Heart xenograft survival with chimeric pig donors and modest immune suppression.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • February 2003

Published In

Volume / Issue

  • 237 / 2

Start / End Page

  • 265 - 272

PubMed ID

  • 12560785

Pubmed Central ID

  • 12560785

International Standard Serial Number (ISSN)

  • 0003-4932

Digital Object Identifier (DOI)

  • 10.1097/01.SLA.0000048456.81319.DA

Language

  • eng

Conference Location

  • United States