Table 3 Some of The MSC-based Animal Studies for Scleroderma
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 injection/mouse (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 ↑Bcl-2 ≠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 ↑CFU-F 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 ↓TNF-α ↓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 injection/mouse (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 |