Systemic administration of a novel human umbilical cord mesenchymal stem cells population accelerates the resolution of acute liver injury

Autor: Andrea Cappon, Antara Banerjee, Debora Bizzaro, Umberto Cillo, Enrico Gringeri, Pier Paolo Parnigotto, Amedeo Carraro, Francesco Paolo Russo, Patrizia Burra, T. Chioato, Silvia Mirandola, Diletta Arcidiacono, Maria Teresa Conconi, Rosa Di Liddo, P. Bo
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Male
Pathology
Biocompatible Materials
Cell Separation
Acute Lung Injury
Albumins
Animals
Biomarkers
Carbon Tetrachloride
Catalase
Cell Differentiation
Cells
Cultured
Cytokines
Glycogen
Humans
Immunohistochemistry
Liver Regeneration
Mice
Transcriptome
Transplantation
Heterologous
Urea
alpha-Fetoproteins
Cord Blood Stem Cell Transplantation
Mesenchymal Stem Cell Transplantation
Medicine
Stem cell transplantation for articular cartilage repair
Heterologous
Cultured
Gastroenterology
Amniotic stem cells
General Medicine
Liver regeneration
Regenerative medicine
Stem cell
Adult stem cell
Research Article
medicine.medical_specialty
Cells
Acute liver injury
lcsh:RC799-869
Umbilical cord
Transplantation
Mesenchymal stem cells
Hepatocyte-like cells
Cell transplantation
business.industry
Mesenchymal stem cell
Hepatic stellate cell
lcsh:Diseases of the digestive system. Gastroenterology
business
Zdroj: Università degli Studi di Padova-IRIS
BMC Gastroenterology
BMC Gastroenterology, Vol 12, Iss 1, p 88 (2012)
Popis: Background Hepatocytes and stem cells transplantation may be an alternative to liver transplantation in acute or chronic liver disease. We aimed to evaluate the therapeutic potential of mesenchymal stem cells from human umbilical cord (UCMSCs), a readily available source of mesenchymal stem cells, in the CCl4-induced acute liver injury model. Methods Mesenchymal stem cells profile was analyzed by flow cytometry. In order to evaluate the capability of our UCMSCs to differentiate in hepatocytes, cells were seeded on three different supports, untreated plastic support, MatrigelTM and human liver acellular matrix. Cells were analyzed by immunocitochemistry for alpha-fetoprotein and albumin expression, qPCR for hepatocyte markers gene expression, Periodic Acid-Schiff staining for glycogen storage, ELISA for albumin detection and colorimetric assay for urea secretion. To assess the effects of undifferentiated UCMSCs in hepatic regeneration after an acute liver injury, we transplanted them via tail vein in mice injected intraperitoneally with a single dose of CCl4. Livers were analyzed by histological evaluation for damage quantification, immunostaining for Kupffer and stellate cells/liver myofibroblasts activation and for UCMSCs homing. Pro- and anti-inflammatory cytokines gene expression was evaluated by qPCR analysis and antioxidant enzyme activity was measured by catalase quantification. Data were analyzed by Mann–Whitney U-test, Kruskal-Wallis test and Cuzick’s test followed by Bonferroni correction for multiple comparisons. Results We have standardized the isolation procedure to obtain a cell population with hepatogenic properties prior to in vivo transplantation. When subjected to hepatogenic differentiation on untreated plastic support, UCMSCs differentiated in hepatocyte-like cells as demonstrated by their morphology, progressive up-regulation of mature hepatocyte markers, glycogen storage, albumin and urea secretion. However, cells seeded on 3D-supports showed a minor or negligible differentiation capacity. UCMSCs-transplanted mice showed a more rapid damage resolution, as shown by histological analysis, with a lower inflammation level and an increased catalase activity compared to CCl4-treated mice. Conclusions Our findings show that UCMSCs can be reliably isolated, have hepatogenic properties and following systemic administration are able to accelerate the resolution of an acute liver injury without any differentiation and manipulation. These features make UCMSCs strong candidates for future application in regenerative medicine for human acute liver disease.
Databáze: OpenAIRE
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