DON-Apt19S bioactive scaffold transplantation promotes in situ spinal cord repair in rats with transected spinal cord injury by effectively recruiting endogenous neural stem cells and mesenchymal stem cells

TL;DR

A bioactive scaffold promotes spinal cord repair in rats by recruiting stem cells and improving motor and sensory functions.

Contribution

A novel DNA aptamer-based scaffold that recruits both neural and mesenchymal stem cells for spinal cord repair.

Findings

DON-Apt19S scaffold effectively recruits endogenous NSCs and MSCs via ALPL binding.

The scaffold promotes neurogenesis and revascularization in the injured spinal cord.

Transplantation of DON-A improves motor and sensory functions in rats with SCI.

Abstract

The spinal cord's limited regeneration is attributed to the scarcity of endogenous stem cells and a poor post-injury microenvironment in adult mammals. To overcome these challenges, we transplanted a DNA aptamer 19S (Apt19S) sustained-release decellularized optic nerve (DON) scaffold (DON-A) into completely transected spinal cord injury (SCI) site in rats and investigated its effect on endogenous stem cell recruitment and differentiation, which subsequently contributed to in situ SCI repair. It has been demonstrated that Apt19S specifically binds to the membrane receptor alkaline phosphatase highly expressed on neural stem cells (NSCs) and mesenchymal stem cells (MSCs), and our study further proved that Apt19S can simultaneously recruit endogenous NSCs and MSCs to the lesion of SCI. In our study, the DON-A promoted stem cell proliferation in the early stage of the injury, followed by the rapid neurogenesis through NSCs and revascularization via MSCs. Synaptic connections between corticospinal tracts and calcitonin gene-related peptide positive nerve fibers with newborn neurons confirmed the formation of endogenous neuronal relays at the injury site, which improved the rats' motor and sensory functions. This study offers a new strategy for recruiting both NSCs and MSCs to synergistically overcome low spinal cord self-repair ability, holding a high potential for clinical translation.

In this study, we developed and transplanted a bioactive DON-A scaffold for in situ spinal cord repair. DON-A ensured sustained Apt19S release and can selectively recruit endogenous NSCs and MSCs into the CNS regenerative microenvironment created by DON-A, where they rapidly initiated tissue regeneration and repair, causing neural pathways reconstruction and revascularization in the spinal cord.Image 1

•DON-A recruited endogenous NSCs and MSCs efficiently by specifically binding to ALPL via sustained Apt19S release.•DON-A created CNS regenerative microenvironment for neurogenesis and revascularization in the spinal cord.•DON-A reconstructed both the ascending and descending neural pathways in injured spinal cord.•DON-A transplantation improved the rats' motor and sensory functions.

DON-A recruited endogenous NSCs and MSCs efficiently by specifically binding to ALPL via sustained Apt19S release.

DON-A created CNS regenerative microenvironment for neurogenesis and revascularization in the spinal cord.

DON-A reconstructed both the ascending and descending neural pathways in injured spinal cord.

DON-A transplantation improved the rats' motor and sensory functions.

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