No abstract

␣ (IL-1R␣), IL-6, IL-8, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemotactic protein 1, nerve growth factor, and hepatocyte growth factor in a volume higher than both BMMSCs and NHDFs. Thus, our findings suggest that ATMSCs may account for their broad therapeutic efficacy in animal models of liver diseases and in the clinical settings for liver disease treatment. STEM CELLS 2008;26: 2705-2712 Disclosure of potential conflicts of interest is found at the end of this article.

Our data highlight the properties of ASC as having a special affinity for hepatocyte differentiation in vitro and liver regeneration in vivo. Thus, ASC may be a superior choice for the establishment of a therapy for injured liver.

The electromagnetic field (EMF) has a great impact on our body. It has been successfully used in physiotherapy for the treatment of bone disorders and osteoarthritis, as well as for cartilage regeneration or pain reduction. Recently, EMFs have also been applied in in vitro experiments on cell/stem cell cultures. Stem cells reside in almost all tissues within the human body, where they exhibit various potential. These cells are of great importance because they control homeostasis, regeneration, and healing. Nevertheless, stem cells when become cancer stem cells, may influence the pathological condition. In this article we review the current knowledge on the effects of EMFs on human adult stem cell biology, such as proliferation, the cell cycle, or differentiation. We present the characteristics of the EMFs used in miscellaneous assays. Most research has so far been performed during osteogenic and chondrogenic differentiation of mesenchymal stem cells. It has been demonstrated that the effects of EMF stimulation depend on the intensity and frequency of the EMF and the time of exposure to it. However, other factors may affect these processes, such as growth factors, reactive oxygen species, and so forth. Exploration of this research area may enhance the development of EMF-based technologies used in medical applications and thereby improve stem cell-based therapy and tissue engineering.

Severe hepatic dysfunctions including hepatic cirrhosis and hepatocarcinoma are life-threatening conditions for which effective medical treatments are needed. With the only effective treatment to date being orthotropic liver transplantation, alternative approaches are needed because of the limited number of donors and the possibility of immune-rejection. One alternative is regenerative medicine, which holds promise for the development of a cell-based therapy enabling hepatic regeneration through transplantation of adipose tissue-derived mesenchymal stem cells (AT-MSCs) or hepatocyte-like cells generated from AT-MSCs. When compared with embryonic stem (ES) cells and induced pluripotent stem (iPS) cells, the use of AT-MSCs as regenerative cells would be advantageous in regard to ethical and safety issues since AT-MSCs are somatic cells and have the potential to be used without in vitro culture. These autologous cells are immuno-compatible and exhibit controlled differentiation and multi-functional abilities and do not undergo post-transplantation rejection or unwanted differentiation such as formation of teratomas. AT-MSC-based therapies may provide a novel approach for hepatic regeneration and hepatocyte differentiation and thereby support hepatic function in diseased individuals.

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The specific features of the plasticity of adult stem cells are largely unknown. Recently, we demonstrated the hepatic differentiation of human adipose tissue-derived mesenchymal stem cells (AT-MSCs). To identify the genes responsible for hepatic differentiation, we examined the gene expression profiles of AT-MSC-derived hepatocytes (AT-MSC-Hepa) using several microarray methods. The resulting sets of differentially expressed genes (1639 clones) were comprehensively analyzed to identify the pathways expressed in AT-MSC-Hepa. Clustering analysis revealed a striking similarity of gene clusters between AT-MSC-Hepa and the whole liver, indicating that AT-MSC-Hepa were similar to liver with regard to gene expression. Further analysis showed that enriched categories of genes and signaling pathways such as complementary activation and the blood clotting cascade in the AT-MSC-Hepa were relevant to liver-specific functions. Notably, decreases in Twist and Snail expression indicated that mesenchymal-to-epithelial transition occurred in the differentiation of AT-MSCs into hepatocytes. Our data show a similarity between AT-MSC-Hepa and the liver, suggesting that AT-MSCs are modulated by their environmental conditions, and that AT-MSC-Hepa may be useful in basic studies of liver function as well as in the development of stem cell-based therapy.

Many studies on stem cell plasticity are challenging the concept that stem cells contain an intrinsically predefined, unidirectional differentiation program. This means that the developmental fate of a stem cell is dependent on the general potential of the cell (pre-determined stem cell fate) as well as on microenvironmental cues, such as stimuli from growth factors (stem cell niche). Here, we reviewed reports that examined the hepatocyte differentiation ability of stem cells from two different sources: embryonic stem cells and adult stem cells. All of those stem cells revealed the ability to give rise to hepatocyte-like cells using different induction strategies. However, it is still not clear which of those stem cells would be the best source for hepatocyte replacement or which would be the best protocol. We herein present the current knowledge regarding available protocols and factors used in order to obtain functional hepatocytes from stem cells. Developmental Dynamics 236:3228 -3241, 2007.