Scaffold derived from GGTA1 and CMAH double knockout pigs elicits only slight inflammation in a gene-edited pig model
Journal
Materialia
Journal Volume
14
Date Issued
2020
Author(s)
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. Statement of significance: Xenograft‐derived scaffold, even acellular thoroughly, still meets a challenge of Neu5Gc antigen presented in the ECM, including SIS- and corneal-ECM. Double knock out (dKO) pigs with depleted α-Gal and nullified Neu5Gc shall be a valuable source for procurement of tissues for biomaterial manufacturing. This value is indicated by the evidences that the SIS-ECM prepared from them, not from wild type (WT) animals, elicited no changes in inflammation indicator and pathological studying if implanted into a humanized porcine model α-Gal and Neu5Gc absent. Scaffold prepared from dKO pigs provides a further improvement of biocompability and those animals should be used as a testing model for evaluating anthropomorphic immune responses of whatever biomaterial or biomedical devices.
SDGs
Publisher
Elsevier B.V.
Type
journal article