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. 2025 Aug 6;33(8):3968-3993.
doi: 10.1016/j.ymthe.2025.04.020. Epub 2025 Apr 18.

In vivo programming of adult pericytes aids axon regeneration by providing cellular bridges for SCI repair

Wenjing Sun  1 , Elliot Dion  1 , Fabio Laredo  2 , Allyson Okonak  1 , Jesse A Sepeda  3 , Esraa Haykal  1 , Min Zhou  1 , Heithem M El-Hodiri  1 , Andy J Fischer  1 , Jerry Silver  4 , Juan Peng  5 , Andrew Sas  6 , Andrea Tedeschi  7
Affiliations

In vivo programming of adult pericytes aids axon regeneration by providing cellular bridges for SCI repair

Wenjing Sun et al. Mol Ther. .

Abstract

Pericytes are contractile cells of the microcirculation that participate in wound healing after spinal cord injury (SCI). Thus far, the extent to which pericytes cause or contribute to axon growth and regeneration failure after SCI remains controversial. Here, we found that SCI leads to profound changes in vasculature architecture and pericyte coverage. We demonstrated that pericytes constrain sensory axons on their surface, causing detrimental structural and functional changes in adult dorsal root ganglion neurons that contribute to axon regeneration failure after SCI. Perhaps more excitingly, we discovered that in vivo programming of adult pericytes via local administration of platelet-derived growth factor BB (PDGF-BB) effectively promotes axon regeneration and recovery of hindlimb function by contributing to the formation of cellular bridges that span the lesion. Ultrastructural analysis showed that PDGF-BB induced fibronectin fibril alignment and extension, effectively converting adult pericytes into a permissive substrate for axon growth. In addition, PDGF-BB localized delivery positively affects the physical and chemical nature of the lesion environment, thereby creating more favorable conditions for SCI repair. Thus, therapeutic manipulation rather than wholesale ablation of pericytes can be exploited to prime axon regeneration and SCI repair.

Keywords: DRG neurons; PDGF-BB; axon regeneration; extracellular matrix; functional recovery; pericytes; spinal cord injury; vasculature remodeling.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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