Early Intravenous Infusion of Mesenchymal Stromal Cells Exerts a Tissue Source Age-Dependent Beneficial Effect on Neurovascular Integrity and Neurobehavioral Recovery After Traumatic Cervical Spinal Cord Injury

Abstract

Localized vascular disruption after traumatic spinal cord injury (SCI) triggers a cascade of secondary events, including inflammation, gliosis, and scarring, that can further impact recovery. In addition to immunomodulatory and neurotrophic properties, mesenchymal stromal cells (MSCs) possess pericytic characteristics. These features make MSCs an ideal candidate for acute cell therapy targeting vascular disruption, which could reduce the severity of secondary injury, enhance tissue preservation and repair, and ultimately promote functional recovery. A moderately severe cervical clip compression/contusion injury was induced at C7‐T1 in adult female rats, followed by an intravenous tail vein infusion 1 hour post‐SCI of (a) term‐birth human umbilical cord perivascular cells (HUCPVCs); (b) first‐trimester human umbilical cord perivascular cells (FTM HUCPVCs); (c) adult bone marrow mesenchymal stem cells; or (d) vehicle control. Weekly behavioral testing was performed. Rats were sacrificed at 24 hours or 10 weeks post‐SCI and immunohistochemistry and ultrasound imaging were performed. Both term and FTM HUCPVC‐infused rats displayed improved ( p < .05) grip strength compared with vehicle controls. However, only FTM HUCPVC‐infusion led to significant weight gain. All cell infusion treatments resulted in reduced glial scarring ( p < .05). Cell infusion also led to increased axonal, myelin, and vascular densities ( p < .05). Although post‐traumatic cavity volume was reduced with cell infusion, this did not reach significance. Taken together, we demonstrate selective long‐term functional recovery alongside histological improvements with HUCPVC infusion in a clinically relevant model of cervical SCI. Our findings highlight the potential of these cells for acute therapeutic intervention after SCI.

Axon Degeneration Is Rescued with Human Umbilical Cord Perivascular Cells: A Potential Candidate for Neuroprotection After Traumatic Brain Injury

“…It is likely that all these events occur simultaneously at 24 and 48 h after injury contributing to the highly variable reports in the literature. Immunohistochemistry revealed that in injured animals, there were areas of neurofilament accumulation (NF200), but not accompanied with maintenance of axonal length, administration of HUCPVCs was associated with preservation of axonal length and less compaction of NF200, and is consistent with other studies [58]. These data suggest that HUCPVCs can support axonal health and integrity that maintains proper signaling after injury and preserve functional outcomes.…”

Differential Expression Profiles and Functional Prediction of tRNA-Derived Small RNAs in Rats After Traumatic Spinal Cord Injury

“…It is estimated that there are approximately 11,000 new patients with SCI in America each year, and currently, there are approximately 250,000 people with SCI (Qin et al, 2018;Hall et al, 2019;Liu et al, 2019). SCI is mostly caused by trauma, including the primary mechanical injury due to a rapid direct compression and contusion of the cord, and the subsequent secondary pathophysiological changes, such as edema, ischemia, apoptosis, autophagy, and oxidative stress, which usually lead to a permanent neurological impairment (Kang et al, 2018;Alizadeh et al, 2019;Vawda et al, 2019). The primary injury is in fact mostly unavoidable.…”

In vitro Evaluation of ASCs and HUVECs Co-cultures in 3D Biodegradable Hydrogels on Neurite Outgrowth and Vascular Organization

“…In this regard, transplantation of MSCs following SCI has shown protective effects to local vasculature (Matsushita et al, 2015;Morita et al, 2016;Vawda et al, 2019). Additionally, MSCs are also capable of promoting neuroprotection and modulation of the immune response toward a more regenerative-prone environment, which broadens the range of their effect and make them a promising candidate to treat SCI (Novikova et al, 2011;Spejo et al, 2013;Ribeiro et al, 2015).…”