The Scaffold Derived from GGTA1 and CMAH Gene Knockout Pigs Provoked Little Inflammatory Responses in a Humanized Pig Model

Abstract

The attempt to produce a porcine small intestinal submucosa extracellular matrix (SIS-ECM) that is fully biocompatible was made. Samples of SIS-ECM were prepared from either wild-type (WT) or double-gene knockout (dKO) pigs without α-Gal and N-glycolylneuraminic acid (Neu5Gc) antigens. The scaffolds, which were sutured into cuts made in the longissimus muscle of the dKO pigs, were expected to exhibit xeno-reactions through natural antibodies as in a human response. A process was established to manufacture ameliorating acellular porcine SIS-ECM implants with consistent quality characteristics, which were assured by analyzing the level of residual DNA, the glycosaminoglycan content, and histochemical stains. Once implanted, the acellular SIS-ECM from the WT pigs caused a significant increase in serum IL-6 levels in the dKO recipient pigs, indicating a host defense through immune reactions. The levels remained unchanged when preparations from the dKO pigs were used. The results together with pathological evidences suggested that dKO pigs without antigenic response to α-Gal or Neu5Gc can serve as biocompatible SIS-ECM donors or as animal models for testing anthropomorphic immune responses to biomedical devices.