Human mesenchymal stromal cells undergo apoptosis and fragmentation after intravenous application in immune-competent mice
| Autor: | Erhard Seifried, Reinhard Henschler, Johannes Leibacher, Veronika Brixner, Anja Vogel, Gabi Spohn, Richard Schäfer, Katrin Dauber, Sabrina Ehser, Katarina Kollar |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research Pathology medicine.medical_specialty Cell Survival Immunology Apoptosis Biology Mesenchymal Stem Cell Transplantation Flow cytometry 03 medical and health sciences chemistry.chemical_compound Annexin medicine Immunology and Allergy Animals Humans Tissue Distribution Propidium iodide Fragmentation (cell biology) Organic Chemicals Genetics (clinical) Cell Size Transplantation medicine.diagnostic_test Cluster of differentiation Mesenchymal stem cell Mesenchymal Stem Cells Cell Biology Flow Cytometry Molecular biology Mice Inbred C57BL 030104 developmental biology Oncology chemistry Injections Intravenous Heterografts Biomarkers |
| Zdroj: | Cytotherapy. 19(1) |
| ISSN: | 1477-2566 |
| Popis: | Background aims The biodistribution of human MSCs after systemic delivery is incompletely understood. We investigated the changes in cell size and cell surface markers of human MSCs after intravenous (IV) injection in immune competent mice. Methods Male human MSCs were labeled with fluorescent vital dye PKH67 and tracked after IV administration in C57/BL6 mice. MSCs were tracked in blood and different murine tissues by human SRY gene quantitative polymerase chain reaction (qPCR) analysis, flow cytometry and fluorescence microscopy. Calibrated microbeads were used to track the size of transplanted MSCs. Results The majority of injected MSCs were detected by qPCR in the lungs 5 min after transplantation, whereas + MSCs and their fragments were found in lungs and liver. PKH + MSCs rapidly became positive for annexin V, propidium iodide and calreticulin, indicating loss of cell integrity. In addition, PKH + fragments co-stained with antibodies against C3b, F4/80 and/or GR-1 indicating opsonization. Preincubation of MSCs in hyperosmolaric hydroxyethyl starch (HyperHAES) decreased MSCs size before transplantation, delayed the loss of viability markers and increased the frequency of traceable MSCs up to 24 h after transplantation. Conclusions PKH67 labeled MSCs are fragmented after IV injection in mice, acquire apoptotic and phagocytic cell markers and accumulate in the lungs and liver. |
| Databáze: | OpenAIRE |
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