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. 2022 Apr 7;13:865888. doi: 10.3389/fimmu.2022.865888

Table 4.

Example of studies in the field of MSC-EV application in experimental models of liver injury and their therapeutic mechanisms.

Injury model Source of MSCs Acute Or chronic phase EVs type Route of administration Dosage (vesicles/animal) Effect(s) Mechanism(s) Year Ref.
CCl4-induced acute liver injury(mouse) hUC-MSCs Chronic Exosome Intrahepatic 250 µg
  1. Inhibited hepatocyte apoptosis

  2. Reduce liver fibrosis

  3. Reduce the serum levels of HA

  1. Suppressed TGF-b signaling and inhibited EMT

  2. Reduced collagen-1 and 3 expression

2013 (169)
Hepatic ischemia-reperfusion (mouse) mBM-MSC Acute EVs Intravenous 2 × 1010
  1. Reduction of inflammatory mediators

  2. inhibition of Apoptosis

  3. Increase the number of F4/80 positive cells

  1. Suppress NF-κB activity

  2. increased CXCL1 release from AML12 hepatocytes in vitro

2017 (170)
In vitro ischemia/reperfusion Partial hepatectomy (mouse) mAD-MSC Acute Secretome (EVs + other soluble factors) Intravenous N/A
  1. Reduce serum IL-6 and TNF-a levels

  2. Reduce serum transaminases

  3. Accelerate liver regeneration

  4. Increase the hepatocyte proliferation

  1. Increased p-STAT3 and PCNA expression

  2. Decreased hepatic expression of SOCS3

  3. increased SIRT1 Increase in survival genes (e.g., Bcl-xL and Mcl-1)

2017 (171)
Thioacetamide induced (rat) Human embryonic MSC Chronic EVs Intrahepatic 350 µg
  1. Reduction of fibrosis

  2. Reduction inflammation

  1. upregulation in MMP9 and MMP13

  2. upregulation of BCL-2

  3. upregulation of TGF-β1 and IL-10

  4. downregulation of Col1α, αSMA and TIMP1

  5. downregulation BAX, TNFα and IL-2

2018 (172)
CCl4-induced acute liver injury(mouse) hUC-MSCs Acute Exosome Intravenous Or intragastric 8, 16, and 32 mg/kg
  1. Reduction of oxidative stress

  2. inhibition of Apoptosis

  3. Increased cell viability

  1. Reduced levels of ROS

  2. Upregulated Bcl2 expression

2017 (173)
S.japonicum-infected mice hUC-MSCs Chronic EVs intravenous 3 × 109
  1. Reduce liver fibrosis

  2. suppress HSCs function

  3. Reduction inflammation

  1. Reduced collagen-1 and 3 expression

  2. Reduced α-SMA expression

  3. significantly decrease TNF-α and IL-1β expression

2020 (174)

MSCs, Mesenchymal stromal/stem cells; EVs, Extracellular vesicles; TGF-β, Transforming growth factor-beta; NF-kB, Nuclear factor kappa-B; MMPs, Matrix metalloproteinase; NLRP, Nucleotide-binding oligomerization domain; ALT, alanine aminotransferase; AST, Aspartate transaminase; ALP, Alkaline Phosphatase; BM, Bone marrow; UC, umbilical cord; AD, adipose tissue; N/A, Not Applicable.