Jurczenko Lidia, Semeniuk Alina, Leszek Jerzy Waldemar
4th Military Clinical Hospital, ul. Rudolfa Weigla 5, 50-981 Wrocław, Poland.
Lower Silesian Center for Oncology, Pulmonology and Hematology, Grabiszyńska 105, 53-439 Wrocław, Poland.
Int J Mol Sci. 2025 Aug 27;26(17):8306. doi: 10.3390/ijms26178306.
Major depressive disorder (MDD) is a prevalent and disabling psychiatric condition with limited treatment options for patients who are resistant to conventional pharmacological and psychotherapeutic interventions. Stem cell (SC)-based therapies have emerged as a promising experimental approach, offering multifaceted mechanisms of action including neurogenesis, immunomodulation, antioxidative protection, and neuromodulation. This narrative review synthesizes current evidence from preclinical studies and early-phase clinical trials on the efficacy of mesenchymal stem cells (MSCs), neural stem cells (NSCs), and induced pluripotent stem cells (iPSCs) in alleviating depressive-like behaviors. Mechanistic insights include enhanced hippocampal neurogenesis, modulation of the brain-derived neurotrophic factor (BDNF)-TrkB pathway, attenuation of neuroinflammation through microglial polarization, and restoration of serotonergic signaling via peripheral-to-central pathways such as via the vagus nerve. In addition, the therapeutic potential of extracellular vesicles (EVs) and intranasal administration as non-invasive delivery strategies is discussed. While animal and first preclinical studies suggest potential benefit, significant translational barriers remain, including issues of scalability, long-term safety, and ethical considerations. Further rigorous studies are needed to validate stem-cell-based therapies as viable treatments for MDD.
重度抑郁症（MDD）是一种常见且使人衰弱的精神疾病，对于那些对传统药物和心理治疗干预有抵抗性的患者，其治疗选择有限。基于干细胞（SC）的疗法已成为一种有前景的实验方法，具有多方面的作用机制，包括神经发生、免疫调节、抗氧化保护和神经调节。本叙述性综述综合了临床前研究和早期临床试验的现有证据，这些证据涉及间充质干细胞（MSC）、神经干细胞（NSC）和诱导多能干细胞（iPSC）在减轻抑郁样行为方面的疗效。其作用机制包括增强海马神经发生、调节脑源性神经营养因子（BDNF）-TrkB通路、通过小胶质细胞极化减轻神经炎症以及通过迷走神经等外周到中枢的途径恢复血清素能信号传导。此外，还讨论了细胞外囊泡（EV）和鼻内给药作为非侵入性给药策略的治疗潜力。虽然动物和首次临床前研究表明有潜在益处，但仍存在重大的转化障碍，包括可扩展性、长期安全性和伦理考量等问题。需要进一步进行严格的研究，以验证基于干细胞的疗法作为MDD可行治疗方法的有效性。
