Abstract
Peripheral nerve injury remains a clinical challenge with severe physiological and functional consequences. Despite the existence of multiple possible therapeutic approaches, until now, there is no consensus regarding the advantages of each option or the best methodology in promoting nerve regeneration. Regenerative medicine is a promise to overcome this medical limitation, and in this work, chitosan nerve guide conduits and olfactory mucosa mesenchymal stem/stromal cells were applied in different therapeutic combinations to promote regeneration in sciatic nerves after neurotmesis injury. Over 20 weeks, the intervened animals were subjected to a regular functional assessment (determination of motor performance, nociception, and sciatic indexes), and after this period, they were evaluated kinematically and the sciatic nerves and cranial tibial muscles were evaluated stereologically and histomorphometrically, respectively. The results obtained allowed confirming the beneficial effects of using these therapeutic approaches. The use of chitosan NGCs and cells resulted in better motor performance, better sciatic indexes, and lower gait dysfunction after 20 weeks. The use of only NGGs demonstrated better nociceptive recoveries. The stereological evaluation of the sciatic nerve revealed identical values in the different parameters for all therapeutic groups. In the muscle histomorphometric evaluation, the groups treated with NGCs and cells showed results close to those of the group that received traditional sutures, the one with the best final values. The therapeutic combinations studied show promising outcomes and should be the target of new future works to overcome some irregularities found in the results and establish the combination of nerve guidance conduits and olfactory mucosa mesenchymal stem/stromal cells as viable options in the treatment of peripheral nerves after injury.
Highlights
Peripheral nerve fibers are extremely fragile and sensitive structures, susceptible to being damaged by crushing, compression, or transection traumas [1]
Olfactory mucosa mesenchymal stem/stromal cells (OMMSCs), despite the few published works, seem to be a type of mesenchymal stem cells (MSCs) with desirable characteristics to be applied in nerve regeneration, and the use of chitosan nerve guidance conduits (NGCs) has proven to be an effective therapy
The initial biological characterization of OM-MSCs allowed confirming through PCR and immunohistochemistry techniques the tendency of these cells to follow a neurogenic differentiation, morphologically and through the expression of neuroglial markers
Summary
Peripheral nerve fibers are extremely fragile and sensitive structures, susceptible to being damaged by crushing, compression, or transection traumas [1] Due to their high prevalence, peripheral nerve injuries (PNI) are one of the most important medical problems among traumatic hospital patients. These injuries lead to behavioral changes, mobility difficulties, changes in consciousness and spatial perception, and loss of cutaneous and joint sensitivity and culminate in lifelong disabilities [2, 3]. These injuries are hard to standardize and treat essentially due to the wide variations that can occur regarding the type, location, severity, and complexity. It is known that the future of PNI treatment will involve the use of multifactorial treatments to promote sensory and motor recovery, and the maintenance of neuromuscular junctions to stimulate the reinnervation of target muscles and organs after periods of denervation is the primary objective
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