Emerging role of mesenchymal stromal cells (MSCs)-derived exosome in neurodegeneration-associated conditions: a groundbreaking cell-free approach

Yari, Hadi; Mikhailova, Maria V.; Mardasi, Mahsa; Jafarzadehgharehziaaddin, Mohsen; Shahrokh, Somayeh; Thangavelu, Lakshmi; Ahmadi, Hosein; Shomali, Navid; Yaghoubi, Yoda; Zamani, Majid; Akbari, Morteza; Alesaeidi, Samira

doi:10.1186/s13287-022-03122-5

Stem Cell Research & Therapy

Table 1 MSCs-derived secretome (e.g., exosome) therapy in preclinical models of acute neurodegeneration

From: Emerging role of mesenchymal stromal cells (MSCs)-derived exosome in neurodegeneration-associated conditions: a groundbreaking cell-free approach

Condition	Model	Cell source	Administration route	Results	Ref.
SCI	Mice	BM	Intravenous	Stimulating functional behavioral restoration via improving M2/M1 macrophage ratio by exosomal miR-216a-5p	[120]
SCI	Rat	AM	Intravenous	Reducing inflammation and eliciting antioxidant effects through MSC-derived exosomes immobilized in hydrogel	[138]
SCI	Rat	UC	Intrathecal	Plummeting pro-inflammatory cytokine TNF-α and IL-1β, while improving IL-10, BDNF, and GDNF levels in brain tissue	[164]
SCI	Rat	BM	Intravenous	Alleviating neurological damage through suppressing Ern1 and promoting M2 macrophage by exosomal microRNA-124-3p	[165]
SCI	Rat	BM	Intravenous	Repairing spinal cord injury by exosomal miRNA-29b	[166]
SCI	Rat	BM	Intravenous	Repairing spinal cord injury by inhibition of A1 neurotoxic reactive astrocytes activation	[117]
SCI	Rat	UC	Intrathecal	Reducing the c-Fos, GFAP, Iba1, TNF-α, and IL-1β, and improving IL-10 and GDNF levels	[137]
SCI	Rat	BM	Intravenous	Inhibition of pericytes migration and improving the BSCB integrity by targeting NF-κB p65 signaling in pericytes	[133]
SCI	Mice	BM	Intraspinal	Promoting angiogenesis and axon growth leading to the functional rescue	[167]
SCI	Rat	BM	Intravenous	Promoting the neurogenesis and angiogenesis, while reducing apoptosis by exosomal miR-126	[128]
SCI	Rat	BM	Intravenous	Hindrance of complement activation	[168]
SCI	Mice	Placental	Intrathecal	Potentiating angiogenesis leading to the ameliorated neurologic function	[129]
SCI	Rat	BM	Intravenous	Improving M2 macrophage polarization	[121]
SCI	Rat	UC	Intravenous	Exerting anti-inflammatory and anti-fibrotic action	[169]
SCI	Rat	NA	Intravenous	Attenuation of inflammation through down-regulation of TLR4/NF-κB signaling pathway by exosomal miR-145-5p	[170]
SCI	Rat	BM	Intravenous	Inhibition of A1 neurotoxic reactive astrocytes activation in part via suppressing NF-κB translocation	[118]
TBI	Rat	BM	Intravenous	Promoting functional recovery through triggering endogenous angiogenesis and neurogenesis and also down-regulation of neuroinflammation	[104]
TBI	Rat	AT	Intracerebroventricular	Reducing microglia activation	[145]
TBI	Rat	BM	Intravenous	Amelioration of sensorimotor and cognitive dysfunction, attenuation of hippocampal neuronal cell loss, inducing the angiogenesis and neurogenesis, and mitigation of neuroinflammation	[143]
TBI	Rat	BM	Intranasal	Exosome efficient migration to the injured Forebrain	[171]
TBI	Rat	BM	Intravenous	Amelioration of neurological functions, decreasing brain edema through favoring BBB integrity	[23]
TBI	Swine	BM	Intravenous	Boosting neural plasticity along with reducing inflammation and apoptosis ensuring reduced brain lesion zone	[147]
TBI	Mice	BM	Intraorbital	Mitigation of early inflammatory responses	[144]
TBI	Rat	BM	Intravenous	Triggering endogenous angiogenesis and neurogenesis	[142]
TBI	Swine	BM	Intravenous	Induction of neuroprotection and supporting BBB integrity	[90]
TBI	Rat	BM	Intravenous	Stimulating neuroprotection via exosomal miR-216a-5p, which up-regulates BDNF expression	[172]
TBI	Mice	BM	Intravenous	Amelioration of cognitive deficits	[173]
Stroke	Mice	AT	Intravenous	Reducing autophagy by exosomal miR-25	[174]
Stroke	Rat	BM	Intravenous	Stimulation of neuritis outgrowth by exosomal miR-133b	[163]
Stroke	Mice	BM	Intravenous	Obstruction of neuroinflammation and averting cerebral infarction by exosomal miR-542-3p	[175]
Stroke	Mice	UC	Intravenous	Attenuation of microglial-mediated neuroinflammation through down-regulation of the IRAK1/TRAF6 signaling axis by exosomal miR-146a-5p	[159]
Stroke	Rat	BM	Intravenous	Promoting the neurorestorative effects	[176]
Stroke	Rat	BM	Intravenous	Suppression of the neuronal apoptosis and M1 macrophage polarization by exosomal miR-146a-5p causes alleviated intracerebral hemorrhage	[177]
Stroke	Mice	BM	Intravenous	Induction of neuroprotection	[178]
Stroke	Rat	BM	Intravenous	Improving the functional recovery and neurovascular plasticity	[179]
Stroke	Rat	UCB	Intravenous	Triggering the functional recovery	[180]
Stroke	Rat	AT	Intravenous	Attenuation of the ischemic brain injuries by targeting miR-21-3p/MAT2B axis	[181]
Stroke	Rat	BM	Intravenous	Promoting the axon–myelin remodeling by exosomal miR-17-92	[182]
Stroke	Mice	BM	Intravenous	Reducing inflammation, pathological alterations and apoptosis by exosomal miR-221-3p	[183]

MSCs mesenchymal stromal cells, TBI traumatic brain injury, SCI spinal cord injury, AT adipose tissue, BM bone marrow, UCB umbilical cord (UC) blood, miRNAs microRNAs, IL interleukin, TNFα tumor necrosis factor α, BSCB blood–spinal cord barrier, GDNF glial cell-derived neurotrophic factor, NF-κB nuclear factor kappa B, TLRs toll-like receptors, BBB blood–brain barrier, TRAF6 TNF receptor-associated factor 6, IRAK1 interleukin 1 receptor-associated kinase 1, BDNF brain-derived neurotrophic factor, NA not applicable

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ISSN: 1757-6512

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