Immune Effects of Mesenchymal Stromal Cells in Experimental Stroke

Scheibe, Franziska; Ladhoff, Juliane; Huck, Jojanneke H.J.; Grohmann, Maik; Blazej, Katja; Oersal, Arif; Baeva, Nevena; Seifert, Martina; Priller, Josef

doi:10.1038/jcbfm.2012.55

Cited by 44 publications

(32 citation statements)

References 37 publications

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“…Although experimental studies have proven stroke-induced immunodepression by showing decreased peripheral IL-6 production, numerous clinical studies have found that IL-6 expression actually increases after stroke in response to strong inflammatory reactions induced by ischaemic brain injury [28–30]. Our results suggest that very strong inflammatory responses occur in SAI patients which activate anti-inflammatory feedback causing increased IL-10.…”

Section: Discussionmentioning

confidence: 63%

Potential specific immunological indicators for stroke associated infection are partly modulated by sympathetic pathway activation

et al. 2016

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BackgroundEvidence has led to the consideration of immunodepression after stroke as an important contributor to stroke associated infection (SAI). However, so far no specific immunological indicator has been identified for SAI, and the underlying mechanism remains poorly understood.ResultsSAI patients had significantly higher IL-6 and IL-10 levels and lower HLA-DR levels than no-infection patients within 48h after stroke onset. NA significantly increased IL-10 levels, reduced HLA-DR expression, and decreased IL-6 expression by increasing β-arrestin2 expression which reduced the activation of the NF-κB pathway. Propranolol reversed this effect of NA by reducing β-arrestin2 expression.Materials and MethodsA systematic search for eligible clinical studies was applied to pool the differences in peripheral cytokine levels between infection and no-infection stroke patients. The underlying mechanism behind these differences was investigated in vitro by applying norepinephrine (NA) and lipopolysaccharide (LPS) to simulate sympathetic pathway activation and sepsis respectively in THP-1 cells. Propranolol was applied to determine the effect of reversing the activation of the sympathetic pathway. Immunological indicators were also detected to assess the immune activation of THP-1 cells and measurements of the expression of β-arrestin2, NF-κB, IκBα and phosphor-IκBα were performed to assess the activation of the sympathetic pathway.ConclusionIL-6, IL-10 and HLA-DR are good candidate biomarkers for SAI. The activation of the sympathetic pathway could partly account for the specific immunological alterations found in SAI patients including HLA-DR decrease and IL-10 increase, which both could be reversed by propranolol. However, the mechanism underlying IL-6 increase still needs further exploration.

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Section: Discussionmentioning

confidence: 63%

Potential specific immunological indicators for stroke associated infection are partly modulated by sympathetic pathway activation

et al. 2016

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“…Scheibe et al raised the question of possible deleterious effects of MSCs on the immune response in stroke in view of the strokeinduced immunodepression associated with cerebral ischemia, which predisposes to bacterial infections with increased mortality. Despite their immunosuppressive effects in vitro, transplantation of MSCs in mice after MCAO did not affect the serum levels of relevant inflammatory cytokines, suggesting that safety concerns for MSC transplantation in stroke are likely to be unwarranted [124].…”

Section: Ischemic Strokementioning

confidence: 92%

Mesenchymal stem cells for the treatment of neurological diseases: Immunoregulation beyond neuroprotection

2015

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“…[1][2][3][4][5] Due to their origin, bone marrow-derived stem cells are less debated from an ethical point of view than embryonic stem cells (ESCs). MSCs can differentiate into a number of mesenchymal phenotypes, including adipocytes, osteocytes, chondrocytes, and myocytes.…”

Section: Introductionmentioning

confidence: 99%

Variability in contrast agent uptake by different but similar stem cell types

Ketkar-Atre

Struys

Soenen

et al. 2013

IJN

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The need to track and evaluate the fate of transplanted cells is an important issue in regenerative medicine. In order to accomplish this, pre-labelling cells with magnetic resonance imaging (MRI) contrast agents is a well-established method. Uptake of MRI contrast agents by non-phagocytic stem cells, and factors such as cell homeostasis or the adverse effects of contrast agents on cell biology have been extensively studied, but in the context of nanoparticle (NP)-specific parameters. Here, we have studied three different types of NPs (Endorem®, magnetoliposomes [MLs], and citrate coated C-200) to label relatively larger, mesenchymal stem cells (MSCs) and, much smaller yet faster proliferating, multipotent adult progenitor cells (MAPCs). Both cell types are similar, as they are isolated from bone marrow and have substantial regenerative potential, which make them interesting candidates for comparative experiments. Using NPs with different surface coatings and sizes, we found that differences in the proliferative and morphological characteristics of the cells used in the study are mainly responsible for the fate of endocytosed iron, intracellular iron concentration, and cytotoxic responses. The quantitative analysis, using high-resolution electron microscopy images, demonstrated a strong relationship between cell volume/surface, uptake, and cytotoxicity. Interestingly, uptake and toxicity trends are reversed if intracellular concentrations, and not amounts, are considered. This indicates that more attention should be paid to cellular parameters such as cell size and proliferation rate in comparative cell-labeling studies.

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Immune Effects of Mesenchymal Stromal Cells in Experimental Stroke

Cited by 44 publications

References 37 publications

Potential specific immunological indicators for stroke associated infection are partly modulated by sympathetic pathway activation

Potential specific immunological indicators for stroke associated infection are partly modulated by sympathetic pathway activation

Mesenchymal stem cells for the treatment of neurological diseases: Immunoregulation beyond neuroprotection

Variability in contrast agent uptake by different but similar stem cell types

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