Stem cell therapy use in patients with dementia: a systematic review

BACKGROUND: Stem cell therapy (SCT) is increasingly recognized for its potential in managing cognitive impairment, particularly that of dementia. The application of SCT aims to restore cognitive functioning in people living with dementia. Beyond pre-clinical studies, several clinical trials have evaluated specific stem cell (SC) types for their efficacy in treating dementia. AIMS & OBJECTIVES: To assess the status and efficacy of pre-clinical and clinical studies utilizing SCs as a therapeutic approach for dementia. METHODS: A systematic review was conducted using two electronic databases: MEDLINE and Embase. We reviewed studies on the application of SCs in dementia, focusing on the following aspects: Animal models used in pre-clinical studies, tissue sources of SCs and donor species, and administrative routes and outcome assessments. Included papers comprised randomized control trials (RCTs) and original studies, while those involving adjuvant therapies for dementia were excluded. Quality assessment criteria included relevance to the research question, type of SCs, stage of SC transplantation, duration and route of administration, methods for outcome assessment, and the total number of animals implicated. RESULTS: A total of 32 papers were included, encompassing 21 clinical trials and 11 preclinical studies. The preclinical studies employed various transgenic animal models to evaluate SCT outcomes. Animal models of dementia, particularly transgenic mice, have proven instrumental in replicating human disease mechanisms. These models facilitate understanding of pathophysiology and preclinical testing of therapeutic interventions. Studies utilizing SCT demonstrated notable improvements in spatial memory, reduced neuroinflammation, and protection against amyloid-beta (Aβ) toxicity. Key mechanisms included modulation of inflammation, microglial immune responses, neurogenesis support, and anti-amyloidogenic effects. Preclinical studies predominantly employed human placenta-derived mesenchymal stem cells (PD-MSCs), umbilical cord-derived MSCs (U-MSCs), and induced pluripotent stem cell-derived neuronal precursors. Administration routes varied, with stereotactic and intravenous injections targeting affected brain regions. Reductions in inflammatory markers such as IL-1β, TNF-α, and increases in anti-inflammatory cytokines like IL-4 and IL-10 were observed. These outcomes emphasize the immunomodulatory and neuroprotective capacities of SCT. CONCLUSION: SCT shows promise in addressing dementia-related pathologies by leveraging diverse therapeutic mechanisms. Continued refinement of preclinical models and translational research is essential to bridge gaps between preclinical findings and clinical applications, potentially paving the way for novel treatments for dementia.