Chimeric Pig Hearts Resist Hyperacute Rejection in ex vivo Perfusion Model

¹ Division of Transplantation, Department of Surgery
² Division of Clinical Perfusion Education, University of Nebraska Medical Center, Omaha, Nebraska
³ Ximerex Inc., Omaha, Nebraska

^* Address correspondence to: Tianyu Yang, MD, Lied Transplant Center, 687690 Nebraska Medical Center, Omaha, NE 68198-7690. E-mail: Tyang@unmc.edu

Received: 15 April 2000
Accepted: 24 July 2001

Abstract

With surrogate tolerogenesis, the recipient immune system is engrafted within the donor pig before organ transplant. Chimeric pig hearts may resist hyperacute rejection by inducing accommodation. This hypothesis was tested using an ex vivo isolated piglet heart perfusion model. Processed sheep marrow was infused into fetal pigs at 45 days gestation. Heart explants from chimeric or nonchimeric pigs were suspended in a Langendorff apparatus and perfused with plasma from unsensitized sheep or sensitized sheep. Nonchimeric hearts perfused with plasma from unsensitized functioned for 240 min (N = 3). Nonchimeric hearts perfused with sensitized plasma deteriorated rapidly, functioning at 19 ± 12 min (N = 6); Immunohistochemistry of heart graft revealed extensive deposition of IgG, IgM in the microvascular. In contrast, chimeric hearts perfused with sensitized plasma functioned for 183 ± 46 min (N = 3)(p <.001); Deposition of IgG, IgM had substantially less. Heart grafts procured from chimeric pigs survived in the presence of antidonor IgG, IgM, and complement, demonstrating that chimeric pig hearts resist hyperacute rejection.