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

BMC Gastroenterology

Francesco Paolo Russo³  Umberto Cillo³  Amedeo Carraro³  Enrico Gringeri³  Silvia Mirandola⁴  Pier Paolo Parnigotto²  Maria Teresa Conconi¹  Patrizio Bo²  Andrea Cappon³  Antara Banerjee³  Rosa Di Liddo¹  Tatiana Chioato¹  Debora Bizzaro³  Diletta Arcidiacono³  Patrizia Burra³ 

[1] Department of Pharmaceutical Sciences, University of Padua, Padua, Italy;Obstetrics and Gynecology Unit, Cittadella Hospital, Padua, Italy;Gastroenterology, Department of Surgical, Oncological and Gastroenterological Sciences, Padova University Hospital, Via Giustiniani 2, Padova, 35128, Italy;VIMM-Venetian Institute of Molecular Medicine, Padua, Italy

关键词: Regenerative medicine;    Acute liver injury;    Cell transplantation;    Hepatocyte-like cells;    Umbilical cord;    Mesenchymal stem cells;   

Others  :  1113008
DOI  :  10.1186/1471-230X-12-88

 received in 2011-11-21, accepted in 2012-07-12,  发布年份 2012

【 摘 要 】

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, Matrigel^TM 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.

【 授权许可】

   
2012 Burra et al.; licensee BioMed Central Ltd.

【 图 表 】

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