Table 4  List of in vivo studies in which the therapeutic potential of the administration of hMSCs for the treatment of autoimmune disorders of the joints was evaluated and the results obtained.
References   Autoimmune disease   Source of hMSC   Variables   Experimental model   Clinical and laboratory effects   Proposed mechanisms for the in vivo action of MSCs
(80)  Rheumatoid arthritis  Bone marrow Menstrual blood  None  Mice  ↓Clinical score Effectiveness MSCs from bone marrow > effectiveness MSCs from menstrual blood  ↓CD8+IFN-γ+ cells↓CD4+IFN-γ+ Th1 cells↓Th17 cells in lymph nodes↑CD4+IL4+IL10+ Treg cells↑Tregs↑IDO↑PD-L1↑PGE2↑Activin A↑IL-5↑IL-10↑IL-13↑IL-6↓TNF-α (bone marrow MSCs)↑TNF-α (menstrual blood MSCs)↓Proinflammatory T cell frequency in the lymph nodes
(152)  Rheumatoid arthritis  Adipose tissue  None  Mice  ↓Clinical score↓Disease incidence  ↓CD4+TNF-α+IFN-γ+ Th1 cells↑CD4+IL-10+ Treg cells↑IL-10 in lymph nodes and joints↑CD4+CD25+FoxP3+ Treg cells↓CCL5 expression↓TNF-α↓IFN-γ↓IL-2↓IL-17↑IL-10↑TGF-β1↓Type II collagen autoantibody↓CXCL2
(153)  Rheumatoid arthritis  Adipose tissue  None  Mice  ↓Clinical score  ↓Pathogenic GM-CSF+CD4+ T cells in the spleen and peripheral blood↑FoxP3+CD4+ T cells in the draining lymph nodes↑IL10+IL17−CD4+ T cells in the draining lymph nodes↑IL-10+ Th17 cells in the draining lymph nodes
(157)  Rheumatoid arthritis  Embryonic stem cells  None  Mice  ↓Clinical score  ↑ CD4+FoxP3+ Treg cells↑ CD4+IFN-γ+ Th1 cells↑IDO1 gene
(158)  Rheumatoid arthritis  Bone marrow Adipose tissue Umbilical cord blood  None  Mice  ↓Clinical score↓Histopathology score Effectiveness bone marrow-derived MSCs = effectiveness adipose tissue-derived MSCs = effectiveness umbilical cord-derived MSCs  ↓IL-1β↓TNF-α↓IL-6↓IFN-γ↑IL-10↑TGF-β↑Treg cells
(86)  Rheumatoid arthritis  Adipose tissue  Administration of adipose tissue-derived MSCs aloneAdministration of adipose tissue-derived MSCs overexpressing CTLA4Ig  Mice  ↓Clinical score↓Serum C-Telopeptide I Effectiveness MSCs overexpressing CTLA4Ig > effectiveness MSCs alone  ↓Type II collagen autoantibody↓T-bet expression in splenocytes↓GATA-3 expression in splenocytes (in vitro)↑Treg/Th17(CD4+CD25+FoxP3+/ CD4+CD25+RORγt) cells ratio
(87)  Rheumatoid arthritis  Adipose tissue  None  Mice  ↓Clinical score↓Disease progression↓Bone destruction  ↑CD25+Foxp3+CD4+ cells regulatory T cells in spleen and draining lymph nodes↑CD4+IL-4+IL10+ Tr1 cells in spleen and draining lymph nodes
(89)  Rheumatoid arthritis  Umbilical cord bood  None  Mice  ↓Clinical score  ↑Shift from CD14+CD86+ M1 to CD14+CD206+ M2 macrophages↓NLRP3 inflammasome-mediated IL-1β secretion↓TNF-α↓IL-1β↓Caspase-1↑IL-10
(90)  Rheumatoid arthritis  Gingiva  None  Mice  ↓Clinical score↓Histopathology scores  ↓IFN-γ↓IL-17↑CD4+CD39+FoxP3+ Treg cells
(91)  Rheumatoid arthritis  Umbilical cord stroma  Administration of CD146+ MSCs Administration of CD146− MSCs  Mice  ↓Clinical score Effectiveness CD146+ MSCs > effectiveness CD146− MSCs  ↓IL-6↑Th17 cells
(92)  Rheumatoid arthritis  Bone marrow  Administration of MSCs transfected with recombinant minicircles encoding etanerceptAdministration of MSCs alone  Mice  ↓Clinical score Effectiveness of MSCs transfected with recombinant minicircles encoding etanercept > effectiveness of MSCs alone  ↓Th17 cells in spleen↓Osteoclastogenesis
(93)  Rheumatoid arthritis  Umbilical cord stroma  None  Mice  ↓Clinical score↓Histopathology score  ↓Th1 cells↓Th17 cells↓Serum levels of autoantibodies↓T follicular helper (Tfh) cells↑Treg cells↓Pathogenic IL17+IFN-γ+ T cells↓Pathogenic IL17+Foxp3+ T cells
(94)  Rheumatoid arthritis  Adipose tissue  None  Mice  ↓Clinical score  ↑IL-10↑TGF-β↑IDO↓Th17 cells↑Treg cells↓IFN-γ+CD4+ Th1 cells↓IL-17+CD4+ Th17 cells
(96)  Rheumatoid arthritis  Adipose tissue  None  Mice  ↓Clinical score↓Histopathology score  ↑Tregs expansion in the peripheral blood and spleen↓TNF-α↓IL-6↓IL-1β↑IL-10↓Type II collagen IgG antibody↓Type II collagen IgG2a antibody↓Proliferation of human primary T cells
(95)  Rheumatoid arthritis  Umbilical cord stroma  None  Rats  ↓Paw edema↓Clinical score Effectiveness umbilical cord-derived MSCs > effectiveness bone marrow-derived MSCs  ↓T-cell activation↑Tregs expansion
Bone marrow
(88)  Rheumatoid arthritis  Placenta  None  Rats  ↓Clinical score↓Histopathology scores  ↓TNF-α↓IFN-γ↑SOD↑GSH-Px↑T-AOC↑CD4+/CD8+ T-cell ratio
(97)  Rheumatoid arthritis  Umbilical cord stroma  None  Rats  ↓Clinical score↓Prothrombotic state  ↑CD4+CD25+ Tregs expansion↑Antithrombin↓IL-1β↓IL-17↓TNF-α↓VEGF↓Tissue factor
(98)  Ankylosing spondylitis  Bone marrow  None  Humans  ↑Proportion of patients who achieved ASAS20↑Proportion of patients who achieved ASAS40↑Mean ASAS20 duration↓Mean Ankylosing Spondylitis Disease Activity Score↓Mean Bath Ankylosing Spondylitis Functional Index  ↓Average total inflammation extent
Both the methodology employed and the results obtained by each article are represented in this table. IL-5, interleukin 5; Tr1 cells, type 1 regulatory T cells; CCL5, C-C motif chemokine ligand 5; CXCL2, C-X-C motif chemokine ligand 2; SOD, superoxide dismutase; GSH-Px, glutathione peroxidase; T-AOC, total antioxidant capacity; NLRP3, NACHT, LRR and PYD domains-containing protein 3; IgG2a, immunoglobulin G2a.