Osteochondral Tissue Chip Derived From iPSCs: Modeling OA Pathologies and Testing Drugs.

Area of Science:

• Biotechnology and Regenerative Medicine
• Stem Cell Biology
• Biomaterials Engineering

Background:

• Osteoarthritis (OA) is a degenerative joint disease affecting cartilage and bone, with no current disease-modifying drugs.
• Existing OA models lack the complexity to fully replicate human disease pathologies and etiologies.
• Microphysiological systems offer potential for more accurate disease modeling.

Purpose of the Study:

• To develop a microphysiological osteochondral (OC) tissue chip using human induced pluripotent stem cells (iPSCs).
• To model human osteoarthritis (OA) pathologies and enable drug screening.
• To investigate the functional crosstalk between bone and cartilage in normal and OA conditions.

Main Methods:

• Induced pluripotent stem cells (iPSCs) were differentiated into mesenchymal progenitor cells (iMPCs).
• iMPCs were encapsulated in gelatin scaffolds and cultured in a dual-flow bioreactor with distinct chondrogenic and osteogenic media.
• Osteoarthritis (OA) was induced using interleukin-1β (IL-1β), and the efficacy of Celecoxib was tested.

Main Results:

• Successfully generated human iPSC-derived osteochondral (OC) tissue chips.
• Demonstrated functional crosstalk between bone and cartilage, with bone accelerating cartilage degradation under OA conditions.
• The OA model showed reduced catabolic and proinflammatory cytokines upon treatment with Celecoxib, a COX-2 inhibitor.

Conclusions:

• The iPSC-derived OC tissue chip is a viable platform for modeling OA.
• This model highlights the active role of bone in OA pathogenesis and cartilage degradation.
• The platform demonstrates utility for high-throughput screening of potential disease-modifying osteoarthritis drugs (DMOADs).