3D Cell Cultures: Technologies and Global Markets

Table of Contents

Chapter 1 Introduction

• Study Goals and Objectives
• Reasons for Doing the Study
• Scope of Report
• What's New in This Report?
• Methodology and Information Sources
• Geographic Breakdown
• Segment Breakdown

Chapter 2 Summary and Highlights

• Market Outlook
• Market Summary

Chapter 3 Market Overview

• An Opening Comment on an Amazing Industry
• Industry Issues
• In Vitro versus In Vivo
• Dimensionality
• The Research Chain for 2D and 3D Cell Culture
• Best Practices
• Standardization
• Regulation
• Genomics Forcing the Hand of the FDA
• Leachables and Extractables
• Broad Issues
• Research Talent Shortages
• The Shifting International Picture
• Pace and Diversification of Innovation
• A Comment on the "Other" Areas of Cell Culture
• Omics Everywhere
• Is 2020 a Watershed Year for the Cell Culture Industry?
• Preliminary Market Analysis
• Cell Culture Market Growth Rate Estimates
• Assessing Large-Scale Media Consumption Needs
• Modeling Future Growth in Biopharmaceuticals
• Base Case for the Cell Culture Market
• Challenges in Projecting Sales and Growth
• Cell Culture Media Market Estimates
• Cell and Gene Therapy Bioprocessing Segment
• Evaluating Media Consumption for Biosimilars
• What About CDMOs?
• Microfluidics
• Bioreactors
• Internal Cell Culture Resources
• Is There Too Much Concentration of Ownership in Biotechnology?
• Characterizing Innovation in 3D Cell Culture
• Bioprinting Strategic Roadmap

Chapter 4 Market, by Type

• Where Did Tissue and Cell Culture Start?
• 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
• Terminology and Concepts
• Tissue and Cell Culture Industry
• Tissue Culture and Cell Culture Definitions
• Cell Lines
• Care and Growth of Cell Culture Systems
• Media, Sera, and Reagents
• Gels and Scaffolds
• Microplates/Microtiter Plates
• Bioanalytical Instruments
• Bioanalytical Imaging
• Bioprinting
• Bioreactors
• Other Equipment for Cell Culture
• Adherent Approaches
• Traditional Roller Bottles
• Other Systems
• Information Technology: Software and Services for the Cell Culture Research Market
• Software for the Research Market in Cell Culture
• Software-Related Support Services
• Bioprocessing Consumables for Cell Culture
• Microcarriers for Large-Scale 3D Culture
• Sera for Large-Scale 3D Culture
• Media for Large-Scale 3D Culture
• Bioreactor Bags for Large-Scale 3D Culture
• Other
• Bioprocessing Equipment
• Analytical Equipment for Bioprocessing
• Automation Systems for Bioprocessing
• Support Equipment for Bioprocessing
• Aspects of Large-Scale Manufacturing 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
• Vaccines
• Vaccine Development as a Catalyst
• Vaccines Developed Using Human Cell Strains
• Exosome Manufacturing
• Viral Vector Manufacturing
• Lentivirus Manufacturing
• Plasmid Manufacturing
• Cell Culture End Users
• Pharma/Biopharma
• Universities
• Government
• CROs/CDMOS
• Other
• Cell Culture Applications
• Drug Discovery
• Clinical Development
• Toxicology
• Basic Research
• Bioprocessing Development
• Other
• Regional Markets
• The Americas
• Europe
• Asia-Pacific
• Rest of the World

Chapter 5 Assays, Imaging and Analysis

• Assays
• Assay Development for Mesenchymal Stem Cells
• In Vitro Testing of Adventitious Agents
• Assays and Assay Kits
• Cell-Based Assays: Overview and Newer Developments
• Cells Used in Cell-Based Assays
• Notes on 3D Cell-Based Assays
• Kinetic Metabolism Assays
• Cell Proliferation
• Viability and Cytotoxicity
• Permeability Assays for Cell Viability and Survival
• Cell Invasion
• Cell Signaling and Communication
• Cytostatic
• Cell Death Assays
• Imaging Technology
• Imaging Assays
• Fluorescence as a Driver of Screening
• Analytical Systems Used in Tissue and Cell Culture
• Understanding "Cellomics"
• HCS Support of 3D Cell Culture
• NGS Discovery Pools
• Multiplex Assays
• Predictive Toxicology
• Neuro Safety
• The Omics Invasion
• Transcriptomics

Chapter 6 Regulation and Standardization

• U.S. Regulatory Status of Bioprinted Products
• Basic Guidance for the Regulation of Biologics
• Guidance for Regenerative Medicine
• Guidance for Xenotransplants
• Guidance for Regenerative Medicine: Emergency Approval
• Regulating Bioprinted Products

Chapter 7 3D Models for Cancer

• Disease Modeling
• Cancer
• Main Classes of Models for Researching Cancer and Other Diseases
• Cell Lines
• Spheroids and Organoids
• Genetically Engineered Mouse Model (GEMM)
• Patient-Derived Tumor Xenografts (PDXs)
• Overview: Cancer at the Cellular Level
• In Vivo (Animal) Testing Standard
• Empire of the Mouse
• Humanized Mice
• 2D Culture
• 3D Requirements
• Cell Number and Viability
• Migration and Invasion
• Unmet Needs: Angiogenesis and Immune System Evasion
• Benefits of 3D Models 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 3D Cultures
• Structure, Polarity and Apoptosis
• Melanoma as a Driver of 3D Cultures
• Moving to Spheroid Configurations
• 3D Systems in Cancer Research
• Multicellular Tumor Spheroids
• Multilayered Cell Cultures
• 3D Engineered Scaffolds
• Natural Materials
• Synthetic Materials
• Human Cancer Model Initiative (HCMI)
• Next-Generation Human Cancer Models
• Drug Sensitivity and Resistance
• Altered Signaling and Sensitivity
• Drug Resistance
• Cellular Signaling
• Cellular Signaling Mediated by Integrins
• Drug Screening
• Approaches and Endpoints
• Spheroid Applications
• Metastasis via 3D 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 (PDXs)
• Evolution of PDX Platforms

Chapter 8 Landscape for Toxicology and Drug Safety Testing

• Introduction
• Liver
• Toxicology Background
• Testing for Adverse Effects on the Skin
• New Assessment Methodologies Impact on 3D Cell Culture
• Toxicology Testing in Cosmetics
• Updated Regulatory Requirements
• Efficacy of Cosmetics and Cosmeceuticals
• Aspects of Cosmetic Toxicity Testing
• 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
• Carcinogenicity and Genotoxicity
• Overview
• In Vitro Methods: Background and Recent Developments
• Regulatory versus Drug Development Applications
• Efforts to Reduce False Positives
• Recent Innovations in 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
• Combination of Zebrafish and Stem Cells
• Biomedical Frontiers: Male Testis
• Endocrine Disruptor Screening
• Background
• Environmental Toxicology Impacts In Vitro Methods
• 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
• 3D Models for Skin
• 3D Corneal System
• Absorption Barrier Models
• Gastrointestinal
• Lung
• Blood-Brain Barrier
• Real Architecture for 3D Tissue Barriers and Extracellular Matrix
• Liver Toxicity
• Uniqueness and Complexity of Liver
• Liver as a Key Driver for 3D Innovation
• In Vitro Liver Applications
• In Vivo Liver Function and Structure
• Liver Metabolism
• In Vitro Liver Models
• Co-cultures of Hepatocytes and Macrophages
• 3D Liver Models
• Bioprinted Liver Tissue
• Detected Hepatosphere Structures and Functionality
• Ideal Criteria
• Drug Resistance
• Transporter Studies
• Achieving Heterotypic Cell-Cell Contacts
• Unmet Needs and Future Drivers of Innovation
• Morphogen Signaling
• Multi-donor Liver Cells
• Kidney Toxicity Applications
• Future Challenge: Stem-Cell Derived Kidney Cells
• Bioprinted Kidney Tissue
• Pancreatic Toxicology Applications
• Cardiovascular Toxicity
• Commercial Avenue
• Collaboration with Regulators
• Cardiovascular Drug Discovery
• Microelectrode Arrays (MEAs) Based on Impedance
• Surrogate for Aortic Ring Assay via Bioprinted Magnetics
• Vasodilator Activity
• 3D Engineered Heart Tissues

Chapter 9 Market Breakdown by Region

• Introduction
• North America
• United States
• Canada
• Europe
• Germany
• United Kingdom
• Asia-Pacific
• China
• Japan
• India
• South Korea
• Singapore
• Rest of the World

Chapter 10 Stem Cell Landscape

• A History of Stem Cells
• Major and Minor Research Areas for Stem Cells
• 3D Stem Cell Culture Systems
• Plate or Culture Dish
• Spinner Flask and Rotating Wall Vessel
• Perfusion Bioreactor and Microcarrier Systems
• Shortcomings
• Microfluidics and Stem Cells
• Short Review of Stem Cell Biology
• Embryogenesis
• Growth, Structure and Morphology of Stem Cells
• Stem Cell Differentiation
• Stem Cell Differentiation versus Proliferation
• Extracellular Matrix and Stem Cells
• Soluble Factors
• Manufacturing Stem Cells
• Controlling Embryoid Body Formation
• Forced Aggregation Cultures
• Hanging-Drop Approach
• Applications
• Stem Cell Markers for High-Throughput Screening
• Teratomas and the Teratoma Assay
• Fujifilm (Cellular Dynamics Inc.)
• Stem Cell Research Breakthroughs
• Stem Cells for Neuroscience Discovery and Development
• Example: Alzheimer's Research
• Background: B-Amyloid Cascade Hypothesis
• Human iPSC-Derived Models
• New 3D Model
• Other Advantages of 3D
• Envisioned Applications
• Other 3D Neuro Applications
• Stem Cells for Cardiovascular Discovery
• Stem Cells for the Development of Regenerative Medicine
• Background: Allogenic versus Autologous
• MicroRNAs
• Induced Pluripotent Stem Cells (IPS)

Chapter 11 Regenerative Medicine: Organ Transplants and Skin Substitutes

• Regenerative Medicine
• Need for Organ Transplants
• Applications in Regenerative Medicine
• Investments in Regenerative Medicine
• Skin Substitutes Industry
• Tissue Culture Allograft and Autograft Products
• Tissue Engineering in Regenerative Medicine

Chapter 12 Company Profiles

• 3D BIOPRINTING SOLUTIONS
• 3D BIOTEK LLC
• 4D TECHNOLOGY CORP.
• ABCAM PLC
• AKRON BIOTECH
• AGILENT TECHNOLOGIES INC.
• ALPCO
• AMSBIO
• BECKMAN COULTER INC.
• BIOINSPIRED SOLUTIONS
• BIOTIME INC.
• BIOVISION INC.
• CELL APPLICATIONS INC.
• CELLINK
• CORNING INC.
• CYPROTEX
• CYTIVA
• CYTOO SA
• EMD MILLIPORE / MERCK KGAA
• EMULATE INC.
• ENVISIONTEC INC.
• EPITHELIX
• EUROFINS SAS
• GREINER BIO-ONE INTERNATIONAL GMBH
• HAMILTON ROBOTICS
• HUB ORGANOIDS
• HUREL CORP.
• INSPHERO
• INVITROCUE
• KIYATEC INC.
• LIFENET HEALTH
• LOREM VASCULAR / CYTORI THERAPEUTICS INC.
• MATTEK
• MIMETAS INC.
• ORGANOVO HOLDINGS INC.
• PERKINELMER INC.
• PLASTICELL LTD.
• PLURISTEM THERAPEUTICS INC.
• POIETIS
• PROMEGA CORP.
• SEAHORSE BIOSCIENCE
• STEMCELL TECHNOLOGIES
• STRATATECH CORP.
• SYNVIVO INC.
• TAP BIOSYSTEMS
• TECAN TRADING AG
• ZEN-BIO INC.

List of Tables

• Summary Table : Global Market for 3D Cell Culture, by Segment, Through 2028
• Table 1 : Dimensionality of Cell Culture
• Table 2 : WHO R&D Roadmap of Priority Infectious Diseases
• Table 3 : 3D Bioprinting Roadmap
• Table 4 : Selected Online Prices for Bioreactors
• Table 5 : Global Market for 3D Cell Culture, by Segment, Through 2028
• Table 6 : Tissue Types
• Table 7 : Cell Types Based on Developmental Origin
• Table 8 : Leading Cell Line Suppliers, April 2020
• Table 9 : Commonly Used Transformed Cells Lines
• Table 10 : Major Primary Cell Lines
• Table 11 : Leading Primary Cell Suppliers
• Table 12 : Main Types of Stem Cells
• Table 13 : Stem Cell Services
• Table 14 : Areas of Interest in 3D Spheroid Research
• Table 15 : Selected Nanoparticle Products Used in Life Science Research
• Table 16 : Results of Liver-Chip Drugs Halted in Previous Clinical Trials Based on Animal Studies
• Table 17 : Companies and Universities Involved in the Organ-on-a-Chip Industry
• Table 18 : Microfluidics Companies
• Table 19 : Selected Recent Patents Issued on Microfluidic Devices Related to Cell Culture Applications
• Table 20 : Selected Papers Published on Recent Microfluidic Advances in Cell Culture
• Table 21 : High-Content Screening Suppliers and Key Attributes
• Table 22 : Selected Patents Issued Related to Flow Cytometers
• Table 23 : Thermo Fisher Imaging Products
• Table 24 : Recent Bioprinting Company Deals and Strategic Partnerships
• Table 25 : Bioprinting Modalities
• Table 26 : Maintaining Cell Viability During Printing
• Table 27 : Bioprinting Instrument Industry
• Table 28 : Biomaterial Components
• Table 29 : Bioink Types
• Table 30 : Classes of Matrix Bioink Hydrogels
• Table 31 : Matrix Bioink Selection Criteria
• Table 32 : Selected Bioink Companies, 2020
• Table 33 : Projected Unit Sales of Research Bioreactors, <10 Liters, 2020
• Table 34 : Leading Bioreactor Suppliers, 2020
• Table 35 : Label-Free Technologies and Suppliers
• Table 36 : Developmental Issues Facing the Commercialization of Exosomes
• Table 37 : Companies Working on Exosome Products
• Table 38 : Global Market for Cell Culture, by End User, Through 2028
• Table 39 : Global Market for Cell Culture, by Application, Through 2028
• Table 40 : Global Market for Cell Culture, by Region, Through 2028
• Table 41 : Typical Assay Endpoints and Tests
• Table 42 : U.S. Patents on Assays Systems, 2019 and 2020
• Table 43 : Selected U.S. Patents on Assay Imaging, 2019 and 2020
• Table 44 : Recently Issued U.S. Patents on Cellomics, 2019
• Table 45 : Toxicology Issues That Need to Be Addressed for FDA-Regulated Products
• Table 46 : Overview of Federal Regulation of the Cell Culture Markets
• Table 47 : FDA List of Cell, Biologic and Tissue Products Regulated Under CBER and CDRH
• Table 48 : FDA "Talking Point" Recommendations for Regenerative Medicine Advanced Therapies (RMATs)
• Table 49 : U.S. Regulatory Considerations for Bioprinted Biologics
• Table 50 : Main Types of Models for Researching Cancer and Other Diseases
• Table 51 : Goals of Funding Opportunity Announcement RFA-CA-19-055
• Table 52 : Common 3D Assays
• Table 53 : Summary of the Benefits and Advantages of EV3D
• Table 54 : ECVAM List of Current Activities, 2020
• Table 55 : In Vitro Testing in Cosmetics, by Test Class
• Table 56 : Global Market for Cell Culture by Region, Through 2028
• Table 57 : North American Market for Cell Culture by Country, Through 2028
• Table 58 : European Market for Cell Culture by Country, Through 2028
• Table 59 : Asia-Pacific Market for Cell Culture by Country, Through 2028
• Table 60 : RoW Market for Cell Culture by Region, Through 2028
• Table 61 : Major and Minor Research Areas in Stem Cells
• Table 62 : Stem Cell Usage in Research
• Table 63 : Recent U.S. Patents Granted on Stem Cell Technologies
• Table 64 : Papers Published on Selected Stem Cell Research Trends
• Table 65 : Comparison of the Number of Citations in the Literature on Cell Culture versus Stem Cell Culture
• Table 66 : Number of Organ Transplants Performed in the United States, 2018 and 2019
• Table 67 : Total Global Financing of Regenerative Medicine
• Table 68 : Total Financing of Regenerative Medicine, by Therapeutic Area
• Table 69 : Leading Tissue Products and Suppliers
• Table 70 : Printed Tissue and Organs: Commercialization Timeframe
• Table 71 : Tissue/Organ Complexity
• Table 72 : 3D Bioprinting Solutions: Company Snapshot
• Table 73 : 3D Biotek LLC: Company Snapshot
• Table 74 : 4D Technology Corp.: Company Snapshot
• Table 75 : Abcam Plc: Company Snapshot
• Table 76 : Abcam PLC: Financial Performance, 2022
• Table 77 : Akron Biotech: Company Snapshot
• Table 78 : Agilent Technologies: Company Snapshot
• Table 79 : Agilent Technologies Inc.: Financial Performance, 2022
• Table 80 : Alpco: Company Snapshot
• Table 81 : Amsbio: Company Snapshot
• Table 82 : Beckman Coulter: Company Snapshot
• Table 83 : Bioinspired Solutions: Company Snapshot
• Table 84 : BioTime Inc.: Company Snapshot
• Table 85 : Biovision Inc.: Company Snapshot
• Table 86 : Cell Applications Inc.: Company Snapshot
• Table 87 : Cellink: Company Snapshot
• Table 88 : Corning Inc.: Company Snapshot
• Table 89 : Corning Inc.: Financial Performance, 2022
• Table 90 : Cyprotex: Company Snapshot
• Table 91 : Cytiva: Company Snapshot
• Table 92 : Cytoo SA: Company Snapshot
• Table 93 : Merck KGAA: Company Snapshot
• Table 94 : Merck KGAA: Financial Performance, 2022
• Table 95 : Emulate Inc.: Company Snapshot
• Table 96 : EnvisionTec Inc.: Company Snapshot
• Table 97 : Epithelix: Company Snapshot
• Table 98 : Greiner Bio-One International GmbH: Company Snapshot
• Table 99 : Hamilton Robotics: Company Snapshot
• Table 100 : HUB Organoids: Company Snapshot
• Table 101 : Hurel Corp.: Company Snapshot
• Table 102 : Insphero: Company Snapshot
• Table 103 : Invitrocue: Company Snapshot
• Table 104 : Kiyatec Inc.: Company Snapshot
• Table 105 : LifeNet Health: Company Snapshot
• Table 106 : Cytori Therapeutics Inc.: Company Snapshot
• Table 107 : Mattek: Company Snapshot
• Table 108 : Mimetas Inc.: Company Snapshot
• Table 109 : Organovo Holdings Inc.: Company Snapshot
• Table 110 : PerkinElmer Inc.: Company Snapshot
• Table 111 : Plasticell Ltd.: Company Snapshot
• Table 112 : Pluristem Therapeutics Inc.: Company Snapshot
• Table 113 : Poietis: Company Snapshot
• Table 114 : Promega Corp.: Company Snapshot
• Table 115 : SeaHorse Bioscience: Company Snapshot
• Table 116 : Stemcell Technologies: Company Snapshot
• Table 117 : Stratatech Corp.: Company Snapshot
• Table 118 : Synvivo Inc.: Company Snapshot
• Table 119 : Tap Biosystems: Company Snapshot
• Table 120 : Tecan Trading AG: Company Snapshot
• Table 121 : Zen-Bio Inc.: Company Snapshot

List of Figures

• Summary Figure : Global Market for 3D Cell Culture, by Segment, 2020-2028
• Figure 1 : Research Chain for Cell Culture
• Figure 2 : A Model for The Evolution of FDA Regulation
• Figure 3 : 3D Cell Cultures: Market Dynamics
• Figure 4 : An Innovation Matrix
• Figure 5 : Bioprinting Strategic Roadmap
• Figure 6 : Global Market Shares of 3D Cell Culture, by Segment, 2022
• Figure 7 : Gastrointestinal Organotype Cultures
• Figure 8 : iCELLis Nanoreactor: Example of Commercial 2D Cell Culture Systems
• Figure 9 : Prototype of 3D Model Lung-on-a-Chip from Wake Forest
• Figure 10 : Recent Photo of the HepaChip
• Figure 11 : Recent Photo of the HepaChip-MWP
• Figure 12 : University of Toronto Handheld Bioprinting Device
• Figure 13 : Collaborative Experiment Conducted by American, Russian and Israeli Scientists
• Figure 14 : Smart Marbles Concept for Quantifying Process Heterogeneity
• Figure 15 : Porcine Intestinal Organoids
• Figure 16 : Diagram of the Components of a Predictive Toxicology System
• Figure 17 : Gleason's Pattern
• Figure 18 : Diagram of PDXs, Cell Lines and Organoid/Spheroid Xenografts
• Figure 19 : Cell Heterogeneity and Its Function
• Figure 20 : Global Market for Cell Culture by Region, 2020-2028
• Figure 21 : North American Market for Cell Culture by Country, 2020-2028
• Figure 22 : European Market for Cell Culture by Country, 2020-2028
• Figure 23 : Asia-Pacific Market for Cell Culture by Country, 2020-2028
• Figure 24 : ROW Market for Cell Culture by Region, 2020-2028
• Figure 25 : Electron Micrograph of Porous Microcarrier for Stem Cell Production
• Figure 26 : Photograph of Apligraf
• Figure 27 : Abcam PLC: Financial Performance, 2021 and 2022
• Figure 28 : Abcam PLC: Revenue Shares, by Country/Region, 2022
• Figure 29 : Agilent Technologies Inc.: Financial Performance, 2021 and 2022
• Figure 30 : Agilent Technologies Inc.: Revenue Shares, by Business Unit, 2022
• Figure 31 : Agilent Technologies Inc.: Revenue Shares, by Country/Region, 2022
• Figure 32 : Corning Inc.: Revenue Shares, by Business Unit, FY 2022
• Figure 33 : Corning Inc.: Revenue Shares, by Region, FY 2022
• Figure 34 : Merck KGAA: Revenue Shares, by Business Unit, FY 2022
• Figure 35 : Merck KGAA: Revenue Shares, by Region, FY 2022