| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Paterson, Yasmin Z Rash, Nicola Garvican, Elaine R Paillot, Romain Guest, Deborah J |
| Abstract | Introduction Autologous mesenchymal stem cells (MSCs) are an attractive concept in regenerative medicine, but their mechanism of action remains poorly defined. No immune response is reported after in vivo injection of allogeneic equine MSCs or embryo-derived stem cells (ESCs) into the equine tendon, which may be due to the cells’ immune-privileged properties. This study further investigates these properties to determine their potential for clinical application in other tissues. Methods Mitomycin C-treated MSCs, ESCs, or differentiated ESCs (dESCs) were cultured with allogeneic equine peripheral blood mononuclear cells (PBMCs), and their effect on PBMC proliferation, in the presence or absence of interferon-gamma (IFN-γ) was determined. MSCs and super-antigen (sAg)-stimulated PBMCs were co-cultured directly or indirectly in transwells, and PBMC proliferation examined. Media from MSC culture were harvested and used for PBMC culture; subsequent PBMC proliferation and gene expression were evaluated and media assayed for IFN-γ, tumor necrosis factor alpha (TNF-α), and interleukin (IL)-10 and IL-6 proteins with enzyme-linked immunosorbent assay (ELISA). Results Co-culture of PBMCs with ESCs or dESCs did not affect baseline proliferation, whereas co-culture with MSCs significantly suppressed baseline proliferation. Stimulation of PBMC proliferation by using super-antigens (sAgs) was also suppressed by co-culture with MSCs. Inhibition was greatest with direct contact, but significant inhibition was produced in transwell culture and by using MSC-conditioned media, suggesting that soluble factors play a role in MSC-mediated immune suppression. The MSCs constitutively secrete IL-6, even in the absence of co-culture with PBMCs. MSC-conditioned media also brought about a change in the cytokine-expression profile of sAg-stimulated PBMCs, significantly reducing PBMC expression of IL-6, IFN-γ, and TNF-α. Conclusions Equine MSCs and ESCs possess a degree of innate immune privilege, and MSCs secrete soluble factors that suppress PBMC proliferation and alter cytokine expression. These properties may make possible the future clinical use of allogeneic stem cells to help standardize and broaden the scope of treatment of tissue injuries. |
| Related Links | https://stemcellres.biomedcentral.com/counter/pdf/10.1186/scrt479.pdf |
| Ending Page | 13 |
| Page Count | 13 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 17576512 |
| DOI | 10.1186/scrt479 |
| Journal | Stem Cell Research & Therapy |
| Issue Number | 4 |
| Volume Number | 5 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2014-07-30 |
| Access Restriction | Open |
| Subject Keyword | Stem Cells Cell Biology Regenerative Medicine Tissue Engineering Biomedical Engineering and Bioengineering Immune Privilege Allogeneic MSCs Injured Tendon Umbilical Cord Blood Stem Cell Undifferentiated ESCs Regenerative Medicine/Tissue Engineering |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine Biochemistry, Genetics and Molecular Biology Molecular Medicine |
| Journal Impact Factor | 7.1/2023 |
| 5-Year Journal Impact Factor | 7.9/2023 |
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