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How do Mesenchymal Stem Cells work?

Mesenchymal stem cells (MSCs) have shown promise in repairing brain injuries or disorders through various mechanisms. These multipotent cells can differentiate into various cell types and release bioactive molecules that promote repair and regeneration.

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Paracrine Effects

MSCs release a wide range of bioactive molecules, including:

  • Cytokines and growth factors (e.g., brain-derived neurotrophic factor [BDNF], vascular endothelial growth factor [VEGF], and insulin-like growth factor-1 [IGF-1]).

  • Extracellular vesicles (EVs) and exosomes containing microRNAs and proteins that support neuronal survival, synaptogenesis, and anti-inflammatory effects.

These factors create a regenerative microenvironment that helps repair damaged neural tissue.

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Immunomodulation

MSCs modulate the immune response by:

  • Reducing neuroinflammation via suppression of pro-inflammatory cytokines (e.g., TNF-α, IL-1β).

  • Enhancing anti-inflammatory cytokines (e.g., IL-10, TGF-β).

  • Inhibiting microglial activation, which reduces secondary brain damage.

This promotes a favorable environment for neural repair and regeneration.

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Neurogenesis and Synaptogenesis

MSCs can stimulate:

  • Neurogenesis: Encouraging the formation of new neurons from existing neural stem/progenitor cells.

  • Synaptogenesis: Enhancing the formation of synaptic connections, which are critical for functional recovery.

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Angiogenesis

MSCs promote angiogenesis, improving blood supply to the brain. This ensures better oxygen and nutrient delivery, essential for neural repair and function. VEGF, a factor secreted by MSCs, plays a key role in new blood vessel formation.

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Direct Differentiation (Limited)

MSCs can differentiate into neuron-like cells and glial cells under specific conditions. However, this process is relatively limited in vivo compared to their paracrine effects.

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Reduction of Oxidative Stress

MSCs reduce oxidative stress by releasing antioxidants and upregulating endogenous antioxidant pathways. This minimizes damage to neurons and glial cells caused by reactive oxygen species (ROS).

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Extracellular Matrix Remodeling

MSCs produce enzymes that remodel the extracellular matrix, clearing debris from injured areas and facilitating tissue repair.

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