Hanyang Med Rev.  2015 Nov;35(4):207-214. 10.7599/hmr.2015.35.4.207.

Advanced Research on Stem Cell Therapy for Hepatic Diseases: Potential Implications of a Placenta-derived Mesenchymal Stem Cell-based Strategy

• Kim GJ

• KMID: 2129473
• DOI: http://doi.org/10.7599/hmr.2015.35.4.207

Abstract

The category of chronic liver diseases comprise one of the most common medical diagnoses worldwide. Currently, orthotopic liver transplantation is the only effective treatment for end-stage hepatic disease, but this procedure is associated with many problems, including donor scarcity, operative damage, high cost, risk of immune rejection and lifelong immunosuppressive treatments. Thus, the development of new therapies is highly desirable. Cell therapy with stem cells is increasingly being used to repair damaged tissue or to promote organ regeneration. Stem cells, which possess self-renewal activity as well as differentiation potential, can be categorized as embryonic stem cells (ESCs) or adult stem cells (ASCs), which include hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). Recently, placenta-derived mesenchymal stem cells (PD-MSCs) have been reported, and they are attracting much interest in stem cell research for their multiple advantages: 1) no ethical concerns, 2) the ability to obtain abundant cell numbers, 3) multi-lineage differentiation potential, and 4) strong immunosuppressive properties. PD-MSCs differentiate into hepatocyte-like cells when exposed to hepatogenic differentiation-inducing conditions and PD-MSCs transplantation has been shown to enhance hepatic regeneration and/or survival in a rat hepatic failure model by suppressing the progression of fibrosis and apoptosis and activating autophagy. In this review, we will explain the characteristics of several kinds of PD-MSCs and discuss recent studies of the therapeutic potential of PD-MSCs in the repair of liver injury and their utility in regenerative medicine. Although many problems remain to be solved, many studies support the potential for human stem cell therapies, including PD-MSCs, as a promising new technology for the therapeutic regeneration of human liver intractably damaged due to chronic disease and/or toxic and environmental insult.

Keyword

Liver Failure; Cell Transplantation; Regeneration

MeSH Terms

Adult Stem Cells
Animals
Apoptosis
Autophagy
Cell Count
Cell Transplantation
Cell- and Tissue-Based Therapy
Chronic Disease
Diagnosis
Embryonic Stem Cells
Fibrosis
Hematopoietic Stem Cells
Humans
Liver
Liver Diseases
Liver Failure
Liver Transplantation
Mesenchymal Stromal Cells
Rats
Regeneration
Regenerative Medicine
Stem Cell Research
Stem Cells*
Tissue Donors

Figure

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  Fig. 1 Potential for hepatogenic differentiation by mesenchymal stem cells (MSCs). (A) The morphological changes (Left), ICG-uptake assay (Middle), and PSA staining for glycogen storage analysis (Right) of MSCs between undifferentiation (Upper) and differentiation (Lower) according to hepatogenic differentiation (×200). (B) Analysis of several hepatogenic-specific genes expression for hepatogenic differentiation using RT-PCR analysis. (C) Urea production in MSCs differentiated into hepatocyte-like cells using ELSIA assay. Data are expressed as means±SD. Statistical analysis was carried out by unpaired Student's t-tests (*P<0.005). Undiff and Diff means undifferentiated MSCs and hepatic differentiated MSCs, respectively. HepG2 cell line was used as a positive control of urea production. Ref. 9 with permission from John Wiley and Sons.

• 

  Fig. 2 Characterization of placenta-derived mesenchymal stem cells (PD-MSCs). (A) Morphology of amnion epithelial cells (AEC), chorionic plate-derived mesenchymal stem cells (CP), villi-derived mesenchymal stem cells (CV), and umbilical cord-derived stem cells (UC). Scale bars=50 µm. (B) RT-PCR for self-renewal markers (Oct-4, Nanog, Sox2, and TERT), three germinal layer markers (NF-68, Cadiac, and AFP) and immunomodulatory marker (HLA-G). β-actin was used as internal control. (C) Immunophenotype of placenta-derived stem cells. Third passage CP-MSCs and UC-MSCs were positive for CD90, CD13 and CD105, and negative for CD45, CD34, and CD31 by analysis of flow cytometry. It shows the data of HLA-ABC, HLA-DR, and HLA-G. Positive cells were evaluated compared with signal of isotype control and the percentages were indicated along with the fluorescence intensities. (D) Differentiation potentials of placenta-derived stem cells into mesodermal lineages including adipogenic (Oil-red O staining, upper), osteogenic (von Kossa staining, middle), and chondrogenic (Alcian Blue staining, lower) lineages. The cells were counterstained with hematoxylin. Scale bars=50 µm. Ref. 24 with permission from Springer.

• 

  Fig. 3 Prospective therapeutic mechanisms of placenta-derived mesenchymal stem cells (PD-MSCs) in rat models of hepatic diseases.

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