AI Article Synopsis
- The study investigates how acute graft-versus-host disease (aGVHD) affects mesenchymal stem cells (MSCs) in the bone marrow (BM) and their role in blood cell reconstitution after stem cell transplantation.
- The findings reveal that aGVHD MSCs show reduced osteogenic and adipogenic capabilities, decreased self-renewal capacity, and diminished support for hematopoiesis compared to non-aGVHD MSCs.
- The research suggests that TNF-α plays a significant role in impairing MSC properties, and blocking TNF-α may help preserve the BM niche in patients with aGVHD.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079531 | PMC |
| http://dx.doi.org/10.1186/s13287-020-01615-9 | DOI Listing |
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