Impact of thrombocytopenia on survival of baboons with genetically modified pig liver transplants

B. Ekser, C. Long, G. J. Echeverri, H. Hara, M. Ezzelarab, C. C. Lin, M. E. De Vera, R. Wagner, E. Klein, R. F. Wolf, D. Ayares, D. K C Cooper, B. Gridelli

Research output: Contribution to journalArticle

Abstract

A lack of deceased human donor livers leads to a significant mortality in patients with acute-on-chronic or acute (fulminant) liver failure or with primary nonfunction of an allograft. Genetically engineered pigs could provide livers that might bridge the patient to allotransplantation. Orthotopic liver transplantation in baboons using livers from α1,3-galactosyltransferase gene-knockout (GTKO) pigs (n = 2) or from GTKO pigs transgenic for CD46 (n = 8) were carried out with a clinically acceptable immunosuppressive regimen. Six of 10 baboons survived for 4-7 days. In all cases, liver function was adequate, as evidenced by tests of detoxification, protein synthesis, complement activity and coagulation parameters. The major problem that prevented more prolonged survival beyond 7 days was a profound thrombocytopenia that developed within 1 h after reperfusion, ultimately resulting in spontaneous hemorrhage at various sites. We postulate that this is associated with the expression of tissue factor on platelets after contact with pig endothelium, resulting in platelet and platelet-peripheral blood mononuclear cell(s) aggregation and deposition of aggregates in the liver graft, though we were unable to confirm this conclusively. If this problem can be resolved, we would anticipate that a pig liver could provide a period during which a patient in liver failure could be successfully bridged to allotransplantation.

Original languageEnglish
Pages (from-to)273-285
Number of pages13
JournalAmerican Journal of Transplantation
Volume10
Issue number2
DOIs
Publication statusPublished - Feb 2010

Fingerprint

Papio
Thrombocytopenia
Swine
Transplants
Liver
Galactosyltransferases
Gene Knockout Techniques
Blood Platelets
Acute Liver Failure
Cell Aggregation
Liver Failure
Thromboplastin
Immunosuppressive Agents
Liver Transplantation
Reperfusion
Endothelium
Allografts
Blood Cells
Complement System Proteins
Tissue Donors

Keywords

  • α1
  • 3-galactosyltransferase gene-knockout
  • Acute
  • Baboon
  • HCD46
  • Liver
  • Pig
  • Xenotransplantation

ASJC Scopus subject areas

  • Transplantation
  • Immunology and Allergy
  • Pharmacology (medical)

Cite this

Ekser, B., Long, C., Echeverri, G. J., Hara, H., Ezzelarab, M., Lin, C. C., ... Gridelli, B. (2010). Impact of thrombocytopenia on survival of baboons with genetically modified pig liver transplants. American Journal of Transplantation, 10(2), 273-285. https://doi.org/10.1111/j.1600-6143.2009.02945.x

Impact of thrombocytopenia on survival of baboons with genetically modified pig liver transplants. / Ekser, B.; Long, C.; Echeverri, G. J.; Hara, H.; Ezzelarab, M.; Lin, C. C.; De Vera, M. E.; Wagner, R.; Klein, E.; Wolf, R. F.; Ayares, D.; Cooper, D. K C; Gridelli, B.

In: American Journal of Transplantation, Vol. 10, No. 2, 02.2010, p. 273-285.

Research output: Contribution to journalArticle

Ekser, B, Long, C, Echeverri, GJ, Hara, H, Ezzelarab, M, Lin, CC, De Vera, ME, Wagner, R, Klein, E, Wolf, RF, Ayares, D, Cooper, DKC & Gridelli, B 2010, 'Impact of thrombocytopenia on survival of baboons with genetically modified pig liver transplants', American Journal of Transplantation, vol. 10, no. 2, pp. 273-285. https://doi.org/10.1111/j.1600-6143.2009.02945.x
Ekser, B. ; Long, C. ; Echeverri, G. J. ; Hara, H. ; Ezzelarab, M. ; Lin, C. C. ; De Vera, M. E. ; Wagner, R. ; Klein, E. ; Wolf, R. F. ; Ayares, D. ; Cooper, D. K C ; Gridelli, B. / Impact of thrombocytopenia on survival of baboons with genetically modified pig liver transplants. In: American Journal of Transplantation. 2010 ; Vol. 10, No. 2. pp. 273-285.
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