Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 27 April 2022 / Approved: 28 April 2022 / Online: 28 April 2022 (05:49:40 CEST)

A peer-reviewed article of this Preprint also exists.

Alvites, R.D.; Branquinho, M.V.; Sousa, A.C.; Lopes, B.; Sousa, P.; Prada, J.; Pires, I.; Ronchi, G.; Raimondo, S.; Luís, A.L.; Geuna, S.; Varejão, A.S.P.; Maurício, A.C. Effects of Olfactory Mucosa Stem/Stromal Cell and Olfactory Ensheating Cells Secretome on Peripheral Nerve Regeneration. Biomolecules 2022, 12, 818. Alvites, R.D.; Branquinho, M.V.; Sousa, A.C.; Lopes, B.; Sousa, P.; Prada, J.; Pires, I.; Ronchi, G.; Raimondo, S.; Luís, A.L.; Geuna, S.; Varejão, A.S.P.; Maurício, A.C. Effects of Olfactory Mucosa Stem/Stromal Cell and Olfactory Ensheating Cells Secretome on Peripheral Nerve Regeneration. Biomolecules 2022, 12, 818.

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.

Keywords

Peripheral Nerve Injury; peripheral nerve regeneration; sciatic nerve; Olfactory Mucosa Mesenchymal Stem/Stromal Cells; Olfactory Ensheating Cells; secretome; conditioned medium; nerve guidance conduit; tibial cranial muscle; rat

Subject

Biology and Life Sciences, Biology and Biotechnology

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