investigations. Unfortunately, the efficiency of MSC treatment is hindered by the poor survival rate after transplantation at the damaged tissue.
The goal of this study was to investigate the fate of MSC exposed to various stimuli mimicking the in vivo microenvironment post transplantation. To this aim, murine bone marrow–derived MSC were stimulated with IFNγ and TNFα under low oxygen (hypoxia) or atmospheric (normoxia) conditions for 24 to 72 hours, in order to better mimic an ischemic injury.
The results showed that MSC pre-stimulation with TNFα and IFNγ enhanced immunosuppressive pathways by over-expression of NOS2, IDO, COX2 and production of NO. However, MSC viability was affected by these two cytokines in dose-dependent and time-dependent manners. Besides, priming with TNFα and/or IFNγ under low oxygen concentrations revealed that significantly increased cell mortality rate and decreased NO production.
Our data suggest that both hypoxia and inflammation could impact the cell survival after transplantation and reinforces the necessity of further investigations to better understand MSC behavior after transplantation in order to identify the MSC-based strategies with the highest therapeutic potential.

Inflammation and Hypoxia Negatively Impact the Survival and Immunosuppressive Properties of Mesenchymal Stromal Cells <italic>In Vitro</italic>

„Nicolae Simionescu” Institute of Cellular Biology and Pathology

Romanian Journal of Cardiology

This work is licensed under the Creative Commons Attribution 4.0 International License.

Inflammation and Hypoxia Negatively Impact the Survival and Immunosuppressive Properties of Mesenchymal Stromal Cells 

Mesenchymal stromal cells (MSC) are nonhematopoietic cells with fibroblast-like morphology and multipotent capacity that are widely used in pre-clinical and...

Inflammation and Hypoxia Negatively Impact the Survival and Immunosuppressive Properties of Mesenchymal Stromal Cells In Vitro

Article Category: Original Article

Online veröffentlicht: 05. Mai 2022

Seitenbereich: 547 - 554

DOI: https://doi.org/10.47803/rjc.2021.31.3.547

Schlüsselwörter
Mesenchymal stromal cells, hypoxia, inflammation, ischemic injury

© 2021 Carmen Alexandra Neculachi et al., published by Sciendo

This work is licensed under the Creative Commons Attribution 4.0 International License.

Inflammation and Hypoxia Negatively Impact the Survival and Immunosuppressive Properties of Mesenchymal Stromal Cells In Vitro

Article Category: Original Article

Online veröffentlicht: 05. Mai 2022

Seitenbereich: 547 - 554

DOI: https://doi.org/10.47803/rjc.2021.31.3.547

SchlüsselwörterMesenchymal stromal cells, hypoxia, inflammation, ischemic injury

© 2021 Carmen Alexandra Neculachi et al., published by Sciendo

This work is licensed under the Creative Commons Attribution 4.0 International License.

Schlüsselwörter
Mesenchymal stromal cells, hypoxia, inflammation, ischemic injury