Human Dental Pulp Stem Cell Secretome Restores Ischemic Stroke-Impaired Motor and Cognitive Functions by...

Area of Science:

• Neuroscience
• Regenerative Medicine
• Biomedical Engineering

Background:

• Ischemic stroke causes significant neuronal damage, leading to lasting motor and cognitive impairments.
• Oxidative stress, neuroinflammation, and synaptic dysfunction are key pathological features of stroke.
• Human dental pulp stem cell (hDPSC) secretome offers a cell-free therapeutic approach with potential neurotrophic, antioxidant, and immunomodulatory properties.

Purpose of the Study:

• To investigate the therapeutic efficacy of hDPSC secretome in a mouse model of ischemic stroke.
• To elucidate the molecular mechanisms underlying the neuroprotective and restorative effects of hDPSC secretome.

Main Methods:

• Utilized a photothrombotic mouse model of ischemic stroke and CoCl2-induced hypoxic BV2 microglial cells.
• Performed proteomic profiling to identify key proteins and pathways affected by hDPSC secretome treatment.
• Assessed infarct volume, neuronal apoptosis, oxidative stress, neuroinflammation, neurogenesis, vascular remodeling, and synaptic organization post-treatment.
• Evaluated behavioral outcomes including motor coordination, spatial learning, memory, and anxiety-like behaviors.

Main Results:

• hDPSC secretome treatment significantly reduced infarct volume, neuronal apoptosis, and reactive oxygen species (ROS) accumulation.
• Treatment attenuated NF-κB-associated inflammatory signaling and shifted microglial polarization towards an M2-associated phenotype.
• Improved hippocampal neurogenesis, vascular remodeling, and synaptic organization were observed.
• Proteomic analysis revealed modulation of pathways involved in oxidative phosphorylation, inflammation, calcium signaling, vesicular transport, and cytoskeletal remodeling.
• Significant improvements in motor coordination, spatial learning, memory, and anxiety-like behaviors were documented.

Conclusions:

• hDPSC secretome demonstrates potent therapeutic effects in an ischemic stroke model.
• The cell-free therapy promotes functional recovery by mitigating oxidative stress, neuroinflammation, and enhancing neurovascular and synaptic repair.
• hDPSC secretome is a promising cell-free therapeutic candidate for post-stroke recovery, targeting redox, inflammatory, neurovascular, and synaptic remodeling pathways.