Heart Xenograft Survival with Chimeric Pig Donors and Modest Immune Suppression

William E. Beschorner, Debra L. Sudan, Stanley J Radio, Tianyu Yang, Kenneth L. Franco, Arthur C. Hill, C. Carson Shearon, Scott C. Thompson, Robert S. Dixon, Noel D. Johnson, Charles A. Kuszynski, Ronald J. Rubocki, Kelly F. Lechtenberg, Aurelio Matamoros, Timothy C. Goertzen, Ira J. Fox, Alan Norman Langnas

Research output: Contribution to journalArticle

Abstract

Objective: To assess the use of donor pigs with cellular chimerism for prevention of acute rejection with modest immune suppression. The clinical use of pig organ xenografts is currently precluded by severe acute rejection, which resists standard immune suppression. Summary Background Data: For long-term survival of pig organ xenografts, immune suppression significantly greater than used with allografts would currently be necessary, leaving the recipient immune deficient and at increased risk for infections. Induction of immune tolerance and tissue accommodation could enhance xenograft survival but would lead to complications and frequent graft failure. Induction of cellular chimerism within the donor pigs, however, could accomplish these goals before transplantation, significantly reducing the risk. Methods: Marrow cells from sheep were infused into fetal pigs. Heart xenografts from chimeric or nonchimeric pigs were transplanted heterotopically into recipient sheep, simultaneous with infusion of splenocytes. Posttransplant suppression consisted of cyclosporine and tapered corticosteroids, comparable with allotransplants. Results: All of the control grafts (n = 12) were rejected by acute vascular rejection in 4 to 8 days. In contrast, only one episode of vascular rejection was observed in the experimental group (n = 13). Four experimental recipients had an episode of moderate diffuse cellular rejection (grade 3) and one had moderate focal cellular rejection (grade 2). Each episode responded to pulse steroids. Seven grafts showed no significant rejection. There was little evidence of immune deficiency, infection, or toxicity. Conclusions: Acute vascular rejection was prevented in a large animal model without the need for severe immune suppression.

Original languageEnglish (US)
Pages (from-to)265-272
Number of pages8
JournalAnnals of Surgery
Volume237
Issue number2
DOIs
StatePublished - Feb 2003

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Heterografts
Swine
Blood Vessels
Chimerism
Transplants
Sheep
Tissue Survival
Immune Tolerance
Infection
Cyclosporine
Allografts
Adrenal Cortex Hormones
Animal Models
Transplantation
Bone Marrow
Steroids

ASJC Scopus subject areas

  • Surgery

Cite this

Heart Xenograft Survival with Chimeric Pig Donors and Modest Immune Suppression. / Beschorner, William E.; Sudan, Debra L.; Radio, Stanley J; Yang, Tianyu; Franco, Kenneth L.; Hill, Arthur C.; Shearon, C. Carson; Thompson, Scott C.; Dixon, Robert S.; Johnson, Noel D.; Kuszynski, Charles A.; Rubocki, Ronald J.; Lechtenberg, Kelly F.; Matamoros, Aurelio; Goertzen, Timothy C.; Fox, Ira J.; Langnas, Alan Norman.

In: Annals of Surgery, Vol. 237, No. 2, 02.2003, p. 265-272.

Research output: Contribution to journalArticle

Beschorner, WE, Sudan, DL, Radio, SJ, Yang, T, Franco, KL, Hill, AC, Shearon, CC, Thompson, SC, Dixon, RS, Johnson, ND, Kuszynski, CA, Rubocki, RJ, Lechtenberg, KF, Matamoros, A, Goertzen, TC, Fox, IJ & Langnas, AN 2003, 'Heart Xenograft Survival with Chimeric Pig Donors and Modest Immune Suppression', Annals of Surgery, vol. 237, no. 2, pp. 265-272. https://doi.org/10.1097/00000658-200302000-00016
Beschorner, William E. ; Sudan, Debra L. ; Radio, Stanley J ; Yang, Tianyu ; Franco, Kenneth L. ; Hill, Arthur C. ; Shearon, C. Carson ; Thompson, Scott C. ; Dixon, Robert S. ; Johnson, Noel D. ; Kuszynski, Charles A. ; Rubocki, Ronald J. ; Lechtenberg, Kelly F. ; Matamoros, Aurelio ; Goertzen, Timothy C. ; Fox, Ira J. ; Langnas, Alan Norman. / Heart Xenograft Survival with Chimeric Pig Donors and Modest Immune Suppression. In: Annals of Surgery. 2003 ; Vol. 237, No. 2. pp. 265-272.
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AU - Sudan, Debra L.

AU - Radio, Stanley J

AU - Yang, Tianyu

AU - Franco, Kenneth L.

AU - Hill, Arthur C.

AU - Shearon, C. Carson

AU - Thompson, Scott C.

AU - Dixon, Robert S.

AU - Johnson, Noel D.

AU - Kuszynski, Charles A.

AU - Rubocki, Ronald J.

AU - Lechtenberg, Kelly F.

AU - Matamoros, Aurelio

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N2 - Objective: To assess the use of donor pigs with cellular chimerism for prevention of acute rejection with modest immune suppression. The clinical use of pig organ xenografts is currently precluded by severe acute rejection, which resists standard immune suppression. Summary Background Data: For long-term survival of pig organ xenografts, immune suppression significantly greater than used with allografts would currently be necessary, leaving the recipient immune deficient and at increased risk for infections. Induction of immune tolerance and tissue accommodation could enhance xenograft survival but would lead to complications and frequent graft failure. Induction of cellular chimerism within the donor pigs, however, could accomplish these goals before transplantation, significantly reducing the risk. Methods: Marrow cells from sheep were infused into fetal pigs. Heart xenografts from chimeric or nonchimeric pigs were transplanted heterotopically into recipient sheep, simultaneous with infusion of splenocytes. Posttransplant suppression consisted of cyclosporine and tapered corticosteroids, comparable with allotransplants. Results: All of the control grafts (n = 12) were rejected by acute vascular rejection in 4 to 8 days. In contrast, only one episode of vascular rejection was observed in the experimental group (n = 13). Four experimental recipients had an episode of moderate diffuse cellular rejection (grade 3) and one had moderate focal cellular rejection (grade 2). Each episode responded to pulse steroids. Seven grafts showed no significant rejection. There was little evidence of immune deficiency, infection, or toxicity. Conclusions: Acute vascular rejection was prevented in a large animal model without the need for severe immune suppression.

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