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Dual islet transplantation modeling of the instant blood-mediated inflammatory reaction.

Publication ,  Journal Article
Martin, BM; Samy, KP; Lowe, MC; Thompson, PW; Cano, J; Farris, AB; Song, M; Dove, CR; Leopardi, FV; Strobert, EA; Jenkins, JB; Collins, BH ...
Published in: Am J Transplant
May 2015

Islet xenotransplantation is a potential treatment for diabetes without the limitations of tissue availability. Although successful experimentally, early islet loss remains substantial and attributed to an instant blood-mediated inflammatory reaction (IBMIR). This syndrome of islet destruction has been incompletely defined and characterization in pig-to-primate models has been hampered by logistical and statistical limitations of large animal studies. To further investigate IBMIR, we developed a novel in vivo dual islet transplant model to precisely characterize IBMIR as proof-of-concept that this model can serve to properly control experiments comparing modified xenoislet preparations. WT and α1,3-galactosyltransferase knockout (GTKO) neonatal porcine islets were studied in nonimmunosuppressed rhesus macaques. Inert polyethylene microspheres served as a control for the effects of portal embolization. Digital analysis of immunohistochemistry targeting IBMIR mediators was performed at 1 and 24 h after intraportal islet infusion. Early findings observed in transplanted islets include complement and antibody deposition, and infiltration by neutrophils, macrophages and platelets. Insulin, complement, antibody, neutrophils, macrophages and platelets were similar between GTKO and WT islets, with increasing macrophage infiltration at 24 h in both phenotypes. This model provides an objective and internally controlled study of distinct islet preparations and documents the temporal histology of IBMIR.

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Published In

Am J Transplant

DOI

EISSN

1600-6143

Publication Date

May 2015

Volume

15

Issue

5

Start / End Page

1241 / 1252

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Time Factors
  • Swine
  • Surgery
  • Phenotype
  • Neutrophils
  • Macrophages
  • Macaca mulatta
  • Islets of Langerhans Transplantation
  • Islets of Langerhans
 

Citation

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Martin, B. M., Samy, K. P., Lowe, M. C., Thompson, P. W., Cano, J., Farris, A. B., … Kirk, A. D. (2015). Dual islet transplantation modeling of the instant blood-mediated inflammatory reaction. Am J Transplant, 15(5), 1241–1252. https://doi.org/10.1111/ajt.13098
Martin, B. M., K. P. Samy, M. C. Lowe, P. W. Thompson, J. Cano, A. B. Farris, M. Song, et al. “Dual islet transplantation modeling of the instant blood-mediated inflammatory reaction.Am J Transplant 15, no. 5 (May 2015): 1241–52. https://doi.org/10.1111/ajt.13098.
Martin BM, Samy KP, Lowe MC, Thompson PW, Cano J, Farris AB, et al. Dual islet transplantation modeling of the instant blood-mediated inflammatory reaction. Am J Transplant. 2015 May;15(5):1241–52.
Martin, B. M., et al. “Dual islet transplantation modeling of the instant blood-mediated inflammatory reaction.Am J Transplant, vol. 15, no. 5, May 2015, pp. 1241–52. Pubmed, doi:10.1111/ajt.13098.
Martin BM, Samy KP, Lowe MC, Thompson PW, Cano J, Farris AB, Song M, Dove CR, Leopardi FV, Strobert EA, Jenkins JB, Collins BH, Larsen CP, Kirk AD. Dual islet transplantation modeling of the instant blood-mediated inflammatory reaction. Am J Transplant. 2015 May;15(5):1241–1252.
Journal cover image

Published In

Am J Transplant

DOI

EISSN

1600-6143

Publication Date

May 2015

Volume

15

Issue

5

Start / End Page

1241 / 1252

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Time Factors
  • Swine
  • Surgery
  • Phenotype
  • Neutrophils
  • Macrophages
  • Macaca mulatta
  • Islets of Langerhans Transplantation
  • Islets of Langerhans