Tumor necrosis factor α in aGVHD patients contributed to the impairment of recipient bone marrow MSC stemness and deficiency of their hematopoiesis-promotion capacity
| العنوان: | Tumor necrosis factor α in aGVHD patients contributed to the impairment of recipient bone marrow MSC stemness and deficiency of their hematopoiesis-promotion capacity |
|---|---|
| المؤلفون: | Heng Zhu, Hong-Mei Ning, Mei Xue, Ning Mao, Xiao-Li Zheng, Heng-Xiang Wang, Dong-Mei Han, Hong-Min Yan, Li Ding, Ling Zhu, Zi-Kuan Guo, Jing Liu, Pei-Lin Li |
| المصدر: | Stem Cell Research & Therapy, Vol 11, Iss 1, Pp 1-14 (2020) Stem Cell Research & Therapy |
| بيانات النشر: | BMC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Medicine (miscellaneous), Graft vs Host Disease, Bone Marrow Cells, Cell morphology, Biochemistry, Genetics and Molecular Biology (miscellaneous), Proinflammatory cytokine, lcsh:Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Bone Marrow, immune system diseases, hemic and lymphatic diseases, medicine, Humans, lcsh:QD415-436, Stemness, Mesenchymal stem cell, lcsh:R5-920, integumentary system, business.industry, Tumor Necrosis Factor-alpha, Research, Mesenchymal Stem Cells, Cell Biology, Bone marrow niche, Acute graft versus host disease, Hematopoiesis, Tumor necrosis factor-α, Transplantation, Haematopoiesis, 030104 developmental biology, medicine.anatomical_structure, MRNA Sequencing, surgical procedures, operative, 030220 oncology & carcinogenesis, Cancer research, Molecular Medicine, Bone marrow, Stem cell, business, lcsh:Medicine (General) |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 1757-6512 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bfe2648be52044e2f34226c37d3bccdc http://link.springer.com/article/10.1186/s13287-020-01615-9 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....bfe2648be52044e2f34226c37d3bccdc |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 17576512 |
|---|