Cell therapy and delivery strategies for spinal cord injury.

Spinal cord injury (SCI) is a complex neuropathological condition that represents a major challenge for clinicians and scientists due to patient's functional dysfunction and paralysis. Several treatments have been proposed including biological factors, drugs and cells administered in various ways. Stem cells arise as good candidates to treat SCI since they are known to secrete neurotrophic factors, improving neuroregeneration, but also due to their role in modulating the inflammatory process, favoring a pro-regenerative status. There are several types of cells that have been tested to treat SCI in experimental and clinical studies, but we still face many unanswered questions; one of them is the type of cells that can offer the best benefits and, also the ideal dose and administration routes. This review aimed to summarize recent research on cell treatment, focusing on current delivery strategies for SCI therapy and their effects in tissue repair and regeneration.

Grafts of human adipose-derived stem cells into a biodegradable poly (acid lactic) conduit enhances sciatic nerve regeneration.

Despite the regenerative potential of the Peripheral Nervous System (PNS), injuries with loss of a nerve segment make the functional recovery a challenge. This work aimed to investigate the effects of the association of biodegradable conduits of poly (lactic acid) (PLA) with human adipose-derived stem cells (hADSCs) on the regeneration of the sciatic nerve. C57BL / 6 male mice were submitted to sciatic nerve transection followed by tubulization with PLA conduit. Animals were allocated in two groups: the first received an injection of DMEM inside the conduit (DMEM) and the second received hADSCs inside it (hADSC). Sensory and motor functions were assessed by the pinprick test and electroneuromiography, respectively. To assess neuronal survival the retrograde tracer fluorogold was injected into the sciatic nerve distally to the lesion site. One week after that, animals were sacrificed, tissues harvested and processed for morphological evaluation. After eight weeks, all animals showed sensory recovery in the pinprick test and there was no significant difference between the two groups. The amplitude of the compound muscle action potential was higher in the hADSCs group. The number of myelinated nerve fibers, muscle cells and motor plates was higher in the hADSC group. There was also greater survival of sensory and motor neurons in the hADSC animals. These results suggest that the association of PLA conduit and cell therapy with hADSCs leads to a better functional and morphological recovery after sciatic nerve transection.

Enhancement of median nerve regeneration by mesenchymal stem cells engraftment in an absorbable conduit: improvement of peripheral nerve morphology with enlargement of somatosensory cortical representation.

We studied the morphology and the cortical representation of the median nerve (MN), 10 weeks after a transection immediately followed by treatment with tubulization using a polycaprolactone (PCL) conduit with or without bone marrow-derived mesenchymal stem cell (MSC) transplant. In order to characterize the cutaneous representation of MN inputs in primary somatosensory cortex (S1), electrophysiological cortical mapping of the somatosensory representation of the forepaw and adjacent body parts was performed after acute lesion of all brachial plexus nerves, except for the MN. This was performed in ten adult male Wistar rats randomly assigned in three groups: MN Intact (n = 4), PCL-Only (n = 3), and PCL+MSC (n = 3). Ten weeks before mapping procedures in animals from PCL-Only and PCL+MSC groups, animal were subjected to MN transection with removal of a 4-mm-long segment, immediately followed by suturing a PCL conduit to the nerve stumps with (PCL+MSC group) or without (PCL-Only group) injection of MSC into the conduit. After mapping the representation of the MN in S1, animals had a segment of the regenerated nerve processed for light and transmission electron microscopy. For histomorphometric analysis of the nerve segment, sample size was increased to five animals per experimental group. The PCL+MSC group presented a higher number of myelinated fibers and a larger cortical representation of MN inputs in S1 (3,383 ± 390 fibers; 2.3 mm(2), respectively) than the PCL-Only group (2,226 ± 575 fibers; 1.6 mm(2)). In conclusion, MSC-based therapy associated with PCL conduits can improve MN regeneration. This treatment seems to rescue the nerve representation in S1, thus minimizing the stabilization of new representations of adjacent body parts in regions previously responsive to the MN.