Self-assembling human skeletal organoids for disease modeling and drug testing

Diana M. Abraham, Calvin Herman, Lukasz Witek, Bruce N. Cronstein, Roberto L. Flores, Paulo G. Coelho

Research output: Contribution to journalArticlepeer-review

Abstract

Skeletal conditions represent a considerable challenge to health systems globally. Barriers to effective therapeutic development include a lack of accurate preclinical tissue and disease models. Most recently, work was attempted to present a novel whole organ approach to modeling human bone and cartilage tissues. These self-assembling skeletal organoids mimic the cellular milieu and extracellular organization present in native tissues. Bone organoids demonstrated osteogenesis and micro vessel formation, and cartilage organoids showed evidence of cartilage development and maturation. Skeletal organoids derived from both bone and cartilage tissues yielded spontaneous polarization of their cartilaginous and bone components. Using these hybrid skeletal organoids, we successfully generated “mini joint” cultures, which we used to model inflammatory disease and test Adenosine (A2A) receptor agonists as a therapeutic agent. The work and respective results indicated that skeletal organoids can be an effective biological model for tissue development and disease as well as to test therapeutic agents.

Original languageEnglish (US)
Pages (from-to)871-884
Number of pages14
JournalJournal of Biomedical Materials Research - Part B Applied Biomaterials
Volume110
Issue number4
DOIs
StatePublished - Apr 2022

Keywords

  • bioactive molecules
  • molecular modeling
  • organoids
  • self-assembling

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering

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