Overview Service Features Published Data FAQs Scientific Resources Related Services
With decades of experience in the field of iPSCs differentiation, Creative Biolabs has been a leading service provider of iPSC-derived differentiated cell in multiple types. Especially, we have extensive experience in producting neuronal cells, hepatocytes, and cardiomyocytes. Now we offer the service of hepatocytes differentiation from iPSC to our clients all over the world.
Introduction of iPSC Derived Hepatocytes
Liver is regarded as an important organ in mamal as it plays a crucial role in protein synthesis, detoxification, metabolism and excretion. Therefore, the generation of healthy hepatocytes is a major goal for hepatic disease therapy. As human induced pluripotent stem cells (hiPSCs) have the potential to differentiat into different cell types, it is possible to generate iPSC-derived hepatocytes for a wide range of applications. Now Creative Biolabs is able to provide hepatocyte differentiation service from iPSC.
Fig.1 The experimental outline of differentiation of human iPSCs into functional hepatocytes.
Processes of Hepatocytes Differentiation from iPSC
Generation of iPSC derived hepatocytes has been served as the potential source for therapeutic applications and enables in vitro study of liver diseases. During embryogenesis, the differentiation processes have been understood well by the comprehensive of molecular correlates in liver development. In mammalian embryos, the ventral foregut endoderm is the tissue from which liver originates. In this case, there are three essential consecutive processes for the generation of hepatocytes which further differentiated into definitive endoderm, hepatic progenitors, and mature hepatocytes. The initial step is the phenotype generation of definitive endoderm which requires exposure to the transforming growth factor b (TGF-b) superfamily members activin A and bone morphogenic protein 4 (BMP4). In addition, short-term exposure to Wnt3a, which is expressed in key stages of human liver development and specifically interacting with activin A, enhances the production of both definitive and hepatic endoderm. The combination of fibroblast growth factors and BMP4 contributes largely to embryonic development. We also found that the presence of fetal bovine serum in medium inhibits some factors for early mammalian embryo development. The second step is the generation of hepatic progenitor cells from definitive endoderm which is accomplished by adding specific factors which includes hepatocyte growth factor (HGF) and hepatocyte nuclear factor 4 alpha (HNF4a). The final step is the induction of hepatocyte maturation via adding oncostatin M (OSM), an interleukin-6 family cytokine, in combination with glucocorticoids in the cell culture medium.
Applications of iPSC Derived Hepatocytes
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Disease Modeling.
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Drug screening, metabolism, and toxicology studies.
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Provide healthy hepatocytes for cell therapy.
Fig.2 Summary of application potential of human iPSC derived hepatocytes.
Services at Creative Biolabs
Based on years of experience and advanced platform, scientists at Creative Biolabs now can customize a project for you to supply hepatocytes to meet your special needs. Moreover, we can also provide iPSC derived neuronal cells, cardiomyocytes, and other cell types via configurated reprogramming and differentiation. Please feel free to contact us if you are interested in our services.
We will provide comprehensive solutions based on the specific needs of our clients.
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Consulting and Project Planning: Our team of experts will work closely with our clients to understand their research goals, timelines and budgetary constraints. We will advise on project feasibility, optimal experimental design, and selection of iPSC cell lines suitable for hepatocyte differentiation.
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iPSC Generation or Procurement: We can generate iPSC from customer-sourced somatic cells through reprogramming techniques or provide selected iPSC lines from our repository. These iPSCs will be used as starting material for hepatocyte differentiation.
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Optimization of Differentiation Protocols: We have developed or acquired state-of-the-art protocols for differentiating iPSC into hepatocytes. Our team will further optimize these protocols to improve the efficiency, yield and function of the derived hepatocytes. This may involve testing various growth factors, small molecules and culture conditions.
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Hepatocyte Differentiation: Using optimized protocols, we will induce iPSC differentiation into hepatocytes in vitro. This process typically involves mimicking multiple steps of embryonic liver development, such as stereotyped endoderm induction, liver specification and maturation.
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Characterization of Hepatocytes: We will thoroughly characterize the derived hepatocytes to ensure their function and purity. This includes assessing hepatocyte identity markers by immunocytochemistry and flow cytometry, evaluating liver functions such as albumin secretion, urea synthesis, cytochrome P450 activity, and drug metabolism, as well as performing gene expression profiling and functional assays.
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Customization and Scale-up: depending on the size of the project, we can customize our services to meet specific requirements. Whether it is a small-scale proof-of-concept study or a large-scale hepatocyte production for drug screening, we can adapt our programs accordingly.
Features of Our Services
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Customizable protocol
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Functional maturation
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Expert guidance
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Rigorous quality control
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Comprehensive reports
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Timely delivery
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Flexibility
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Post-delivery support
Published Data
Below are the findings presented in the article related to hepatocyte differentiation from iPSC.
Menglu Li, et al. used label-free Raman microscopy to assess the differentiation of hiPSC into the hepatocyte lineage based on intracellular chemical content. They first confirmed the hepatic differentiation of hiPSC on quartz dishes, as quartz is a suitable substrate for Raman observation.
HiPSCs are progressively producing HLC through endoderm differentiation, liver specification, hepatocyte differentiation and maturation. As shown below, immunostaining of hiPSC, definitive endoderm (DE) cells, hepatoblast-like (HB) cells, and HLC cellular markers including NANOG, CXCR4, HNF4α, CYP3A4, and albumin (ALB), respectively, as well as SOX2, SOX17, HNF4α, CYP3A4 and ALB gene expression levels all confirmed hepatic differentiation of hiPSC on quartz dishes.
Fig. 3 Generation of hiPSC-differentiated HLCs on quartz dishes.3
FAQs
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Q: What are the advantages of using iPSC-derived hepatocytes compared to primary hepatocytes in research applications?
A: iPSC-derived hepatocytes offer several advantages over primary hepatocytes, including a virtually unlimited supply, consistent quality, and the ability to derive patient-specific cells for disease modeling and personalized medicine applications. Additionally, iPSC-derived hepatocytes can be genetically modified or manipulated for targeted research purposes.
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Q: What are the advantages of using your service for hepatocyte differentiation compared to in-house protocols or other commercial offerings?
A: Our service offers several advantages, including optimized protocols, extensive quality control, technical expertise, and customizable options tailored to specific research needs. Additionally, outsourcing hepatocyte differentiation to us saves time, resources, and effort compared to developing and maintaining in-house protocols.
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Q: What are the key characteristics of the hepatocytes generated through this service?
A: The hepatocytes produced exhibit key functional and phenotypic characteristics of primary hepatocytes, including expression of hepatocyte-specific markers, metabolic activity, and drug metabolism capability, making them ideal for various scientific experiments.
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Q: How much does the iPSC hepatocyte differentiation service cost?
A: The cost of the service can vary depending on the specifics of your project, such as the number of cell lines to be differentiated, and the scale of differentiation. We strive to make our services as cost-effective as possible while maintaining high standards. Please contact us for a personalized quote according to your requirements.
Scientific Resources
References
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Sauer, V. (2014). “Induced pluripotent stem cells as a source of hepatocytes.” Curr Pathobiol Rep 2(1), 11-20.
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Irudayam, J.I. (2014). “Modeling liver diseases using induced pluripotent stem cell (ipsc)-derived hepatocytes.” 4(7), 218.
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Li, Menglu, et al. "Label-Free Evaluation of Maturation and Hepatotoxicity of Human iPSC-Derived Hepatocytes Using Hyperspectral Raman Imaging." Analytical Chemistry 95.24 (2023): 9252-9262.
For Research Use Only. Not For Clinical Use.
