Let the iPSC expert generate high-quality, induced pluripotent stem cell (iPSC) lines and derived physiologically relevant cell line models for your basic research, drug discovery, drug screening, and preclinical cell regeneration projects:
iPSC Generation Services Categories
- Highly optimized protocols with high reprogramming efficiency (>95% success rate)
- From healthy/diseased samples
- iPSC generation from PBMCs, fibroblast, HSC, MSCs, CD34+ cord blood, urine, and more
- integration-free (episomal/ mRNA/ viral-based) or retroviral reprogramming
- Feeder-free protocols; optional feeder-dependent protocols available
- iPSCs characterized for morphology and pluripotency markers. Additional characterization such as G-banding, RT-PCR, STR profiling, directed-differentiation are also available.
Allogenic and Immunocompatible
Rapid Automated Cell Line Editing (RACE™) in iPSCs! Engineer predictive cell line models in the more physiologically relevant iPSC lines. After >11 years’ genome editing and stem cell expertise, & having engineered 500+ unique cell line models, Applied StemCell offers you the best CRISPR-iPSC service with:
- Up to 60% faster turnaround times than traditional protocols
- High success rate (>98%)
- Your patient iPSC lines or our master iPSCs
- Automated & efficient CRISPR & single cell cloning protocols
- Pluripotency maintained throughout genome editing
Any type of modification to suit your needs: Complex and mainstream genetic modifications. And, one of the few providers for integrated upstream iPSC generation & downstream differentiation services.
iPSC differentiated cell lines offer the convenience of cell line models with the biorelevance of primary cells but without the sourcing difficulties and lot-to-lot variability issues associated with primary human cells. Applied StemCell offers comprehensive service for iPSC differentiation to lineage-committed cell types thereby expanding the scope of your research, drug discovery, or drug screening projects.
- Lineage-committed cell lines as determined by lineage-specific markers
- Differentiation from Healthy/disease iPSC lines: customer cell lines. ASC’s control iPSC lines or genetically engineered iPSCs
- High purity cell lines
- Non-integrating differentiation protocols
- Development of co-culture models with multiple lineages available
Custom “Master” iPSC Cell Line Generation using TARGATT™ technology! The TARGATT™ Master Human iPSC Line contains an attP “docking site” at the hROSA26 safe harbor genomic locus. Any gene of interest can be stably inserted at the docking site using a corresponding “attB” containing TARGATT™ donor plasmid, with guaranteed gene expression. The efficiency of this phiC31 integrase-mediated recombination is up to 100% efficiency with drug selection and up to 30% without drug selection.
Our cell line model generation experts can also engineer your safe harbor locus knock-in iPSC lines using CRISPR/Cas9 for a multi-technology approach to generate a cell line model for your specific research needs.
The true potential of iPSCs and ESCs rest in its directed differentiation to different somatic lineages. As part of our comprehensive stem cell service platform, researchers can leverage our expertise in stem cell technologies and our cost-effective, reliable Stem Cell Differentiation Services for their developmental biology, disease mechanisms, and drug discovery research.
Neural Stem Cell Differentiation Categories
- Differentiate your patient-derived iPSCs into microglia and self-renewing, multipotent neural stem cells (NSCs) and further to neurons and glial cells.
- High differentiation efficiency and cell purity
- Cells fully characterized for microglia and NSC biomarkers
iPSC-derived T cells, NK cells, dendritic cells and others provide a next generation toolset for understanding cancer and disease pathology as well as developing successful immunotherapies (adoptive therapies like CAR-T, CAR-NK, TCR-T and more). Applied StemCell with its world-class comprehensive stem cell platform which includes iPSC generation, genome editing and differentiation, can differentiate your iPSCs into CD34+ hematopoietic lineage progenitor cells and further into high-quality lineage committed immune cells: CD8+ T cells, NK cell, dendritic cells, monocytes, and more. These cells are ideal for immunotherapy research for cancer and immune disorders as well as to develop complex co-culture models to screen drugs and understand immune cell activation and function.
Applied StemCell provides top quality service for directed-differentiation of iPSCs into cardiomyocytes using our proprietary induction protocol and reagents. We deliver ready-to-use, functional cardiomyocytes that are desirable in vitro models for high content toxicity and drug screening, and cell regeneration research. They are a feasible and physiologically relevant alternative to embryonic stem cell, primary cells, and animal models.
We can generate differentiated cardiomyocytes from iPSC derived from healthy or disease patient samples.
Applied StemCell provides custom differentiation of your induced pluripotent stem cells (iPSCs) into high-quality hepatocytes for developing liver disease models, discovering therapeutic treatments, drug targets, and understanding drug induced hepatotoxicity.
Using our proprietary induction protocol and reagents, we can generate differentiated hepatocytes very efficiently and with high purity from your own healthy or disease iPSCs.
Our Hepatocytes Differentiation Service includes:
- Expansion of a host-derived iPSCs
- Progenitor cell differentiation
- Characterization of progenitor cells
- Terminal differentiation
- Characterization of Progenitor Cells/ Differentiated Cells by ICC (per marker)
Human iPSC-derived retinal pigment epithelium (RPE) provides a physiologically relevant cell line model to understand basic ocular biology and ocular diseases. ASC’s iPSC-derived RPE protocol provides high quality RPEs with expression of lineage-committed markers and functional phenotype such as phagocytosis, and by providing an unlimited source of these cells.
- RPE-like cells with typical cobblestone morphology and pigmentation
- High quality and purity cells (60-80% purity) expressing RPE-specific markers Bestrophin 1 (BEST1)/ RPE65
- iPSC reprogrammed from fibroblast/ PBMC/ CD34+ cord blood cells
- From healthy/ disease/ engineered iPSCs
- Optional! Control lines differentiated from “master” iPSC lines available
Applied StemCell offers iPSC differentiation to Myogenin+ and MHC+ skeletal muscle-like cells that form neuromuscular junctional models when co-cultured with motor neurons. We can also help you establish the co-culture model with your iPSC-derived cell lines using our high efficiency motor neuron differentiation protocol.
Stringent molecular and functional assays are necessary to evaluate pluripotency and to rule-out genetic aberrations due to reprogramming and stress from in vitro culture in iPSC lines. Loss of genetic integrity can affect desired cellular phenotype and compromise interpretation and translation of results to a clinical setting.
ASC offers comprehensive services needed to completely characterize your human and mouse pluripotent stem cell lines (PSCs):
- Pluripotency and lineage-specific marker immunostaining
- Karyotyping (Chromosome counting, G-banding, array analysis)
- qPCR, RNA-seq
- Trilineage differentiation potential: embryoid body (EB) formation, qRT-PCR
- HLA typing, whole genome sequencing (WGS), single tandem repeat (STR) genotyping, copy number variations (CNV) and more
Our comprehensive start-to-finish ipsc and stem cell platform offers downstream services to advance your iPSC-based projects to the next stage. We offer preclinical CRO solutions for drug screening, protocol development for cell regeneration and adoptive transfer model, CAR-T research, universal and immunocompatible cell line, and more. We can customize every stage of your project and find the best fit to suit your research needs.
Applied StemCell has a staff of talented scientists that can help you with the more complex to the daily laboratory tasks required of iPSC cell culture. Give your staff the freedom to focus on other project, while Applied StemCell takes care of your cell culture needs.
We offer standard and customized cell culture services including mycoplasma testing.
- iPSC expansion services
- iPSC scale-up services
- Neural Stem Cells, Differentiated Cells scale-up services
- 3D-culture and morphology testing
Please contact us to discuss your needs with our technical service specialists.
3D culture systems for use with stem cells (iPSCs) are gaining popularity as matrix grown cells have longer pluripotency, better differentiation potential, proliferation and cellular function, and are more physiologically relevant in in vitro models.
Applied StemCell is a leader in stem cell technologies and provides custom service for 3D-iPSC culture of customer-provided iPSCs. We use our MyEZGel™ 3D-iPSC Matrix, a xeno-free nanopeptide hydrogel matrix that is specially formulated to provide an in vivo-like microenvironment to culture and generate spheroidal, physiologically relevant iPSCs.
- Cell-based assay development and validation
- Disease modeling
- Drug discovery and screening
- Tissue and organ engineering
- Cell replacement therapies
We Understand Cell Lines! Leverage our expert, comprehensive CRISPR/Cas9 cell line modeling service for a stress-free research. With 1300+ unique cell line models engineered from >200 distinct mammalian cell lines, we can engineer perfectly suited cell line models for your research using highly optimized and efficient CRISPR/Cas9 genome editing strategies and protocols:
Cell Line Model Generation Categories
- Engineer a variety of mutations; or correct mutations, including fusion gene(s)
- Variety of cell lines: cancer, hard-to-transfect, blood lineage, stem cell lines and many more
- Start-to finish cell line generation workflow; optional downstream cell line validation
- Custom deliverables: homozygous/ heterozygous clones; point mutation with/without silent mutation
- >97% success rate; turnaround time as fast as 2 months
Cell Line Model
CRISPR Stem Cell
Knockout, SNV/Tag Knock-in & More
CRISPR/Cas9 Cell Line
Service - Hematopoietic Cells
(Jurkat and TF-1)
CRISPR Gene Fusion
Cell Line Generation
ASC is one of the earliest service providers of CRISPR/Cas9 technology, and has successfully delivered >500 CRISPR mouse models in as little as 3 months. Our animal model portfolio offers competitive pricing and turnaround times for generating CRISPR knockout, conditional knockout, locus-specific/ safe harbor knock-in, controlled gene expression and gene correction, and more.
Mouse Models Categories
- Most up-to-date CRISPR designing strategies and protocols
- 100% target-site cutting efficiency using optimized, proprietary gRNA validation methods
- Animal IP belongs to researchers
- Project management and scientific support to discuss your project needs and suitable strategic options to fit your budget
- NEW! Downstream electrophysiology and behavioral assessments for your mouse models
CRISPR Conditional Knockout
CRISPR Knockout, Knock-in,
Point Mutation Mouse Models
Homologous Recombination Conditional Knockout Mouse Model and Knock-in Mouse Models
Transgenic Mice Models
With the need to physiologically relevant animals models on the rise for more predictive research findings, genetically engineered rat models are becoming increasingly popular. Get ahead of your competition by leveraging Applied StemCell’s expertise in CRISPR/Cas9 and TARGATT™ genome editing technologies and animal models engineering to generate the ideal rat model to meet your specifications and budget.
Rat Models Categories
- Global leader in genetically engineered rat models (Nature article, “CRISPR mouse model boom, rat model renaissance”)
- Detailed discussion to understand project requirements, optimal project design for precise genetic modification and dedicated project management for timely updates
CRISPR Knock-In, Knock-Out,
Conditional Knock-Out Rat
Bacterial Artificial Chromosome (BAC) Knock-in and Conditional Knock-In Rat Models
Applied StemCell’s proprietary site-specific, integrase-based TARGATT™ technology can be used to generate stable, knock-in cells lines with large transgenes including stem cells, very efficiently and quickly. Knock-in is mediated by the integrase at a pre-engineered “docking site” in an intergenic, transcriptionally active genomic locus (safe harbor locus) for high level gene expression without disruption of internal genes. This technology allows only a single-copy integration with very high efficiency with or without clonal selection.
Use our TARGATT™ technology to generate your ”Master” cell lines, reporter/tag lines, for iPSC generation, conditional gene expression models and more.
Also, try our ready-to-use TARGATT™ Master Cell Lines to knock-in transgenes in your own lab.TARGATT™ Cell Line Categories
TARGATT™ High Resolution Protein Screening
ASC’s proprietary TARGATT™ knockin technology enables highly efficient and site-specific gene knockin mouse model generation. This technology uses serine integrase, PhiC31 (ΦC31) to insert any gene of interest into a preselected intergenic and transcriptionally active genomic locus that has been engineered with a docking site for stable, site-specific transgene integration.
- High efficiency insertion (up to 65%)
- Site-specific into a genetically active safe harbor locus
- Large fragment knockin (up to 22 kb)
- Single copy in an active locus: avoid gene silencing and genomic instability.
- High level, stable gene expression
- Germline transmitted F1 mice in 5-8 months
Mouse models: Gene overexpression, conditional expression, humanized gene knockin, gene knockdown, reporter genes
Applied StemCell’s proprietary TARGATT™ technology enables generation of physiologically relevant transgenic rat models suitable for a variety of applications including reporter gene expression, gene knock-down, conditional gene expression and disease models. This technology uses the Phic31 integrase to mediate an irreversible integration of large transgene(s) into a preselected, safe harbor locus with very high efficiency.
- Site-specific, single copy transgene integration overcomes challenges associated with random integration
- TARGATT™ knock-in rats in 6-9 months
- Direct microinjection of the TARGATT™ reagents into rat zygotes
Using the TARGATT™ technology, ASC has also developed Neural Specific Cre-Rat Lines in a Sprague Dawley rat background.
TARGATT™ CHO Cells for Recombinant Proteins and Antibody Bioproduction! Applied StemCell’s TARGATT™ Master CHO cell lines leverage the site-specific gene integration capacity of serine integrase, PhiC31 to knockin transgene(s) into transcriptionally active genomic hotspots, such as the H11 or the proprietary ASC2 (A2) safe harbor locus. These master cell lines enable highly efficient and rapid gene, and high levels recombinant protein/ antibody expression.
Our Master TARGATT™ CHO cell lines can exceed the capabilities of the traditionally made CHO antibody production cells and offers a platform for affordable and feasible bioproduction for antibodies and other recombinant proteins for companies and projects of all sizes.
TARGATT™ Rabbit for Biopharming and High-Yield Recombinant Protein and Antibody Production
Animal bioproduction uses transgenic animal mammary gland as a bioreactor for the production of recombinant proteins. Animal bioproduction, compared to CHO bioproduction, has the advantages of lower upfront and maintenance costs; is easy to contain, control and transport; involves faster development processes and no scale-up issues; and has a unique low-cost bulk holding stage (frozen milk). However existing technological methods such as random integration to create transgenic animals have many limitations. Applied StemCell has overcome these limitations with our proprietary TARGATT™ technology to reproducibly, and consistently, control the knock-in locus, copy number and expression of the target protein in transgenic animals.
Applied StemCell provides lentiviral and retroviral custom virus packaging services for your CRISPR/Cas9 components, CAR-T expression vectors and other transgenes, for efficient delivery into cell lines (such as hard-to-transfect cell lines, primary cell lines) as well as direct injection into animal models.
- Rapid, custom lentivirus or retrovirus virus packaging
- Ready-to-transduce viral particles provided to you
- High quality, high titer viral particles in 10 days
- VSV-G pseudotyped viruses that exhibit broad tropism across a range of cell types
- High titer amplification of viruses, up to 10^9 infectious units per ml
- Accurate viral titers quantified by qRT-PCR
- Confirmation by DNA sequencing
- Large scale production, clonal expansion and cryopreservation
Applied StemCell is one of the earliest licensees and provider of CRISPR/Cas9 genome editing services. We are experts in designing and cloning components for CRISPR-based gene editing in cell lines and animal models using benchmark strategies and optimized protocols. Our scientists have designed > 1000 CRISPR projects for researchers worldwide, and we use the latest sequencing and next generation sequencing (NGS) protocols to validate your gRNAs and to ensure high efficiency gene modification in your gene of interest.
We offer CRISPR/Cas9 vector design, construction and gRNA validation for:
- Cell line gene modification
- Microinjection into embryos for animal model generation
- Virus packaging
We also offer comprehensive custom CRISPR cell line and mouse/ rat model generation services.
Applied StemCell has extensive expertise in anything DNA-related. We can develop the best strategy to tackle your cloning projects, and find solutions to all your technical problems.
- Comprehensive services for genome engineering for in vivo and in vitro applications
- Restriction fragment cloning
- Design and validation of CRISPR/Cas9 components: gRNA design and in vitro validation by next generation sequencing (NGS)
- Gene targeting vectors for homologous recombination
- Design and construction of vectors for transient mammalian transgene expression
- Bacterial artificial chromosome recombineering for large fragment insertion
- Design of RNAi and inducible vectors, gene tagging, and site-directed mutagenesis
- Vector design for generation of random transgenic cell line and animal models
Bacterial Artificial Chromosomes (BACs) are ultra-low copy vectors that can hold up to 300 kb of genomic fragments, making them ideal vectors for introduction of entire genes including the regulatory regions for disease modeling with transgenic animals. BACs are traditionally difficult to modify with restriction enzymes and ligases because of their large size. Applied StemCell uses homologous recombination to introduce precise changes into BACs for your specific experimental needs. Virtually any desired modification can be introduced into a BAC, including insertion of reporter genes, point mutations, Lox-STOP-Lox conditional modifications, and more.
Our custom BAC services include:
Applied StemCell can also help you create transgenic rats using BACs.
As a long-standing leader in genetically engineered animal models, Applied StemCell also offers a comprehensive custom research solutions platform for downstream assays in mouse and rat models. Our state-of-the-art vivarium is equipped with automated cages & devices for behavioral assessments, sample collection and in vivo measurements (ECG, EEG) of the animals. We have a multidisciplinary team of expert scientists who can design a comprehensive project plan to fit any requirement/stage of your research pipeline and for drug discovery and screening.
- Designing and engineering research animal disease models
- Adoptive transfers/transplantation
- In vivo functional screening assays
- End-of-study in vitro assays
ASC offers a full suite of comprehensive services tailored towards your preclinical-stage cell and gene therapy (CGT) projects. Leverage our fully integrated service platform starting with in vitro model generation and cell-based assays, followed by custom animal models and in vivo assays for target validation for early go-no-go decisions of your biotherapeutics. We have a unique team of scientists with multidisciplinary expertise in CRISPR/ genome engineering technologies, stem cell biology, immuno-oncology, gene therapy models, and viral vectors to plan and execute every aspect of your CGT projects. We can generate in vitro and in vivo models, design viral vectors (AAV, lentivirus) and develop proof-of-concept and target validation assays specific to your therapeutic pipeline needs.Discovery: Preclinical Cell & Gene Therapy Services Categories
Cell Line Model Validation
Animal Model Validation
Cell and Gene Therapy (CGT) drugs have their unique mechanism of action and require a more tailor-made approach for drug development and regulatory approval. Starting from custom cell line and animal model generation for the targeted disease, ASC’s multidisciplinary team of experts can develop preclinical assays to determine efficacy, pharmacodynamic, dose-ranging studies, biodistribution, and develop other IND-enabling assays to measure potency (AAV potency, DNA/ RNA/ protein levels) and toxicity of the drug in multiple species samples including NHPs, immunogenicity of the drug, and more. We will work with you every step of the way including pre-IND meetings with the FDA/ respective regulatory bodies to develop the right assay matrix for your CGT candidates.
Detailed Chemistry, Manufacturing & Control (CMC) information submission is a critical part of your IND-submission irrespective of the class of therapeutic under investigation in order to validate the identity, purity, potency, viability, titers, potency, cell dose of your drug candidate. ASC offers expert CMC consultation and assay support for your investigational biotherapeutics: Lot release specifications, stability analysis, potency analysis at DNA/ RNA/ protein levels, titration, cGMP cell line characterization for cell therapies, we offer you a support and resources to navigate the guidelines provided by the FDA or other regulatory authorities to enable regulatory compliance.
Make Informed Go-No-Go Decisions Early in Your Drug Development Process!
Leverage Applied StemCell’s unique expertise in CRISPR/Cas9 and induced pluripotent stem cell (iPSC) technologies to engineer predictive and reliable in vitro disease models as an alternative to animal models for preliminary drug screening.
Our ISO:9001 certified service platform offers full flexibility in choosing assay modules with a wide-range of functional endpoints for early-stage in vitro screening of preclinical drug candidates. We have a comprehensive cell-based test battery from which you can choose assays for efficacy, safety or target discovery that suit your therapeutic pipeline. We provide the scientific expertise, accurate and efficient screening to help you make informed decisions about your small/ large molecules early in your drug development process.