Systematic Reviews
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World J Stem Cells. Apr 26, 2022; 14(4): 287-302
Published online Apr 26, 2022. doi: 10.4252/wjsc.v14.i4.287
Dental stem cell-conditioned medium for tissue regeneration: Optimization of production and storage
Batoul Chouaib, Frédéric Cuisinier, Pierre-Yves Collart-Dutilleul
Batoul Chouaib, Frédéric Cuisinier, Pierre-Yves Collart-Dutilleul, Laboratory Bioengineering and Nanosciences UR_UM104, University of Montpellier, Montpellier 34000, France
Author contributions: Chouaib B conducted the bibliographic research and selected the targetted articles; Chouaib B and Collart-Dutilleul PY analyzed the selected articles; Chouaib B and Collart-Dutilleul PY wrote the main draft; Cuisinier F corrected the manuscript and supervised the findings of this work; all authors discussed the results and contributed to the final manuscript.
Conflict-of-interest statement: All authors declare that they have no conflict of interest.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Pierre-Yves Collart-Dutilleul, DDS, PhD, Associate Professor, Laboratory Bioengineering and Nanosciences UR_UM104, University of Montpellier, 545 Avenue du Professeur Jean-Louis Viala, Montpellier 34000, France. pierre-yves.collart-dutilleul@umontpellier.fr
Received: March 28, 2021
Peer-review started: March 28, 2021
First decision: May 12, 2021
Revised: May 19, 2021
Accepted: April 21, 2022
Article in press: April 21, 2022
Published online: April 26, 2022
Processing time: 393 Days and 16.6 Hours
ARTICLE HIGHLIGHTS
Research background

Dental Mesenchymal stem cells are progenitor populations recovered from dental and periodontal tissues easily accessible when a tooth is extracted (and usually discarded as medical waste). One of the main effects of Mesenchymal stem cells on tissue regeneration is due to their paracrine activity, mediated by their secreted substances defined as secretome or conditioned medium. Conditioned medium represents a cell-free product with wide potential applications for various diseases treatment and tissue regeneration.

Research motivation

Conditioned medium manufacturing suffers from variable procedures and protocols. Results presented by various studies are difficult to compare, due to the different methods of production. Moreover, there is no well-defined optimized procedure to specifically target specialized tissue in regenerative medicine.

Research objectives

To describe potential consensus for the standardization and optimization of manufacturing procedures, mandatory for further clinical applications. In this systematic review, we focused on conditioned medium produced from Dental Mesenchymal stem cells. We explored the current parameters and culture conditions used in the manufacturing protocols.

Research methods

The bibliographic research was conducted in accordance with the PRISMA guidelines. All articles published between 2006 and 2020 investigating the effects of Dental Mesenchymal stem cells secretome on tissue regeneration were selected. We used the electronic PubMed database with these search terms: ((dental stem cells) AND ((conditioned medium) OR (secretome))) / ((dental stem cells) AND ((extravesicles) OR (exosomes))). Only publications in English were considered.

Research results

Based on the inclusion criteria, 118 articles were included in the systematic review. Conditioned medium production was considered at three levels: before recovery (cell sources), during production (culture conditions) and after production (secretome treatment). We identified key points that were often taken into account in the published experimental works.

Research conclusions

Among all the considered key points, no consensus could be highlighted. However, some tendencies could be described: cells used were mainly from donors under 30 years of age, with cell passage between 1 and 5, at a confluence of 70% to 80%. Conditioned medium was usually collected during the first 48 h, and kept frozen at -80°C. The various microenviroenmental cues were shown many times to have a significant impact on protein content, and improved effects on specifically targeted applications: each preconditioning manipulation induced a specific protein expression profile.

Research perspectives

Standardization of procedures is of prior importance to develop clinical-grade products. However, the protein contents of secretome is more linked to preconditioning than to specific technical methods. The challenge to overcome in the near future is to define specific preconditioning protocols to produce tissue specific conditioned medium (i.e, osteogenic environement, neuronal environment, cell incubation with inflammatory proteins…).