Weiss, Andreas R. R. and Lee, Olivia and Eggenhofer, Elke and Geissler, Elisabeth and Korevaar, Sander S. and Soeder, Yorick and Schlitt, Hans J. and Geissler, Edward K. and Hoogduijn, Martin J. and Dahlke, Marc H. (2020) Differential effects of heat-inactivated, secretome-deficient MSC and metabolically active MSC in sepsis and allogenic heart transplantation. STEM CELLS, 38 (6). pp. 797-807. ISSN 1066-5099, 1549-4918
Full text not available from this repository. (Request a copy)Abstract
Mesenchymal stem cells (MSCs) are used in various clinical and preclinical models for immunomodulation. However, it remains unclear how the immunomodulatory effect of MSC is communicated. MSC-induced immunomodulation is known to be mediated through both MSC-secreted cytokines and direct cell-cell interactions. Recently, it has been demonstrated that metabolically inactive, heat-inactivated MSCs (HI-MSCs) have similar anti-inflammatory capacities in LPS-induced sepsis compared with viable MSC. To further investigate the immunomodulatory effects of MSC, we introduced MSC and HI-MSC in two animal models with different immunological causes. In the first model, allogeneic hearts were transplanted from C57BL/6 mice to BALB/c recipients. MSC in combination with mycophenolate mofetil (MMF) significantly improved graft survival compared with MMF alone, whereas the application of HI-MSC had no effect on graft survival. We revealed that control MSC dose-dependently inhibited CD3(+) and CD8(+) T-cell proliferation in vitro, whereas HI-MSC had no effect. In the second model, sepsis was induced in mice via cecal ligation and puncture. HI-MSC treatment significantly improved the overall survival, whereas control MSCs had no effect. in vitro studies demonstrated that HI-MSCs are more effectively phagocytosed by monocytes than control MSCs and induced cell death in particular of activated CD16(+) monocytes, which may explain the immune protective effect of HI-MSC in the sepsis model. The results of our study demonstrate that MSC-mediated immunomodulation in sepsis is dependent on a passive recognition of MSC by monocytes, whereas fully functional MSCs are required for inhibition of T-cell-mediated allograft rejection.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MESENCHYMAL STEM-CELLS; MARROW STROMAL CELLS; PROGENITOR CELLS; ADIPOSE-TISSUE; MONOCYTES; SURVIVAL; DELIVERY; MEMORY; heat-inactivated mesenchymal stem cells; immunomodulation; mesenchymal stem cells; monocytes; organ transplantation; sepsis; T cells |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Mar 2021 12:27 |
| Last Modified: | 22 Mar 2021 12:27 |
| URI: | https://pred.uni-regensburg.de/id/eprint/44497 |
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