CD34+ Telocytes Drive Angiogenesis and Wound Healing Through Sema3c Signaling

CD34+ telocytes, a recently identified population of interstitial cells, have long been suspected of helping blood vessels grow and skin wounds close, but direct evidence for how they do so has been scarce. A new study published in Biology Direct on 14 October 2026 now reports a specific mechanism: these cells signal to endothelial cells through semaphorin 3 C (Sema3c), which acts via the PlexinD1 receptor on the endothelial side.

The researchers first showed that Matrigel plugs, a standard implant used to study new blood vessel formation in mice, became enriched with a large population of telocytes. Using single-cell RNA sequencing, they profiled these cells and then used lentiviral-mediated knockdown to test what happens when Sema3c production is reduced. Functional assays confirmed that blocking the Sema3c-PlexinD1 axis significantly impaired the angiogenic effects normally mediated by CD34+ telocytes, pointing to endothelial cell migration as a key downstream process.

The team then moved to a murine full-thickness excisional wound model. When CD34+ telocytes were delivered in gelatin methacryloyl (GelMA) hydrogels, the treated wounds showed significantly enhanced healing and angiogenesis, measured by improved wound closure rates and an increase in CD31+ vascular structures. Knocking down Sema3c in the telocytes attenuated these pro-healing effects, which the authors say underscores the specificity of the pathway.

The findings, the researchers conclude, highlight the central role of telocyte-derived paracrine Sema3c in angiogenesis and skin wound healing, and support a cell-based therapeutic strategy for angiogenesis-related diseases. Because the work was performed in mouse models, translating the approach to human patients will require further study, and the published version is an early shared, peer-reviewed accepted manuscript that may still undergo editorial edits before the final Version of Record.

Subject of Research: How CD34+ telocytes regulate angiogenesis and skin wound healing in mice via Sema3c-PlexinD1 signaling

Article Title: CD34+ telocytes regulate Matrigel plug angiogenesis and wound healing via Sema3c

Article References: Yue, J., Xing, Y., Huang, H., Zhang, Z., Mei, L., Zhu, X., Luo, Y., Shi, Y., & Chen, Q. (2026). CD34+ telocytes regulate Matrigel plug angiogenesis and wound healing via Sema3c. Biology Direct. https://doi.org/10.1186/s13062-026-01018-5

Image Credits: AI Generated

DOI: 10.1186/s13062-026-01018-5

Keywords: telocytes, CD34+, angiogenesis, Sema3c, PlexinD1, wound healing, single-cell RNA sequencing, GelMA hydrogel, Matrigel plug, endothelial cells, CD34, regulate