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- 3次元细胞模型 -

Inadequate representation of the human tissue environment during a preclinical screen can result in inaccurate predictions of a drug candidate's effects. Thus, pharmaceutical investigators are searching for preclinical models that closely resemble original tissue for predicting clinical outcome. Three-dimensional cell culture recapitulates normal and pathological tissue architectures that provide physiologically relevant models to study normal development and disease. However, challenges remain for high-throughput screening as researchers must procure large numbers of identical 3D cell cultures, develop assays and obtain fast, automated readouts from these more complex assays. Join cell biologists, tissue engineers, assay developers, screening managers and drug developers at Cambridge Healthtech Institute's Fourth Annual 3D Cellular Models: Engineering Predictive Preclinical Screening Models conference as they discuss strategies that accelerate the identification of novel therapeutic leads.



Final Agenda

Wednesday, June 20

11:00 am Registration Open

11:50 Bridging Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:20 pm Dessert and Coffee Break in the Exhibit Hall with Poster Viewing


1:00 PLENARY KEYNOTE SESSION

2:30 Refreshment Break in the Exhibit Hall with Poster Viewing

TAKING SCREENING INTO THE THIRD DIMENSION

3:10 Chairperson's Opening Remarks

Jonathan Garlick, DDS, PhD, Professor, Oral Diagnosis, School of Dental Medicine, School of Medicine and Engineering, Tufts University


3:15 KEYNOTE PRESENTATION: Drug Discovery in the Third Dimension and Beyond

Marc_FerrerMarc Ferrer, PhD, Team Lead, NIH Chemical Genomics Center, NCATS, NIH

Three-dimensional (3D) cell cultures that mimic the spatial organization of cells in a live tissue are now being developed to test the activity of therapeutics in more predictive assay systems. Progress towards the development of an assay platform of 3D tissue models ranging from spheroids to 3D bioprinted tissues will be presented from the perspective of a laboratory focused on drug screening and discovery.

3:45 A Pharma Consortium Strategy for Engaging Novel MPS Technologies

Yvonne_WillYvonne Will, PhD, Senior Director & Head, Science and Technology Strategy, Drug Safety Research and Development, Pfizer

A consortium of pharmaceutical scientists was formed to provide a venue for collaboration among pharma and between pharma and technology developers. This group has aimed to share perspectives on potential uses for these novel platforms, biological and analytical standards, approaches to validation and a path to adoption and ultimate qualification for their clinical relevance. Partnerships among the various stakeholders is fundamental to the success of these efforts. Capability developers will benefit from a clear line of sight to a drug development application. Drug developers will need to adopt a novel decision-making framework. Regulators will want to gain experience and confidence in a unique form of evidence to support therapeutic and safety claims.

4:15 Presentation to be Announced


4:30 Presentation to be Announced

ENGINEERING MODELS

4:45 What 3D Skin Models Teach Us: Lessons Learned from 20 Years of Building from the Ground Up

Jonathan Garlick, DDS, PhD, Professor, Oral Diagnosis, School of Dental Medicine, School of Medicine and Engineering, Tufts University

3D engineered tissue models of human skin have emerged as a platform technology for drug screening and modeling of human skin disease. These tissue models have evolved through integration of new understandings of stem cell biology, the cell microenvironment and tissue engineering principles. This presentation provides an overview of what we have learned about engineering skin models over the past 20 years and what can be utilized going forward in other models.

5:05 Putting 3D Bioprinting to the Use of Tissue Model Fabrication

Yu_Shrike_ZhangYu Shrike Zhang, PhD, Research Faculty & Associate Bioengineer, Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School & Harvard-MIT Division of Health Sciences and Technology

The talk discusses our recent efforts on developing a series of bioprinting strategies including sacrificial bioprinting, microfluidic bioprinting, and multi-material bioprinting, along with various cytocompatible bioink formulations, for the fabrication of biomimetic 3D tissue models. These platform technologies will likely provide new opportunities in constructing functional organoids with a potential of achieving precision therapy by overcoming certain limitations associated with conventional models based on planar cell cultures and animals.

5:25 Engineered in vitro Disease Models for Personalized Medicine

Gulden_Camci-UnalGulden Camci-Unal, PhD, Assistant Professor, Chemical Engineering, University of Massachusetts Lowell

Dr. Camci-Unal's research aims to control and modulate cellular behavior for directing repair and regeneration of tissues. To achieve this goal, she uses diverse tools taken from chemistry, cell biology, materials science, and engineering. She talks about new engineered biomaterial platforms to generate multicellular and compartmentalized tissue-mimetics for clinical applications including endothelialization of cardiovascular tissues, regeneration of bone, and invasion of tumors.

5:45 Close of Day and Dinner Short Course Registration*

*Separate registration required.

Thursday, June 21

7:30 am Registration Open and Morning Coffee

SCREENING FOR DRUG TOXICITY

8:00 Chairperson's Remarks

Stephen S. Ferguson, PhD, Chemist, Division of the National Toxicology Program (NTP), Biomolecular Screening Branch (BSB) & NTP Laboratories, National Institute of Environmental Health Sciences (NIEHS)

8:05 Bioengineered Tissue Models of Human Development and Disease

Shay_SokerShay Soker, PhD, Professor, Regenerative Medicine, Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine

We have created 3D human tissue model systems (organoids) that can be studied in vitro for several weeks. The organoids replicate native tissue structure and function and thus are superior to traditional 2D cultures in order to study organ development, function and drug toxicity. Other applications focus on diseases such as tissue fibrosis and cancer, specifically, to study tumor growth and drug response for future use in personalized/precision medicine.

8:35 Development and Application of Organotypic in vitro Liver Models to Screen Compounds for Drug-Induced Liver Injury and Transcriptomic Pathway Perturbations

Stephen S. Ferguson, PhD, Chemist, Division of the National Toxicology Program (NTP), Biomolecular Screening Branch (BSB) & NTP Laboratories, National Institute of Environmental Health Sciences (NIEHS)

9:05 Microfabricated Organ-on-Chip Models of Tissue with High-Throughput Compatibility for Drug Screening

Joseph Charest, PhD, Program Manager, Commercial Programs, Draper

Draper's PREDICT-96 system has 96 independent tissue replicates within a standard 96 well plate footprint, resulting in a high-throughput organ-on-chip technology. For each of the 96 independent replicates, the system has 2 microchannels with individual pumps, a transepithelial electrical resistance (TEER) readout, and the ability to image with confocal and high-content screening systems. In addition, the system has been applied to several tissue and organ types which will be discussed.

9:35 Find Your Table and Meet Your Moderator

9:40 Interactive Breakout Discussion Groups

This session features various discussion groups that are led by a moderator/s who ensures focused conversations around the key issues listed. Attendees choose to join a specific group and the small, informal setting facilitates sharing of ideas and active networking.

The Use of 3D Cellular Models, Organ-on-a-Chip Technologies, or Microphysiological Systems in Preclinical Evaluation of Pharmaceuticals

William Daly, PhD, Managing Director & Faculty Scientist, Orthopedics and Rehabilitation, University of Wisconsin - Madison

  • What are the key barriers to adoption of 3D cellular models in preclinical workflows?
  • What are pharmaceutical wish lists (biomarkers, function, histology, etc.) for validation of 3D cellular models (groups to split into organ of choice)?
  • Where is the ideal fit for 3D cellular models in the drug development pipeline / pharmaceutical testing?
  • What are the missing models / unmet needs for preclinical evaluation and efficacy testing?
  • Are single organs enough or is there a strong need for multi-organ testing?

3D Models of Human Organs: Challenges and Prospects

Samira Musah, PhD, Dean's Postdoctoral Fellow, Wyss Institute at Harvard University and Harvard Medical School

  • Inducing stem cell differentiation, cell maturation, and functionality
  • Organoids, organs-on-chips, 3D-bioprinted tissues
  • Applications in disease modeling and therapeutic discovery

10:20 Coffee Break in the Exhibit Hall with Poster Viewing

SCREENING FOR CNS

11:05 Vascularized 3D Models of the Developing Blood-Brain Barrier and Cerebral Cortex for Developmental Neurotoxicity Screening and Disease Modeling

William_DalyWilliam Daly, PhD, Managing Director & Faculty Scientist, Orthopedics and Rehabilitation, University of Wisconsin - Madison

Here, we present a 3D vascularized stem cell derived organoid model (/microphysiological system) of the cerebral cortex in a microfluidics platform that has distinct neural, vascular and microglial components. The model captures the initial vascularization of the developing brain (i.e., blood-brain barrier formation) from the perineural vascular plexus in an enhanced throughput microfluidics model. The model has been used to screen for developmental neurotoxins and to model MeCP2 spectrum disorders.

11:35 Blood-Brain Barrier Spheroids as an in vitro Screening Platform for Brain-Penetrating Agents

Sean_LawlerSean Lawler, PhD, Assistant Professor & Managing Director, Harvey Cushing Neurooncology Laboratories, Neurosurgery, Brigham and Women's Hospital

The BBB represents a major obstacle to the delivery of drugs to the brain. We have recently developed a 3D in vitro model of the BBB, composed of astrocytes, pericytes, and endothelial cells, which spontaneously form spheroids with BBB properties. We have identified novel peptide agents which can cross the BBB using this approach. This talk describes BBB spheroids and their capabilities as a predictive and screening tool.

12:05 pm Neurospheroid Arrays for in vitro Studies of Alzheimer's Disease

Daniel Irimia, MD, PhD, Associate Professor, Division of Surgery, Science & Bioengineering, Massachusetts General Hospital, Harvard Medical School, and Shriners Hospitals for Children - Boston

12:35 Session Break

12:40 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:10 Ice Cream Break in the Exhibit Hall with Poster Viewing

ADVANCING MODELS & APPLICATIONS

1:55 Chairperson's Remarks

William Daly, PhD, Managing Director & Faculty Scientist, Orthopedics and Rehabilitation, University of Wisconsin - Madison

2:00 Engineering Patient-Specific Organs-on-Chips from Human-Induced Pluripotent Stem Cells

Samira_MusahSamira Musah, PhD, Dean's Postdoctoral Fellow, Wyss Institute at Harvard University and Harvard Medical School

This talk describes our lab's use of interdisciplinary approaches to control stem cell fate decisions and engineer functional microfluidic conduits of the human kidney glomerulus. Our most recent work involves the establishment of a robust stem cell-based method to generate blood-filtering cells (podocytes), and integrating these cells with a microfluidic organ-on-a-chip system to recapitulate the structure, function, and specific drug toxicity of the human kidney's blood filtration unit.

2:30 Advanced Kidney and Liver Platforms for Drug Discovery

Piyush Bajaj, PhD, Scientist II, Investigative Toxicology, Drug Safety Research and Evaluation, Takeda Pharmaceuticals

In this talk, I discuss some advanced in vitro liver and kidney platforms (stem cell derived, spheroids/organoids, and organ-on-a-chip) and their applications towards different stages of drug discovery.

3:00 Application of in vitro Models to De-Risk Drug-Induced Liver Injury in Pharmaceutical Development

Wen Kang, PhD, Principal Scientist, Safety Assessment & Laboratory Animal Resources, Merck & Co., Inc.

Drug-induced liver injury (DILI) remains a major safety concern in pharmaceutical development. Implementation of physiologically relevant in vitro liver models enables the assessment of a compound's liver safety profiles early in development. We summarize the characterization, evaluation and qualification of the micropatterned co-culture liver model HepatoPac®, and discuss how we have used the model, in conjunction with molecular and metabolomics approaches, to inform on the DILI risk of drug candidates. Lastly, we lay out the challenges for future model development, and the next steps to refine such in vitro tools to optimize their potential.

3:30 CLOSING PANEL DISCUSSION: What Is the Biggest Bottleneck for Applying 3D Models in Discovery Research?

All agree on the potential of preclinical 3D cellular models to predict clinical outcome. However, challenges remain for high-throughput screening as researchers must procure large numbers of identical 3D cell cultures, develop assays and obtain fast, automated readouts from these more complex assays. This panel discusses progress in:

  • Standardization of the models
  • Validation of the models
  • Inter-laboratory reproducibility

Moderator: William Daly, PhD, Managing Director & Faculty Scientist, Orthopedics and Rehabilitation, University of Wisconsin - Madison

Panelists to be Announced

4:00 Close of Conference


Recommended Event Package

Short Course 6: Collecting, Storing, and Utilizing Precious Patient-Derived Tumors for Drug Discovery and Development

Short Course 9: How to Best Utilize 3D Cells, Spheroids, PDX Models in Oncology

Short Course 14: Advanced Bioprinting Strategies for Generation of 3D Tissue Models

Conference: Tumoroids for Oncology Research

Conference: 3D Cellular Models


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* 活动内容有可能不事先告知作更动及调整。