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

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]