ArticleStem cell research & therapy2021
Liver development is restored by blastocyst complementation of HHEX knockout in mice and pigs.
Article in Stem cell research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 35 citations in OpenAlex.
- The making of cells and organs in xenogeneic animal bioreactor.Signal transduction and targeted therapy · 2026Review
- Rat cell-derived kidney generation via interspecies blastocyst complementation in an Osr1-KO mouse model.Stem cell reports · 2026Article
- A single-cell transcriptomic dataset of enterocyte-specific HHEX knockdown in the Drosophila larval midgut.Scientific data · 2025Article
- Gastruloid patterning reflects division of labor among biased stem cell clones.bioRxiv : the preprint server for biology · 2025Article
- Blastocyst complementation: current progress and future directions in xenogeneic organogenesis.Stem cell research & therapy · 2025Review
- Review
- Foxa1 disruption enhances human cell integration in human-mouse interspecies chimeras.Cell and tissue research · 2025Article
- Blastocyst complementation-based rat-derived heart generation reveals cardiac anomaly barriers to interspecies chimera development.iScience · 2024Article
- Producing Human Livers From Human Stem Cells Via Blastocyst Complementation.Current opinion in biomedical engineering · 2024Article
- Genetic engineering drives the breakthrough of pig models in liver disease research.Liver research (Beijing, China) · 2024Review
- The HHEX-ABI2/SLC17A9 axis induces cancer stem cell-like properties and tumorigenesis in HCC.Journal of translational medicine · 2024Article
- Chimeric Livers: Interspecies Blastocyst Complementation and Xenotransplantation for End-Stage Liver Disease.Hepatic medicine : evidence and research · 2024Review
- Human and Pig Pluripotent Stem Cells: From Cellular Products to Organogenesis and Beyond.Cells · 2023Review
- Novel Haplotype in theGenes · 2023Article
- Development of a Method for the In Vivo Generation of Allogeneic Hearts in Chimeric Mouse Embryos.International journal of molecular sciences · 2023Article
- The Haematopoietically-expressed homeobox transcription factor: roles in development, physiology and disease.Frontiers in immunology · 2023Review
- Towards human organ generation using interspecies blastocyst complementation: Challenges and perspectives for therapy.Frontiers in cell and developmental biology · 2023Review
- From a Single Cell to a Whole Human Liver: Disease Modeling and Transplantation.Seminars in liver disease · 2022Article
- Review
- Characterization of the intraspecies chimeric mouse brain at embryonic day 12.5.Cell transplantationArticle
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThere are over 17,000 patients in the US waiting to receive liver transplants, and these numbers are increasing dramatically. Significant effort is being made to obtain functional hepatocytes and liver tissue that can for therapeutic use in patients. Blastocyst complementation is a challenging, innovative technology that could fundamentally change the future of organ transplantation. It requires the knockout (KO) of genes essential for cell or organ development in early stage host embryos followed by injection of donor pluripotent stem cells (PSCs) into host blastocysts to generate chimeric offspring in which progeny of the donor cells populate the open niche to develop functional tissues and organs.
methodsThe HHEX gene is necessary for proper liver development. We engineered loss of HHEX gene expression in early mouse and pig embryos and performed intraspecies blastocyst complementation of HHEX KO embryos with eGFP-labeled PSCs in order to rescue the loss of liver development.
resultsLoss of HHEX gene expression resulted in embryonic lethality at day 10.5 in mice and produced characteristics of lethality at day 18 in pigs, with absence of liver tissue in both species. Analyses of mouse and pig HHEX KO fetuses confirmed significant loss of liver-specific gene and protein expression. Intraspecies blastocyst complementation restored liver formation and liver-specific proteins in both mouse and pig. Livers in complemented chimeric fetuses in both species were comprised of eGFP-labeled donor-derived cells and survived beyond the previously observed time of HHEX KO embryonic lethality.
conclusionsThis work demonstrates that loss of liver development in the HHEX KO can be rescued via blastocyst complementation in both mice and pigs. This complementation strategy is the first step towards generating interspecies chimeras for the goal of producing human liver cells, tissues, and potentially complete organs for clinical transplantation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.