Innovative Stem Cell-Based Therapeutic Modalities to Address Major Depression and Treatment-Resistant Depression: A Review
نویسندگان
1 Regenerative Medicine, Organ Procurement and Transplantation Multi-Disciplinary Center, Razi Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
2 Regenerative Medicine, Organ Procurement and Transplantation Multi-Disciplinary Center, Razi Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
3 Department of Regenerative Medicine, Cell Science Research Center, Royan institute for stem cell biology and technology, ACECR, Tehran, Iran
4 Experimental Cancer Medicine, Institution for Laboratory Medicine, Karolinska Institute, Stockholm, Sweden
5 Department of Medicine, Guilan university of Medical Sciences (Gums), Rasht, Guilan, Iran
6 Regenerative Medicine, Organ Procurement and Transplantation Multi-Disciplinary Center, Razi Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
7 Department of Tissue Engineering, School of Advanced Medical Sciences and Technologies, Hamadan University of Medical Sciences, Hamadan, Iran
doi
10.22074/cellj.2025.2046068.1727چکیده
Depression is among the most widespread mental health conditions worldwide, with a significant number of patientsshowing inadequate responses to pharmacological treatments. Despite the development of numerous pharmacologicaltherapies over the past six decades, a substantial proportion of patients with major depressive disorder (MDD) remainunresponsive to conventional therapies, prompting the exploration of innovative therapeutic strategies. This reviewcritically examines the potential of stem cell-based therapies as a novel alternative to conventional antidepressanttreatments, with a particular focus on individuals diagnosed with MDD. This study explores the molecular pathwaysthat mediate neuroinflammatory responses in MDD, emphasizing the contributions of key pro-inflammatory cytokinesto impaired neuroplasticity, mitochondrial dysfunction, and heightened oxidative stress. In addition, this study discussesthe immunomodulatory properties of mesenchymal stromal cells (MSCs), highlighting their capacity to enhance antiinflammatorysignaling, promote neurogenesis, and restore neurotransmitter homeostasis. Moreover, this reviewunderscores the neuroprotective role of MSCs in mitigating oxidative stress–induced neuronal injury, with particularemphasis on their ability to secrete neurotrophic factors such as brain-derived neurotrophic factor (BDNF), whichsupport neuronal integrity and survival.
