The synergistic immunoregulatory effects of culture-expanded mesenchymal stromal cells and CD4(+)25(+)Foxp3+ regulatory T cells on skin allograft rejection.
Mesenchymal stromal cells (MSCs) are seen as an ideal source of cells to induce graft acceptance; however, some reports have shown that MSCs can be immunogenic rather than immunosuppressive. We speculate that the immunomodulatory effects of regulatory T cells (Tregs) can aid the maintenance of immun...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3733648?pdf=render |
| _version_ | 1819265432301862912 |
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| author | Jung Ho Lee Eun-Joo Jeon Nayoun Kim Young-Sun Nam Keon-Il Im Jung-Yeon Lim Eun-Jung Kim Mi-La Cho Ki Taik Han Seok-Goo Cho |
| author_facet | Jung Ho Lee Eun-Joo Jeon Nayoun Kim Young-Sun Nam Keon-Il Im Jung-Yeon Lim Eun-Jung Kim Mi-La Cho Ki Taik Han Seok-Goo Cho |
| author_sort | Jung Ho Lee |
| collection | DOAJ |
| description | Mesenchymal stromal cells (MSCs) are seen as an ideal source of cells to induce graft acceptance; however, some reports have shown that MSCs can be immunogenic rather than immunosuppressive. We speculate that the immunomodulatory effects of regulatory T cells (Tregs) can aid the maintenance of immunoregulatory functions of MSCs, and that a combinatorial approach to cell therapy can have synergistic immunomodulatory effects on allograft rejection. After preconditioning with Fludarabine, followed by total body irradiation and anti-asialo-GM-1(ASGM-1), tail skin grafts from C57BL/6 (H-2k(b)) mice were grafted onto the lateral thoracic wall of BALB/c (H-2k(d)) mice. Group A mice (control group, n = 9) did not receive any further treatment after preconditioning, whereas groups B and C (n = 9) received cell therapy with MSCs or Tregs, respectively, on days -1, +6 and +13 relative to the skin transplantation. Group D (n = 10) received cell therapy with MSCs and Tregs on days -1, +6 and +13. Cell suspensions were obtained from the spleens of five randomly chosen mice from each group on day +7, and the immunomodulatory effects of the cell therapy were evaluated by flow cytometry and real-time PCR. Our results show that allograft survival was significantly longer in group D compared to the control group (group A). Flow cytometric analysis and real-time PCR for splenocytes revealed that the Th2 subpopulation in group D increased significantly compared to the group B. Also, the expression of Foxp3 and STAT 5 increased significantly in group D compared to the conventional cell therapy groups (B and C). Taken together, these data suggest that a combined cell therapy approach with MSCs and Tregs has a synergistic effect on immunoregulatory function in vivo, and might provide a novel strategy for improving survival in allograft transplantation. |
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| id | doaj.art-181121d264284164b23f3122058a11e5 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T20:45:17Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-181121d264284164b23f3122058a11e52022-12-21T17:31:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0188e7096810.1371/journal.pone.0070968The synergistic immunoregulatory effects of culture-expanded mesenchymal stromal cells and CD4(+)25(+)Foxp3+ regulatory T cells on skin allograft rejection.Jung Ho LeeEun-Joo JeonNayoun KimYoung-Sun NamKeon-Il ImJung-Yeon LimEun-Jung KimMi-La ChoKi Taik HanSeok-Goo ChoMesenchymal stromal cells (MSCs) are seen as an ideal source of cells to induce graft acceptance; however, some reports have shown that MSCs can be immunogenic rather than immunosuppressive. We speculate that the immunomodulatory effects of regulatory T cells (Tregs) can aid the maintenance of immunoregulatory functions of MSCs, and that a combinatorial approach to cell therapy can have synergistic immunomodulatory effects on allograft rejection. After preconditioning with Fludarabine, followed by total body irradiation and anti-asialo-GM-1(ASGM-1), tail skin grafts from C57BL/6 (H-2k(b)) mice were grafted onto the lateral thoracic wall of BALB/c (H-2k(d)) mice. Group A mice (control group, n = 9) did not receive any further treatment after preconditioning, whereas groups B and C (n = 9) received cell therapy with MSCs or Tregs, respectively, on days -1, +6 and +13 relative to the skin transplantation. Group D (n = 10) received cell therapy with MSCs and Tregs on days -1, +6 and +13. Cell suspensions were obtained from the spleens of five randomly chosen mice from each group on day +7, and the immunomodulatory effects of the cell therapy were evaluated by flow cytometry and real-time PCR. Our results show that allograft survival was significantly longer in group D compared to the control group (group A). Flow cytometric analysis and real-time PCR for splenocytes revealed that the Th2 subpopulation in group D increased significantly compared to the group B. Also, the expression of Foxp3 and STAT 5 increased significantly in group D compared to the conventional cell therapy groups (B and C). Taken together, these data suggest that a combined cell therapy approach with MSCs and Tregs has a synergistic effect on immunoregulatory function in vivo, and might provide a novel strategy for improving survival in allograft transplantation.http://europepmc.org/articles/PMC3733648?pdf=render |
| spellingShingle | Jung Ho Lee Eun-Joo Jeon Nayoun Kim Young-Sun Nam Keon-Il Im Jung-Yeon Lim Eun-Jung Kim Mi-La Cho Ki Taik Han Seok-Goo Cho The synergistic immunoregulatory effects of culture-expanded mesenchymal stromal cells and CD4(+)25(+)Foxp3+ regulatory T cells on skin allograft rejection. PLoS ONE |
| title | The synergistic immunoregulatory effects of culture-expanded mesenchymal stromal cells and CD4(+)25(+)Foxp3+ regulatory T cells on skin allograft rejection. |
| title_full | The synergistic immunoregulatory effects of culture-expanded mesenchymal stromal cells and CD4(+)25(+)Foxp3+ regulatory T cells on skin allograft rejection. |
| title_fullStr | The synergistic immunoregulatory effects of culture-expanded mesenchymal stromal cells and CD4(+)25(+)Foxp3+ regulatory T cells on skin allograft rejection. |
| title_full_unstemmed | The synergistic immunoregulatory effects of culture-expanded mesenchymal stromal cells and CD4(+)25(+)Foxp3+ regulatory T cells on skin allograft rejection. |
| title_short | The synergistic immunoregulatory effects of culture-expanded mesenchymal stromal cells and CD4(+)25(+)Foxp3+ regulatory T cells on skin allograft rejection. |
| title_sort | synergistic immunoregulatory effects of culture expanded mesenchymal stromal cells and cd4 25 foxp3 regulatory t cells on skin allograft rejection |
| url | http://europepmc.org/articles/PMC3733648?pdf=render |
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