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A study is conducted to demonstrate that Wnt signaling molecules activate the expression of distinct sets of genes characteristic for cardiac and skeletal muscle cells in mesenchymal adult stem cells (MASCs). The contribution of adult stem cells to the development of IL-4 and NFATc2/c3 mutant embryos was prevented by the disruption of IL-4 and NFATc2/c3 thus depicting the inability of the adult stem cells to fully differentiate into striated muscle in a cell-autonomous manner.

High-grade gliomas (HGG) exert systemic immunosuppression, which is of particular importance as immunotherapeutic strategies such as therapeutic vaccines are increasingly used to treat HGGs. In a first cohort of 61 HGG patients we evaluated a panel of 30 hematological and 34 plasma biomarkers. Then, we investigated in a second cohort of 11 relapsed HGG patients receiving immunomodulation with metronomic cyclophosphamide upfront to a DC-based vaccine whether immune abnormalities persisted and whether they hampered induction of IFNγ+ T-cell responses. HGG patients from the first cohort showed increased numbers of leukocytes, neutrophils and MDSCs and in parallel reduced numbers of CD4+/CD8+ T-cells, plasmacytoid and conventional DC2s. MDSCs and T-cell alterations were more profound in WHO IV° glioma patients. Moreover, levels of MDSCs and epidermal growth factor were negatively associated with survival. Serum levels of IL-2, IL-4, IL-5 and IL-10 were altered in HGG patients, however, without any impact on clinical outcome. In the immunotherapy cohort, 6-month overall survival was 100%. Metronomic cyclophosphamide led to > 40% reduction of regulatory T cells (Treg). In parallel to Treg-depletion, MDSCs and DC subsets became indistinguishable from healthy controls, whereas T-lymphopenia persisted. Despite low T-cells, IFNγ-responses could be induced in 9/10 analyzed cases. Importantly, frequency of CD8+VLA-4+ T-cells with CNS-homing properties, but not of CD4+ VLA-4+ T-cells, increased during vaccination. Our study identifies several features of systemic immunosuppression in HGGs. Metronomic cyclophosphamide in combination with an active immunization alleviates the latter and the combined treatment allows induction of a high rate of anti-glioma immune responses. [ABSTRACT FROM AUTHOR]

Multipotent stromal cells have become of increasing interest due to their potential to provide therapeutic approaches for autologous tissue repair. However, these cells are not well defined in the guinea pig, which represents an important model in hearing research. Adipose-tissue-derived stem cells (ADSC) and bone-marrow-derived stem cells (BMSC) were isolated from different donor sites, and growth curves were generated to judge the proliferation potential. Adipogenic, chondrogenic and osteogenic differentiation was induced and confirmed histologically. Finally, the capability of guinea pig ADSC to differentiate into neuron-like cells was investigated. With regard to the expansion potential, total cell number and doubling time, ADSC from the neck were the most suitable cells of the tested donor sites. Both ADSC and BMSC showed nearly identical behaviour and ability to undergo multilineage differentiation. Thus, we identified ADSC from the neck as a promising cell source for autologous cell-based approaches in hearing research using the guinea pig model. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article examines the effects of the transplantation of alleged cardiac stem cells into diseased hearts after myocardial infarction. The effects exerted by skeletal myoblasts and embryonic stem cell-derived cardiomyocytes were compared after implantation into infarcted mouse hearts. It was found that both cell types led to a long-lasting improvement of left ventricle function and to an improvement of tissue architecture.

During embryogenesis, various cell types can be programmed by potent inducers to follow distinct differentiation paths. In adult life, this ability seems to be restricted to specific multipotent cells. We have identified two cell populations from adult murine bone marrow which express various ‘sternness’ genes. Treatment with Wnt molecules induced transcription of different skeletal muscle marker genes and evoked expression of cardiomyocyte markers. Further characterization of Wnt-induced intracellular signaling cascades revealed that the skeletal muscle program depended on canonical Wnt signaling, while the induction of cardiomyocyte markers seems to require a protein kinase C-dependent pathway. CDO, another component of the machinery, directing skeletal muscle induction and expansion, selectively activated skeletal muscle- but not cardiomyocyte- specific genes. Although we were able to turn on various cell-type-specific markers by different induction regimens, we never obtained fully differentiated, functional cells. We conclude that the differentiation of adult stem cells is incomplete and lacks certain cues necessary to acquire a truly functional status. [ABSTRACT FROM AUTHOR]