Your new experience awaits. Try the new design now and help us make it even better

BRIEF RESEARCH REPORT article

Front. Pharmacol.

Sec. Drugs Outcomes Research and Policies

Volume 16 - 2025 | doi: 10.3389/fphar.2025.1542837

This article is part of the Research TopicBone Marrow Failure Syndromes: From Biology to Cure - Volume IIView all articles

Recombinant human thrombopoietin improves hematopoietic stem cell differentiation and T-cell immune homeostasis in patients with severe aplastic anemia by upregulating c-MPL

Provisionally accepted
Ling  DengLing Deng1Chenchen  LiuChenchen Liu2Yiyu  GuoYiyu Guo1Chunyan  LiuChunyan Liu1*Rong  FuRong Fu1*
  • 1Department of Hematology, Tianjin Medical University General Hospital, Tianjin, China
  • 2Department of Respiratory, Tianjin Medical University General Hospital Airport Hospital, Tianjin, China

The final, formatted version of the article will be published soon.

Background: Recombinant 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. Methods: This 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. Results: The 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. Conclusion: rhTPO 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.

Keywords: Severe aplastic anemia, RhTPO, C-mpl, T-cell immune homeostasis, hematopoietic stem cell

Received: 10 Dec 2024; Accepted: 01 Aug 2025.

Copyright: © 2025 Deng, Liu, Guo, Liu and Fu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Chunyan Liu, Department of Hematology, Tianjin Medical University General Hospital, Tianjin, 300052, China
Rong Fu, Department of Hematology, Tianjin Medical University General Hospital, Tianjin, 300052, China

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.