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Table 2 Improvement in the efficacy of MSC-derived soluble factors in treating liver diseases via different mechanisms

From: Mesenchymal stem cell-based cell-free strategies: safe and effective treatments for liver injury

Animal of origin

Tissue of origin

Pretreatment

Type of MSC derivatives

Quantity

Route

Liver injury

Model

Effect

Mechanism

Ref.

Mouse

Bone marrow

Hypoxia

MSC-CM

5 mg

Intraperitoneal

Acetaminophen

Mouse

Improve biochemical parameters and histological scores

Reduce inflammation; improve liver regeneration

[95]

Human

Adipose

Hypoxia

25-fold concentrated MSC-CM

0.1 ml

Tail vein

Partial hepatectomy

Mouse

Increase the number of proliferative liver cells

Activate JAK/STAT3 signaling

[96]

Mouse

Bone marrow

Hypoxia

Protein composition

10 mg/ml

Intraperitoneal

Acetaminophen

Mouse

Reduce oxygen levels; accelerate healing in damaged liver tissue

Inhibit the activation of inflammation; attenuate hepatocyte necrosis

[97]

Rat

Bone marrow

Coculture with hepatocytes

25-fold concentrated MSC-CM

7.2 ml

Tail vein

D-GalN

Rat

Prolong the survival time of ALF rats

Prevent liver injury; promote liver tissue repair

[98]

Mouse

Bone marrow

miR-223 overexpression

Exosomes

N/A

Intraperitoneal

Liver antigens S100

Mouse

Reverse autoimmune hepatitis

Downregulate the release of cytokines such as NLRP3 and caspase-1

[101]

Mouse

Adipose tissue

miR181-5p overexpression

Exosomes

40 μg

Intrasplenic

CCl4

Mouse

Inhibit the deposition of collagen I, vimentin, α-SMA and fibronectin in the liver

Activate autophagy; downregulate Stat3 and Bcl-2 in HSCs

[102]