In light of ongoing shortage of donor organs for transplantation, alternative sources for donor organ sources have been examined to address this supply-demand mismatch. Of these, xenotransplantation, or the transplantation of organs across species, has been considered, with early applications dating back to the 1600s. The purpose of this review is to summarize the early experiences of xenotransplantation, with special focus on heart xenotransplantation. It aims to highlight the important ethical concerns of animal-to-human heart xenotransplantation, identify the key immunological barriers to successful long-term xenograft survival, as well as summarize the progress made in terms of development of pharmacological and genetic engineering strategies to address these barriers. Lastly, we discuss more recent attempts of porcine-to-human heart xenotransplantation, as well as provide some commentary on the current concerns and possible applications for future clinical heart xenotransplantation.
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http://dx.doi.org/10.3389/frtra.2023.1125047 | DOI Listing |
Xenotransplantation
January 2025
Division of Cardiac Surgery, Department of Surgery, Children's Hospital of Los Angeles, Los Angeles, California, USA.
Introduction: There is no standard protocol for management of organ preservation for orthotopic, life-sustaining cardiac xenotransplantation, particularly for hearts from pediatric sized donors. Standard techniques and solutions successful in human allotransplantation are not viable. We theorized that a solution commonly used in reparative cardiac surgery in human children would suffice by exploiting the advantages inherent to xenotransplantation, namely the ability to reduce organ ischemic times by co-locating the donor and recipient.
View Article and Find Full Text PDFNat Med
January 2025
Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Following our previous experience with cardiac xenotransplantation of a genetically modified porcine heart into a live human, we sought to achieve improved results by selecting a healthier recipient and through more sensitive donor screening for potential zoonotic pathogens. Here we transplanted a 10-gene-edited pig heart into a 58-year-old man with progressive, debilitating inotrope-dependent heart failure due to ischemic cardiomyopathy who was not a candidate for standard advanced heart failure therapies. He was maintained on a costimulation (anti-CD40L, Tegoprubart) blockade-based immunomodulatory regimen.
View Article and Find Full Text PDFCarbohydr Polym
March 2025
Glycomics and Glycan Bioengineering Research Center (GGBRC), College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, China. Electronic address:
The major hurdle of xenotransplantation is the immune response triggered by human natural antibodies interacting with carbohydrate antigens on the transplanted animal organ. Specifically, terminal glycoprotein motifs such as galactose-α1,3-galactose (α-Gal) and N-glycolylneuraminic acid (Neu5Gc) are significant obstacles. Little is known about the abundance and compositions of asparagine-linked complex carbohydrates (N-glycans) carrying these motifs in mammalian organs.
View Article and Find Full Text PDFJ Heart Lung Transplant
January 2025
Division of Cardiac Surgery, Department of Surgery, Children's Hospital Los Angeles, Los Angeles, CA. Electronic address:
Objective: Genetically engineered porcine hearts may have an application for infants in need of a bridge to cardiac allotransplantation. The current animal model that resulted in 2 human applications has been validated in adult non-human primates only. We sought to create an infant animal model of life sustaining cardiac xenotransplantation to understand limitations specific to this age group.
View Article and Find Full Text PDFClin Transl Med
January 2025
Earle A. Chiles Research Institute, Providence Cancer Center, Portland, Oregon, USA.
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