Transgenic swine lungs expressing human CD59 are protected from injury in a pig-to-human model of xenotransplantation

David M. Kulick, Christopher T. Salerno, Agustin P. Dalmasso, Soon J. Park, Manuel Guzman Paz, William L. Fodor, R. Morton Bolman

Research output: Contribution to journalArticle

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Abstract

Background: Pulmonary xenotransplantation is currently limited by hyperacute rejection mediated in part by xenoreactive natural antibody and complement. Transgenic swine organs that express the human complement regulatory protein CD59 have demonstrated improved survival in models of pig- to-primate xenotransplantation. Objective: The purpose of this study was to evaluate transgenic swine lungs that express the human complement regulatory protein CD59 in a model of pig-to-human xenotransplantation. Methods: Transgenic swine lungs (n = 5, experimental group) and outbred swine lungs (n = 6, control group) were perfused with fresh, whole human blood through a centrifugal pump on an ex vivo circuit. Functional data were collected throughout perfusion. Immunoglobulin and complement studies were performed on perfusate samples, and both histologic and immunofluorescent analyses were performed on tissue sections. Results: Mean lung survival for the experimental group was increased when compared with controls, 240 ± 0 minutes versus 35.3 ± 14.5 minutes, respectively, with a P value of less than .01. A decreased rise in pulmonary vascular resistance at 15 minutes was observed in the experimental group (343 ± 87 mm Hg · L-1 · min-1, in contrast to the control group (1579 ± 722 mm Hg · L-1 · min-1; P < .01). Pulmonary compliance at 15 minutes was improved for the experimental group versus control group (9.31 ± 1.41 mL · cm-2 H2O and 4.11 ± 2.84 mL · cm-2 H2O, respectively; P < .01). SC5b-9 generation in the plasma perfusate was delayed for the experimental group versus the control group. Immunofluorescent examination of tissue sections demonstrated equivalent deposition of immunoglobulin G, immunoglobulin M, C1q, and C3 in both groups, with reduced deposition of C9 in the experimental group. Conclusions: Transgenic swine pulmonary xenografts that express the human complement regulatory protein CD59 demonstrated improved function and survival in an ex vivo model of pig-to-human xenotransplantation.

Original languageEnglish (US)
Pages (from-to)690-699
Number of pages10
JournalJournal of Thoracic and Cardiovascular Surgery
Volume119
Issue number4 I
StatePublished - 2000
Externally publishedYes

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Heterologous Transplantation
Swine
Lung
Wounds and Injuries
Control Groups
Complement System Proteins
Lung Compliance
Survival
Heterografts
Vascular Resistance
Primates
Immunoglobulin M
Immunoglobulins
Perfusion
Immunoglobulin G
Antibodies

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

Kulick, D. M., Salerno, C. T., Dalmasso, A. P., Park, S. J., Paz, M. G., Fodor, W. L., & Bolman, R. M. (2000). Transgenic swine lungs expressing human CD59 are protected from injury in a pig-to-human model of xenotransplantation. Journal of Thoracic and Cardiovascular Surgery, 119(4 I), 690-699.

Transgenic swine lungs expressing human CD59 are protected from injury in a pig-to-human model of xenotransplantation. / Kulick, David M.; Salerno, Christopher T.; Dalmasso, Agustin P.; Park, Soon J.; Paz, Manuel Guzman; Fodor, William L.; Bolman, R. Morton.

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 119, No. 4 I, 2000, p. 690-699.

Research output: Contribution to journalArticle

Kulick, DM, Salerno, CT, Dalmasso, AP, Park, SJ, Paz, MG, Fodor, WL & Bolman, RM 2000, 'Transgenic swine lungs expressing human CD59 are protected from injury in a pig-to-human model of xenotransplantation', Journal of Thoracic and Cardiovascular Surgery, vol. 119, no. 4 I, pp. 690-699.
Kulick, David M. ; Salerno, Christopher T. ; Dalmasso, Agustin P. ; Park, Soon J. ; Paz, Manuel Guzman ; Fodor, William L. ; Bolman, R. Morton. / Transgenic swine lungs expressing human CD59 are protected from injury in a pig-to-human model of xenotransplantation. In: Journal of Thoracic and Cardiovascular Surgery. 2000 ; Vol. 119, No. 4 I. pp. 690-699.
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T1 - Transgenic swine lungs expressing human CD59 are protected from injury in a pig-to-human model of xenotransplantation

AU - Kulick, David M.

AU - Salerno, Christopher T.

AU - Dalmasso, Agustin P.

AU - Park, Soon J.

AU - Paz, Manuel Guzman

AU - Fodor, William L.

AU - Bolman, R. Morton

PY - 2000

Y1 - 2000

N2 - Background: Pulmonary xenotransplantation is currently limited by hyperacute rejection mediated in part by xenoreactive natural antibody and complement. Transgenic swine organs that express the human complement regulatory protein CD59 have demonstrated improved survival in models of pig- to-primate xenotransplantation. Objective: The purpose of this study was to evaluate transgenic swine lungs that express the human complement regulatory protein CD59 in a model of pig-to-human xenotransplantation. Methods: Transgenic swine lungs (n = 5, experimental group) and outbred swine lungs (n = 6, control group) were perfused with fresh, whole human blood through a centrifugal pump on an ex vivo circuit. Functional data were collected throughout perfusion. Immunoglobulin and complement studies were performed on perfusate samples, and both histologic and immunofluorescent analyses were performed on tissue sections. Results: Mean lung survival for the experimental group was increased when compared with controls, 240 ± 0 minutes versus 35.3 ± 14.5 minutes, respectively, with a P value of less than .01. A decreased rise in pulmonary vascular resistance at 15 minutes was observed in the experimental group (343 ± 87 mm Hg · L-1 · min-1, in contrast to the control group (1579 ± 722 mm Hg · L-1 · min-1; P < .01). Pulmonary compliance at 15 minutes was improved for the experimental group versus control group (9.31 ± 1.41 mL · cm-2 H2O and 4.11 ± 2.84 mL · cm-2 H2O, respectively; P < .01). SC5b-9 generation in the plasma perfusate was delayed for the experimental group versus the control group. Immunofluorescent examination of tissue sections demonstrated equivalent deposition of immunoglobulin G, immunoglobulin M, C1q, and C3 in both groups, with reduced deposition of C9 in the experimental group. Conclusions: Transgenic swine pulmonary xenografts that express the human complement regulatory protein CD59 demonstrated improved function and survival in an ex vivo model of pig-to-human xenotransplantation.

AB - Background: Pulmonary xenotransplantation is currently limited by hyperacute rejection mediated in part by xenoreactive natural antibody and complement. Transgenic swine organs that express the human complement regulatory protein CD59 have demonstrated improved survival in models of pig- to-primate xenotransplantation. Objective: The purpose of this study was to evaluate transgenic swine lungs that express the human complement regulatory protein CD59 in a model of pig-to-human xenotransplantation. Methods: Transgenic swine lungs (n = 5, experimental group) and outbred swine lungs (n = 6, control group) were perfused with fresh, whole human blood through a centrifugal pump on an ex vivo circuit. Functional data were collected throughout perfusion. Immunoglobulin and complement studies were performed on perfusate samples, and both histologic and immunofluorescent analyses were performed on tissue sections. Results: Mean lung survival for the experimental group was increased when compared with controls, 240 ± 0 minutes versus 35.3 ± 14.5 minutes, respectively, with a P value of less than .01. A decreased rise in pulmonary vascular resistance at 15 minutes was observed in the experimental group (343 ± 87 mm Hg · L-1 · min-1, in contrast to the control group (1579 ± 722 mm Hg · L-1 · min-1; P < .01). Pulmonary compliance at 15 minutes was improved for the experimental group versus control group (9.31 ± 1.41 mL · cm-2 H2O and 4.11 ± 2.84 mL · cm-2 H2O, respectively; P < .01). SC5b-9 generation in the plasma perfusate was delayed for the experimental group versus the control group. Immunofluorescent examination of tissue sections demonstrated equivalent deposition of immunoglobulin G, immunoglobulin M, C1q, and C3 in both groups, with reduced deposition of C9 in the experimental group. Conclusions: Transgenic swine pulmonary xenografts that express the human complement regulatory protein CD59 demonstrated improved function and survival in an ex vivo model of pig-to-human xenotransplantation.

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