Eggenhofer, Elke and Popp, Felix C. and Renner, Philipp and Slowik, Pczemyslaw and Neuwinger, Annette and Piso, Pompiliu and Geissler, Edward K. and Schlitt, Hans J. and Dahlke, Marc H. (2008) Allogeneic bone marrow transplantation restores liver function in Fah-knockout mice. EXPERIMENTAL HEMATOLOGY, 36 (11). pp. 1507-1513. ISSN 0301-472X,
Full text not available from this repository. (Request a copy)Abstract
Objective. In murine models, transplantation of wild-type bone marrow cells (BMC) can counterbalance genetic liver defects by fusion between transplanted marrow cells and resident hepatocytes. This phenomenon, however, is of no immediate clinical use because all syngeneic BMC harbor the same underlying genetic defect. Materials and Methods. Describing the fusion between transplanted allogeneic BMC and resident hepatocytes in a murine model of hereditary tyrosinemia type I (fumarylacetoacetate hydrolase [Fah] knockout mouse), we transplanted BMC from fully allogeneic BALB/c donors into Fah(-/-) recipients after lethal total body irradiation. Results. Following hematopoietic reconstitution, recipients remained healthy without pharmacological support (withdrawal of 2-2-nitro-4-fluoromethylbenzoyl-1,3-cyclohexanedione [NTBC]). Metabolic serum parameters improved nearly to wild-type levels. Livers of recipient animals contained up to 10% functional hepatocytes that stained positive for wild-type Fah, as well as both donor and recipient major histocompatibility complex. Flow cytometry confirmed this coexpression on a single cell level. Application of T-cell-depleted bone marrow reduced onset of early graft-vs-host disease. Conclusions. We introduce the observation that allogeneic bone marrow transplantation can lead to stable cell fusion of BMC with recipient hepatocytes and restored liver function in a model of otherwise lethal genetic liver disease. Thus, in principle, allogeneic cell fusion can be a possible management of hereditary liver diseases. Long-term immunological properties of fusion cells have to be further investigated. (c) 2008 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | VERSUS-HOST-DISEASE; HEMATOPOIETIC STEM-CELLS; MYELOMONOCYTIC CELLS; MUSCLE REGENERATION; HEPATIC-DYSFUNCTION; SKELETAL-MUSCLE; FUSION; HEPATOCYTES; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 19 Oct 2020 09:44 |
| Last Modified: | 19 Oct 2020 09:44 |
| URI: | https://pred.uni-regensburg.de/id/eprint/30096 |
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