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
Abstract
BACKGROUND

Mesenchymal stem cells (MSC) effects on tissue regeneration are mainly mediated by their secreted substances (secretome), inducing their paracrine activity. This Conditioned medium (CM), including soluble factors (proteins, nucleic acids, lipids) and extracellular vesicles is emerging as a potential alternative to cell therapy. However, the manufacturing of CM suffers from variable procedures and protocols leading to varying results between studies. Besides, there is no well-defined optimized procedure targeting specific applications in regenerative medicine.

AIM

To focus on conditioned medium produced from dental MSC (DMSC-CM), we reviewed the current parameters and manufacturing protocols, in order to propose a standardization and optimization of these manufacturing procedures.

METHODS

We have selected all publications investigating the effects of dental MSC secretome in in vitro and in vivo models of tissue regeneration, in accordance with the PRISMA guidelines.

RESULTS

A total of 351 results were identified. And based on the inclusion criteria described above, 118 unique articles were included in the systematic review. DMSC-CM production was considered at three stages: before CM recovery (cell sources for CM), during CM production (culture conditions) and after production (CM treatment).

CONCLUSION

No clear consensus could be recovered as evidence-based methods, but we were able to describe the most commonly used protocols: donors under 30 years of age, dental pulp stem cells and exfoliated deciduous tooth stem cells with cell passage between 1 and 5, at a confluence of 70% to 80%. CM were often collected during 48 h, and stored at -80 °C. It is important to point out that the preconditioning environment had a significant impact on DMSC-CM content and efficiency.

Keywords: Tissue engineering; Mesenchymal stem cells; Dental; Conditioned medium; Secretome; Regeneration

Core Tip: Dental Mesenchymal stem cells (DMSC) effects on tissue regeneration are highly mediated by their secreted substances [conditioned medium (CM)] such as soluble factors and extracellular vesicles. The manufacturing of CM products suffers from variable procedures and protocols leading to different results between studies. Focusing on CM produced from DMSC (DMSC-CM), we reviewed the current parameters and manufacturing protocols, aiming to facilitate the standardization and optimization of manufacturing procedures, in accordance with PRISMA guideline. No clear consensus could be recovered as evidence-based methods, but it clearly appeared that the preconditioning environment had a significant impact on DMSC-CM content and efficiency.