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

Biomolecules. 2022 Jun 11;12(6):818. doi: 10.3390/biom12060818.

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: conditioned medium; nerve guidance conduit; olfactory ensheating cells; olfactory mucosa mesenchymal stem/stromal cells; peripheral nerve injury; peripheral nerve regeneration; rat; sciatic nerve; secretome; tibial cranial muscle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Culture Media, Conditioned / pharmacology
  • Nerve Regeneration
  • Olfactory Mucosa
  • Peripheral Nerve Injuries* / therapy
  • Rats
  • Sciatic Nerve / injuries
  • Secretome
  • Stromal Cells

Substances

  • Culture Media, Conditioned

Grants and funding

This research was funded by Projects PEst-OE/AGR/UI0211/2011 from FCT, COMPETE 2020, from ANI–Projetos ID&T Empresas em Copromoção, by the project “insitu.Biomas–Reinvent biomanufacturing systems by using an usability approach for in situ clinic temporaryimplants fabrication” with the reference POCI-01-0247-FEDER-017771, by the project “Print-on-Organs–Engineering bioinks and processes for direct printing on organs” with the reference POCI-01-0247-FEDER-033877, by the project “Bone2Move-Development of “in vivo” experimental techniques and modelling methodologies for the evaluation of 4D scaffolds for bone defect in sheep model: an integrative research approach” with the reference POCI-01-0145-FEDER-031146. and by the PhD scholarships Mariana Vieira Branquinho (SFRH/BD/146172/2019), Ana Catarina Sousa (SFRH/BD/146689/2019), and Bruna Lopes (2021.05265.BD). The participation of Justina Prada, Isabel Pires, and Artur S. P. Varejão was supported by the projects UIDB/CVT/00772/2020 and LA/P/0059/2020, funded by the Portuguese Foundation for Science and Technology (FCT). The author Rui D. Alvites acknowledges the Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente (ICETA), Porto University (UP), and Fundação para a Ciência e Tecnologia (FCT) for the funding and availability of all technical, structural, and human resources necessary for the development of this work. The work was supported through the project UIDB/00211/2020 funded by FCT/MCTES through national funds.