Breast Cancer Reconstruction: Design Criteria for a Humanized Microphysiological System

Trivia Frazier, Christopher Williams, Michael Henderson, Tamika Duplessis, Emma Rogers, Xiying Wu, Katie Hamel, Elizabeth C. Martin, Omair Mohiuddin, Shahensha Shaik, Ram Devireddy, Brian G. Rowan, Daniel J. Hayes, Jeffrey M. Gimble

Research output: Contribution to journalArticlepeer-review

Abstract

International regulatory agencies such as the Food and Drug Administration have mandated that the scientific community develop humanized microphysiological systems (MPS) as an in vitro alternative to animal models in the near future. While the breast cancer research community has long appreciated the importance of three-dimensional growth dynamics in their experimental models, there are remaining obstacles preventing a full conversion to humanized MPS for drug discovery and pathophysiological studies. This perspective evaluates the current status of human tissue-derived cells and scaffolds as building blocks for an "idealized"breast cancer MPS based on bioengineering design principles. It considers the utility of adipose tissue as a potential source of endothelial, lymphohematopoietic, and stromal cells for the support of breast cancer epithelial cells. The relative merits of potential MPS scaffolds derived from adipose tissue, blood components, and synthetic biomaterials is evaluated relative to the current "gold standard"material, Matrigel, a murine chondrosarcoma-derived basement membrane-enriched hydrogel. The advantages and limitations of a humanized breast cancer MPS are discussed in the context of in-process and destructive read-out assays. Regulatory authorities have highlighted microphysiological systems as an emerging tool in breast cancer research. This has been led by calls for more predictive human models and reduced animal experimentation. This perspective describes how human-derived cells, extracellular matrices, and hydrogels will provide the building blocks to create breast cancer models that accurately reflect diversity at multiple levels, that is, patient ethnicity, pathophysiology, and metabolic status.

Original languageEnglish (US)
Pages (from-to)479-488
Number of pages10
JournalTissue Engineering - Part A
Volume27
Issue number7-8
DOIs
StatePublished - Apr 2021

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Biochemistry
  • Biomaterials
  • Biomedical Engineering

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