Table 1: Studies of animals treated with bleomycin and results after MSC therapy.

Study

Model

Cell Type

Delivery/Dose

Safety/Efficacy Results

Jun et al., [54]

Mouse

Allogeneic LuMSC

i.v. 15 - 25 × 104

Reduced induced lung fibrosis

Kumamoto  et al., [71]

Mouse

BM-MSC

i.v. 5 × 105, 3 days after BLM

Reduced induced lung fibrosis

Ono  et al., [73]

Mouse

Xenogeneic cells (human)

BM-MSC

i.v. 5 × 105, Cells were given 24 hours after BLM

Normal histopathology, Decreased TGF- β, Decreased lung collagen

Gao  et al., [74]

Rat

Xenogeneic cells (human)

uMSC

i.v. 2.5 × 105, Cells were given 3 days after BLM

Increased TNF-α protein level when measured 13 days after MSC administration , Better with improvement ACE2

Lee  et al., [39]

Rat

BM-MSC

i.v. 1 × 106, 4 days after BLM

 

Decrease inflammation, Decreased TGF- β, Decreased BAL IL-6

No effect on lung collagen content, Improve the Ashcroft score, BAL total cell count and neutrophil count

Ortiz  et al., [42]

Mouse

AllogeneicBM-MSC

i.v. 5 × 105, Cells were given immediately after BLM or 7 days later

Decrease inflammation, Decreased MMP-2, MMP-9 and MMP-13 mRNA levels

Lee  et al., [72]

Mouse

Xenogeneic cells (human)

AD-MSC

i.p. 3 × 105, Cells were given at weeks 8, 10, 12, and 14 at the same time as BLM

Decrease inflammation, Improved fibrosis, improvement in alveolar injury, Decreased TGF- β Decreased IL-1 levels

Garcia  et al., [70]

Mouse

Xenogeneic cells (human)

AFSC

i.v. 1 × 106, Cells were given two hours after BLM or 14 days later

Improved fibrosis, Improvement in alveolar injury, Decreased lung collagen

Zhao  et al., [69]

Rat

BM-MSC

i.t. 5 × 106, Cells were given 12 hours after BLM

Improved fibrosis, Normal histopathology, Improvement in alveolar injury, Decreased TGF-β

Huang  et al., [68]

Rat

BM-MSC

i.v. 2.5 × 106, Cells were given the same day as BLM and 7 days later

Improved fibrosis, Improvement in alveolar injury, better effects on hydroxyproline content and alveolitis and fibrosis scores

Moodley  et al., [40]

Mouse

Xenogeneic cells (human)

uMSC

i.v. 1 × 106, Cells were given 24 hours after BLM

Decrease inflammation, Decreased TGF- β & TNF-α  mRNA levels, No change in lung IL-1, IL-6 mRNA levels, Increased MMP-2, No change in MMP-9 or MMP-13, Decreased lung collagen

Moodley  et al., [75]

Mouse

Xenogeneic cells

AM-MSC [vs BM-MSC]

i.v. 1 × 106, Cells were administered after 10 days of the first dose of BLM

Decreased TGF- β; TNF-α, IL-1 and IL-6 protein levels, No change in MMP-2 or MMP-13, Increased MMP-9 levels, Decreased lung collagen

Aguilar  et al., [76]

Mouse

BM-MSC

i.v. 5 × 105, Cells were administered after 8 hours after BLM

Lung collagen assessed at 14 days was decreased

Min  et al., [77]

Mouse

Xenogeneic cells (human)

uMSC

 

No change in TNF-α, IL-1 or IL-6 levels, Increased MMP-2, reduced MMP-9, Decreased lung collagen

Ortiz  et al., [78]

Mouse

AllogeneicBM-MSC

i.v. 5 × 105, Cells were given immediately after BLM or 7 days later

No significant change in lung TNF-α mRNA level.

Gazdhar  et al., [79]

Rat

BM-MSC

i.t. 3 × 106, Cells were instilled after 7 days of bleomycin treatment

Reduced induced lung fibrosis

Cargnoni  et al., [41]

Mouse

Allogeneic & Xenogeneic cells (human)

AM-MSC

i.v./i.t. 1 × 106, i.p. 4 × 106 Cells were administered after 15 min after BLM

Reduced induced lung fibrosis, Decrease in neutrophil infiltration

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Abbreviations: BLM = bleomycin; MSC = mesenchymal stem cells; BM-MSC = bone marrow–derived mesenchymal stem cells; LuMSC = Lung MSC; AD-MSC = adipose tissue-derived MSC; AM-MSC = amniotic membrane MSC; uMSC = umbilical cord MSC; AFSC = Amniotic Fluid Stem Cells; BAL = bronchoalveolar lavage; TGF- β = transforming growth factor β; TNF-α = tumor necrosis factor-α; IL-1 = interleukin 1; IL-6 = interleukin 6; MMP-2 = matrix metalloproteinase-2; MMP-9 = matrix metalloproteinase-9; MMP-13 = matrix metalloproteinase-13; i.v. = intravenous; i.p. = intraperitoneal; i.t. = intratracheal