Abstract
The convergence of 3D bioprinting and genetic engineering is rapidly advancing the field of organ transplantation. Two major breakthroughs stand out: the creation of functional, vascularized liver tissue using 3D printing and the successful transplantation of CRISPR-edited pig organs into non-human primates and humans. These innovations are addressing the critical shortage of donor organs and hold promise for the future of regenerative medicine. This review summarizes recent achievements, underlying technologies, and presents a case study highlighting the clinical application of xenotransplantation.
1. Introduction
Organ transplantation remains the only definitive treatment for many end-stage organ diseases, yet the demand far exceeds the supply of donor organs. Innovations in 3D bioprinting and xenotransplantation-particularly using CRISPR gene editing-are creating new pathways to address this gap. This article reviews the latest scientific advances, focusing on bioprinted liver tissue and genetically engineered pig organs for transplantation.
2. 3D Bioprinted Liver Tissue: From Bench to Preclinical Testing
2.1 Technology Overview
3D bioprinting enables the precise layering of living cells and biomaterials to fabricate tissue constructs that mimic the architecture and function of native organs. A key challenge has been creating vascularized tissue that can survive and function after transplantation.
2.2 Recent Breakthrough
In 2024, researchers successfully printed functional, vascularized liver patches and transplanted them into mice. These patches demonstrated integration with host vasculature and maintained liver-specific functions, marking a significant step toward the development of implantable human liver tissue[Advanced Materials, 2024].
2.3 Implications
This achievement suggests that 3D bioprinted tissues could one day serve as bridge therapies or even as permanent organ replacements, reducing reliance on donor organs and improving outcomes for patients with liver failure.
3. CRISPR-Edited Pig Organs for Xenotransplantation
3.1 Scientific Advances
Xenotransplantation-the transplantation of organs from one species to another-has been revolutionized by CRISPR-Cas9 gene editing. By modifying pig genomes, scientists have created organs less likely to trigger immune rejection in humans and free of endogenous pig viruses[4][5][9].
Key genetic modifications include:
- Removing pig genes that provoke human immune responses
- Adding human genes to improve compatibility
- Inactivating porcine endogenous retroviruses to prevent infection[4][5][9]
3.2 Recent Successes
- Non-human primate studies: CRISPR-edited pig kidneys and hearts have been transplanted into primates, with survival times extending to several months[6][8].
- Human case studies: In 2024, a genetically edited pig kidney was transplanted into a living human with end-stage renal disease. The kidney functioned for over seven weeks, providing valuable data on safety and immune response[10].
- First pig-to-human heart transplants: Performed in 2022 and 2023, these procedures demonstrated that gene-edited pig hearts can provide life-sustaining function for several weeks in humans, although long-term survival remains a challenge[10].
3.3 Ongoing Clinical Trials
The FDA has approved formal clinical trials to test genetically modified pig kidneys in patients with kidney failure. These trials will provide standardized data on safety, efficacy, and long-term viability, moving the field closer to routine clinical application[7][9].
4. Case Study: Pig-to-Human Kidney Transplant
In March 2024, Massachusetts General Hospital performed a landmark surgery, transplanting a kidney from a CRISPR-edited pig (with 69 gene edits) into a 62-year-old patient with end-stage renal disease[10]. The kidney functioned well for 52 days, and there was no evidence of infection from pig viruses. Although the patient died from cardiac arrhythmia unrelated to the kidney, the case demonstrated the feasibility of using gene-edited pig organs to address organ shortages and provided critical insights into immune management and organ compatibility[10].
5. Discussion
These advances illustrate the transformative potential of combining 3D bioprinting with genetic engineering. Bioprinted tissues could eventually replace or supplement donor organs, while xenotransplantation with CRISPR-edited pig organs is already entering clinical trials. Major challenges remain, including long-term immune tolerance, risk of infection, and ethical considerations, but the progress achieved in recent years marks a new era in transplantation medicine.
6. Conclusion
Lab-grown organs and xenotransplantation are rapidly progressing from experimental models to clinical reality. 3D bioprinted liver tissues and CRISPR-edited pig organs offer hope for overcoming the global organ shortage, with early clinical results demonstrating both feasibility and promise. Continued research, regulatory oversight, and ethical debate will be essential as these technologies move toward wider clinical adoption.
Keywords: 3D bioprinting, liver tissue, xenotransplantation, CRISPR, gene editing, pig organs, organ transplantation, regenerative medicine.
Citations:
[1] Engineered Pig Organs for Human Transplant – Wyss Institute https://wyss.harvard.edu/technology/engineered-pig-organs-for-human-transplant/
[2] World’s First Genetically-Edited Pig Kidney Transplant into Living … https://www.massgeneral.org/news/press-release/worlds-first-genetically-edited-pig-kidney-transplant-into-living-recipient
[3] Gene-modified pig-to-human liver xenotransplantation – Nature https://www.nature.com/articles/s41586-025-08799-1
[4] In a First, Genetically Edited Pig Kidney Is Transplanted Into Human https://hms.harvard.edu/news/first-genetically-edited-pig-kidney-transplanted-human
[5] Pig kidney transplant raises hope but we’re far from fixing organ … https://www.sydney.edu.au/news-opinion/news/2024/04/10/first-pig-kidney-transplant-raises-hope–but-we-re-still-far-from-fixing-organ-shortages.html
[6] Driving Pig Organ Xenotransplantation Towards Clinical Trials https://advances.massgeneral.org/cardiovascular/article.aspx?id=1506
[7] The science behind the first pig-organ transplant trial in humans https://www.nature.com/articles/d41586-025-00368-w
[8] Genome editing for pig heart xenotransplantation – PubMed Central https://pmc.ncbi.nlm.nih.gov/articles/PMC10124774/
[9] FDA greenlights first clinical trials for genetically modified pig kidney … https://www.kidneyfund.org/article/fda-greenlights-first-clinical-trials-genetically-modified-pig-kidney-transplants-humans
[10] International Xenotransplantation Association (IXA) Position Paper … https://pmc.ncbi.nlm.nih.gov/articles/PMC11977855/
