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3D Cell Cultures: Technologies and Global Markets

3D Cell Cultures: Technologies and Global Markets

The three-dimensional cell culture market reached $1.0 billion in 2016 and should reach $3.9 billion in 2021, with a compound annual growth rate (CAGR) of 42.6% from 2016 to 2021.

Report Includes
An overview of the global markets and technologies for 3D cell cultures.
Analyses of global market trends, with data from 2015, estimates for 2016, and projections of compound annual growth rates (CAGRs) through 2021.
Information on 3D technologies, with a focus on representative platforms, including cube, spherical droplet, stacked plate, magnetic bead, and other platforms.
Value-chain analysis at the following levels: key innovation or founding intellectual property, prototyping, beta testing, and research collaborations or relationship building.
Analysis of the market's dynamics, specifically growth drivers, restraints, and opportunities.
Relevant patent analysis, including recent activity and a list of key patents.
Profiles of major players in the industry.

Report Scope
The scope of the report encompasses the major types of 3D cell culture that have been used, as well as the major applications being developed by industry, academic researchers and their commercialization offices, and government agencies. It analyzes current market status, examines future market drivers and presents forecasts of growth over the next five years. Technology developments, including the latest trends, are discussed. Other influential factors such as screening strategies for pharmaceuticals have also been included.


Chapter 1: Introduction
Study Goals and Objectives
Reasons for Doing the Study
Scope of Report
Intended Audience
Methodology and Information Sources
Analyst's Credentials
Related BCC Research Reports
Chapter 2: Summary and Highlights
New Applications Identified Since 2015 Report
Changes from 2015 Report
Chapter 3: Market and Technology Background
Tissue and Cell Culture
Tissue
Cells
Cell Types
Tissue Culture and Cell Culture Definitions
Obtaining Cell Cultures
Isolating Cells from Tissues
Maintaining Cells in Culture
Plating Density and Sub-culturing
Cryogenic Storage
Obtaining Cells from Other Sources: Issue of Cross-contamination
Cell Types Based on Morphology
Cell Types Based on Hybridomas
Cell Culture: Basic Requirements
Avoiding Contamination
Important Indicators of Cell Culture Health
Maintaining Optimal Cell Culture Conditions
Basic Cell Culture Systems
Adherent Cells Requiring Attachment Substrate
Suspension Cell Cultures
History and Early Applications
Invention of Tissue Culture
Development of Sustained Cell Lines
First Cell Culture Flask and Rigorous Techniques
Lindbergh: The Cell Culture Equipment Pioneer
Establishing Continuous Cell Lines
Key Developments in Equipment
Vaccine Development as Catalyst
Cell Strains and Cell Lines
Vaccines Developed Using Human Cell Strains
Continued Catalyst
Chapter 4: Tissue and Cell Culture Systems Landscape
Large-Scale Manufacture of Biopharmaceuticals and Vaccines
Suspension Proteins and Monoclonal Antibodies
Adherent-Cell-based Therapies and Vaccines
Small-Scale Adherent to Make Somatic Cells, Stem Cells and Tissues
Technology Overview by Cell Culture Type
Suspension Approaches
Innovation and Challenges
Single-Use Technology
Mini- and MicroBioreactors: Clone Selection and Development
Adherent Approaches
Traditional Roller Bottles
Other Systems
New Understanding of Cell Attachment and Detachment
Three-dimensional Bioreactors
Applications in Regenerative Medicine
Tissue Culture – Early 3D Pioneers
Revenue Estimate
Chapter 5: Research Landscape and Products Used in Three-dimensional Cell Culture
Microplates
Standards Setting
Continuous Innovation
Microplate Readers
Liquid-Handling Equipment
Cellomics Overview
Fluorescence as Driver of Screening
High Content Screening
Imaging Advances
Flow Cytometry
Future Vision for High-content Screening
Label-Free Platforms
Electrophysiology
Assays and Assay Kits
Cell-Based Assays: Overview and Newer Developments
Cells Used in Cell-Based Assays
Two-dimensional Cultures vs. Three-dimensional Cultures
Key Suppliers
Basic 3D Cell Culture Variables
Cell Adhesion
Cell Migration
Cell Invasion
Viability and Cytotoxicity
Cell Signaling and Communication
Enhanced Functionality and Confirming Assays
Cytotoxicity: A Major Category
Permeability Assays for Cell Viability and Survival
Metabolic Assays for Cell Viability and Survival
Cell Death Assays
Cytostatic or Long-Term Impact Assays
Multiplex Assays
Composite Screening Strategies
High Throughput Screening (HTS) Applications
Three-dimensional Cytotoxicity Applications
Correlation with Gene-Expression Data
1,536-Well Formats
Kinetic Metabolism Assays
3D Assay Open Innovation Platform
Chapter 6: Three-dimensional Technologies and Basic Products
Microtiter Plates Provide Platform
Supportive Standards
Microplate Well Inserts
Three-dimensional Cell Culture Technologies
Three-dimensional Adoption Status
Importance of 2D vs. 3D Systems
Paracrine vs. Autocrine Signaling
Basic 3D Cell Culture Variables
Cell Adhesion
Cell Migration
Cell Invasion
Basic Assay Types
Three-dimensional Technology and Products
Three-dimensional Matrices to Replicate the Extracellular Matrix
Foundational Tools: Gels and Basement Membranes
Scaffolds
Examples of Innovation
Scaffold-Free Formats
Applications Overview
Analytical Methods
Imaging
Liquid Handling
High-throughput Screening Capability
Continued Spheroid Adoption
Organotypic Models
Directional Culture
Microfluidics
Glass/Silicon-Based Platforms
Polymer-based Platforms
Chip Technology
Organ/Tissue-On-Chip Industry
Bioprinting
Current Dominant Technologies
Bioprint Instrument Industry
Bioink Technologies
Bioink Industry
Applications
Toxicology Testing in Cosmetics
Organs and Organoids
Organoids
Tissue Engineering in Regenerative Medicine
Skin Substitutes Industry
Recent Example: Skin and Hair
U.S. Regulatory Status of Bioprinted Products
Organ Transplants
Acquisitions and Strategic Alliances
Regenerative Medicine
Future Challenges
Increasing Integration and Evolution
Revenue Summary
Market Estimate
Chapter 7: Three-dimensional Models for Cancer
Cancer at the Cellular Level Overview
Approaches to Date
In Vivo (Animal) Testing Standard
Xenografts
Two-dimensional Learnings and Drawbacks
Three-dimensional Requirements
Cell Number and Viability
Migration and Invasion
Unmet Needs: Angiogenesis and Immune System Evasion
Three-dimensional Benefits to Cancer Research
Greater Distinction in Cell Morphology and Proliferation
Greater Gene Expression and Cell Behavior
Better Models of Cell Migration and Invasion
Cell Heterogeneity
Breast Cancer as a Driver of Three-dimensional Cultures
Structure, Polarity and Apoptosis
Melanoma as a Driver of Three-dimensional Cultures
Moving to Spheroid Configurations
Three-dimensional Systems in Cancer Research
Multicellular Tumor Spheroids
Multilayered Cell Cultures
Three-dimensional Engineered Scaffolds
Natural Materials
Synthetic Materials
Learnings from Drug Sensitivity and Resistance
Altered Signaling and Sensitivity
Drug Resistance
Cellular Signaling
Cellular Signaling Mediated by Integrins
Drug Screening
Approaches and Endpoints
Spheroids Applications
Metastasis via Three-dimensional Cell Migration Model
Metastasis via Lung-on-Chip
Cancer Metabolism
Future Horizons
Metastases
Co-culture
Vascularization
Cancer-associated Fibroblasts
Cancer Stem Cells
Combination Therapies
Biologics Development
Tumor Recurrence
Patient-derived Cells
Patient-derived Tumor Xenografts
Evolution of PDX Platforms
Ex Vivo Models
Ex Vivo Applications
Ex Vivo Shortcomings
Ex Vivo PDX in 3D Cell Culture
Combining Ex Vivo with NGS
Preserving Heterogeneity in Cancer Models
High-Throughput Drug Screening
Revenue Forecast
Chapter 8: Landscape for Toxicology and Drug Safety Testing
Toxicology Background
Testing for Adverse Effects on the Skin
Toxicology Testing in Cosmetics
Updated Regulatory Requirements
Efficacy of Cosmetics and Cosmeceuticals
Bioprinting
Skin Irritation
Skin Corrosion
Phototoxicity
Skin Sensitization
Eye Irritation
Acute Systemic Toxicity
Acute Toxicity Testing
Cytotoxicity Assays for Acute Toxicity Testing
Chronic and Repeated Dose Toxicity
Chronic and Repeated Dose Toxicity Study Goals
Development of Repeated Dose Toxicity Testing In Vitro
Carcinogenicity and Genotoxicity
Overview
In Vitro Methods: Background and Recent Developments
Regulatory vs. Drug Development Applications
Efforts to Reduce False Positives
Recent Innovations for Screening
Future Challenge: Non-Genotoxic Carcinogens
Reproductive and Developmental Toxicity
Background
Following the Reproductive Cycle
Development and Reproductive Tox Testing Types
Zebrafish Model for Developmental Toxicity Screening
Combinations of Zebrafish and Stem Cells
Biomedical Frontiers: Male Testis
Endocrine Disruptor Screening
Background
Environmental Toxicology Impacts In Vitro Methods
High-Production Volume Chemicals
ToxCast and Tox 21 Initiatives
Future Challenge: Thyroid Disruption
BG1 Assay
Toxicokinetics and ADME
In Vitro Developments
Metabolism
Pharmacokinetics of Low Turnover Compounds
Organotypic Models
Three-dimensional Models for Skin
Three-dimensional Corneal System
Absorption Barrier Models
Gastrointestinal
Lung
Blood-Brain Barrier
Blood-Brain Barrier on a Chip
Real Architecture for Three-dimensional Tissue Barriers and Extracellular Matrix
Liver Toxicity
Uniqueness and Complexity of Liver
Liver as a Key Driver for Three-dimensional Innovation
In Vitro Liver Applications
Liver Toxicity Testing
Primary Hepatocyte Use
Learnings From Monolayer Cultures
Learnings from Co-Cultures Contribution to the Development of Cytotoxicity and Three-dimensional Assays
In Vivo Liver Function and Structure
Hepatocytes or Parenchymal Cells
Specialized Liver Endothelial Cells
Endothelial Cells Surround Hepatocyte Core
Non-Parenchymal Stellate and Kupffer Cells
Liver Metabolism
Sub-Cellular Liver Enzyme Fractions
Extracellular Matrix as a Driver of Differentiation
Toxicity Studies and Non-Parenchymal Cells Drive In Vitro Development
Challenges
Liver In Vitro Models
Isolated Perfused Rat Liver
Precision-Cut Liver Slices
Human Hepatocyte Isolation
Isolated Hepatocyte Shipping
Co-Cultures of Hepatocytes and Macrophages
Two-Chamber Systems
Micropatterning
Three-dimensional Liver Models
Two-dimensional Sandwich
Sandwich-Culture Model
Hydrogel Three-dimensional Scaffolds
Synthetic Scaffolds
Self-Assembled Hepatospheres
Hepatospheres-Derived from Cell lines vs. Primary Cells
Bioprinted Liver Tissue
Detected Hepatosphere Structures and Functionality
Extracellular Matrix
Cell-cell Contacts: Learnings from In Vitro Tox
Oxygen Supply
Co-culture with Non-parenchymal Cells In Three-dimensional Spheroids
Refinements to Co-culture
Ideal Criteria
Drug Resistance
Transporter Studies
Achieving Heterotypic Cell-cell Contacts
Summary Learnings
Unmet Needs and Future Drivers of Innovation
Regeneration
Achievement of Hepatocyte Expansion Still Elusive
Inflammation Models
Immune-mediated Drug-induced Liver Injury
High-content Imaging and Analysis
Stem Cell-Derived Hepatocyte Potential
Morphogen Signaling
Microfluidics Applications
Dielectrophoretic Forces
Learnings from Microfluidics
Self-organizing Systems
Multi-Donor Liver Cells
Kidney Toxicity Applications
Future Challenge: Stem-Cell Derived Kidney Cells
Bioprinted Kidney Tissue
Pancreatic Toxicology Applications
Cardiovascular Safety Testing of New Drug Candidates
Commercial Avenue
Collaboration with Regulators
In Silico: Model-Based Drug Development
Microelectrode Arrays Based on Impedance
Surrogate for Aortic Ring Assay via Bioprinted Magnetics
Vasodilator Activity
Three-dimensional Engineered Heart Tissues
Revenue Estimate
Chapter 9: 3D Culture Role in Stem Cells
Introduction
Early Learnings
Embryogenesis
Growth, Structure and Morphology
Differentiation
Differentiation vs. Proliferation
Extracellular Matrix
Soluble Factors
Mechanical Forces
MicroRNAs
Three-dimensional Stem Cell Culture Systems
Plate or Culture Dish
Spinner Flask and Rotating Wall Vessel
Perfusion Bioreactor and Microcarrier Systems
Shortcomings
Controlling Embryoid Body Formation
Forced Aggregation Cultures
Hanging-Drop Approach
Applications
Stem Cell Microenvironments
Stem Cell Markers for High-throughput Screening
Teratomas and the Teratoma Assay
Status and Drivers
Fujifilm (Cellular Dynamics Inc.)
Breakthroughs Resulting from Stem Cells Research
Revenue Estimate
Chapter 10: Three-dimensional Next-Generation Outlook
Overview
Cancer
CDx Based on Ex Vivo 3D
Immuno-Oncology
Predictive Toxicology
Neuro Safety
Stem Cells for Neuroscience Discovery and Development
Example: Alzheimer’s Research
Background: B-Amyloid Cascade Hypothesis
Human iPSC-derived Models
New 3D Model
Other 3D Advantages
Envisioned Applications
Other 3D Neuro Applications
Stem Cells for Cardiovascular Discovery
Stem Cells for Development of Regenerative Medicine
Background: Allogenic vs. Autologous
Induced Pluripotent Stem Cells (IPS)
Revenue Estimate
Chapter Appendix: Liver
Integration with “-Omics”
Chapter 11: Company Profiles
Appendix: Patent Analysis
About BCC Research
About BCC Research
BCC Library Access
BCC Custom Research
List of Tables
Summary Table Global Three-dimensional Cell Culture Market, Through 2021 ($ Millions)
Table 1 Tissue Types
Table 2 Cell Types
Table 3 Cell Culture Applications
Table 4 Leading Bioreactor Suppliers, 2017
Table 5 Leading Tissue Products and Suppliers, October 2016
Table 6 Global Market for Three-dimensional Bioreactors and Microcarriers, Through 2021 ($ Millions)
Table 7 High-Content Screening Suppliers and Key Attributes, January 2017
Table 8 Label-Free Technologies and Suppliers, January 2017
Table 9 Automated Patch Clamping Companies and Technologies, January 2017
Table 10 Leading Cell Line Suppliers, January 2017
Table 11 Leading Primary Cell Suppliers, January 2017
Table 12 Leading Stem Cell Suppliers, January 2017
Table 13 Typical Assay Endpoints and Tests
Table 14 Organ-On-Chip Industry
Table 15 Bioprinting Instrument Technologies
Table 16 Maintaining Cell Viability During Printing
Table 17 Bioprinting Instrument Industry
Table 18 Bioink Components
Table 19 Bioink Types
Table 20 Matrix Bioink Hydrogel Classes
Table 21 Matrix Bioink Selection Criteria
Table 22 Selected Bioink Companies
Table 23 In Vitro Testing in Cosmetics
Table 24 Bioprinting Industry Alliances in Cosmetics, 2015
Table 25 Printed Tissue and Organs: Commercialization Timeframe
Table 26 Tissue/Organ Complexity
Table 27 Skin Substitute Products and Market Focus
Table 28 U.S. Regulatory Considerations
Table 29 Number of United States Organ Transplants, January-June 2016
Table 30 Bioprinting Industry Acquisitions and Strategic Alliances, January 2014-February 2016
Table 31 Leading Reagent, Media and Microplate Suppliers, January 2017
Table 32 Three-dimensional Technology Product Market, Through 2021 ($ Millions)
Table 33 Common Three-dimensional Assays
Table 34 Three-dimensional Tumor Models Developed for Drug Discovery, June 2017
Table 35 Summary of EV3D Benefits/Advantages
Table 36 Global Market for Three-dimensional Culture Used in Cancer Drug Development, Through 2021 ($ Millions)
Table 37 In Vitro Testing in Cosmetics
Table 38 Alliances Between Bioprinting and Cosmetics Companies, 2015
Table 39 In Vitro and In Vivo Assays in the Tier 1 Screening Battery, January 2014
Table 40 Global Market for Three-dimensional Cultures Used in Predictive Tox Applications, Through 2021 ($ Millions)
Table 41 Global Market for Three-dimensional Cultures Used in Stem Cell Research Applications, Through 2021 ($ Millions)
Table 42 New Applications That Have Emerged Since the 2015 Report
Table 43 Global Market for Next-Generation 3D Applications, Through 2021 ($ Millions)
Table 44 Patents Assigned in 3D Cell Culture, 2009-2017
List of Figures
Summary Figure Global Three-dimensional Cell Culture Market, 2015-2021 ($ Millions)
Figure 1 Technology Maturity

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