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