Date: Sunday, May 3, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
There is evolving interest in the use of mesenchymal stem cells (MSC) as a cell therapeutic agent after solid organ transplantation. The nature of the immunomodulatory response after MSC infusion is, however, still largely unknown. The in vitro immunomodulatory effects of MSC depend on soluble factors and membrane proteins induced on MSC by inflammatory conditions. However, recent data demonstrate that MSC have a short survival time after infusion, suggesting that the mechanisms of MSC mediated immunomodulation in vivo are different. In this study we sought to investigate whether MSCs excert their immunomodulatory effect in vivo by interaction with immune cells via cell surface molecules or via actively secreted factors.
To distinguish between effects via cell-cell contact or actively secreted factors of MSC, we killed MSC by heat inactivation (HI) at 50 °C and examined their immunophenotype and secretome. Immunomodulatory effects of HI and living MSC were evaluated in healthy and LPS induced septic mice.
FACS analysis for MSC markers showed no difference between HI and living MSC indicating that cell surface markers of MSC are still intact after HI. Measurement of cytokine titers in supernatants showed that HI successfully inactivates the secretome of MSC. After intravenous infusion of living but also HI MSC in healthy mice an increase in mRNA expression of TGF-β, IL-10 and IL-1β in the lungs was found. Systemic increases in G-CSF, MCP-1, IL-6 and CXCL1 levels were measured, indicative of an immunomodulatory effect of MSC. In LPS induced septic mice infusion of living and HI MSC both induced high serum levels of IL-10 and reduced IFN-γ compared to the PBS controls.
HI of MSC does not affect MSC cell surface epitopes but it does inactivate their secretome. Dead and living MSC induce the same immunomodulatory responses in healthy mice and reduced systemic inflammation in septic mice. These data suggest that viability of MSC is not required for the in vivo immunomodulatory effect of MSC. Understanding the immunomodulatory mechanisms of MSC treatment will contribute to the development of effective immune therapy with MSC.
To cite this abstract in AMA style:Luk F, Rhijn MRoemeling-van, Witte Sde, Korevaar S, Bruin Rde, Betjes M, Baan C, Hoogduijn M. Living and Dead Mesenchymal Stem Cells Induce an Immunosuppressive Response in an Experimental Sepsis Model [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/living-and-dead-mesenchymal-stem-cells-induce-an-immunosuppressive-response-in-an-experimental-sepsis-model/. Accessed January 28, 2021.
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