Harnessing the Secretome of Mesenchymal Stromal Cells for Traumatic Spinal Cord Injury: Multi-cell Comparison and Assessment of In Vivo Efficacy

Cell therapy offers significant promise for traumatic spinal cord injury (SCI), which despite many medical advances, has limited treatment strategies. Able to address the multi-factorial and dynamic pathophysiology of SCI, cells present various advantages over standard pharmacological approaches. However, the use of live cells is also severely hampered by logistical and practical considerations. These include specialized equipment and expertise, standardisation of cell stocks, sustained cell viability post-thawing and cryopreservation-induced delayed-onset cell death (CIDOCD). For this reason, we suggest a novel and clinically translatable alternative to live cell systemic infusion, which retains the efficacy of the latter whilst overcoming many of its limitations. This strategy involves the administration of concentrated cell secretome and exploits the trophic mechanism by which stromal cells function. Here, we compare the efficacy of intravenously delivered concentrated conditioned media (CM) from human umbilical cord matrix cells (HUCMCs), bone marrow mesenchymal stromal cells (BMSCs), as well as newborn and adult fibroblasts in a rat model of moderately severe cervical clip compression/contusion injury (C7-T1, 35-gram). This is further paired with a thorough profile of the CM cytokines, chemokines and angiogenic factors. The HUCMC-derived CM was most effective at limiting acute (48 hours post-SCI) vascular pathology, specifically lesion volume and functional vascularity. PCA, hierarchical clustering, and interaction analysis of proteins highly expressed in the HUCMC secretome, suggest involvement of the MAPK/ERK, JAK/STAT, and immune cell migratory pathways. This 'secretotherapeutic' strategy represents a novel and minimally invasive method to target multiple organ systems and several pathologies shortly after traumatic SCI.