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Immunomodulatory effects of human foetal liver-derived mesenchymal stem cells
C Götherström1, O Ringdén, M Westgren
1Division of Clinical Immunology, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden.
Abstract:
Adult mesenchymal stem cells (MSCs) have been suggested to decrease lymphocyte proliferation in vitro. We hypothesised that foetal MSCs (fMSCs) would have an immunosuppressive effect on allograft responses in vitro. Human MSCs were isolated and cultured from first-trimester foetal livers and characterised by flow cytometry. fMSC stained positive for CD29, CD44, CD166, CD105, SH-3 and SH-4, and negative for CD14, CD34 and CD45. When plated on adipogenic, chondrogenic and osteogenic media, fMSC differentiated into the respective cell lineage. Compared to adult MSC (aMSC), the proliferative capacity of fMSC was higher. Mitogen stimulation of PBL was inhibited by fMSC. The greatest inhibition (78%) was seen when 30,000 fMSCs were added to 150,000 lymphocytes stimulated by phytohaemagglutinin. Adult and fMSCs were added to mixed lymphocyte cultures (MLC) containing peripheral blood lymphocytes or foetal liver cells. Unlike aMSC, fMSCs did not inhibit MLC. fMSC could be culture-expanded several million folds with no loss of phenotype characteristics, which makes them ideal for ex vivo expansion. fMSC inhibit lymphocyte proliferation induced by mitogens, but not alloreactivity as measured by MLC.
Insights
Foetal mesenchymal stem cells (fMSCs) inhibit lymphocyte proliferation from mitogen stimulation but do not suppress allograft responses in mixed lymphocyte cultures. Adult MSCs (aMSCs) showed no immunosuppressive effects in this study.
Area of Science:
- Immunology
- Stem Cell Biology
- Regenerative Medicine
Background:
- Mesenchymal stem cells (MSCs) are known for their immunosuppressive properties.
- The immunomodulatory potential of foetal MSCs (fMSCs) compared to adult MSCs (aMSCs) requires further investigation, particularly regarding allograft responses.
Purpose of the Study:
- To investigate the immunosuppressive effects of human fMSCs on lymphocyte proliferation and allograft responses in vitro.
- To compare the immunomodulatory capacity of fMSCs with adult MSCs (aMSCs).
Main Methods:
- Human fMSCs were isolated from first-trimester foetal livers and characterized using flow cytometry and differentiation assays.
- fMSCs and aMSCs were tested for their ability to inhibit mitogen-stimulated peripheral blood lymphocyte (PBL) proliferation.
- The effect of fMSCs and aMSCs on mixed lymphocyte cultures (MLC) was assessed.
Main Results:
- fMSCs exhibited higher proliferative capacity than aMSCs and maintained their phenotype after extensive culture expansion.
- fMSCs significantly inhibited mitogen-induced PBL proliferation, with up to 78% inhibition observed.
- Unlike aMSCs, fMSCs did not inhibit alloreactivity in MLC, indicating a lack of suppression against allogeneic responses.
Conclusions:
- fMSCs possess potent immunosuppressive activity against mitogen-stimulated lymphocytes but do not inhibit alloreactivity in MLC.
- The ability of fMSCs to inhibit lymphocyte proliferation makes them a promising candidate for therapeutic applications involving immune modulation.
- fMSCs' robust expansion potential and specific immunomodulatory profile warrant further research for ex vivo applications.