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

Abstract

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.

Expansion of human umbilical cord derived mesenchymal stem cells in regenerative medicine

“…The therapeutic application of MSCs demands the characterization of stem cell products based on their molecular and cellular characteristics[ 47 ]. The paracrine activity of MSCs via the secretome and their unique stem cell features such as proangiogenic, anti-inflammatory, immunomodulatory, and antioxidant potential are the mechanisms behind the utilization of MSCs for therapeutic purposes[ 48 , 49 ]. Studies have observed the significant therapeutic promise of MSCs to treat fatal disorders in numerous clinical trials[ 50 - 53 ].…”

Ultrasound Landmarks in the Approach to the Common Peroneal Nerve in a Sheep Model—Application in Peripheral Nerve Regeneration

“…The imaging approach has been sparsely used and has only recently gained more importance in this area as dramatic advances are observed in the quality of the techniques that can be used. In traditional and smaller animal models such as rodents, some commonly used imaging approaches include techniques such as transgenic labeling, nervous stereology, and muscle histomorphometry [ 6 , 11 ]. In larger animal models, however, although these routine techniques can and should also be used, other methods closer to those likely to be applied in real clinical settings, such as ultrasound, are also an option that should be considered [ 19 ].…”

“…The overwhelming majority of works in which new therapeutic alternatives for the treatment of PNI are studied are based on more traditional animal models, such as rodents [ 3 ], in which significant advances have been achieved in the establishment of new innovative treatments, namely in the fields of regenerative medicine and based on cell-based therapies and application of biomaterials [ 4 ]. For instance, previously, our research group has developed several new therapeutic combinations based on the use of innovative biomaterials and mesenchymal stem cell-derived products, which have demonstrated good results when applied in the rat model [ 5 , 6 ].…”

Human nasal olfactory stem cells, purified as advanced therapy medicinal products, improve neuronal differentiation

“…In two previous studies on rat models of peripheral nerve injury, we demonstrated the efficacy of OE-MSCs in improving motor functional recovery of the lower limb or face (Bonnet et al, 2020;Alvites et al, 2022). To assess whether the clinical grade cultured OE-MSCs stimulate axonal regrowth through extruded factors, a N2a cell line was cultivated with a 50:50 mixture of fresh differentiation medium and the conditioned medium collected from a 24 h or a 48 h-long culture of OE-MSCs.…”