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.

Cell Reports. Medicine
|March 20, 2024
PubMed

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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