NovaHep AB

Stockholm, Sweden

NovaHep AB

Stockholm, Sweden

Time filter

Source Type

Patent
NovaHep AB | Date: 2015-05-27

The present disclosure relates to methods for recellularization of valves in valve-bearing veins. This method is useful for producing an allogeneic venous valve, wherein a donor valve-bearing vein is decellularized and then recelluiarized using whole blood or bone marrow stem cells. The allogeneic valves produced by the methods disclosed herein are advantageous for implantation, transplantation, or grafting into patients with vascular diseases.


Patent
Novahep Ab | Date: 2016-06-01

The present invention relates to methods for recellurization of blood vessels. This method is particularly useful for producing an allogeneic vein, wherein a donor vein is decellularized and then recellularized using whole blood or bone marrow stem cells. The allogeneic veins produced by the methods disclosed herein are particularly advantageous for implantation or transplantation into patients with vascular diseases.


Patent
Novahep AB | Date: 2017-04-05

The present disclosure relates to methods for recellularization of valves in valve-bearing veins. This method is useful for producing an allogeneic venous valve, wherein a donor valve-bearing vein is decellularized and then recelluiarized using whole blood or bone marrow stem cells. The allogeneic valves produced by the methods disclosed herein are advantageous for implantation, transplantation, or grafting into patients with vascular diseases.


Godoy P.,TU Dortmund | Godoy P.,University of Concepción | Schmidt-Heck W.,Leibniz Institute for Natural Product Research and Infection Biology | Natarajan K.,University of Cologne | And 19 more authors.
Journal of Hepatology | Year: 2015

Background & Aims The differentiation of stem cells to hepatocyte-like cells (HLC) offers the perspective of unlimited supply of human hepatocytes. However, the degree of differentiation of HLC remains controversial. To obtain an unbiased characterization, we performed a transcriptomic study with HLC derived from human embryonic and induced stem cells (ESC, hiPSC) from three different laboratories. Methods Genome-wide gene expression profiles of ESC and HLC were compared to freshly isolated and up to 14 days cultivated primary human hepatocytes. Gene networks representing successful and failed hepatocyte differentiation, and the transcription factors involved in their regulation were identified. Results Gene regulatory network analysis demonstrated that HLC represent a mixed cell type with features of liver, intestine, fibroblast and stem cells. The "unwanted" intestinal features were associated with KLF5 and CDX2 transcriptional networks. Cluster analysis identified highly correlated groups of genes associated with mature liver functions (n = 1057) and downregulated proliferation associated genes (n = 1562) that approach levels of primary hepatocytes. However, three further clusters containing 447, 101, and 505 genes failed to reach levels of hepatocytes. Key TF of two of these clusters include SOX11, FOXQ1, and YBX3. The third unsuccessful cluster, controlled by HNF1, CAR, FXR, and PXR, strongly overlaps with genes repressed in cultivated hepatocytes compared to freshly isolated hepatocytes, suggesting that current in vitro conditions lack stimuli required to maintain gene expression in hepatocytes, which consequently also explains a corresponding deficiency of HLC. Conclusions The present gene regulatory network approach identifies key transcription factors which require modulation to improve HLC differentiation. © 2015 European Association for the Study of the Liver.


Grant
Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2016 | Award Amount: 4.03M | Year: 2016

The main objective of Training4CRM is to train a new generation of 15 highly inter-disciplinary early stage researchers at the highest international level and quality, who will be immediately employable in both the academic and industrial sectors due to their highly sought after cross- and interdisciplinary insights and expertise. Training4CRM addresses existing gaps within Cell-based Regenerative Medicine for treatment of neurodegenerative disorders (e.g. Parkinsons, Huntingtons, Epilepsy), which occur as a result of progressive loss of structure, function and/or death of neurons in the brain. The disorders have a high prevalence and are associated with impairments and disabilities with high emotional, financial and social burden. New scientific discoveries and technologies are needed, and Training4CRM sets out with the ambition to educate and train students within and across different scientific disciplines to be able to master the design, fabrication and testing of completely new tools and materials within the fields of: Micro- and Nanoengineering (nano/microstructures, 3D scaffolds and 3D lab-on-a-chip devices of different materials, geometries, architectures and properties, wireless electronic components; Biotechnology (human stem cells, human induced pluripotent stem cells, optogenetics, tissue engineering; Pre-clinical studies for the purpose of investigating in vivo, in experimental animals, how the developed cells, materials, structures affect the animal at the physiological and behavioral levels, unravelling the therapeutic effects of the developed strategies.


PubMed | University of Tübingen, University of Edinburgh, University of Cologne, TU Dortmund and 7 more.
Type: Journal Article | Journal: Journal of hepatology | Year: 2015

The differentiation of stem cells to hepatocyte-like cells (HLC) offers the perspective of unlimited supply of human hepatocytes. However, the degree of differentiation of HLC remains controversial. To obtain an unbiased characterization, we performed a transcriptomic study with HLC derived from human embryonic and induced stem cells (ESC, hiPSC) from three different laboratories.Genome-wide gene expression profiles of ESC and HLC were compared to freshly isolated and up to 14days cultivated primary human hepatocytes. Gene networks representing successful and failed hepatocyte differentiation, and the transcription factors involved in their regulation were identified.Gene regulatory network analysis demonstrated that HLC represent a mixed cell type with features of liver, intestine, fibroblast and stem cells. The unwanted intestinal features were associated with KLF5 and CDX2 transcriptional networks. Cluster analysis identified highly correlated groups of genes associated with mature liver functions (n=1057) and downregulated proliferation associated genes (n=1562) that approach levels of primary hepatocytes. However, three further clusters containing 447, 101, and 505 genes failed to reach levels of hepatocytes. Key TF of two of these clusters include SOX11, FOXQ1, and YBX3. The third unsuccessful cluster, controlled by HNF1, CAR, FXR, and PXR, strongly overlaps with genes repressed in cultivated hepatocytes compared to freshly isolated hepatocytes, suggesting that current in vitro conditions lack stimuli required to maintain gene expression in hepatocytes, which consequently also explains a corresponding deficiency of HLC.The present gene regulatory network approach identifies key transcription factors which require modulation to improve HLC differentiation.


Begum S.,Sahlgrenska University Hospital | Begum S.,Karolinska Institutet | Joshi M.,Sahlgrenska University Hospital | Joshi M.,Karolinska Institutet | And 4 more authors.
Cytotherapy | Year: 2010

Background aims. Cultured human hepatocytes have extensive diagnostic and clinical applications. However, the setting-up of new in vitro culture techniques allowing the long-term survival and functional maintenance of adult human hepatocytes represents a formidable challenge. Fetal liver cells (FLC) are attractive candidate donor cells because of their high proliferative capacity. Methods. Using cell culture and molecular techniques, we studied the in vitro and in vivo characteristics of FLC grown long-term in serum-free conditions. Results. Serum-free FLC obtained from 610-week-old human fetal livers grew as multiple clusters in suspension and could be subcultured for at least six passages. These cells maintained stable hepatocyte phenotypes and gene expression patterns in culture for up to 6 months. When a cluster of these cells in various passages was placed on collagen-coated plates, they formed a monolayer and morphologically resembled hepatocytes. The cells expressed α -fetoprotein, cytokeratin (CK) 8, CK18 and CK19 and albumin (ALB). Hepatocyte nuclear factor 4α and 1β and cytochrome P450 (CYP) 3A4 and CYP3A7 mRNA expression was demonstrated by reverse transcriptasepolymerase chain reaction (RT-PCR). Cells at different passages, when transplanted into nude mice with liver injury, engrafted successfully, as detected by in situ hybridization using a human-specific DNA probe. Colonies of human-specific CK8, CK18, c-Met nuclear antigen (Ag), mitochondrial Ag, hepatocyte-specific Ag and ALB-expressing cells were present in the livers of recipient animals. Conclusions. Primary human FLC can be kept in culture consistently over a long time period and are potential candidates for cell therapy and in vitro diagnostics. © Informa UK Ltd.


Holmgren G.,University of Skövde | Holmgren G.,Gothenburg University | Sjogren A.-K.,Astrazeneca | Barragan I.,Karolinska Institutet | And 10 more authors.
Drug Metabolism and Disposition | Year: 2014

Human pluripotent stem cells (hPSC) have the potential to become important tools for the establishment of new models for in vitro drug testing of, for example, toxicity and pharmacological effects. Late-stage attrition in the pharmaceutical industry is to a large extent caused by selection of drug candidates using nonpredictive preclinical models that are not clinically relevant. The current hepatic in vivo and in vitro models show clear limitations, especially for studies of chronic hepatotoxicity. For these reasons, we evaluated the potential of using hPSC-derived hepatocytes for long-term exposure to toxic drugs. The differentiated hepatocytes were incubated with hepatotoxic compounds for up to 14 days, using a repeated-dose approach. The hPSC-derived hepatocytes became more sensitive to the toxic compounds after extended exposures and, in addition to conventional cytotoxicity, evidence of phospholipidosis and steatosis was also observed in the cells. This is, to the best of our knowledge, the first report of a longterm toxicity study using hPSC-derived hepatocytes, and the observations support further development and validation of hPSC-based toxicity models for evaluating novel drugs, chemicals, and cosmetics. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.


Patent
Novahep Ab | Date: 2013-03-01

The present invention relates to methods for recellularization of blood vessels. This method is particularly useful for producing an allogeneic vein, wherein a donor vein is decellularized and then recellularized using whole blood or bone marrow stem cells. The allogeneic veins produced by the methods disclosed herein are particularly advantageous for implantation or transplantation into patients with vascular diseases.


Patent
Novahep Ab | Date: 2015-05-28

The present invention relates to methods for recellurization of blood vessels. This method is particularly useful for producing an allogeneic vein, wherein a donor vein is decellularized and then recellularized using whole blood or bone marrow stem cells. The allogeneic veins produced by the methods disclosed herein are particularly advantageous for implantation or transplantation into patients with vascular diseases.

Loading NovaHep AB collaborators
Loading NovaHep AB collaborators