Stem cell–mediated neuroplasticity and psychological recovery in cancer survivors: Mechanisms, evidence, and translational challenges

Abstract Advances in cancer treatment have substantially improved survival rates; however, a growing number of cancer survivors experience persistent neurocognitive impairment and psychological distress after therapy, commonly referred to as cancer therapy–related cognitive impairment (CRCI). These long‐term sequelae significantly affect quality of life and functional outcomes, yet effective restorative treatments remain limited. This narrative review aims to synthesize current evidence on stem cell–mediated mechanisms of neuroplasticity and examine their potential relevance to psychological recovery in cancer survivors. A narrative review was conducted based on peer‐reviewed literature retrieved from PubMed, Web of Science, and Scopus databases, covering publications from 2000 to 2024. Search strings combined MeSH terms and free‐text keywords (e.g., “stem cells AND neuroplasticity AND cancer survivorship,” “extracellular vesicles AND CRCI”). Studies were included if they addressed neural stem cells, mesenchymal stem cells, induced pluripotent stem cell–derived approaches, or extracellular vesicle biology in the context of neuroregeneration or cancer‐related neural injury. CRCI‐specific preclinical studies, including chemotherapy‐ and radiation‐induced neurotoxicity models, were prioritized where available. Articles focused solely on tumor biology without relevance to survivorship neurocognition were excluded. Stem cells exert neuroprotective and neuroregenerative effects primarily through paracrine signaling, immunomodulation, extracellular vesicle release, and restoration of the neural microenvironment rather than direct neuronal replacement. These mechanisms support synaptic remodeling, neurogenesis, and regulation of neurotrophic factors, which are closely linked to cognitive function and emotional regulation. However, it must be emphasized that the hypothesis linking stem cell–mediated neuroplasticity to psychological recovery in cancer survivors remains speculative and has not been tested in prospective clinical trials. The majority of current evidence derives from preclinical models and mechanistic studies; direct clinical evidence in cancer survivor populations remains limited. Stem cell–mediated neuroplasticity represents a promising biological framework for addressing both cognitive and psychological impairments in cancer survivorship. Future translational efforts should focus on integrating regenerative strategies with psychosocial and behavioral interventions to achieve durable improvements in brain health and quality of life.