Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion
Abstract
Hepatic transdifferentiation of bone marrow cells has been previously demonstrated by intravenous administration of donor cells, which may recirculate to the liver after undergoing proliferation and differentiation in the recipient's bone marrow. In the present study, to elucidate which cellular components of human bone marrow more potently differentiate into hepatocytes, we fractionated human bone marrow cells into mesenchymal stem cells (MSCs), CD34+ cells, and non-MSCs/CD34- cells and examined them by directly xenografting to allylalcohol (AA)-treated rat liver. Hepatocyte-like cells, as revealed by positive immunostaining for human-specific alpha-fetoprotein (AFP), albumin (Alb), cytokeratin 19 (CK19), cytokeratin 18 (CK18), and asialoglycoprotein receptor (AGPR), and by reverse transcription-polymerase chain reaction (RT-PCR) for expression of AFP and Alb mRNA, were observed only in recipient livers with MSC fractions. Cell fusion was not likely involved since both human and rat chromosomes were independently identified by fluorescence in situ hybridization (FISH). The differentiation appeared to follow the process of hepatic ontogeny, reprogramming of gene expression in the genome of MSCs, as evidenced by expression of the AFP gene at an early stage and the albumin gene at a later stage. In conclusion, we have demonstrated that MSCs are the most potent component in hepatic differentiation, as revealed by directly xenografting into rat livers. (Blood. 2005;106:756-763)
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The efficacy of hepatocyte-like differentiation of MSCs is markedly low, comprising less than 1% of the total liver mass, despite direct intrahepatic or intrasplenic injections.
“Nevertheless, the efficacy of hepatocyte-like differentiation of MSCs is markedly low, comprising less than 1% of the total liver mass, despite direct intrahepatic or intrasplenic injections [93, 94].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [93]
BM-hMSCs directly xenografted into allyl alcohol-treated rat livers can differentiate into HLCs without cell fusion.
“Sato et al. demonstrated that BM-hMSCs directly xenografted into allyl alcohol-treated rat livers could differentiate into HLCs without cell fusion [93].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [93]
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“Nevertheless, the efficacy of hepatocyte-like differentiation of MSCs is markedly low, comprising less than 1% of the total liver mass, despite direct intrahepatic or intrasplenic injections [93, 94].”
- Authors
- Sato, Y., Araki, H., Kato, J., Nakamura, K., Kawano, Y., Kobune, M., Sato, T., Miyanishi, K., Takayama, T., Takahashi, M., Takimoto, R., Iyama, S., Matsunaga, T., Ohtani, S., Matsuura, A., Hamada, H., & Niitsu, Y.
- Affiliations
- Sapporo Medical University (JP)
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2005-07-15
- Volume
- 106
- Issue
- 2
- Pages
- 756-763
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2161820725
- Cited by
- 610
- References
- 1
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 5 · 2023: 3 · 2022: 8 · 2021: 19 · 2020: 18 · 2019: 20 · 2018: 26 · 2017: 26 · 2016: 28 · 2015: 34 · 2014: 47 · 2013: 53 · 2012: 51
- FWCI
- 20.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- mesenchymal stem cells, hepatocyte differentiation, bone marrow cells, xenotransplantation, cell fusion, alpha-fetoprotein, albumin, cytokeratin, asialoglycoprotein receptor, gene expression reprogramming, CD34+ cells
- MeSH terms
- Albumins, alpha-Fetoproteins, Animals, Cell Count, Cell Differentiation, Female, Humans, Immunohistochemistry, Keratins, Liver, Membrane Fusion, RNA, Messenger, Transplantation, Heterologous, Gene Expression, Rats, Sprague-Dawley, In Situ Hybridization, Fluorescence, Antigens, CD34, Hepatocytes, Asialoglycoprotein Receptor, Mesenchymal Stem Cell Transplantation, Rats, Mesenchymal Stem Cells
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