No abstract available.
Activins* ; Regeneration*

No abstract available.
Activins* ; Humans ; Telangiectasia, Hereditary Hemorrhagic* ; Telangiectasis*

No abstract available.
Activins* ; Humans ; Telangiectasia, Hereditary Hemorrhagic* ; Telangiectasis*

PURPOSE: The most important consideration for therapy using MSCs is the differentiation of the target organ's cell type. For in-vitro hepatogenic differentiation of MSCs, the main focus is efficient induction of the MSCs into the endoderm stage. Activin A, which is a signaling molecule that is similar to Nodal, promotes the induction of definitive endoderm from both ESs and MSCs. The protocols for induction into definitive endoderm have shown different efficiency and reproducibility depending on the researchers or the sources of the MSCs. Thus, a study on the various conditions of Activin A is needed to efficiently differentiate MSCs into the definitive endoderm lineage of MSCs. METHODS: MSCs were isolated from human adipose tissues and these were cultured in MCM (MSCs Culture Medium) on a human fibronectin coated plate. At 70~80% confluence, the MSCs were harvested and cultured in MCM supplemented with Activin A, at a 50 ng/mL concentration, and FGF4. The expression of the genes related with MSCs or primitive endoderm were analyzed by RT-PCR. The changes of cell morphology for differentiation were also observed by a light microscope & a SEM. RESULTS: The expression of genes related with primitive foregut endoderm was seen in the groups that were treated with a higher concentration of Activin A. The morphology of the cells that differentiated into definitive endoderm were not different from those of the undifferentiated MSCs. The expression of genes related with functional primitive hepatocytes was seen in the early phase during hepatic differentiation. The cell morphology was changed to a similar cuboidal form in a time-dependent manner. CONCLUSION: Activin A promotes a more rapid induction of definitive endoderm. It also makes an efficient condition for the differentiation into primitive foregut endoderm at a higher concentration.
Activins ; Endoderm ; Fibronectins ; Hepatocytes ; Humans ; Light

PURPOSE: The most important consideration for therapy using MSCs is the differentiation of the target organ's cell type. For in-vitro hepatogenic differentiation of MSCs, the main focus is efficient induction of the MSCs into the endoderm stage. Activin A, which is a signaling molecule that is similar to Nodal, promotes the induction of definitive endoderm from both ESs and MSCs. The protocols for induction into definitive endoderm have shown different efficiency and reproducibility depending on the researchers or the sources of the MSCs. Thus, a study on the various conditions of Activin A is needed to efficiently differentiate MSCs into the definitive endoderm lineage of MSCs. METHODS: MSCs were isolated from human adipose tissues and these were cultured in MCM (MSCs Culture Medium) on a human fibronectin coated plate. At 70~80% confluence, the MSCs were harvested and cultured in MCM supplemented with Activin A, at a 50 ng/mL concentration, and FGF4. The expression of the genes related with MSCs or primitive endoderm were analyzed by RT-PCR. The changes of cell morphology for differentiation were also observed by a light microscope & a SEM. RESULTS: The expression of genes related with primitive foregut endoderm was seen in the groups that were treated with a higher concentration of Activin A. The morphology of the cells that differentiated into definitive endoderm were not different from those of the undifferentiated MSCs. The expression of genes related with functional primitive hepatocytes was seen in the early phase during hepatic differentiation. The cell morphology was changed to a similar cuboidal form in a time-dependent manner. CONCLUSION: Activin A promotes a more rapid induction of definitive endoderm. It also makes an efficient condition for the differentiation into primitive foregut endoderm at a higher concentration.
Activins ; Endoderm ; Fibronectins ; Hepatocytes ; Humans ; Light

Pregnancy ; Female ; Humans ; Activins ; Hypertension ; Biomarkers

BACKGROUND: B cell-activating factor belonging to the TNF family (BAFF) is primarily expressed by macrophages and dendritic cells, and stimulates B cell proliferation, differentiation, survival, and Ig production. In the present study, we explored the effect of activin A on BAFF expression by APCs. METHODS: To investigate the effect of activin A on BAFF expression by mouse APCs, we measured the level of BAFF expression at the transcriptional and protein levels using RT-PCR and ELISA. RESULTS: Activin A markedly enhanced BAFF expression in mouse macrophages and dendritic cells at both the transcriptional and protein levels. SB431542, an activin receptor-like kinase 4 (ALK4) inhibitor, completely abrogated activin A-induced BAFF transcription. Furthermore, overexpression of DN-Smad3 abolished activin-induced BAFF expression at the transcriptional and protein levels. CONCLUSION: These results demonstrate that activin A can enhance BAFF expression through ALK4-Smad3 pathway.
Activin Receptors ; Activins ; Animals ; Benzamides ; Cell Proliferation ; Dendritic Cells ; Dioxoles ; Humans ; Macrophages ; Mice

PURPOSE: Whole liver transplantation has limitation including donor shortage and fatal surgical complications. Hepatocyte transplantation, which is simpler and less expensive than whole liver transplantation, allows the use of living related donors, permits the use of a single donor organ for multiple recipients. However, hepatocytes have limitation in proliferation and lose their property during culture period. To over come these problems, here we performed differentiation of human embryonic stem cells (hESCs) into definitive endoderm in order to differentiate into hepatocytes efficiently. METHODS: Undifferentiated hESCs were maintained on mouse embryo fibroblast feeder (MEF) layer for 5~7 days. For endoderm differentiation, we used modified Kevin A D'Amour's method that added 100 ng/mL Activin A for 5 days. After differentiation, differentiated endodermal cells were collected and RT-PCR and immunostain analysis were performed. RESULTS: After 5 days of differentiation period, hES cells showed endoderm committed-cells and increased expression of endoderm-specific marker genes (Sox17 and Foxa2). Also differentiated endoderm cells were stained with Sox17 and Foxa2 whereas undifferentiated hES cells were not stained with Sox17, Foxa2. CONCLUSION: In vitro differentiotion from hES cells to definitive endoderm was done repetitively by our methods. Further well defined protocol for differentiation of definitive endoderm to hepatocytes should be made.
Activins ; Animals ; Embryonic Stem Cells* ; Embryonic Structures ; Endoderm* ; Fibroblasts ; Hepatocytes ; Humans* ; Liver Transplantation ; Mice ; Tissue Donors

It is not fully clear why there is a higher contribution of pluripotent stem cells (PSCs) to the chimera produced by injection of PSCs into 4-cell or 8-cell stage embryos compared with blastocyst injection. Here, we show that not only embryonic stem cells (ESCs) but also induced pluripotent stem cells (iPSCs) can generate F0 nearly 100% donor cell-derived mice by 4-cell stage embryo injection, and the approach has a "dose effect". Through an analysis of the PSC-secreted proteins, Activin A was found to impede epiblast (EPI) lineage development while promoting trophectoderm (TE) differentiation, resulting in replacement of the EPI lineage of host embryos with PSCs. Interestingly, the injection of ESCs into blastocysts cultured with Activin A (cultured from 4-cell stage to early blastocyst at E3.5) could increase the contribution of ESCs to the chimera. The results indicated that PSCs secrete protein Activin A to improve their EPI competency after injection into recipient embryos through influencing the development of mouse early embryos. This result is useful for optimizing the chimera production system and for a deep understanding of PSCs effects on early embryo development.
Activins ; metabolism ; Animals ; Cells, Cultured ; Embryonic Development ; Germ Layers ; metabolism ; Mice ; Pluripotent Stem Cells ; cytology ; metabolism

Delivery of follistatin (FST) represents a promising strategy for both muscular dystrophies and diabetes, as FST is a robust antagonist of myostatin and activin, which are critical regulators of skeletal muscle and adipose tissues. FST is a multi-domain protein, and deciphering the function of different domains will facilitate novel designs for FST-based therapy. Our study aims to investigate the role of the N-terminal domain (ND) of FST in regulating muscle and fat mass in vivo. Different FST constructs were created and packaged into the adeno-associated viral vector (AAV). Overexpression of wild-type FST in normal mice greatly increased muscle mass while decreasing fat accumulation, whereas overexpression of an N terminus mutant or N terminus-deleted FST had no effect on muscle mass but moderately decreased fat mass. In contrast, FST-I-I containing the complete N terminus and double domain I without domain II and III had no effect on fat but increased skeletal muscle mass. The effects of different constructs on differentiated C2C12 myotubes were consistent with the in vivo finding. We hypothesized that ND was critical for myostatin blockade, mediating the increase in muscle mass, and was less pivotal for activin binding, which accounts for the decrease in the fat tissue. An in vitro TGF-beta1-responsive reporter assay revealed that FST-I-I and N terminus-mutated or -deleted FST showed differential responses to blockade of activin and myostatin. Our study provided direct in vivo evidence for a role of the ND of FST, shedding light on future potential molecular designs for FST-based gene therapy.
Activins ; Animals ; Follistatin* ; Genetic Therapy ; In Vitro Techniques ; Mice ; Muscle Fibers, Skeletal ; Muscle, Skeletal ; Muscular Dystrophies ; Myostatin ; Negotiating