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Table 3 Some of The MSC-based Animal Studies for Scleroderma

From: Mesenchymal stem cell as a novel approach to systemic sclerosis; current status and future perspectives

References Animal models Origin and dose of MSCs The site of stem cell injection Observed outcomes
(Okamura et al. 2020) Bleomycin intradermic
injection/mouse(daily,4 weeks) and Scl-cGVHD(irradiated with 400 cGy twice a day/1 day)
2 × 105 syngeneic AD-MSCs intravenous ↓dermal thickness
↓skin fibrosis (both models)
↓lung fibrosis (both models)
↓infiltration of immune cells into the skin
↓COL1A2 mRNA expression
↓IL-6 and IL-13
↓IL-10 and IFN-γ
↓frequency of cytokine producing CD4+ T cells and effector B cells in the spleen
(Maria et al. 2018) HOCl intradermic
(daily, 42 days)
2.5 × 105 syngeneic BM-MSCs intravenous ↓ skin thickness
↓ IL-1β, TNF-α, IL-6, and IL-10 expression
↓ cellular infiltrates
≠anti-scl70 autoantibody producing
≠skin inflammation
↓myofibroblastic activation (MSC injected on d42)
↑MMP1 (MSC injected on d42)
↓TIMP1 (MSC injected on d42)
*all the other results are from MSC injection on d0
(Rubio et al. 2018) Bleomycin intratracheal/mouse 5 × 105 syngeneic AD-MSCs intravenous ≠skin fibrosis
≠lung fibrosis
↓ total wound size
↓ expression of miR-199-3p in skin wound tissue and lungs
≠CAV-1 downregulating
≠AKT Phosphorylating
≠inflammatory markers upregulating
≠αv-integrin mRNA upregulating
(Lan et al. 2017) Bleomycin intratracheal/mouse 2.5 × 105 syngeneic OSM preconditioned BM-MSCs intratracheal ↑wound healing
↓collagen content
↓ECM synthesis
↓inflammatory mediators
↓lung edema
↓total cells and neutrophils in BAL fluid
↓fibrotic factors in the lung
↓histological changes
(Jiang et al. 2017) Bleomycin subcutaneous/mouse(daily,21 days) 1 × 106 syngeneic BM-MSCs overexpressing Trx-1 subcutaneous ↓apoptosis
↓ Bax
↓cleaved caspase 3
≠Dermal thickening
↓TGFβ, α-SMA, fibronectin and collagen 1 expression in the skin
(Huleihel et al. 2017) Bleomycin intratracheal/mouse 5 × 105 human BM-MSCs overexpressing let7d intravenous ↓weight loss
↓CD45 positive cells in the lung
↓collagen transcript levels
NC in α-SMA, HMGA-2, N-Cadherin and FSP-1 expression
(Chen et al. 2017b) Tsk1/+ mouse 1 × 105 allogeneic BM-MSC /10 g bodyweight intravenous ↑osteoblast and osteoclast numbers in the femurs
↑serum levels of type I collagen cross-linked telopeptide (CTX) and sRANKL
↑bone formation rate
Improvement of osteogenic differentiation of BM-MSCs in mice
↑Runx2, ALP, and OCN
↓adipocytes in the bone marrow
↓PPARγ and LPL expression
(Maria et al. 2016b) HOCl intradermic
injection/mouse(daily, 42 days)
2.5 105 human BM-MSCs/ AD-MSCs intravenous ↓rate in skin thickness formation
↓total collagen deposition in skin and lungs
↓COL1, COL3 and α-SMA gene expression
↓infiltration of CD3+ T lymphocytes and F4/80+ macrophages
↑MMP1/TIMP1 ratio(higher in human AD-MSCs)
↓TNF-α, IL-1b and IL-10 in skin(lower in human AD-MSCs)
↓pulmonary fibrosis
↓COL1 and α-SMA transcripts
↓IL-1b (lower in human AD-MSCs)
NC in IL-10
(Cahill et al. 2016) Bleomycin intranasal/mice 5 × 104 allogeneic or HGF knockdown BM-MSCs/g bodyweight intravenous ↓collagen deposition in the lung
↓mRNA expression of IL-1b in the lung
↓protection against fibrosis(treatment with HGF knockdown stem cell)
↓epithelial apoptosis in the lung
(Maria et al. 2016a) HOCl intradermic
(daily, 42 days)
2.5 × 105(the most efficient dose), 5 * 105, or 106 syngeneic BM-MSCs intravenous ↓skin thickness
↓total collagen content in the skin
↓of COL1, COL3, TGFβ1, and α-SMA in skin
↓Col3 and TGFβ1 in the lung(in a single dose injection on day21)
↓deposition of collagen in lung
↓less ECM deposition
↓cellular infiltration
↓serum AOPP production
↑serum antioxidant capacity
↓anti–Scl-70 antibody serum levels
  1. Scl-cGVHD Sclerodermatous chronic Graft Versus Host Disease, COL1A2 Collagen type I alpha 2 chain, miR Micro RNA, CAV-1 Caveolin-1, OSM Oncostatin M, BAL Bronchoalveolar lavage, Trx-1 Thioredoxin 1, FSP-1 Fibroblast-specific protein 1, HMGA High mobility group A, sRANKL Soluble Receptor Activator of Nuclear Factor, CFU-F Colony-Forming Unit–Fibroblastic, OCN Osteocalcin, ALP Alkaline phosphatase, Runx2 Runt-related transcription factor 2, LPL Lipoprotein Lipase, PPARγ Peroxisome Proliferator-Activated Receptor γ, TIMP1 Tissue Inhibitor of Metalloproteinase 1, MMP Matrix Metalloproteinases, α-SMA Alpha-Smooth Muscle Actin, AD Adipose, TNF-α Tumour Necrosis Factor Alpha, HGF Hepatocyte Growth Factor, BM Bone Marrow, IL Interleukin, HOCl Hypochlorous Acid, MSC Mesenchymal Stem Cell, COL Collagen, TGFβ Transforming Growth Factor beta, ECM Extracellular Matrix, AOPP Advanced Oxidation Protein Products, NC No Change