A distinct chondrogenic progenitor population from human umbilical cord derived mesenchymal stromal cells for osteoarthritis therapy

Gao, X.; Han, J.; Zhai, Y.; Song, J.; Tian, J.; Li, L.; Liang, D.; Chen, Z.; Xu, J.; Liao, Y.; Ahmad,; Lin, R.; Cui, L.; Xu, B.; Xiao, Q.; Xu, R.; Liu, Y.

doi:10.64898/2026.11.08.765201

bioRxiv · 10.64898/2026.11.08.765201

A distinct chondrogenic progenitor population from human umbilical cord derived mesenchymal stromal cells for osteoarthritis therapy

Gao, X.·Han, J.·Zhai, Y.·Song, J.·Tian, J.·Li, L.·Liang, D.·Chen, Z.·Xu, J.·Liao, Y.·Ahmad,·Lin, R.·Cui, L.·Xu, B.·Xiao, Q.·Xu, R.·Liu, Y.

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Abstract

Stem cell-based cartilage regeneration remains constrained by functional heterogeneity and phenotypic drift in conventional cell sources, compromising durable structural repair. Human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) represent an accessible, off-the-shelf cell source; however, their broad clinical utility is hampered by cellular heterogeneity, leaving the key chondrogenic subpopulation responsible for cartilage repair unresolved. By integrating single-cell transcriptomics with functional assays, we identified and prospectively isolated a distinct, highly expandable subpopulation of skeletal stem cell-like progenitors (U-CPCs) from the human umbilical cord, establishing an extra-skeletal cell source uniquely primed for joint restoration. Single-cell transcriptomics reveal their inherent regulatory landscape, uncovering a distinct transcriptional state uniquely primed for chondrogenesis. In comparison with conventional stem cells and other tissue-derived SSC-like populations (from umbilical cord, bone marrow, adipose tissue, and dental pulp), U-CPCs exhibit a markedly enhanced chondrogenic capacity. In both a mouse cartilage injury model and a rat osteoarthritis model, the administration of U-CPCs effectively mitigates joint degeneration and drives the restoration of a structurally sound, hyaline-like matrix. Mechanistically, U-CPCs secrete extracellular vesicles enriched with microRNA Let-7a-5p, which specifically modulates DUSP7/MAPK/ERK signaling in recipient chondrocytes, thereby restoring extracellular matrix homeostasis and promoting cartilage repair. By characterizing these specialized extra-skeletal progenitors and elucidating both their intrinsic chondrogenic priming and paracrine regulation of host tissue, this study establishes U-CPCs as a robust, lineage-restricted cellular source for osteoarthritis therapy.

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Gao, X., Han, J., Zhai, Y., Song, J., Tian, J., Li, L., Liang, D., Chen, Z., Xu, J., Liao, Y., Ahmad,, Lin, R., Cui, L., Xu, B., Xiao, Q., Xu, R., Liu, Y.. 2026-11-10. A distinct chondrogenic progenitor population from human umbilical cord derived mesenchymal stromal cells for osteoarthritis therapy. https://doi.org/10.64898/2026.11.08.765201

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