Microchimerism after liver transplantation is considered to promote graft tolerance or tissue repair, but its significance is controversial. By using multiplex polymerase chain reaction (PCR) of short tandem repeat (STR) loci after laser capture microdissection of hepatocyte nuclei, we compared the proportions of recipient-derived hepatocytes in long-term stable liver allografts and late dysfunctional allografts caused by chronic rejection or idiopathic post-transplantation hepatitis. Through fluorescence in situ hybridization (FISH), we also analyzed the presence of recipient-derived Y-positive hepatocytes in the biopsies of livers transplanted from female donors to male recipients. The study population comprised 24 pediatric liver transplant recipients who survived with the initial graft, whose 10-year protocol biopsy records were available, and who had normal liver function (stable graft, SG; n=13) or a late dysfunctional graft (LDG; n=11) with similar follow-up periods (mean 10.8years in the SG group and 11.2years in the LDG group). STR analysis revealed that hepatocyte chimerism occurred in 7 of 13 (54%) SGs and 5 of 11 (45%) LDGs (p=0.68). The proportion of hepatocyte chimerism was low, with a mean of 3% seen in 2 of 3 female-to-male transplanted livers (one each of SG and LDG). In conclusion, hepatocyte chimerism was a constant event. The extent of engraftment of recipient-derived hepatocytes does not seem to correlate with the degree of hepatic injury in long-term liver allografts.
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http://dx.doi.org/10.1016/j.trim.2012.12.002 | DOI Listing |
Liver Int
June 2023
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Background And Aims: Human bone marrow mesenchymal stem cells (hBMSCs) are important for developing a dual-humanized mouse model to clarify disease pathogenesis. We aimed to elucidate the characteristics of hBMSC transdifferentiation into liver and immune cells.
Methods: A single type of hBMSCs was transplanted into immunodeficient Fah-/- Rag2-/- IL-2Rγc-/- SCID (FRGS) mice with fulminant hepatic failure (FHF).
J Viral Hepat
March 2023
Research Center for Hepatology and Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.
Although human hepatocyte-transplanted immunodeficient mice support infection with hepatitis viruses, these mice fail to develop viral hepatitis due to the lack of an adaptive immune system. In this study, we generated new immunodeficiency cDNA-urokinase-type plasminogen activator (uPA)/SCID/Rag2 /Jak3 mice and established a mouse model with both a humanized liver and immune system. Transplantation of human hepatocytes with human leukocyte antigen (HLA)-A24 resulted in establishment of a highly replaced liver in cDNA-uPA/SCID/Rag2 /Jak3 mice.
View Article and Find Full Text PDFStem Cell Reports
November 2021
Department of Surgery, Division of Transplant Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. Electronic address:
A reliable source of human hepatocytes and transplantable livers is needed. Interspecies embryo complementation, which involves implanting donor human stem cells into early morula/blastocyst stage animal embryos, is an emerging solution to the shortage of transplantable livers. We review proposed mutations in the recipient embryo to disable hepatogenesis, and discuss the advantages of using fumarylacetoacetate hydrolase knockouts and other genetic modifications to disable hepatogenesis.
View Article and Find Full Text PDFSci Rep
February 2021
Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
In order to increase the contribution of donor HSC cells, irradiation and DNA alkylating agents have been commonly used as experimental methods to eliminate HSCs for adult mice. But a technique of HSC deletion for mouse embryo for increase contribution of donor cells has not been published. Here, we established for the first time a procedure for placental HSC transplantation into E11.
View Article and Find Full Text PDFBiol Blood Marrow Transplant
April 2020
Pediatric Immuno-Hematology and Rheumatology Unit, Necker Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, AP-HP, Paris, France.
Congenital erythropoietic porphyria (CEP) is a rare disease characterized by erosive photosensitivity and chronic hemolysis due to a defect of the enzyme uroporphyrinogen-III-synthase (UROS). To date, hematopoietic stem cell transplantation (HSCT) is the only curative therapy for the devastating early and severe form of the disease. We describe 6 patients with CEP treated with HSCT (3 of them twice after failure of a first graft) between 1994 and 2016 in our center, including 2 of the very first living patients treated more than 20 years ago.
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