Olfactory Mucosa Mesenchymal Stem Cells and Biomaterials: A New Combination to Regenerative Therapies after Peripheral Nerve Injury

The peripheral nerve injury after trauma is a common occurrence in both human and veterinary medicine and has severe consequences for the survival and quality of life of the patients. Despite the continuous efforts and the creation of diverse medical and surgical techniques, the harmful effects of this type of injury are far from being overcome. Regenerative medicine has been growing in the scientific milieu as a new therapeutic approach for different situations. Among the cell-based therapies explored, the mesenchymal stem cells are evidenced by their features, versatility and potential applications. The olfactory mucosa mesenchymal stem cells, components of the olfactory system and identified in the lamina propria, were newly identified and are still undergoing characterization, appearing as a new promise in the regenerative therapy of several tissues but with special emphasis on the nervous system in general and the peripheral nervous system in particular, for which they appear to have special regenerative aptitude

Biomaterials and Cellular Systems at the Forefront of Peripheral Nerve Regeneration

Peripheral nerve injuries remain a common clinical complication, and currently available therapies present significant limitations, often resulting in poor and suboptimal outcomes. Despite significant developments in microsurgical approaches in the last decades, no effective treatment options have been disclosed. Current research focuses on the optimization of such microsurgical techniques and on their combination with other pro-regenerative factors, such as mesenchymal stem cells or biomaterials. Mesenchymal stem cells present a remarkable capacity for bioactive molecule production that modulates inflammatory and regenerative processes, stimulating peripheral nerve regeneration. In parallel, efforts have been directed towards the development of biomaterial nerve guidance channels and nerve conduits. These biomaterials have been optimized in terms of biodegradability, ability to release bioactive factors, incorporation of cellular agents, and internal matrix architecture (to enable cellular migration and mimic native tissue morphology and to generate and bear specific electrical activity). The current literature review presents relevant advances in the development of mesenchymal stem cell and biomaterial-based therapeutic approaches aiming at the peripheral nerve tissue regeneration in diverse lesion scenarios, also exploring the advances achieved by our research group in this field in recent years

Dynamic feet distance: a new functional assessment during treadmill locomotion in normal and thoracic spinal cord injured rats

Of all the detrimental effects of spinal cord injury (SCI), one of the most devastating is the disruption of the ability to perform functional movement. Very little is known on the recovery of hindlimb joint kinematics after clinically-relevant contusive thoracic lesion in experimental animal models. A new functional assessment instrument, the dynamic feet distance (DFD) was used to describe the distance between the two feet throughout the gait cycle in normal and affected rodents. The purpose of this investigation was the evaluation and characterization of the DFD during treadmill locomotion in normal and T9 contusion injured rats, using three-dimensional (3D) instrumented gait analysis. Despite that normal and injured rats showed a similar pattern in the fifth metatarsal head joints distance excursion, we found a significantly wider distance between the feet during the entire gait cycle following spinal injury. This is the first study to quantify the distance between the two feet, throughout the gait cycle, and the biomechanical adjustments made between limbs in laboratory rodents after nervous system injury.This research was supported by the Project UID/CVT/00772/2013 from FCT.info:eu-repo/semantics/publishedVersio

Effects of Olfactory Mucosa Stem/Stromal Cell and Olfactory Ensheating Cells Secretome on Peripheral Nerve Regeneration

Cell secretome has been explored as a cell-free technique with high scientific and medical interest for Regenerative Medicine. In this work, the secretome produced and collected from Olfactory Mucosa Mesenchymal Stem Cells and Olfactory Ensheating Cells was analyzed and therapeutically applied to promote peripheral nerve regeneration. The analysis of the conditioned medium revealed the production and secretion of several factors with immunomodulatory functions, capable of intervening beneficially in the phases of nerve regeneration. Subsequently, the conditioned medium was applied to sciatic nerves of rats after neurotmesis, using Reaxon® as tube-guides. Over 20 weeks, the animals were subjected to periodic functional assessments, and after this period, the sciatic nerves and cranial tibial muscles were evaluated stereologically and histomorphometrically, respectively. The results obtained allowed to confirm the beneficial effects resulting from the application of this therapeutic combination. The administration of conditioned medium from Olfactory Mucosal Mesenchymal Stem Cells led to the best results in motor performance, sensory recovery, and gait patterns. Stereological and histomorphometric evaluation also revealed the ability of this therapeutic combination to promote nervous and muscular histologic reorganization during the regenerative process. The therapeutic combination discussed in this work shows promising results and should be further explored to clarify irregularities found in the outcomes and to allow establishing the use of cell secretome as a new therapeutic field applied in the treatment of peripheral nerves after injury