Calcium Imaging Reveals Host-Graft Synaptic Network Formation in Spinal Cord Injury

Abstract

Neural stem/progenitor cell grafts integrate into sites of spinal cord injury (SCI) and form anatomical and electrophysiological neuronal relays across lesions. To determine how grafts become synaptically organized and connect with host systems, we performed calcium imaging of neural progenitor cell grafts within sites of SCI, using both in vivo imaging and spinal cord slices. Stem cell grafts organize into localized synaptic networks that are spontaneously active. Following optogenetic stimulation of host corticospinal tract axons regenerating into grafts, distinct and segregated neuronal networks respond throughout the graft. Moreover, optogenetic stimulation of graft axons extending out from the lesion into the denervated spinal cord also trigger responses in local host neuronal networks. In vivo imaging reveals that behavioral stimulation of host elicits focal synaptic responses within grafts. Thus, remarkably, neural progenitor cell grafts form functional synaptic subnetworks in patterns paralleling the normal spinal cord.

Therapeutic repair for spinal cord injury: combinatory approaches to address a multifaceted problem

“…NPCs, on the other hand, were recently shown to extend “hundreds of thousands of axons into the spinal cord” (Rosenzweig et al, ), and injured motor and sensory axons regenerated into appropriate domains of NPC grafts (Dulin et al, ). Furthermore, these NPC grafts form host–graft synaptic network formation in patterns paralleling the normal spinal cord (preprint: Ceto et al, ). Aside from direct tissue replacement, both MSCs and NPCs confer permissive substrates for growth whereby injured host axons grow into the cellular grafts (Hofstetter et al, ; Lu et al, ; Ankeny et al, ).…”

Cell membrane-targeting NIR fluorescent probes with large Stokes shifts for ultralong-term transplanted neural stem cell tracking

“…However, due to the lengthy self-repair process of hNSCs, the detailed therapeutic mechanism of hNSCs is still unclear. It was thought that long-term and real-time tracking of transplanted hNSCs is the first step to studying the mechanism of stem cell therapy (Zhang et al, 2016;Ceto et al, 2020). Hence, developing effective tracking tools for long-term and real-time monitoring of the differentiation process of transplanted hNSCs could help us learn more about the therapeutic mechanism of stem cells.…”