Stem cell exosomes: New hope for recovery from diabetic brain hemorrhage

Table 1 Key mechanisms of action of stem cell–derived exosomes for neurological recovery post–diabetic cerebral hemorrhage

Mechanism of action	Description	Ref.
miR-129-5p modulation	Bone marrow–derived mesenchymal stem cell–derived exosomes deliver miR-129-5p, which targets and downregulates HMGB1. This leads to reduced neuroinflammation and improved neurological outcomes	Wang et al[1], 2024
Attenuation of oxidative stress	Exosomes reduce oxidative stress by modulating the expression of antioxidant enzymes and by reducing the production of reactive oxygen species, thereby protecting neurons from damage	Gómez-de Frutos et al[2], 2024
Promotion of neurogenesis	Stem cell–derived exosomes promote neurogenesis by delivering growth factors and microRNAs that support the proliferation and differentiation of neural progenitor cells in the damaged brain	Cheng et al[4], 2024
Inhibition of apoptosis	Exosomes carry antiapoptotic signals, such as miRNAs and proteins, which inhibit the activation of apoptotic pathways in neurons, reducing cell death in the affected brain regions	Larsson et al[3], 2024
Reduction of blood–brain barrier disruption	Bone marrow–derived mesenchymal stem cell–derived exosomes strengthen the blood–brain barrier by enhancing tight junction protein expression and reducing vascular permeability, thus preventing further brain injury post-hemorrhage	Lv et al[5], 2024
Modulation of immune response	Exosomes modulate the immune response by altering the activity of microglia and macrophages, reducing the production of proinflammatory cytokines, and promoting a neuroprotective environment	Southerland et al[6], 2024
Enhancement of angiogenesis	Bone marrow–derived mesenchymal stem cell–derived exosomes promote angiogenesis by delivering proangiogenic factors such as VEGF, which support the formation of new blood vessels and improve blood supply to the injured brain tissue	Wang et al[1], 2024
Regulation of autophagy	Exosomes influence autophagy processes in neurons and glial cells, contributing to the clearance of damaged proteins and organelles and supporting cellular homeostasis and survival	Wang et al[1], 2024
miRNA-mediated gene expression modulation	Through the delivery of various miRNAs, exosomes modulate the expression of genes involved in inflammation, cell survival, and repair processes, facilitating recovery from brain injury	Gómez-de Frutos et al[2], 2024
Neuroprotection through anti-inflammatory effects	Bone marrow–derived mesenchymal stem cell–derived exosomes reduce the expression of proinflammatory genes and increase anti-inflammatory cytokines, protecting neural tissue from secondary damage post-hemorrhage	Cheng et al[4], 2024

The table presents the key mechanisms through which stem cell–derived exosomes contribute to neurological recovery following diabetic cerebral hemorrhage. These exosomes modulate various molecular pathways, including the regulation of miR-129-5p, oxidative stress reduction, neurogenesis promotion, apoptosis inhibition, and immune response modulation. They also play a crucial role in strengthening the blood–brain barrier, enhancing angiogenesis, and regulating autophagy, thereby offering a multifaceted therapeutic approach to mitigating brain injury and promoting recovery. HMGB1: High-mobility group box 1; VEGF: Vascular endothelial growth factor.