Stem Cell Differentiation Service
Human induced Pluripotent Stem Cells (hiPSCs) have the ability to multiply indefinitely and to differentiate into all cell types of the human body. Accordingly , they provide a limitless supply of hard-to-source cell types and can thus help to develop highly physiological models cells.
Our scientific team offers a profound stem cell knowledge and function as extended workbench for your routine iPSC differentiation projects. Furthermore, to streamline the pharmaceutical development process of our clients, trenzyme is developing new protocols for iPSC differentiation into cells of various lineages according to your specific project requirements.
Differentiation of human induced Pluripotent Stem Cells
hiPSCs can be routinely generated from somatic cells of healthy donors or even patient-specific disease samples. After differentiation into tissue-specific cell types like neurons, cardiomyocytes or hepatocytes, hiPSCs can serve as next generation disease models in-a-dish, facilitating many applications in basic research, drug discovery and preclinical development.
Up to now, many applications in academia, biotech and pharmaceutical industry still rely on immortalized cancer cell lines as model system with all the drawbacks like genetic instability, aberrant gene expression patterns and dysfunctional signal pathways. Even the use of human primary cells has severe disadvantages like ethical problems, donor-to-donor variability and other general limitations (e.g. availability, limited expansion).
However, hiPSCs do not exhibit these limitations, have an unlimited expansion potential and can be differentiated into all cell types of the three germ layer lineages (ectoderm, mesoderm, endoderm). Moreover, intermediate differentiation stages can be further amplified.
“trenzyme is one of our preferred service providers for cell line development and molecular biology services. The impressive level of personal customer liaison and the scientific competence are decisive factors for us to cooperate with trenzyme for many years and even to intensify in the area of demanding iPS cell line projects.”
Run-Through Differentiation Service
If you have a proven hiPS cell line and an already established differentiation protocol including validated QC markers available, we will be able to serve as your time- and cost-saving extended workbench and provide you with the differentiated cells ready-to-use for your assays.
Our expert service includes:
- Feasibility check
- Continuous reporting accompanying the whole project
- Final report at the end of the project (protocol procedures, marker analysis)
- Generated cells
Customized Differentiation Service
If you do not have an established differentiation protocol and may also need to source the hiPS cell line as starting point, our experts will be able to support you with a milestone based R&D project.
We have extensive knowledge in development of protocols or may have the required protocol readily available. With access to a huge network of partners and technologies, we can ensure the progress of such a custom R&D project generating your desired cell type.
Our highly modular expert service includes:
- State-of-the-art literature research & feasibility check
- Close collaboration & technical discussion
- Continuous reporting accompanying the whole project
- Final report at the end of the project & delivery of test samples (protocol procedures, marker analysis)
- Generated cells
Services like karyotyping, pluripotency test, tri-lineage differentiation or cell specific data packages based on transcriptomic (qPCR), proteomic (FACS, IF) or even functional level are usually part of the customized differentiation service package. On request, they are also available for the run-through differentiation service package.
Examples for our Inhouse-Differentiation-Capabilities
Ectoderm
Neuronal differentiation
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Characterization - IF staining
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Mesoderm
Cardiomyocyte differentiation
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Characterization - FACS analysis, Tox analysis & In vitro tox assay
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Endoderm
Hepatocyte differentiation
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Characterization - RT-PCR. ELISA
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Your benefits from working with us
Transparency & Communication
Our dedicated project management will guide your project through every step of the process and keep you constantly informed on the progress. Transparency and high quality service are our mission.
Longstanding Expertise
With the extensive knowledge of our highly qualified scientific experts and with access to a huge network of partners and technologies, we complete your project successfully and efficiently.
Groundbreaking Technology
Since iPSC can be derived from healthy donors and disease patients, they serve as ideal systems for modelling disease phenotypes needed for drug screening and pharmaceutical development.
High Quality Standards
As an ISO-certified company working with a LIMS based documentation, all projects are completed following highest standards.
Relevant Publications
Functional human iPSC-derived alveolar-like cells cultured in a miniaturized 96‑Transwell air–liquid interface model. Sci Rep 11, 17028 (2021)
Bluhmki T, Traub S, MĂĽller AK, Bitzer S, Schruf E, Bammert MT, Leist M, Gantner F, Garnett JP, and Heilker R
Establishment of a human iPS cell-derived neuronal model cell to study synaptic signaling (2020)
Traub S
Kinetic modeling of stem cell transcriptome dynamics to identify regulatory modules of normal and disturbed neuroectodermal differentiation. Nucleic Acids Res. 2020 Dec 16;48(22):12577-12592. doi: 10.1093/nar/gkaa1089. PMID: 33245762; PMCID: PMC7736781. (2020)
Meisig J, Dreser N, Kapitza M, Henry M, Rotshteyn T, RahnenfĂĽhrer J, Hengstler JG, Sachinidis A, Waldmann T, Leist M, and BlĂĽthgen N
Differentiation of hiPS Cells into Definitive Endoderm for High-Throughput Screening. In: Mandenius CF., Ross J. (eds) Cell-Based Assays Using iPSCs for Drug Development and Testing. Methods in Molecular Biology, vol 1994. Humana, New York, NY. (2019)
Bluhmki T, Traub S, Schruf E, Gantner F, Garnett JP, Bischoff D, and Heilker R
Upscaling of hiPS Cell–Derived Neurons for High-Throughput Screening (2017)
Traub S, Stahl H, Rosenbrock H, Simon E, and Heilker R
Pharmaceutical Characterization of Tropomyosin Receptor Kinase B-Agonistic Antibodies on Human Induced Pluripotent Stem (hiPS) Cell-Derived Neurons. J. Pharmacol. Exp. Ther. 361, 355–365. (2017)
Traub S, Stahl H, Rosenbrock H, Simon E, Florin L, Hospach L, Hörer S, and Heilker R
Impairment of human neural crest cell migration by prolonged exposure to interferon-beta. Arch Toxicol. 2017 Oct;91(10):3385-3402. doi: 10.1007/s00204-017-1966-1. Epub 2017 Apr 1. Erratum in: Arch Toxicol. 2019 Jun;93(6):1771. PMID: 28365849; PMCID: PMC5608792. (2017)
Pallocca G, Nyffeler J, Dolde X, Grinberg M, Gstraunthaler G, Waldmann T, RahnenfĂĽhrer J, Sachinidis A, and Leist M
Stem Cell Transcriptome Responses and Corresponding Biomarkers That Indicate the Transition from Adaptive Responses to Cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922. doi: 10.1021/acs.chemrestox.6b00259. Epub 2016 Dec 21. PMID: 28001369. (2017)
Waldmann T, Grinberg M, König A, Rempel E, Schildknecht S, Henry M, Holzer AK, Dreser N, Shinde V, Sachinidis A, Rahnenführer J, Hengstler JG, and Leist M
Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864. doi: 10.1007/s00204-016-1741-8. Epub 2016 May 17. PMID: 27188386; PMCID: PMC5306084. (2017)
Shinde V, Hoelting L, Srinivasan SP, Meisig J, Meganathan K, Jagtap S, Grinberg M, Liebing J, Bluethgen N, Rahnenführer J, Rempel E, Stoeber R, Schildknecht S, Förster S, Godoy P, van Thriel C, Gaspar JA, Hescheler J, Waldmann T, Hengstler JG, Leist M, and Sachinidis A
Design of a high-throughput human neural crest cell migration assay to indicate potential developmental toxicants. ALTEX. 2017;34(1):75-94. doi: 10.14573/altex.1605031. Epub 2016 Jul 27. PMID: 27463612. (2016)
Nyffeler J, Karreman C, Leisner H, Kim YJ, Lee G, Waldmann T, and Leist M
Comparison of a teratogenic transcriptome-based predictive test based on human embryonic versus inducible pluripotent stem cells. Stem Cell Res Ther. 2016 Dec 30;7(1):190. doi: 10.1186/s13287-016-0449-2. PMID: 28038682; PMCID: PMC5203708. (2016)
Shinde V, Perumal Srinivasan S, Henry M, Rotshteyn T, Hescheler J, RahnenfĂĽhrer J, Grinberg M, Meisig J, BlĂĽthgen N, Waldmann T, Leist M, Hengstler JG, and Sachinidis A
A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618. doi: 10.1007/s00204-015-1573-y. Epub 2015 Aug 14. PMID: 26272509; PMCID: PMC4551554. (2015)
Rempel E, Hoelting L, Waldmann T, Balmer NV, Schildknecht S, Grinberg M, Das Gaspar JA, Shinde V, Stöber R, Marchan R, van Thriel C, Liebing J, Meisig J, Blüthgen N, Sachinidis A, Rahnenführer J, Hengstler JG, and Leist M
Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation. J Vis Exp. 2015 Jun 17;(100):e52333. doi: 10.3791/52333. PMID: 26132533; PMCID: PMC4544843. (2015)
Shinde V, Klima S, Sureshkumar PS, Meganathan K, Jagtap S, Rempel E, RahnenfĂĽhrer J, Hengstler JG, Waldmann T, Hescheler J, Leist M, and Sachinidis A
Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20. doi: 10.1021/tx400402j. Epub 2014 Jan 21. PMID: 24383497; PMCID: PMC3958134. (2014)
Waldmann T, Rempel E, Balmer NV, König A, Kolde R, Gaspar JA, Henry M, Hescheler J, Sachinidis A, Rahnenführer J, Hengstler JG, Leist M
Lineage-specific regulation of epigenetic modifier genes in human liver and brain. PLoS One. 2014 Jul 23;9(7):e102035. doi: 10.1371/journal.pone.0102035. PMID: 25054330; PMCID: PMC4108363. (2014)
Weng MK, Natarajan K, Scholz D, Ivanova VN, Sachinidis A, Hengstler JG, Waldmann T, and Leist M
Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43. doi: 10.1007/s00204-012-0967-3. Epub 2012 Nov 21. PMID: 23179753; PMCID: PMC3535399. (2013)
Krug AK, Kolde R, Gaspar JA, Rempel E, Balmer NV, Meganathan K, Vojnits K, Baquié M, Waldmann T, Ensenat-Waser R, Jagtap S, Evans RM, Julien S, Peterson H, Zagoura D, Kadereit S, Gerhard D, Sotiriadou I, Heke M, Natarajan K, Henry M, Winkler J, Marchan R, Stoppini L, Bosgra S, Westerhout J, Verwei M, Vilo J, Kortenkamp A, Hescheler J, Hothorn L, Bremer S, van Thriel C, Krause KH, Hengstler JG, Rahnenführer J, Leist M, and Sachinidis A
Epigenetic changes and disturbed neural development in a human embryonic stem cell-based model relating to the fetal valproate syndrome. Hum Mol Genet. 2012 Sep 15;21(18):4104-14. doi: 10.1093/hmg/dds239. Epub 2012 Jun 20. PMID: 22723015. (2012)
Balmer NV, Weng MK, Zimmer B, Ivanova VN, Chambers SM, Nikolaeva E, Jagtap S, Sachinidis A, Hescheler J, Waldmann T, and Leist M
Extensive transcriptional regulation of chromatin modifiers during human neurodevelopment. PLoS One. 2012;7(5):e36708. doi: 10.1371/journal.pone.0036708. Epub 2012 May 9. PMID: 22590590; PMCID: PMC3348879. (2012)
Weng MK, Zimmer B, Pöltl D, Broeg MP, Ivanova V, Gaspar JA, Sachinidis A, Wüllner U, Waldmann T, and Leist M
Rapid, complete and large-scale generation of post-mitotic neurons from the human LUHMES cell line. J Neurochem. 2011 Dec;119(5):957-71. doi: 10.1111/j.1471-4159.2011.07255.x. Epub 2011 Apr 13. PMID: 21434924. (2011)
Scholz D, Pöltl D, Genewsky A, Weng M, Waldmann T, Schildknecht S, and Leist M
Coordinated waves of gene expression during neuronal differentiation of embryonic stem cells as basis for novel approaches to developmental neurotoxicity testing. Cell Death Differ. 2011 Mar;18(3):383-95. doi: 10.1038/cdd.2010.109. Epub 2010 Sep 24. PMID: 20865013; PMCID: PMC3131999. (2011)
Zimmer B, Kuegler PB, Baudis B, Genewsky A, Tanavde V, Koh W, Tan B, Waldmann T, Kadereit S, and Leist M
Markers of murine embryonic and neural stem cells, neurons and astrocytes: reference points for developmental neurotoxicity testing. ALTEX. 2010;27(1):17-42. PMID: 20390237. (2010)
Kuegler PB, Zimmer B, Waldmann T, Baudis B, Ilmjärv S, Hescheler J, Gaughwin P, Brundin P, Mundy W, Bal-Price AK, Schrattenholz A, Krause KH, van Thriel C, Rao MS, Kadereit S, and Leist M
Stem Cell Differentiation FAQs
How long does it take to generate an iPSC-derived cell type?
It’s depending on the cell type and the applied differentiation protocol. Together with our clients, we select a reliable differentiation protocol and define reasonable project milestones.
What kind of quality control is performed to ensure a successful differentiation?
We routinely perform immunofluorescence staining, FACs analysis and qPCR in order to characterize the stages of differentiation. For special read-outs, do not hesitate to contact our experts.
How can I get in touch during the realization of the project?
During the project, regular telephone calls, email correspondence and short reports ensure detailed exchange of information and results. Furthermore, technical discussions will help to implement key experiment layouts according to your needs.
Stefanie Traub, PhD
Scientific Coordination Advanced Cell Systems
We would be happy to provide you with support on your stem cell research project. Let us know your questions and requests, our scientific experts will reply shortly.
Get In Contact With Our Scientific Experts