Mesenchymal stem cells therapy for spinal cord contusion: a comparative study on small and large animal models

Abstract

Here, we provided a first comparative study of the therapeutic potential of allogeneic mesenchymal stem cells derived from bone marrow (BM-MSCs), adipose tissue (AD-MSCs), and dental pulp (DP-MSCs) embedded in fibrin matrix in a small (rat) and large (pig) spinal cord injury (SCI) model during sub-acute period of spinal contusion. Results of behavioral, electrophysiological, histological assessment, as well as results of immunohistochemistry and RT-PCR analysis suggest that application of AD-MSCs combined with a fibrin matrix in a subacute period in rats (2 weeks after injury) provides significantly higher post-traumatic regeneration compared to a similar application of BM-MSCs or DP-MSCs. Within the rat model, use of AD-MSCs resulted in a marked change in (1) restoration of locomotor activity and conduction along spinal axons, (2) reduction of post-traumatic cavitation and enhancing tissue retention, and (3) modulation of microglial and astroglial activation. The effect of therapy with an autologous application of AD-MSCs was also confirmed in subacute period after spinal contusion in pigs (6 weeks after injury), however, with only partial replication of the findings observed in rats, i.e. (1) partial restoration of the somatosensory spinal pathways, (2) reduction of post-traumatic cavitation and enhancing tissue retention, and (3) modulation of astroglial activation in dorsal root entry zone. The results of this study suggest that application of AD-MSCs embedded in fibrin matrix at the site of SCI during the subacute period can facilitate regeneration of nervous tissue in rats and pigs. These results, for the first time, provide robust support for the use of AD-MSC to treat subacute SCI.