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Table 3 Mesenchymal stem/stromal cells (MSC)-based therapy for common immune-mediated musculoskeletal disorders (animal studies)

From: Mesenchymal stem/stromal cells as a valuable source for the treatment of immune-mediated disorders

Condition Model Main consequences Ref
OA Sprague-Dawley rat Inhibition of OA progress by miR-140-5p-overexpressing synovial MSC (SMSC-140s) transplantation [167]
OA Cynomolgus monkey MSC migration into OA joint upon IV injection [168]
OA Mouse Pain reduction and cartilage damage rescue by MSC secretome [169]
RA Mouse Inhibition of inflammation upon suppression of TH17 differentiation by BM-MSC injection [170]
RA Mouse Alleviation of articular tissue inflammation and cartilage damage upon targeting IL-9 expression by MSCs [171]
OA Nude rat Induction of cartilage repair by synovial fluid- derived MSC (SF-MSC) intra-articular injections [172]
OA Beagle dogs OA rescue by AT-MSCs and platelet-rich plasma administration [173]
OA Rabbit Induction of cartilage protection by up regulation of expression of growth factors, ECM markers, and anti-inflammatory cytokines by MSC injection [174]
RA Mouse Modification of migration and invasion of FLS and inhibition of tube formation in HUVECs through affecting MMP14 and VEGF by MSC-derived miR-150-5p exosomes [175]
OA Rat Obstruction of central sensitization of pain and promotion of the expression of the anti-inflammatory and cartilage protective factor TSG-6 by MSC intra-articular injection [176]
OA Rat Hindrance of OA progression by keeping subchondral bone, supporting matrix homeostasis, and improving autophagy by balancing the ratio of MMP-13 to TIMP-1 in cartilage upon injection of conditioned medium of MSC (MSC-CM) [177]
RA Mouse Induction of a decrease in COMP, TIMP1, MMP1, IL-1R, TNF-α, MCP-1 gene expression by combination therapy of MSCs and IL-4 [178]
OA Mouse Attenuation of chondrocytes apoptosis by lncRNA-KLF3-AS1/miR-206/GIT1 axis upon MSC-derived exosome (MSC-Exo) injection [179]
RA Rat Attenuation of expression of RANKL mediated by reduction in the levels of IL-22, leading to alleviated bone destruction [180]
RA Rat Inhibition of the proliferation of T lymphocytes, downregulation of RORγt expression, reduction in Th17 cell ratio, promotion of Foxp3 expression, and elevated Treg cell ratio in the spleen of experimental models upon UC-MSC injection [181]
OA Rabbit Reduction of cartilage degeneration, osteophyte development, and subchondral sclerosis by intra-articular injection of MSC secretome [182]
RA Mouse Cartilage protective effects upon suppression of Th17 cell activation by CD146+ MSC transplantation [183]
OA Mouse Cartilage damage amelioration mediated by miR100-5p-associated inhibition of mTOR-autophagy pathway by MSC-Exo [184]
OA Horse Absence of significant efficacy of MSC transplantation [185]
RA Mouse Experimental RA recovery by suppressing miR-548e-mediated IκB inhibition upon MSC injection [186]
OA Sprague-Dawley rat Improving of cartilage repair and inhibition of OA progression through upregulation of collagen II (CII) by BM-MSC injection [187]
OA Mouse Inhibition of TNF-α-induced upregulation of matrix proteases and inflammatory cytokines upon intra-articular injection of MSC [188]
RA Mouse Inhibition of arthritis progression by a reduction in Tfh cells activation mediated by IDO upon MSC injection [189]
RA Mouse Inhibition of inflammation by a diminishment in TNF-α levels after administration of MSC-CM [190]
OA Fischer 344 rat Moderation of MMPs expression and CII degradation upon AT-MSC injection [191]
OA Rabbit Induction of cartilage tissue regeneration by hyaluronan-based scaffold (Hyaff11) seeded with BM-MSC implantation [192]
OA New Zealand rabbit Reduction of inflammatory cytokine levels and improvement of the level of biochemical environment in the articular cavity upon transplantation of UC-MSCs loaded with graphene oxide granular lubrication [193]
RA Porcine Establishing of new cartilage tissue by xenogenic hBM-MSC-derived chondroprogenitor scaffolds implantation [194]
OA Guinea pigs Significant cartilage repair upon intra-articular transplantation of hyaluronic acid (HA)-based scaffold seeded with MSCs [195]
OA C57BL/6J mice Supporting of the chondrocyte phenotype by promotion of CII synthesis and attenuation of ADAMTS5 expression in the presence of IL-1β by MSC-Exo injection [196]
RA Mouse Amelioration of OA symptoms by IDO upregulation upon embryonic stem cell-MSC injection [197]
OA Horse Diminution of inflammation in concomitant with upregulation of CII and TGF-β1 and downregulation of COX-2 and IL-1β in OA joints [198]
OA Rat Induction of reduced pain but not degenerative changes upon MSC injection [199]
RA Mouse Induction of T cell apoptosis by the FasL/Fas pathway following transplantation of gingival tissue-derived MSCs (GMSCs) [200]
RA Mouse Inhibition of RANKL-induced osteoclastogenesis and T cell responses together with enhancement in the peripheral regulatory T and B cells frequencies following AT-MSC injection [201]
RA Mouse Stimulation of macrophage polarization (M1 to M2 phenotype) and inhibition of inflammasome activation to restore RA by UC-MSC transplantation [202]
OA Sheep Reduction in PGE2, TNF-α and TGF-β levels in synovial fluid and promotion in aggrecan and CII levels and downregulation of MMP-13 expression after BM-MSC transplantation [203]
  1. Note: COMP cartilage oligomeric matrix protein, TIMP1 tissue inhibitor metalloproteinase-1, MMP1 matrix metalloproteinase1, IL-1R interleukin-1 receptor, FLS fibroblast-like synoviocytes, IDO indoleamine 2,3-dioxygenase, MMPs matrix metalloproteinases, CII type II collagen, TGF-β1 transforming growth factor β1, COX-2 cyclooxygenase-2, PGE2 prostaglandin E2, RANKL receptor activator of nuclear factor (NF)-kB-ligand, ADAMTS5 A disintegrin-like and metalloproteinase with thrombospondin-1 motifs5, mTOR mammalian target of rapamycin, lncRNA long non-coding RNAs, RORγ RAR-related orphan receptor gamma, Foxp3 Forkhead box P3, HUVECs human umbilical vein endothelial cells, TSG6 TNF-α-stimulated gene-6, OA osteoarthritis, RA arthritis rheumatoid, BM bone marrow, AT adipose tissue, UC umbilical cord