Table 1 Imbalanced microenvironment regulation of different sources of MSCs

Inflammatory microenvironment

UCMSCs

Zbtb16, Per3, and Hif3a genes↑

Promote M1 to M2 of microglial

[115, 116]

TSG-6↑

Inhibit A1 astrocyte formation

[118,119,120,121,122]

sTNFR1 ↑

Counteract TNF-α

[132]

Inhibit NLRP3 formation

IL-1β, IL-18 ↓

[145]

BMSCs

Secrete EVs (NO, IDO, TGF-β)

Inhibit T cell proliferation and activation

[126, 127]

IL-6, IFN-1β, GM-CSF ↑

Inhibit neutrophil apoptosis

[87, 98, 99]

Secrete EVs (miR-21)

Transform the phenotype of astrocytes to A2

[123]

Increase autophagy through PELI1 axis

Inhibit pyroptosis

[151]

NMDA receptor subunit mRNA↓

Inhibit excitotoxicity of neurons

[154]

BMSCs, ADMSCs

Anti-inflammatory cytokines↑

Pro-inflammatory cytokines↓

IL-4, IL-10, IL13 and TGF-β ↑

IL-6 and TNF-α ↓

[102, 129]

ADMSCs

Inhibiting the Jagged1/Notch pathway

Reduce JAK/STAT3 phosphorylation in astrocytes

[124]

3-NT, 4HNE, and PC↓

Anti-oxidation

[139]

CBMSCs

CCL2↑

attract macrophages, induce into M2

[138]

EFMSCs

Inhibit NLRP3 formation

Bax↓ Bcl-2↑

[144]

Nutrient microenvironment

UCMSCs

GDNF↑

Promote tissue repair

[156]

BDNF↑, upregulate β3 & γ2 and KCC2

balance excitation and inhibition in injured neurons

[159]

BMSCs

BDNF, NGF↑

Stimulate recovery of SCI

[155]

NGF↑

increase the area of grey matter and white matter

[157]

pro-NGF↓

Improve nutrient microenvironment

[158]

AFMSCs

HGF↑

VEGF and HIF-1α↑, promote angiogenesis

[165]

Regeneration microenvironment

UCMSCs

Secrete miR-29b-3p

PTEN↓, promote axon growth

[168]

Inhibit reactive astrocytes

Inhibit scar formation

[166]

MMP-2↑

CSPG↓, inhibit scar formation

[170]

UCMSCs, ADMSCs

GFAP↓

Decrease cavity size and tissue loss

[169]

BMSCs

‘Cell bridge' and 'cell towing'

Facilitate neuronal growth

[172]

CMSCs

RhoA↓

Promote growth cone formation

[167]

UCBMSCs

BDNF↑

CSPG↓, mitigate cavity formation

[171]