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Sartipy P.,Cellartis | Bjorquist P.,Cellartis
Stem Cells | Year: 2011

Considering the costs associated with drug development, there are billions of dollars to be saved by reducing latestage attrition in the pharmaceutical industries. Reports on the use of human pluripotent stem cells (hPSCs) and their functional derivatives in applications for safety assessment of drugs have begun to appear in the scientific literature. These reports are encouraging and fuel further developments of improved human cellular models that may increase the clinical relevance and reduce the need of experimental animals in preclinical drug discovery. However, a few factors still limit the general and wide-spread industry implementation of these new stem cell-based models, including cost of manufacture, level of functionality of the differentiated cells, assay validation, verification of human relevance, and benchmarking to conventional models. This review discusses the emerging field of hPSC-based models for drug discovery and development with a focus on cardiac and hepatic toxicity testing and how these approaches may improve current applications used in the pharmaceutical industry. Although much research remains to make hPSC-based models mainstream tools in the industry, importantly, this review highlights currently available opportunities. in addition, a forward looking discussion on novel applications using tissue preparations generated from hPSCs illustrates the opportunities to create complex models in vitro with the aim of simulating the systemic response of a drug in vivo. © AlphaMed Press.


The present invention relates to the use of 3D culturing systems for the derivation of hepatocyte-like cells from human pluripotent stem cells (hPS). In particular, the invention concerns the directed differentiation and maturation of human pluripotent stem cells into hepatocyte like cells in 3D hollow fiber capillary bioreactors.


The present invention relates to a novel hepatocyte-like cell population derived from hBS cells and to the potential use of such heopatocyte-like cells in e.g. medical treatment, drug screening and toxicity testing. Furthermore, the invention relates to 5 hepatoblast-like cells that may have suitable characteristics so that they can be used for the same applications as the hepatocyte-like cells and that furthermore may be used in in vitro studies of hepatogenesis such as early hepatogenesis or hepatoregenerative disorders. Both the hepatocyte-like and the hepatoblast-like cells according to the invention express drug transporter and/or drug metabolising 10 characteristics either at the gene or protein expression level.


Provided are improved methods using Glycogen synthase kinase 3 (GSK3) inhibitors by which endodermal cells, notably endodermal cells derived from human pluripotent stem cells (hPS), such as but not limited to hiPS-cells and hES-cells may be differentiated into hepatocyte like cells. The specific modulation of wingless integration gene (WNT)-signalling pathway and use of GSK3 inhibitors achieve direct differentiation and maturation of hepatocytes derived from human pluripotent stem (hPS) cells. GSK-3 inhibitors, when added to the growth medium at certain developmental stages, leads to more mature and functional features for the hepatocyte like cells as well as more pure and homogenous populations of hepatocyte like cells. Provided are also hepatocyte like cells obtained by these methods as well as compositions comprising them.


A novel population of multipotent cardiac precursor (MCP) cells derived from human blastocysts derived stem cells is disclosed, methods for the preparation thereof and use of the cells for in vitro testing. Basement cells derived from hBS cells are also disclosed and method for the preparation of MCP cells from basement cells. The MCP cells have the following characteristicsi) the cells exhibit no antigen expression of one or more markers for undifferentiated cell, the marker being selected from the group consisting of SSEA-3, SSEA-4, TRA-1-60, TRA-1-81 and Oct-4,ii) the cells exhibit no protein expression of one or more of a neural marker including nestin or GFAPiii) the cells exhibit protein and/or gene expression of one or more of a mesodermal marker including brachyury, vimentin or desminiv) the cells exhibit no protein and/or gene expression of one or more early stage cardiac marker such as, e.g., islet-1, cTNI, cTNT, Nkx2.5, alpha-MHC or connexin 43. Furthermore, the MCP cells have a characteristic morphology. They grow as clusters of small, round and phase-bright cells; individual cells are 5-20 m in diameter and each cluster is composed of 2-500 cells. They form clusters of round or elongated shape, that appear as loosely adherent cell clumps that as illustrated in figure 2 panel a, b and c. Furthermore, they have a relatively high nucleus-to-cytoplasma ratio, e.g. 1:2 - 1:64 of the total volume of the cell and/or appear as balloons on a string, as illustrated in figure 18, schematic sketch. Moreover, the MCP cells are non-contracting.


The present invention relates to the use of 3-dimensional (3D) synthetic or animal-derived bioscaffolds as substrates for the improved growth and differentiation of hPS (Human pluripotent stem cells); these scaffolds being adapted for use in conjunction with existing cell culture lab plastic-ware. More specifically, it relates to the seeding of these scaffolds, either alone or in conjunction with various biologic matrix coatings, with hPS cells for the improved differentiation of said hPS cells into hepatocyte or hepatocyte-like cell types. The invention also relates to the seeding of partially-differentiated hepatocyte progenitors onto scaffolds for further differentiation into more mature hepatocyte-cell types.


The present invention relates to the use of 3-dimensional (3D) synthetic or animal-derived bioscaffolds as substrates for the improved growth and differentiation of hPS (Human pluripotent stem cells); these scaffolds being adapted for use in conjunction with existing cell culture lab plastic-ware. More specifically, it relates to the seeding of these scaffolds, either alone or in conjunction with various biologic matrix coatings, with hPS cells for the improved differentiation of said hPS cells into hepatocyte or hepatocyte-like cell types. The invention also relates to the seeding of partially-differentiated hepatocyte progenitors onto scaffolds for further differentiation into more mature hepatocyte-cell types.


The present invention relates to a combined scalable in vitro differentiation and assay system based on human pluripotent cells. The present invention makes it possible to merge both the differentiation and the assay parts of the system into one. The advantage of the combined assay system is that the pluripotent stem cells and the cells derived therefrom in the differentiation system are directly applicable for assays, in large variety of assay units, such as different multiwell plates. The herein presented system is therefore a major improvement compared to the prior art, since the cells are differentiated in the same format as they are further being subject to analysis in. The starting cell material can be homogenously distributed across a variety of different plates, for use and can be cultured attached, semi attached or in suspension.


Patent
Cellartis and Novo Nordisk AS | Date: 2010-05-28

The present invention relates to a method to control differentiation of human pluripotent stem cells, including human balstocyst derived stem (hBS) cells and to obtain specific endoderm cells. In particular, present invention relates to the use of FGF2 as the key factor in a specific concentration to control differentiation of definitive endoderm cells derived from hPS cells to specific endoderm cells. The invention also provides methods of obtaining endoderm cells comprising the use of FGFR and activation of the MAPK signalling pathway.


The competitive landscape of the stem cells market is characterized by the rivalry between the leading participants, finds a report recently published by Transparency Market Research (TMR). The top players, namely, STEMCELL Technologies Inc., Advanced Cell Technology Inc., BioTime Inc., Cellular Engineering Technologies Inc., and Cellartis AB are engaged in extensive research activities, which has intensified the rivalry between them. With the increasing technological advancement of products, the competition is likely to intensify further over the next few years. According to TMR, the worldwide market for stem cells, which reached a value of US$62.2 bn in 2015, is likely to expand at an exponential CAGR of 24.20% between 2012 and 2018 and present a whopping opportunity worth US$119.5 bn by the end of the forecast period. Currently, adult stem cells report a higher demand than other stem cells and will continue to do so over the forecast period. Analysts predict the revenue generated from adult stem cells to reach US$103.8 bn by 2018. The study also presents an evaluation of the global stem cells market on the geographical basis. North America, Asia, Europe, and the Rest of the World have been identified as the main geographical segments of this market in this report. North America has been leading the demand for stem cells due to the increased prevalence of cardiovascular and neurological disorders in this region. Over the forecast period, North America is likely to remain dominant and offer an opportunity worth US$71.7 bn by 2012. Asia is also expected to register strong growth in the demand for stem cells due to the swift rise in medical tourism and contract research outsourcing during the forecast period, notes the study. Growing Awareness Level among Consumers Regarding Benefits of Stem Cells to Boost Demand “The growing awareness level among consumers regarding the benefits stem cells offer in the treatment of various diseases, such as cancer, is boosting their popularity across the world,” says the author of this study. Besides this, the rising government support to increase research activities in the field of stem cell has also emerged as an important factor behind the growth of this market. For instance, the surge in the Federal funding for the research of stem cells, after the bans were lifted from embryonic stem cells research in 2009, is likely to boost the market in the U.S. in the coming years. Similarly, the Europe market is expected to be propelled by the increasing involvement of government as well as private organizations to support research activities in stem cells. Implementation of Stringent Government Norms Regarding Stem Cell Harvesting to Hamper Market’s Growth While the market is witnessing lucrative growth prospects, the implementation of stringent government norms pertaining to the harvesting of stem cells is projected to limit their application substantially in the near future. Apart from this, treatments that apply stem cells are extremely expensive, which also is projected to hinder their adoption rate over the next few years, reflecting negatively on the overall growth of this market, states the research report. The study presented here is based on a report by Transparency Market Research (TMR) titled “Stem Cells Market (Adult, Human Embryonic , Induced Pluripotent, Rat-Neural, Umbilical Cord, Cell Production, Cell Acquisition, Expansion, Sub-Culture) - Global Industry Analysis, Size, Share, Growth, Trends and Forecast, 2012 - 2018.” Transparency Market Research (TMR) is a market intelligence company, providing global business information reports and services. Our exclusive blend of quantitative forecasting and trends analysis provides forward-looking insight for thousands of decision makers. TMR’s experienced team of analysts, researchers, and consultants, use proprietary data sources and various tools and techniques to gather, and analyze information. Our business offerings represent the latest and the most reliable information indispensable for businesses to sustain a competitive edge. Each TMR syndicated research report covers a different sector - such as pharmaceuticals, chemicals, energy, food & beverages, semiconductors, med-devices, consumer goods and technology. These reports provide in-depth analysis and deep segmentation to possible micro levels. With wider scope and stratified research methodology, TMR’s syndicated reports strive to provide clients to serve their overall research requirement.

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