Adoptive Transfer of Treg Cells Combined with Mesenchymal Stem Cells Facilitates Repopulation of Endogenous Treg Cells in a Murine Acute GVHD Model
Open accessAbstract
Therapeutic effects of combined cell therapy with mesenchymal stem cells (MSCs) and regulatory T cells (Treg cells) have recently been studied in acute graft-versus-host-disease (aGVHD) models. However, the underlying, seemingly synergistic mechanism behind combined cell therapy has not been determined. We investigated the origin of Foxp3+ Treg cells and interleukin 17 (IL-17+) cells in recipients following allogeneic bone marrow transplantation (allo-BMT) to identify the immunological effects of combined cell therapy. Treg cells were generated from eGFP-expressing C57BL/6 mice (Tregegfp cells) to distinguish the transferred Treg cells; recipients were then examined at different time points after BMT. Systemic infusion of MSCs and Treg cells improved survival and GVHD scores, effectively downregulating pro-inflammatory Th×and Th17 cells. These therapeutic effects of combined cell therapy resulted in an increased Foxp3+ Treg cell population. Compared to single cell therapy, adoptively transferred Tregegfp cells only showed prolonged survival in the combined cell therapy group on day 21 after allogeneic BMT. In addition, Foxp3+ Treg cells, generated endogenously from recipients, significantly increased. Significantly higher levels of Tregegfp cells were also detected in aGVHD target organs in the combined cell therapy group compared to the Treg cells group. Thus, our data indicate that MSCs may induce the long-term survival of transferred Treg cells, particularly in aGVHD target organs, and may increase the repopulation of endogenous Treg cells in recipients after BMT. Together, these results support the potential of combined cell therapy using MSCs and Treg cells for preventing aGVHD.
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In a murine model of acute graft-versus-host disease, co-transfer of Treg cells and MSCs proved more beneficial than single-cell treatment with Treg cells alone, resulting in enhanced survival outcomes.
“In a murine model of acute graft-versus-host disease (GvHD), co-transfer of Treg cells and MSCs proved more beneficial than single-cell treatment with Treg cells alone, resulting in enhanced survival outcomes [376].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [376]
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- Authors
- Lee, E.-S., Lim, J.-Y., Im, K.-I., Kim, N., Nam, Y.-S., Jeon, Y.-W., & Cho, S.-G.
- Affiliations
- Catholic University of Korea (KR)
- The Catholic University of Korea Seoul St. Mary's Hospital (KR)
- Corresponding author
- Cho, Seok-Goo
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2015-09-22
- Volume
- 10
- Issue
- 9
- Pages
- e0138846
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4578951
- OpenAlex
- W2293085954
- Cited by
- 34
- References
- 48
- Citations by year
- 2025: 1 · 2023: 7 · 2021: 6 · 2020: 5 · 2019: 3 · 2018: 6 · 2017: 3 · 2016: 2 · 2015: 1
- FWCI
- 3.14
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- acute graft-versus-host disease, regulatory T cells, mesenchymal stem cells, adoptive cell transfer, combined cell therapy, allogeneic bone marrow transplantation, Th17 cells, Th1 cells, IL-17, graft-versus-host disease prophylaxis
- MeSH terms
- Acute Disease, Animals, Cells, Cultured, Combined Modality Therapy, Disease Models, Animal, Graft Survival, Graft vs Host Disease, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Transgenic, Transplantation, Homologous, Gene Expression, Bone Marrow Transplantation, Treatment Outcome, Microscopy, Confocal, Adoptive Transfer, Reverse Transcriptase Polymerase Chain Reaction, Mesenchymal Stem Cell Transplantation, Green Fluorescent Proteins, T-Lymphocytes, Regulatory, Forkhead Transcription Factors
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