Basic–Liver, Pancreas, and Biliary TractStem Cell Therapy for Liver Disease: Parameters Governing the Success of Using Bone Marrow Mesenchymal Stem Cells
Section snippets
Materials and Methods
Details of the materials and methods used are described in the supplementary material (see supplementary material online at www.gastrojournal.org). A brief summary of the animal model and cells used for transplantation is given in the following text.
MSCs and MDHs Rescue Lethal Fulminant Hepatic Failure
The lethality of CCl4 on NOD-SCID mice was tested by gavage. We determined that doses at ≤0.24 mL/kg body wt could not induce sufficient lethality, while doses at ≥0.32 mL/kg body wt elicited hyperacute injuries leading to rapid death. A dose of 0.28 mL/kg body wt was deemed optimal, resulting in lethality in all animals at 6 days after administration of CCl4 (Figure 1A). All subsequent experiments were therefore performed at this dose. Biochemical assays showed a dramatic elevation in the
Discussion
Using a murine model of lethal chemically induced FHF, we investigated various parameters governing the success and efficacy of using MSCs as an alternative cell source to hepatocyte transplantation for treatment of liver disease. Our data show that MDHs are a potential alternative transplantable cell source for the treatment of FHF. However, transplantation of MSCs improved the rescuing efficiency compared with MDHs. Further enhancements were accomplished by systemic transplantation compared
References (46)
Liver transplantation: current status and novel approaches to liver replacement
Gastroenterology
(2001)- et al.
Efficacy and safety of repeated hepatocyte transplantation for significant liver repopulation in rodents
Gastroenterology
(1996) - et al.
Hepatocyte transplantation
J Hepatol
(2004) - et al.
Liver from bone marrow in humans
Hepatology
(2000) - et al.
Isolation of multipotent mesenchymal stem cells from umbilical cord blood
Blood
(2004) - et al.
Stem cell characteristics of human trabecular bone-derived cells
Bone
(2002) - et al.
Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion
Blood
(2005) - et al.
Hepatocyte transplantation in acute liver failure
Liver Transpl
(2000) - et al.
A subset of human rapidly self-renewing marrow stromal cells preferentially engraft in mice
Blood
(2006) - et al.
Specificity of a phenobarbital-induced cytochrome P-450 for metabolism of carbon tetrachloride to the trichloromethyl radical
Biochem Pharmacol
(1982)
Detection of free radical formation in various tissues after acute carbon tetrachloride administration in gerbil
Life Sci
Mesenchymal stem cells remain of host origin even a long time after allogeneic peripheral blood stem cell or bone marrow transplantation
Exp Hematol
Therapeutic effect of transplanting HGF-treated bone marrow mesenchymal cells
J Hepatol
Advances in hepatocyte transplantation: a myth becomes reality
J Clin Invest
Emerging therapies in hepatology: liver-directed gene transfer and hepatocyte transplantation
Cells Tissues Organs
Liver repopulation: a new concept of hepatocyte transplantation
Surg Today
Cryopreservation of hepatocytes: a review of current methods for banking
Cell Tissue Bank
Bone marrow as a potential source of hepatic oval cells
Science
Hepatocytes from non-hepatic adult stem cells
Nature
Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion
Nature
Cell fusion is the principal source of bone-marrow-derived hepatocytes
Nature
Transplanted bone marrow regenerates liver by cell fusion
Nature
Mesenchymal stem cells in autoimmune disease
Stem Cells Dev
Cited by (428)
Liver Regeneration in Acute on Chronic Liver Failure
2023, Clinics in Liver DiseaseFuture regenerative medicine developments and their therapeutic applications
2023, Biomedicine and Pharmacotherapy
Supported by the National Science Council, Taiwan (grants NSC 95-2745-B-075-002-MY3 and NSC 95-2314-B-075-014-MY2), by the intramural grant from the Taipei Veterans General Hospital, Taiwan (grant V96S4-026), and by the Liver Disease Prevention and Treatment Research Foundation, Taiwan.
The authors report that no conflicts of interest exist.