Regulatory T Cells Boost Efficacy of Post-Infarction Pluripotent Stem Cell-Derived Cardiovascular Progenitor Cell Transplants
Cell therapy is promising for heart failure treatment, with growing interest in cardiovascular progenitor cells (CPCs) from pluripotent stem cells. A major challenge is managing the immune response, due to their allogeneic source. Regulatory T cells (Treg) offer an alternative to pharmacological imm...
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2025-06-01
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| author | Aline Derisio de Lima Hernán Gonzalez-King Garibotti Qing-Dong Wang Cecilia Graneli Tania Incitti Valérie Bellamy Maria Eduarda Anastácio Borges Corrêa Myriam Assal Makoto Miyara Jean-Sébastien Silvestre Karin Jennbacken Philippe Menasché |
| author_facet | Aline Derisio de Lima Hernán Gonzalez-King Garibotti Qing-Dong Wang Cecilia Graneli Tania Incitti Valérie Bellamy Maria Eduarda Anastácio Borges Corrêa Myriam Assal Makoto Miyara Jean-Sébastien Silvestre Karin Jennbacken Philippe Menasché |
| author_sort | Aline Derisio de Lima |
| collection | DOAJ |
| description | Cell therapy is promising for heart failure treatment, with growing interest in cardiovascular progenitor cells (CPCs) from pluripotent stem cells. A major challenge is managing the immune response, due to their allogeneic source. Regulatory T cells (Treg) offer an alternative to pharmacological immunosuppression by inducing immune tolerance. This study assesses whether Treg therapy can mitigate the xeno-immune response, improving cardiac outcomes in a mouse model of human CPC intramyocardial transplantation. CPCs stimulated immune responses in allogeneic and xenogeneic settings, causing proliferation in T cell subsets. Tregs showed immunosuppressive effects on T lymphocyte populations when co-cultured with CPCs. Post infarction, CPCs were transplanted intramyocardially into an immune-competent mouse model 3 weeks after myocardial infarction. Human or murine Tregs were intravenously administered on transplantation day and three days later. Control groups received CPCs without Tregs or saline (PBS). CPCs with Tregs improved LV systolic function in three weeks, linked to reduced myocardial fibrosis and enhanced angiogenesis. This was accompanied by decreased splenocyte NK cell populations and pro-inflammatory cytokine levels in cardiac tissue. Treg therapy with CPC transplantation enhances cardiac functional and structural outcomes in mice. Though it does not directly avert graft rejection, it primarily affects NKG2D+ cytotoxic cells, indicating systemic immune modulation and remote heart repair benefits. |
| format | Article |
| id | doaj-art-3b4e2778b64f4bfcb1f2357c102b172b |
| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-3b4e2778b64f4bfcb1f2357c102b172b2025-08-20T03:28:25ZengMDPI AGCells2073-44092025-06-01141395610.3390/cells14130956Regulatory T Cells Boost Efficacy of Post-Infarction Pluripotent Stem Cell-Derived Cardiovascular Progenitor Cell TransplantsAline Derisio de Lima0Hernán Gonzalez-King Garibotti1Qing-Dong Wang2Cecilia Graneli3Tania Incitti4Valérie Bellamy5Maria Eduarda Anastácio Borges Corrêa6Myriam Assal7Makoto Miyara8Jean-Sébastien Silvestre9Karin Jennbacken10Philippe Menasché11Integrative Physiopathology and Therapeutics of Cardiovascular Diseases, University of Paris Cité, INSERM Unit 970, Paris Cardiovascular Research Center (PARCC), 56 Rue Leblanc, F-75015 Paris, FranceResearch and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Pepparedsleden 1, 43150 Mölndal, SwedenResearch and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Pepparedsleden 1, 43150 Mölndal, SwedenResearch and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Pepparedsleden 1, 43150 Mölndal, SwedenResearch and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Pepparedsleden 1, 43150 Mölndal, SwedenIntegrative Physiopathology and Therapeutics of Cardiovascular Diseases, University of Paris Cité, INSERM Unit 970, Paris Cardiovascular Research Center (PARCC), 56 Rue Leblanc, F-75015 Paris, FranceIntegrative Physiopathology and Therapeutics of Cardiovascular Diseases, University of Paris Cité, INSERM Unit 970, Paris Cardiovascular Research Center (PARCC), 56 Rue Leblanc, F-75015 Paris, FranceIntegrative Physiopathology and Therapeutics of Cardiovascular Diseases, University of Paris Cité, INSERM Unit 970, Paris Cardiovascular Research Center (PARCC), 56 Rue Leblanc, F-75015 Paris, FranceImmunology Department, INSERM Unit 1135, Centre d’Immunologie et des Maladies Infectieuses (CIMI), AP-HP, Sorbonne Université, Hôpital Pitié-Salpêtrière, 47-83 Bd de l’Hôpital, F-75013 Paris, FranceIntegrative Physiopathology and Therapeutics of Cardiovascular Diseases, University of Paris Cité, INSERM Unit 970, Paris Cardiovascular Research Center (PARCC), 56 Rue Leblanc, F-75015 Paris, FranceResearch and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Pepparedsleden 1, 43150 Mölndal, SwedenIntegrative Physiopathology and Therapeutics of Cardiovascular Diseases, University of Paris Cité, INSERM Unit 970, Paris Cardiovascular Research Center (PARCC), 56 Rue Leblanc, F-75015 Paris, FranceCell therapy is promising for heart failure treatment, with growing interest in cardiovascular progenitor cells (CPCs) from pluripotent stem cells. A major challenge is managing the immune response, due to their allogeneic source. Regulatory T cells (Treg) offer an alternative to pharmacological immunosuppression by inducing immune tolerance. This study assesses whether Treg therapy can mitigate the xeno-immune response, improving cardiac outcomes in a mouse model of human CPC intramyocardial transplantation. CPCs stimulated immune responses in allogeneic and xenogeneic settings, causing proliferation in T cell subsets. Tregs showed immunosuppressive effects on T lymphocyte populations when co-cultured with CPCs. Post infarction, CPCs were transplanted intramyocardially into an immune-competent mouse model 3 weeks after myocardial infarction. Human or murine Tregs were intravenously administered on transplantation day and three days later. Control groups received CPCs without Tregs or saline (PBS). CPCs with Tregs improved LV systolic function in three weeks, linked to reduced myocardial fibrosis and enhanced angiogenesis. This was accompanied by decreased splenocyte NK cell populations and pro-inflammatory cytokine levels in cardiac tissue. Treg therapy with CPC transplantation enhances cardiac functional and structural outcomes in mice. Though it does not directly avert graft rejection, it primarily affects NKG2D+ cytotoxic cells, indicating systemic immune modulation and remote heart repair benefits.https://www.mdpi.com/2073-4409/14/13/956immune tolerancecell therapymyocardial infarctionregulatory T cellscardiovascular progenitor cells |
| spellingShingle | Aline Derisio de Lima Hernán Gonzalez-King Garibotti Qing-Dong Wang Cecilia Graneli Tania Incitti Valérie Bellamy Maria Eduarda Anastácio Borges Corrêa Myriam Assal Makoto Miyara Jean-Sébastien Silvestre Karin Jennbacken Philippe Menasché Regulatory T Cells Boost Efficacy of Post-Infarction Pluripotent Stem Cell-Derived Cardiovascular Progenitor Cell Transplants Cells immune tolerance cell therapy myocardial infarction regulatory T cells cardiovascular progenitor cells |
| title | Regulatory T Cells Boost Efficacy of Post-Infarction Pluripotent Stem Cell-Derived Cardiovascular Progenitor Cell Transplants |
| title_full | Regulatory T Cells Boost Efficacy of Post-Infarction Pluripotent Stem Cell-Derived Cardiovascular Progenitor Cell Transplants |
| title_fullStr | Regulatory T Cells Boost Efficacy of Post-Infarction Pluripotent Stem Cell-Derived Cardiovascular Progenitor Cell Transplants |
| title_full_unstemmed | Regulatory T Cells Boost Efficacy of Post-Infarction Pluripotent Stem Cell-Derived Cardiovascular Progenitor Cell Transplants |
| title_short | Regulatory T Cells Boost Efficacy of Post-Infarction Pluripotent Stem Cell-Derived Cardiovascular Progenitor Cell Transplants |
| title_sort | regulatory t cells boost efficacy of post infarction pluripotent stem cell derived cardiovascular progenitor cell transplants |
| topic | immune tolerance cell therapy myocardial infarction regulatory T cells cardiovascular progenitor cells |
| url | https://www.mdpi.com/2073-4409/14/13/956 |
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