Ferreira LVO, de Oliveira PHD, Amorim RM. Phytocannabinoid-induced priming and differentiation of mesenchymal stem cells: Therapeutic potential. World J Stem Cells 2026; 18(4): 116829 [DOI: 10.4252/wjsc.v18.i4.116829]
Corresponding Author of This Article
Rogério Martins Amorim, Associate Professor, Department of Veterinary Clinic, School of Veterinary Medicine and Animal Science, São Paulo State University, Prof. Dr. Walter Maurício Corrêa Street, s/n, Botucatu 18618-681, São Paulo, Brazil. rogerio.amorim@unesp.br
Research Domain of This Article
Cell & Tissue Engineering
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
World J Stem Cells. Apr 26, 2026; 18(4): 116829 Published online Apr 26, 2026. doi: 10.4252/wjsc.v18.i4.116829
Phytocannabinoid-induced priming and differentiation of mesenchymal stem cells: Therapeutic potential
Lucas Vinícius de Oliveira Ferreira, Pedro Henrique Domingues de Oliveira, Rogério Martins Amorim
Lucas Vinícius de Oliveira Ferreira, Pedro Henrique Domingues de Oliveira, Rogério Martins Amorim, Department of Veterinary Clinic, School of Veterinary Medicine and Animal Science, São Paulo State University, Botucatu 18618-681, São Paulo, Brazil
Lucas Vinícius de Oliveira Ferreira, Pedro Henrique Domingues de Oliveira, Rogério Martins Amorim, Center for Translational Research in Regenerative Medicine, Institute of Biotechnology, São Paulo State University, Botucatu 18607-440, São Paulo, Brazil
Author contributions: Ferreira LVO, de Oliveira PHD, and Amorim RM prepared and wrote the manuscript, and made equal contributions to this study; and all authors have read and approved the final manuscript.
Supported by the Doctoral Scholarship granted by the São Paulo Research Foundation (FAPESP), No. 2024/19980-0.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Rogério Martins Amorim, Associate Professor, Department of Veterinary Clinic, School of Veterinary Medicine and Animal Science, São Paulo State University, Prof. Dr. Walter Maurício Corrêa Street, s/n, Botucatu 18618-681, São Paulo, Brazil. rogerio.amorim@unesp.br
Received: November 21, 2025 Revised: December 27, 2025 Accepted: February 9, 2026 Published online: April 26, 2026 Processing time: 150 Days and 14 Hours
Abstract
Mesenchymal stem cells (MSCs) are multipotent progenitor cells extensively studied for their immunomodulatory and regenerative potential. Despite their therapeutic promise, MSC efficacy can be limited by poor survival, reduced homing, and variable immunoregulatory activity in inflammatory microenvironments. To overcome these challenges, priming strategies have been developed to precondition MSCs, enhancing their functional performance. Among these, phytocannabinoids, bioactive compounds derived from Cannabis sativa, have gained attention due to their ability to modulate MSC behavior. Beyond cannabidiol and Δ9-tetrahydrocannabinol, several phytocannabinoids interact with a broad spectrum of receptors, including classical cannabinoid receptors (cannabinoid receptor 1 and cannabinoid receptor 2), G protein-coupled receptor 55, transient receptor potential vanilloid channels, and peroxisome proliferator-activated receptor gamma, influencing intracellular signaling, cytokine expression, migration, viability, and importantly, both MSC priming and lineage differentiation. This mini-review critically examines current in vitro and in vivo evidence on phytocannabinoid-mediated priming and differentiation of MSCs, highlighting their effects on immunomodulation, differentiation, and regenerative potential. Collectively, these findings suggest that phytocannabinoid priming represents a promising approach to enhance MSC therapeutic efficacy, although further studies are required to elucidate receptor-specific mechanisms and optimize priming protocols for clinical translation.
Core Tip: Phytocannabinoids have emerged as promising modulators of mesenchymal stem cell (MSC) behavior, influencing immunomodulation and differentiation. Although a few in vivo studies exist, the majority of evidence comes from in vitro models. However, challenges remain for the clinical application of MSC priming with phytocannabinoids or the secretome derived from primed cells. Standardized priming protocols, deeper mechanistic insights, and comprehensive in vivo validation are crucial to fully harness their therapeutic potential.
