Early detection of aberrant cell fate and repair using circulating progenitor cells in patients with heterotopic...

Heterotopic ossification (HO), the abnormal formation of bone in soft tissues, is a debilitating complication that occurs after severe burns, trauma, and joint replacement surgery. Current diagnostic methods detect HO only after substantial progression, limiting opportunities for early intervention. In this study, we show that circulating mesenchymal progenitor cells (cMPCs), isolated using a microfluidic iChip from patients undergoing hip replacement and a mouse model of traumatic HO, exhibit HO-associated gene expression as early as 6 hours post-injury-41 days before radiographic detection. RNA sequencing of cMPCs enabled development of a liquid biopsy-based HO risk prediction model, achieving up to 90% sensitivity and 100% specificity in human subjects. Furthermore, the model detected significant reductions in HO risk following prophylactic treatment, correlating with decreased HO volume. These findings establish a noninvasive platform for early detection and monitoring of HO and suggest broader utility for diseases involving aberrant mesenchymal cell fate. This approach enables high-throughput screening of at-risk patients and real-time assessment of therapeutic efficacy.