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