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The potential of adult human adipose tissue stem cells (hASCs) to differentiate into hepatocytes has generated much excitement over the possible use of hASCs in therapeutic applications. An understanding of the molecular mechanisms that underlie the plasticity of hASCs toward hepatocytes will help to make this possibility a reality. Herein, we show that a homogenous population of hASCs characterized by a high level of CD73, CD90, and CD105 express the pluripotent transcription factors OCT4, SOX2, NANOG, and SALL4 under proliferation conditions. A high level of activin A allows for hASCs acquiring the fate of definitive endoderm (DE) cells and expressing the specific transcription factors HEX, FOXA2, SOX17, and GATA4 synchronously. Using a reproducible three-stage method by mimicking liver embryogenesis, hASCs were directed to differentiate into functional hepatocytes. In the first stage, hASCs were induced to become DE cells by 2 days cultured in serum-free medium and 3 days of activin A treatment. Next, the presence of fibroblast growth factor (FGF) 4 and bone morphogenetic protein (BMP) 2 in the medium for 5 days induced efficient hepatic differentiation from DE cells. After 10 days of further maturated by the sequential exposure to hepatocyte growth factor (HGF), oncostatin M (OSM), and dexamethasone (DEX), the hASC-derived hepatocytes expressed mature hepatocytes marker and exhibited functional characterization, including albumin secretion, glycogen storage, urea production, activity of drug transporters, and cytochrome P450 activity. These findings will be useful for the implementation of hASC-derived hepatocytes in therapeutic purposes, metabolic analyses, drug toxicity screening, and studies of hepatocyte function., (© 2013 Wiley Periodicals, Inc.)

The correct functioning of hepatocytes requires the establishment and maintenance of hepatocyte polarity. However, the mechanisms regulating the generation of hepatocyte polarity are not completely understood. The differentiation of human fetal hepatic progenitor cells (hFHPCs) into functional hepatocytes provides a powerful in vitro model system for studying the molecular mechanisms governing hepatocyte development. In this study, we used a two-stage differentiation protocol to generate functional polarized hepatocyte-like cells (HLCs) from hFHPCs. Global gene expression profiling was performed on triplicate samples of hFHPCs, immature-HLCs and mature-HLCs. When the differential gene expression was compared based on the differentiation stage, a number of genes were identified that might be essential for establishing and maintaining hepatocyte polarity. These genes include those that encode actin filament-binding protein, protein tyrosine kinase activity molecules, and components of signaling pathways, such as PTK7, PARD3, PRKCI and CDC42. Based on known and predicted protein-protein interactions, the candidate genes were assigned to networks and clustered into functional categories. The expression of several of these genes was confirmed using real-time RT-PCR. By inactivating genes using small interfering RNA, we demonstrated that PTK7 and PARD3 promote hepatic polarity formation and affect F-actin organization. These results provide unique insight into the complex process of polarization during hepatocyte differentiation, indicating key genes and signaling molecules governing hepatocyte differentiation.

To investigate the effectiveness of adipose tissue-derived stem cells sheet combined with atelocollagen matrix on a mouse model of radiation-induced skin injury, adipose tissue-derived stem cells were harvested from the bilateral groin of mice and were screened out by fluorescence-activated cell sorting. Cell sheets were created on a temperature-responsive cell culture surface. The wound recovery rate was detected by measuring the injury area and the recovery shapes of wound were monitored by hematoxylin–eosin, Masson's trichrome, and immunohistochemical staining. Quantitative reverse transcription polymerase chain reaction and Western blot analysis were conducted to detect relative mRNA expression level of interleukin-1β and protein expression level of vascular endothelial growth factor, respectively. As results, the three-layer adipose tissue-derived stem cells sheet combined with atelocollagen matrix treatment promoted wound healing significantly compared to other treatments. More collagen, higher vessel density, and milder inflammation were observed in the group of three-layer adipose tissue-derived stem cells sheet combined with atelocollagen matrix compared with other treatments. Moreover, both mRNA expression level of interleukin-1β and protein expression level of vascular endothelial growth factor were drastically decreased in that group. In conclusion, three-layer adipose tissue-derived stem cells sheet combined with atelocollagen matrix could promote wound healing synergistically, providing a substantial advance in cell-based tissue engineering and wound healing. [ABSTRACT FROM AUTHOR]

Varicella-zoster virus (VZV) causes varicella (chicken pox) and establishes latency in ganglia. A reactivation of latent VZV leads to herpes zoster (shingles). Herpes zoster often causes herpetic pain that can last for months or years after the rash has healed. Prolonged herpetic pain is defined as post-herpetic neuralgia (PHN). There is an unmet need to explore novel therapeutic approaches for intractable PHN. Postmortem studies have shown that VZV induces neuro-inflammation and damage to the ganglia and spinal cord. These pathological changes may be critical factors resulting in PHN. Accumulated evidence suggests that stem cells may alleviate neuropathic pain in animal models through immunomodulatory actions and neuronal repair. Unfortunately, exogenous stem cell transplantation has limited clinical use due to safety concerns, immune rejection, and complications. Pharmacological mobilization of endogenous bone marrow stem cells may overcome these obstacles. Plerixafor is a SDF-1/CXCR4 axis blocker which can stimulate the release of stem cells from the bone marrow into blood circulation. We propose a hypothesis that endogenous stem cells mobilized by plerixafor may relieve the symptoms of PHN. If so, it may represent a novel approach for the treatment of intractable PHN. [ABSTRACT FROM AUTHOR]