ArticleStem cell research & therapy2023
Adipose tissue-derived human mesenchymal stromal cells can better suppress complement lysis, engraft and inhibit acute graft-versus-host disease in mice.
Article in Stem cell research & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 27 citations in OpenAlex.
- [Research advances in mesenchymal stem cell therapy for graft-versus-host disease].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2026Review
- State-of the-art and future perspective in co-culture systems for tendon engineering.Biomaterials and biosystems · 2025Article
- Biglycan fragment modulates TGF-β activity in intervertebral disc via an eIF6-coupled intracellular path.Science advances · 2025Article
- Differential Expression of IFI16, IL-33 and CD55 Link Potential Common Pathogenic Mechanisms for COVID-19 and Ulcerative Colitis.Journal of multidisciplinary healthcare · 2025Article
- CRISPR/Cas-edited iPSCs and mesenchymal stem cells: a concise review of their potential in thalassemia therapy.Frontiers in cell and developmental biology · 2025Review
- Multiple tail vein injections of adipose-derived mesenchymal stem cells ameliorate allergic rhinitis in mice: superior efficacy of prolonged regimens.Frontiers in immunology · 2025Article
- Human Liver MSCs Retain Their Basic Cellular Properties in Chronically Inflamed Liver Tissue.International journal of molecular sciences · 2024Article
- Pharmacologic or genetic targeting of peripheral nerves prevents peri-articular traumatic heterotopic ossification.Bone research · 2024Article
- Mesenchymal stromal cells secretome restores bioenergetic and redox homeostasis in human proximal tubule cells after ischemic injury.Stem cell research & therapy · 2023Article
- Evaluation of safety and efficacy of allogeneic adipose tissue-derived mesenchymal stem cells in pediatric bronchiolitis obliterans syndrome (BoS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Stem cell research & therapy · 2023Article
- Adipose-Derived Mesenchymal Stem Cell Facilitate Hematopoietic Stem Cell Proliferation via the Jagged-1/Notch-1/Hes Signaling Pathway.Stem cells international · 2023Article
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAcute graft-versus-host disease (aGvHD) is a life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT). Transplantation of immunosuppressive human mesenchymal stromal cells (hMSCs) can protect against aGvHD post-HSCT; however, their efficacy is limited by poor engraftment and survival. Moreover, infused MSCs can be damaged by activated complement, yet strategies to minimise complement injury of hMSCs and improve their survival are limited.
methodsHuman MSCs were derived from bone marrow (BM), adipose tissue (AT) and umbilical cord (UC). In vitro immunomodulatory potential was determined by co-culture experiments between hMSCs and immune cells implicated in aGvHD disease progression. BM-, AT- and UC-hMSCs were tested for their abilities to protect aGvHD in a mouse model of this disease. Survival and clinical symptoms were monitored, and target tissues of aGvHD were examined by histopathology and qPCR. Transplanted cell survival was evaluated by cell tracing and by qPCR. The transcriptome of BM-, AT- and UC-hMSCs was profiled by RNA-sequencing. Focused experiments were performed to compare the expression of complement inhibitors and the abilities of hMSCs to resist complement lysis.
resultsHuman MSCs derived from three tissues divergently protected against aGvHD in vivo. AT-hMSCs preferentially suppressed complement in vitro and in vivo, resisted complement lysis and survived better after transplantation when compared to BM- and UC-hMSCs. AT-hMSCs also prolonged survival and improved the symptoms and pathological features of aGvHD. We found that complement-decay accelerating factor (CD55), an inhibitor of complement, is elevated in AT-hMSCs and contributed to reduced complement activation. We further report that atorvastatin and erlotinib could upregulate CD55 and suppress complement in all three types of hMSCs.
conclusionCD55, by suppressing complement, contributes to the improved protection of AT-hMSCs against aGvHD. The use of AT-hMSCs or the upregulation of CD55 by small molecules thus represents promising new strategies to promote hMSC survival to improve the efficacy of transplantation therapy. As complement injury is a barrier to all types of hMSC therapy, our findings are of broad significance to enhance the use of hMSCs for the treatment of a wide range of disorders.
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