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The role of human CD46 in early xenoislet engraftment in a dual transplant model.

Publication ,  Journal Article
Samy, KP; Gao, Q; Davis, RP; Song, M; Fitch, ZW; Mulvihill, MS; MacDonald, AL; Leopardi, FV; How, T; Williams, KD; Devi, GR; Collins, BH ...
Published in: Xenotransplantation
November 2019

BACKGROUND: Membrane cofactor protein CD46 attenuates the complement cascade by facilitating cleavage of C3b and C4b. In solid organ xenotransplantation, organs expressing CD46 have been shown to resist hyperacute rejection. However, the incremental value of human CD46 expression for islet xenotransplantation remains poorly defined. METHODS: This study attempted to delineate the role of CD46 in early neonatal porcine islet engraftment by comparing Gal-knocked out (GKO) and hCD46-transgenic (GKO/CD46) islets in a dual transplant model. Seven rhesus macaques underwent dual transplant and were sacrificed at 1 hour (n = 4) or 24 hours (n = 3). Both hemilivers were recovered and fixed for immunohistochemistry (CD46, insulin, neutrophil elastase, platelet, IgM, IgG, C3d, C4d, CD68, Caspase 3). Quantitative immunohistochemical analysis was performed using the Aperio Imagescope. RESULTS: Within 1 hour of intraportal infusion of xenografts, no differences were observed between the two types of islets in terms of platelet, antibody, or complement deposition. Cellular infiltration and islet apoptotic activity were also similar at 1 hour. At 24 hours, GKO/CD46 islets demonstrated significantly less platelet deposition (P = 0.01) and neutrophil infiltration (P = 0.01) compared to GKO islets. In contrast, C3d (P = 0.38) and C4d (P = 0.45) deposition was equal between the two genotypes. CONCLUSIONS: Our findings suggest that expression of hCD46 on NPIs potentially provides a measurable incremental survival advantage in vivo by reducing early thrombo-inflammatory events associated with instant blood-mediated inflammatory reaction (IBMIR) following intraportal islet infusion.

Duke Scholars

Published In

Xenotransplantation

DOI

EISSN

1399-3089

Publication Date

November 2019

Volume

26

Issue

6

Start / End Page

e12540

Location

Denmark

Related Subject Headings

  • Transplants
  • Transplantation, Heterologous
  • Surgery
  • Membrane Cofactor Protein
  • Macaca mulatta
  • Islets of Langerhans Transplantation
  • Islets of Langerhans
  • Inflammation
  • Humans
  • Graft Rejection
 

Citation

APA
Chicago
ICMJE
MLA
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Samy, K. P., Gao, Q., Davis, R. P., Song, M., Fitch, Z. W., Mulvihill, M. S., … Kirk, A. D. (2019). The role of human CD46 in early xenoislet engraftment in a dual transplant model. Xenotransplantation, 26(6), e12540. https://doi.org/10.1111/xen.12540
Samy, Kannan P., Qimeng Gao, Robert Patrick Davis, Mingqing Song, Zachary W. Fitch, Michael S. Mulvihill, Andrea L. MacDonald, et al. “The role of human CD46 in early xenoislet engraftment in a dual transplant model.Xenotransplantation 26, no. 6 (November 2019): e12540. https://doi.org/10.1111/xen.12540.
Samy KP, Gao Q, Davis RP, Song M, Fitch ZW, Mulvihill MS, et al. The role of human CD46 in early xenoislet engraftment in a dual transplant model. Xenotransplantation. 2019 Nov;26(6):e12540.
Samy, Kannan P., et al. “The role of human CD46 in early xenoislet engraftment in a dual transplant model.Xenotransplantation, vol. 26, no. 6, Nov. 2019, p. e12540. Pubmed, doi:10.1111/xen.12540.
Samy KP, Gao Q, Davis RP, Song M, Fitch ZW, Mulvihill MS, MacDonald AL, Leopardi FV, How T, Williams KD, Devi GR, Collins BH, Luo X, Kirk AD. The role of human CD46 in early xenoislet engraftment in a dual transplant model. Xenotransplantation. 2019 Nov;26(6):e12540.
Journal cover image

Published In

Xenotransplantation

DOI

EISSN

1399-3089

Publication Date

November 2019

Volume

26

Issue

6

Start / End Page

e12540

Location

Denmark

Related Subject Headings

  • Transplants
  • Transplantation, Heterologous
  • Surgery
  • Membrane Cofactor Protein
  • Macaca mulatta
  • Islets of Langerhans Transplantation
  • Islets of Langerhans
  • Inflammation
  • Humans
  • Graft Rejection