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Updated: Nov 4, 2025
Murine Heterotopic Heart Transplant Technique
Published on: July 8, 2014
Preventing alloimmune rejection using circular RNA FSCN1-silenced dendritic cells in heart transplantation
Bowen Wang1, Qinfeng Zhou2, Toni Li3
1Department of Cardiovascular Surgery, The Second Affiliated Hospital, Jilin University, Changchun, China; Department of Pathology and Laboratory Medicine, Western University, London, Ontario Canada.
Background:
While heart transplantation is used as a standard treatment for heart failure, transplant rejection continues to pose a challenge. Recent evidence has shown that circular RNA (circRNA) is a new type of gene regulator in cell development. Our aim was to demonstrate that treatment with tolerogenic dendritic cells (Tol-DCs) generated by circular RNA FSCN1 (circFSCN1) silencing could prevent alloimmune rejection and prolong heart graft survival in heart transplantation.
Methods:
Bone marrow-derived DCs were transfected with circFSCN1 siRNA in vitro. The circFSCN1 level was measured by qRT-PCR. DC maturation was determined by flow cytometry. Mixed lymphocyte reactions (MLRs) were conducted to assess the function of DCs to activate T cells and to generate regulatory T cells (Tregs). In situ RNA hybridization and fluorescent microscopy were performed to detect the distribution of circFSCN1 in DCs. A heterotopic allogeneic murine heart transplantation was conducted where recipients were pre-treated with donor derived circFSCN1-silenced Tol-DCs. Heartbeat was monitored to assess immune rejection.
Results:
Exonic circFSCN1 was highly expressed in the cytoplasm of mature DCs. Knockdown of circFSCN1 using siRNA arrested DCs at an immature state, impaired DC's ability to activate T cells and enhanced Treg generation. Treatment with circFSCN1-silenced Tol-DCs prevented alloimmune rejection, prolonged allograft survival, reduced fibrosis, and induced Tregs in vivo.
Conclusions:
Knockdown of circFSCN1 induces Tol-DCs and treatment with these Tol-DCs prevents alloimmune rejection and prolongs allograft survival. This is a promising therapeutic target to combat transplant rejection in heart transplantation and increases our understanding of circRNA in the immune system.
Insights
Silencing circular RNA FSCN1 (circFSCN1) in dendritic cells (DCs) creates tolerogenic DCs. These cells prevent heart transplant rejection and improve graft survival, offering a new therapeutic strategy.
Area of Science:
- Immunology
- Molecular Biology
- Transplantation Science
Background:
- Heart transplantation is a standard treatment for heart failure, but transplant rejection remains a significant clinical challenge.
- Circular RNAs (circRNAs) are emerging as key regulators of cellular development and immune responses.
- Investigating novel therapeutic targets for preventing transplant rejection is crucial.
Purpose of the Study:
- To investigate the role of circular RNA FSCN1 (circFSCN1) in dendritic cell (DC) function.
- To determine if silencing circFSCN1 in DCs can generate tolerogenic DCs (Tol-DCs).
- To evaluate the efficacy of circFSCN1-silenced Tol-DCs in preventing allogeneic heart transplant rejection and prolonging graft survival.
Main Methods:
- Dendritic cells (DCs) were treated with circFSCN1 siRNA to assess circFSCN1 levels and DC maturation.
- Mixed lymphocyte reactions (MLRs) were used to evaluate DC-mediated T cell activation and regulatory T cell (Treg) generation.
- A murine heterotopic heart transplantation model was employed, with recipients pre-treated with circFSCN1-silenced Tol-DCs.
Main Results:
- circFSCN1 knockdown resulted in immature DCs with impaired T cell activation but enhanced Treg generation.
- Treatment with circFSCN1-silenced Tol-DCs significantly prevented alloimmune rejection in heart transplant recipients.
- Allograft survival was prolonged, fibrosis was reduced, and Tregs were induced in vivo following Tol-DC treatment.
Conclusions:
- Silencing circFSCN1 effectively induces tolerogenic DCs (Tol-DCs).
- Treatment with these Tol-DCs is a promising strategy to prevent allograft rejection and extend graft survival in heart transplantation.
- This study highlights the potential of circRNAs as therapeutic targets in transplantation immunology.
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