Tumor necrosis factor α in aGVHD patients contributed to the impairment of recipient bone marrow MSC stemness and deficiency of their hematopoiesis-promotion capacity
Abstract Background Though accumulated evidence has demonstrated visceral organ involvement in acute graft-versus-host disease (aGVHD), how aGVHD influences the bone marrow (BM) niche and the reconstitution of hematopoiesis post-hematopoietic stem cell transplantation remains largely unknown. Method...
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doaj-c5470ee69297455481370ff33fd4819b2020-11-25T02:30:46ZengBMCStem Cell Research & Therapy1757-65122020-03-0111111410.1186/s13287-020-01615-9Tumor necrosis factor α in aGVHD patients contributed to the impairment of recipient bone marrow MSC stemness and deficiency of their hematopoiesis-promotion capacityLi Ding0Hong-Mei Ning1Pei-Lin Li2Hong-Min Yan3Dong-Mei Han4Xiao-Li Zheng5Jing Liu6Ling Zhu7Mei Xue8Ning Mao9Zi-Kuan Guo10Heng Zhu11Heng-Xiang Wang12Medical Center of Air ForcesThe Fifth Medical Center of Chinese PLA General HospitalBeijing Institute of Radiation MedicineMedical Center of Air ForcesMedical Center of Air ForcesMedical Center of Air ForcesMedical Center of Air ForcesMedical Center of Air ForcesMedical Center of Air ForcesBeijing Institute of Basic Medical SciencesBeijing Institute of Radiation MedicineBeijing Institute of Radiation MedicineMedical Center of Air ForcesAbstract Background Though accumulated evidence has demonstrated visceral organ involvement in acute graft-versus-host disease (aGVHD), how aGVHD influences the bone marrow (BM) niche and the reconstitution of hematopoiesis post-hematopoietic stem cell transplantation remains largely unknown. Methods In the current study, the cell morphology, immunophenotype, multi-differentiation capacity, self-renewal capacity, and hematopoiesis promotion of the MSCs from aGVHD and non-aGVHD patients were investigated. Additionally, the stemness and hematopoiesis-promoting property of healthy donor-derived MSCs were evaluated in the presence of BM supernatant from aGVHD patients. Mechanistically, antibodies targeting inflammatory cytokines involved in aGVHD were added into the MSC culture. Furthermore, a recombinant human tumor necrosis factor (TNF-α) receptor-Ig fusion protein (rhTNFR:Fc) was used to protect healthy donor-derived MSCs. Moreover, mRNA sequencing was performed to explore the underlying mechanisms. Results The aGVHD MSCs exhibited morphological and immunophenotypic characteristics that were similar to those of the non-aGVHD MSCs. However, the osteogenic and adipogenic activities of the aGVHD MSCs significantly decreased. Additionally, the colony formation capacity and the expression of self-renewal-related genes remarkably decreased in aGVHD MSCs. Further, the hematopoiesis-supporting capacity of aGVHD MSCs significantly reduced. The antibody neutralization results showed that TNF-α contributed to the impairment of MSC properties. Moreover, rhTNFR:Fc exhibited notable protective effects on MSCs in the aGVHD BM supernatants. The mRNA sequencing results indicated that the TNF-α pathway and the Toll-like receptor pathway may be activated by TNF-α. Conclusions Thus, our data demonstrate MSCs as cellular targets of aGVHD and suggest a potential role of TNF-α blockage in maintaining the BM niche of aGVHD patients.http://link.springer.com/article/10.1186/s13287-020-01615-9Acute graft versus host diseaseBone marrow nicheMesenchymal stem cellStemnessTumor necrosis factor-α |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Li Ding Hong-Mei Ning Pei-Lin Li Hong-Min Yan Dong-Mei Han Xiao-Li Zheng Jing Liu Ling Zhu Mei Xue Ning Mao Zi-Kuan Guo Heng Zhu Heng-Xiang Wang |
spellingShingle |
Li Ding Hong-Mei Ning Pei-Lin Li Hong-Min Yan Dong-Mei Han Xiao-Li Zheng Jing Liu Ling Zhu Mei Xue Ning Mao Zi-Kuan Guo Heng Zhu Heng-Xiang Wang Tumor necrosis factor α in aGVHD patients contributed to the impairment of recipient bone marrow MSC stemness and deficiency of their hematopoiesis-promotion capacity Stem Cell Research & Therapy Acute graft versus host disease Bone marrow niche Mesenchymal stem cell Stemness Tumor necrosis factor-α |
author_facet |
Li Ding Hong-Mei Ning Pei-Lin Li Hong-Min Yan Dong-Mei Han Xiao-Li Zheng Jing Liu Ling Zhu Mei Xue Ning Mao Zi-Kuan Guo Heng Zhu Heng-Xiang Wang |
author_sort |
Li Ding |
title |
Tumor necrosis factor α in aGVHD patients contributed to the impairment of recipient bone marrow MSC stemness and deficiency of their hematopoiesis-promotion capacity |
title_short |
Tumor necrosis factor α in aGVHD patients contributed to the impairment of recipient bone marrow MSC stemness and deficiency of their hematopoiesis-promotion capacity |
title_full |
Tumor necrosis factor α in aGVHD patients contributed to the impairment of recipient bone marrow MSC stemness and deficiency of their hematopoiesis-promotion capacity |
title_fullStr |
Tumor necrosis factor α in aGVHD patients contributed to the impairment of recipient bone marrow MSC stemness and deficiency of their hematopoiesis-promotion capacity |
title_full_unstemmed |
Tumor necrosis factor α in aGVHD patients contributed to the impairment of recipient bone marrow MSC stemness and deficiency of their hematopoiesis-promotion capacity |
title_sort |
tumor necrosis factor α in agvhd patients contributed to the impairment of recipient bone marrow msc stemness and deficiency of their hematopoiesis-promotion capacity |
publisher |
BMC |
series |
Stem Cell Research & Therapy |
issn |
1757-6512 |
publishDate |
2020-03-01 |
description |
Abstract Background Though accumulated evidence has demonstrated visceral organ involvement in acute graft-versus-host disease (aGVHD), how aGVHD influences the bone marrow (BM) niche and the reconstitution of hematopoiesis post-hematopoietic stem cell transplantation remains largely unknown. Methods In the current study, the cell morphology, immunophenotype, multi-differentiation capacity, self-renewal capacity, and hematopoiesis promotion of the MSCs from aGVHD and non-aGVHD patients were investigated. Additionally, the stemness and hematopoiesis-promoting property of healthy donor-derived MSCs were evaluated in the presence of BM supernatant from aGVHD patients. Mechanistically, antibodies targeting inflammatory cytokines involved in aGVHD were added into the MSC culture. Furthermore, a recombinant human tumor necrosis factor (TNF-α) receptor-Ig fusion protein (rhTNFR:Fc) was used to protect healthy donor-derived MSCs. Moreover, mRNA sequencing was performed to explore the underlying mechanisms. Results The aGVHD MSCs exhibited morphological and immunophenotypic characteristics that were similar to those of the non-aGVHD MSCs. However, the osteogenic and adipogenic activities of the aGVHD MSCs significantly decreased. Additionally, the colony formation capacity and the expression of self-renewal-related genes remarkably decreased in aGVHD MSCs. Further, the hematopoiesis-supporting capacity of aGVHD MSCs significantly reduced. The antibody neutralization results showed that TNF-α contributed to the impairment of MSC properties. Moreover, rhTNFR:Fc exhibited notable protective effects on MSCs in the aGVHD BM supernatants. The mRNA sequencing results indicated that the TNF-α pathway and the Toll-like receptor pathway may be activated by TNF-α. Conclusions Thus, our data demonstrate MSCs as cellular targets of aGVHD and suggest a potential role of TNF-α blockage in maintaining the BM niche of aGVHD patients. |
topic |
Acute graft versus host disease Bone marrow niche Mesenchymal stem cell Stemness Tumor necrosis factor-α |
url |
http://link.springer.com/article/10.1186/s13287-020-01615-9 |
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