Baqiyatallah University of Medical Sciences Journal of Applied Biotechnology Reports 2322-1186 13 2 2026 06 30 Cannabidiol Drives Efficient Neural Differentiation of Human Wharton’s Jelly Mesenchymal Stem Cells: A Small-Molecule Approach for In Vitro Neurogenesis 2080 2088 247500 10.30491/jabr.2025.540602.1903 EN Erfan Motalebzadeh Department of Biology, Basic Science Faculty, Science and Research Branch, Islamic Azad University, Tehran, Iran 0000-0001-8865-0195 Akram Tajik Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran 0009-0008-5863-6489 Raheleh Halabian Applied Microbiology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran 0000-0002-3363-8276 Nafiseh Abbasabadi Department of Biology, Science and Research branch, Islamic Azad University, Tehran, Iran Hanieh Ahmadi Department of Cell and Molecular Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran Ali Salimi Tissue Engineering and Regenerative Medicine Research Center, New Health Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran Journal Article 2025 08 11 Introduction: Over the past decade, research on small molecules such as cannabidiol (CBD) has expanded due to their ability to modulate biological pathways through protein interactions. Understanding how mesenchymal stem cells (MSCs) differentiate into neural-like cells is crucial for developing effective therapies for neurological disorders. This study aimed to investigate the efficacy of cannabidiol, as a cost-effective small-molecule inducer, in promoting the neural differentiation of human Wharton’s jelly MSCs (hWJ-MSCs) in vitro and to determine the optimal non-cytotoxic dose for this purpose. Materials and Methods: The optimal CBD dose (5 μg/ml) was first determined using the MTT assay and acridine orange/ethidium bromide (AO/EB) staining. To evaluate neural differentiation potential, the expression of neural marker genes, MAP-2, NSE, Oligo-2, β-tubulin III, and GFAP, was assessed by real-time PCR at 7 and 14 days’ post-induction. Results: The results demonstrated significant upregulation of neural marker genes at 7 and 14 days after CBD treatment, confirming successful induction of neural differentiation. Conclusions: The designed protocol is highly effective and efficient for inducing neural differentiation. Further in vivo studies using biocompatible scaffolds are necessary to elucidate the underlying mechanisms and therapeutic implications of these findings.

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