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Updated: Jun 30, 2025

Mitigation of Blood Borne Cell Attachment to Metal Implants through CD47-Derived Peptide Immobilization
Published on: December 3, 2020
Expression of a mutant CD47 protects against phagocytosis without inducing cell death or inhibiting angiogenesis
Lu Xu1, Xiaodan Wang1, Ting Zhang1
1Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, Institute of Immunology, First Hospital of Jilin University, Changchun, Jilin 130062, China; National-Local Joint Engineering Laboratory of Animal Models for Human Disease, Jilin University, Changchun, Jilin 130062, China.
Abstract:
CD47 is a ligand of SIRPα, an inhibitory receptor expressed by macrophages, dendritic cells, and natural killer (NK) cells, and, therefore, transgenic overexpression of CD47 is considered an effective approach to inhibiting transplant rejection. However, the detrimental effect of CD47 signaling is overlooked when exploring this approach. Here, we construct a mutant CD47 by replacing the transmembrane and intracellular domains with a membrane anchor (CD47-IgV). In both human and mouse cells, CD47-IgV is efficiently expressed on the cell surface and protects against phagocytosis in vitro and in vivo but does not induce cell death or inhibit angiogenesis. Furthermore, hematopoietic stem cells expressing transgenic CD47-IgV show no detectable alterations in engraftment or differentiation. This study provides a potentially effective means of achieving transgenic CD47 expression that may help to produce gene-edited pigs for xenotransplantation and hypoimmunogenic pluripotent stem cells for regenerative medicine.
Insights
Researchers developed a modified CD47 protein (CD47-IgV) to prevent transplant rejection without harmful side effects. This engineered protein protects cells from immune attack, offering promise for xenotransplantation and regenerative medicine.
Area of Science:
- Immunology
- Regenerative Medicine
- Transplantation Biology
Background:
- CD47 is a cell surface protein that interacts with SIRPα, an inhibitory receptor on immune cells.
- Overexpressing CD47 is explored to prevent transplant rejection by inhibiting immune cells like macrophages.
- The negative impacts of standard CD47 signaling are often disregarded in this therapeutic approach.
Purpose of the Study:
- To engineer a modified CD47 protein (CD47-IgV) that retains protective functions without detrimental signaling.
- To evaluate the efficacy and safety of CD47-IgV in preventing phagocytosis and its impact on cell functions.
- To explore the potential of CD47-IgV for applications in xenotransplantation and regenerative medicine.
Main Methods:
- Constructed a CD47 mutant (CD47-IgV) by fusing the CD47 IgV domain to a membrane anchor.
- Expressed CD47-IgV on human and mouse cells.
- Assessed CD47-IgV expression, phagocytosis inhibition in vitro and in vivo, cell death, angiogenesis, and hematopoietic stem cell engraftment and differentiation.
Main Results:
- CD47-IgV was efficiently expressed on the cell surface of both human and mouse cells.
- CD47-IgV protected cells from phagocytosis in vitro and in vivo.
- CD47-IgV did not induce cell death, inhibit angiogenesis, or affect hematopoietic stem cell engraftment and differentiation.
Conclusions:
- CD47-IgV represents a potentially safer method for achieving the benefits of CD47 overexpression.
- This modified CD47 protein may facilitate the production of gene-edited pigs for xenotransplantation.
- CD47-IgV holds promise for generating hypoimmunogenic pluripotent stem cells for regenerative medicine.
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