In vivo programming of adult pericytes aids axon regeneration by providing cellular bridges for SCI repair
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 DRG 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. Overall design: Spinal cords were obtained from adult (12-14 weeks old) NG2-eGFP mice at 3, 7 and 14 days (e.g., 10, 14 and 21 days after SCI) after vehicle and PDGF-BB administration. Three (for naïve, 3 and 7 days) and two (for 14 days) cords (~2 mm centered at the lesion site) were pulled to obtain ~20-25 mg of tissue mass for each time point/experimental condition and analyzed using scRNA-Seq