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The Importance of Dosing, Timing, and (in)Activation of Adipose Tissue-Derived Mesenchymal Stromal Cells on Their Immunomodulatory Effects.
- Source :
-
Stem cells and development [Stem Cells Dev] 2020 Jan 01; Vol. 29 (1), pp. 38-48. Date of Electronic Publication: 2019 Dec 09. - Publication Year :
- 2020
-
Abstract
- Mesenchymal stromal cells (MSCs) are attractive candidates for immunomodulatory cell therapy. However, it remains unknown how far therapeutic efficacy and potency are dependent on the dosage and activity of the MSCs. We previously observed that infusion of MSCs leads to rapid and transient changes in cytokine expression in blood, lung, and liver. In the present study, increasing doses of syngeneic adipose tissue-derived MSCs were infused in healthy mice and systemic changes in G-CSF, IL6, IL-10, and CXCL5 were detected 2 h after administration of 3 × 10 <superscript>5</superscript> MSCs per animal, but not at lower doses. In lung and liver tissue, dose-dependent effects of MSCs on cytokine mRNA expression levels were detected from doses as low as 3 × 10 <superscript>3</superscript> MSCs. Infusion of secretome-deficient or IFNγ-activated MSCs in healthy mice had similar effects on systemic cytokine levels as control MSCs, suggesting that in vivo at least the initial systemic effect of MSC administration is independent of the level of activity of MSCs, but depends on the response of host cells to MSCs. The results of this study reveal a rapid dose-dependent effect of MSCs and stress the important role of host cells in MSC treatment. This knowledge contributes to the design of rational MSC trials and to the quest for clinical efficacy of MSC therapy.
- Subjects :
- Animals
Cell Count
Cells, Cultured
Cytokines blood
Cytokines genetics
Cytokines metabolism
Female
Gene Expression
Humans
Interferons pharmacology
Liver metabolism
Lung metabolism
Mesenchymal Stem Cells drug effects
Mice, Inbred C57BL
Time Factors
Adipose Tissue cytology
Immunomodulation
Mesenchymal Stem Cell Transplantation methods
Mesenchymal Stem Cells cytology
Subjects
Details
- Language :
- English
- ISSN :
- 1557-8534
- Volume :
- 29
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Stem cells and development
- Publication Type :
- Academic Journal
- Accession number :
- 31696786
- Full Text :
- https://doi.org/10.1089/scd.2019.0225