Pre-Regenerative Endothelial Cells Empowered by Antler Blood Exosomes Orchestrate Peripheral Nerve Repair

The pre-regenerative vascular niche (PVN) is indispensable for peripheral-nerve repair, yet the endothelial cell (EC) blueprint underlying PVN formation remains to be fully defined. Herein, we mapped the sciatic-nerve endothelium and identified angiogenic ECs (AECs) as the dominant pre-regenerative subset triggered by injury. However, the molecular circuitry governing AEC-mediated regeneration awaits elucidation. Unexpectedly, we found that antler blood, routinely discarded during velvet antler harvesting, contains potent regenerative cues that strongly boost endothelial-driven repair. By integrating a single-cell atlas of antler with the proteomics of antler blood-derived exosomes (AB-EXO), we traced the vesicles to their cellular origins and demonstrated that AB-EXO encapsulate the antler's potent regenerative signature. Further mechanistic interrogation showed that AB-EXO induced pro-angiogenic phenotypes in ECs via the upregulation of IMP U3 small nucleolar ribonucleoprotein 3 (IMP3). Overlaying IMP3 expression onto our EC atlas pinpointed IMP3-high AECs (IMP3+AECs) as the pivotal vascular drivers of nerve repair. Ultimately, our findings establish IMP3+AECs as the critical component of the pre-regenerative EC atlas within the peripheral nerve and position AB-EXO as an effective therapy for nerve repair.