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The Sertoli Cell Complement Signature: A Suspected Mechanism in Xenograft Survival
Rachel L Washburn1,2, Dalia Martinez-Marin1,2, Ksenija Korać1
1Department of Cell Biology and Biochemistry, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79424, USA.
International Journal of Molecular Sciences
|February 11, 2023
Summary
Sertoli cells protect against transplant rejection by secreting complement inhibitors. This study reveals how these cells regulate the complement system, offering insights for improving xenograft survival.
Area of Science:
- Immunology
- Transplantation Biology
- Cell Biology
Background:
- The complement system is a key factor in transplant rejection.
- Sertoli cells exhibit unique immune-regulatory properties and long-term survival across immunological barriers.
- Understanding Sertoli cell mechanisms is crucial for advancing transplantation strategies, particularly in xenotransplantation.
Purpose of the Study:
- To investigate the role of Sertoli cells in inhibiting the complement system within the context of xenotransplantation.
- To identify specific complement inhibitors secreted by Sertoli cells and understand their protective mechanisms.
Main Methods:
- In vitro studies exposing neonatal pig Sertoli cells (NPSCs), neonatal pig islet (NPI) aggregates, and pig aortic endothelial cells (PAECs) to activated human complement.
- Culture of PAECs in NPSC-conditioned media with human complement.
- Bioinformatic and molecular analyses to identify complement inhibitors and factors expressed by NPSCs.
- RNA sequencing to analyze the complement signature of NPSCs.
Main Results:
- NPSCs demonstrated significant survival in activated human complement, unlike NPI aggregates and PAECs.
- NPSC-conditioned media enhanced PAEC survival by 200% in the presence of human complement, indicating secreted protective factors.
- Bioinformatic and molecular analyses identified 21 complement inhibitors in NPSCs, with several upregulated compared to NPIs and PAECs.
- RNA sequencing revealed the expression of 25 additional complement factors, including cascade components and receptors, in NPSCs.
Conclusions:
- NPSCs possess a comprehensive complement-inhibiting signature, utilizing redundant mechanisms for complement regulation.
- The identified complement inhibitors secreted by Sertoli cells are critical for their survival and offer potential for enhancing xenograft viability.
- Further investigation into complement system regulation by Sertoli cells is warranted to extend xenograft survival in transplantation.
