On-chip 3D potency assay for prediction of clinical outcomes for cell therapy candidates for osteoarthritis.

Abstract

The lack of clinically predictive potency assays for cell products significantly impedes translation of these therapies. Here, we describe a microfluidic on-chip 3D system for rapid evaluation of a subset of patient-derived bone marrow aspirate concentrate (BMAC) samples used in a phase 3 multicenter trial (NCT03818737) evaluating autologous cells for relieving knee osteoarthritis pain. BMAC clinical samples cultured in the on-chip 3D system exhibit elevated levels of immunomodulatory and trophic proteins compared to 2D culture. Using analyte information from in vitro assays and patient-matched clinical data, we build linear regression prediction models for clinical outcomes. We demonstrate improved clinical prediction by cross-validation accuracy for the on-chip 3D platform compared to 2D culture. Additionally, on-chip 3D assay metrics display higher correlative power with patient pain scores compared to the 2D assay. This study establishes a potency assay with improved prediction power to accelerate translation of cell therapies.