Recombinant human thrombopoietin improves hematopoietic stem cell differentiation and T-cell immune homeostasis in patients with severe aplastic anemia by upregulating c-MPL
BackgroundRecombinant human thrombopoietin (rhTPO) regulates platelet production by promoting megakaryocyte proliferation and has shown promising therapeutic effects in hematopoietic recovery for severe aplastic anemia (SAA). However, its potential impact on immune cells remains unclear.MethodsThis...
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Frontiers Media S.A.
2025-08-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1542837/full |
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| author | Ling Deng Ling Deng Ling Deng Chenchen Liu Yiyu Guo Yiyu Guo Yiyu Guo Chunyan Liu Chunyan Liu Chunyan Liu Rong Fu Rong Fu Rong Fu |
| author_facet | Ling Deng Ling Deng Ling Deng Chenchen Liu Yiyu Guo Yiyu Guo Yiyu Guo Chunyan Liu Chunyan Liu Chunyan Liu Rong Fu Rong Fu Rong Fu |
| author_sort | Ling Deng |
| collection | DOAJ |
| description | BackgroundRecombinant human thrombopoietin (rhTPO) regulates platelet production by promoting megakaryocyte proliferation and has shown promising therapeutic effects in hematopoietic recovery for severe aplastic anemia (SAA). However, its potential impact on immune cells remains unclear.MethodsThis study included 23 patients with SAA, who were divided into two groups based on whether they received rhTPO. Flow cytometry was used to assess the proportions of peripheral immune cells and hematopoietic stem cells (HSCs), as well as their c-MPL expression. Further validation was performed by in vitro culture experiments and SAA mice.ResultsThe rhTPO group exhibited an upward trend in platelet counts (PLT), as well as a higher proportion of peripheral CD4+ T cells and an increased CD4+/CD8+ T cell ratio. The expression of the receptor of rhTPO, c-MPL, was significantly increased on CD4+ T cells and regulatory T cells (Tregs). More important is we found c-MPL expression on bone marrow CD34+ cells was unregulated in the rhTPO group. In vitro stimulation of bone marrow mononuclear cells from patients with SAA using rhTPO elevated the proportion of Tregs and the CD4+/CD8+ T cell ratio. Furthermore, CsA combined with rhTPO treatment in SAA mice significantly restored the proportion of peripheral Tregs.ConclusionrhTPO can induce the upregulation of c-MPL expression on HSCs, CD4+ T cells, and Tregs in patients with SAA. It accelerates platelet production and regulates the proliferation of CD4+ T cells and Tregs, thereby promoting immune homeostasis restoration in SAA. |
| format | Article |
| id | doaj-art-d9ed1b1ce2994793b16f22f5b70aee68 |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-d9ed1b1ce2994793b16f22f5b70aee682025-08-25T05:25:28ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-08-011610.3389/fphar.2025.15428371542837Recombinant human thrombopoietin improves hematopoietic stem cell differentiation and T-cell immune homeostasis in patients with severe aplastic anemia by upregulating c-MPLLing Deng0Ling Deng1Ling Deng2Chenchen Liu3Yiyu Guo4Yiyu Guo5Yiyu Guo6Chunyan Liu7Chunyan Liu8Chunyan Liu9Rong Fu10Rong Fu11Rong Fu12Department of Hematology, Tianjin Medical University General Hospital, Tianjin, ChinaTianjin Key Laboratory of Bone Marrow Failure and Malignant Hemopoietic Clone Control, Tianjin, ChinaTianjin Institute of Hematology, Tianjin, ChinaDepartment of Hematology, Tianjin Medical University General Hospital Airport Hospital, Tianjin, ChinaDepartment of Hematology, Tianjin Medical University General Hospital, Tianjin, ChinaTianjin Key Laboratory of Bone Marrow Failure and Malignant Hemopoietic Clone Control, Tianjin, ChinaTianjin Institute of Hematology, Tianjin, ChinaDepartment of Hematology, Tianjin Medical University General Hospital, Tianjin, ChinaTianjin Key Laboratory of Bone Marrow Failure and Malignant Hemopoietic Clone Control, Tianjin, ChinaTianjin Institute of Hematology, Tianjin, ChinaDepartment of Hematology, Tianjin Medical University General Hospital, Tianjin, ChinaTianjin Key Laboratory of Bone Marrow Failure and Malignant Hemopoietic Clone Control, Tianjin, ChinaTianjin Institute of Hematology, Tianjin, ChinaBackgroundRecombinant human thrombopoietin (rhTPO) regulates platelet production by promoting megakaryocyte proliferation and has shown promising therapeutic effects in hematopoietic recovery for severe aplastic anemia (SAA). However, its potential impact on immune cells remains unclear.MethodsThis study included 23 patients with SAA, who were divided into two groups based on whether they received rhTPO. Flow cytometry was used to assess the proportions of peripheral immune cells and hematopoietic stem cells (HSCs), as well as their c-MPL expression. Further validation was performed by in vitro culture experiments and SAA mice.ResultsThe rhTPO group exhibited an upward trend in platelet counts (PLT), as well as a higher proportion of peripheral CD4+ T cells and an increased CD4+/CD8+ T cell ratio. The expression of the receptor of rhTPO, c-MPL, was significantly increased on CD4+ T cells and regulatory T cells (Tregs). More important is we found c-MPL expression on bone marrow CD34+ cells was unregulated in the rhTPO group. In vitro stimulation of bone marrow mononuclear cells from patients with SAA using rhTPO elevated the proportion of Tregs and the CD4+/CD8+ T cell ratio. Furthermore, CsA combined with rhTPO treatment in SAA mice significantly restored the proportion of peripheral Tregs.ConclusionrhTPO can induce the upregulation of c-MPL expression on HSCs, CD4+ T cells, and Tregs in patients with SAA. It accelerates platelet production and regulates the proliferation of CD4+ T cells and Tregs, thereby promoting immune homeostasis restoration in SAA.https://www.frontiersin.org/articles/10.3389/fphar.2025.1542837/fullsevere aplastic anemiarhTPOc-MPLT-cell immune homeostasishematopoietic stem cells |
| spellingShingle | Ling Deng Ling Deng Ling Deng Chenchen Liu Yiyu Guo Yiyu Guo Yiyu Guo Chunyan Liu Chunyan Liu Chunyan Liu Rong Fu Rong Fu Rong Fu Recombinant human thrombopoietin improves hematopoietic stem cell differentiation and T-cell immune homeostasis in patients with severe aplastic anemia by upregulating c-MPL Frontiers in Pharmacology severe aplastic anemia rhTPO c-MPL T-cell immune homeostasis hematopoietic stem cells |
| title | Recombinant human thrombopoietin improves hematopoietic stem cell differentiation and T-cell immune homeostasis in patients with severe aplastic anemia by upregulating c-MPL |
| title_full | Recombinant human thrombopoietin improves hematopoietic stem cell differentiation and T-cell immune homeostasis in patients with severe aplastic anemia by upregulating c-MPL |
| title_fullStr | Recombinant human thrombopoietin improves hematopoietic stem cell differentiation and T-cell immune homeostasis in patients with severe aplastic anemia by upregulating c-MPL |
| title_full_unstemmed | Recombinant human thrombopoietin improves hematopoietic stem cell differentiation and T-cell immune homeostasis in patients with severe aplastic anemia by upregulating c-MPL |
| title_short | Recombinant human thrombopoietin improves hematopoietic stem cell differentiation and T-cell immune homeostasis in patients with severe aplastic anemia by upregulating c-MPL |
| title_sort | recombinant human thrombopoietin improves hematopoietic stem cell differentiation and t cell immune homeostasis in patients with severe aplastic anemia by upregulating c mpl |
| topic | severe aplastic anemia rhTPO c-MPL T-cell immune homeostasis hematopoietic stem cells |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1542837/full |
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