Chondrogenic Differentiation in vitro of Murine Two-Factor Induced Pluripotent Stem Cells is Comparable to Murine Embryonic Stem Cells
ABSTRACT Differentiation of embryonic stem (ES) cells via embryoid bodies has been established as an appropriate model to study the development of various cell types in vitro. Here, we show that murine induced pluripotent stem (iPS) cells, reprogrammed by exogenous expression of the two transcription factors Oct4 and Klf4 (2F OK iPS), differentiate into chondrocytes in vitro characterized by the appearance of Alcian blue-stained nodules and the expression of cartilage-associated genes and proteins. Quantitatively, the chondrogenic differentiation potential of 2F OK iPS and ES cells was found to be similar. Further, we demonstrate the induction of chondrogenic iPS cell differentiation by certain members of the transforming growth factor-β family (BMP-2, TGF-β(1)). The number of Alcian blue-positive nodules and the expression of the cartilage marker molecule collagen type II increased after application of BMP-2, whereas simultaneous treatment with both BMP-2 and TGF-β(1) showed no significant effect on gene expression.
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ABSTRACT: Bone morphogenesis proteins (BMPs) are multi-functional growth factors. They are expressed in retina, retinal pigment epithelium (RPE) and sclera and serve as a regulator in the growth and development of the eye. This article reviewed the chondrogenic potency of the sclera, biochemical and pathological changes of myopic scleral tissue and the differentiation of chondrogenesis by BMP-2. We proposed the hypothesis that BMP-2 can regulate differentiate of scleral fibroblasts and affect the development of myopia.International Journal of Ophthalmology 01/2014; 7(1):152-156. DOI:10.3980/j.issn.2222-3959.2014.01.28 · 0.50 Impact Factor
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ABSTRACT: The evolution of articular cartilage repair procedures has resulted in a variety of cell-based therapies that use both autologous and allogeneic mesenchymal stromal cells (MSCs). As these cells are increasingly available and show promising results both in vitro and in vivo, cell-based strategies, which aim to improve ease of use and cost-effectiveness, are progressively explored. The use of MSCs in cartilage repair makes it possible to develop single-stage cell-based therapies. However, true single-stage procedures rely on one intervention, which will limit cell sources to fraction concentrates containing autologous MSCs or culture-expanded allogeneic MSCs. So far, it seems both autologous and allogeneic cells can safely be applied, but clinical studies are still ongoing and little information on clinical outcome is available. Further development of cell-based therapies may lead to clinical-grade, standardized, off-the-shelf products with easy handling for orthopedic surgeons. Although as of yet no preclinical or clinical studies are ongoing which explore the use of induced pluripotent stem cells for cartilage repair, a good manufacturing practice-grade induced pluripotent stem cell line might become the basis for such a product in the future, providing that cell fate can be controlled. The use of stem cells in clinical trials brings along new ethical issues, such as proper controls and selecting primary outcome measures. More clinical trials are needed to estimate detailed risk-benefit ratios and trials must be carefully designed to minimize risks and burdens for patients while choosing outcome measures that allow for adequate comparison with results from similar trials. In this review, we discuss the different aspects of new stem cell-based treatments, including safety and ethical issues, as well as provide an overview of current clinical trials exploring these approaches and future perspectives.Stem Cell Research & Therapy 05/2015; 6(1). DOI:10.1186/s13287-015-0086-1 · 4.63 Impact Factor