Table 1 Trials about MSCs in RA, SLE, IBD
MSC source | No. of patients | Dosage and usage | Result | Adverse events | Indicatora | References |
|---|---|---|---|---|---|---|
hUC- MSCs | 63 RA | 1 × 106 cells/kg intravenous infusion | 53.3% (MSCT), 93.3% (MSCT+IFN-γ) in 3-month follow-up | No safety issues in 1-year follow-up | HAQ, DAS28, ESR, CRP, RF, Tregs/Th17 anti- CCP | [37] |
UCMSCs | 105 RA | 1 × 106 cells/kg intravenous infusion | 53.85% in 3-month follow-up, last for 48 weeks | No serious adverse events | HAQ, DAS28, platelet, Treg/Th17, IL-6, TNF-α anti-CCP, RF, IL-1β, IL-2R, IL-8 hemoglobin, albumin, IL-10, IFN-γ | [58] |
adMSCs | 110 CIA animal model | 1 × 106/mouse intravenous infusion (tail vein) | 14 days |  | GM-CSF+CD4+T, Lag3+Tr1 Tregs, Tr1, (Tregs+Tr1)/GM-CSF+CD4+T | [64] |
hUCB-MSCs | 9 RA | 2.5 × 107, 5 × 107, 1 × 108 cells intravenous infusion | 4 weeks | no short-term safety concerns | DAS28, IL-1β, IL-6, IL-8, TNF-α (in 1 × 108 group), ESR VAS, HAQ, ALT, ANC, AST,BUN,hs-CRP,MTX,WBC, Creatinine, Glucose, Triglyceride, Albumin, Albumin, Total protein IL-10 (in 5 × 107 group), Uric Acid | [60] |
UC-MSC | 64 RA | 4 × 107 cells/RA intravenous injection | 1 year 3 years | 4% showed flu-like symptoms | DAS28, HAQ, ESR, CRP, RF, globulin, Platelet (1 year, 3 year) anti-CCP (3 year) TP, ALB, WB, MCV | [61] |
BMSC | 30 RA | 4 × 107cells /joint intra-articular knee implantation | 12 months | pain /articular swelling and other minor adverse events | WOMAC, time to jelling and pain-free walking distance, MTX and prednisolone intake DAS 28, ESR, CRP, MRI imaging score | [62] |
BM-MSCs/ UC-MSC | 81 SLE | 1 × 106 cells/kg intravenous infusion | 34% (remission for 5 years) 84% (survival rate for 5 years) 24% (relapse within 5 years) | renal dysfunction, diarrhea, infection, myocardial infarction, diabetes | proteinuria C4, serum urea nitrogen, creatinine, and uric acid albumin, C3, WBC, hemoglobin, platelet | [59] |
BM-/UC-MSCs | 69 SLE | 1 × 106 cells/kg intravenous infusion | 58%(LDA) 23%(remission) |  |  | [80] |
hUC-MSC | 18 LN | 2 × 108 cells intravenous infusion | 75%(remission) | leucopenia, pneumonia, subcutaneous abscess |  | [82] |
BM-/UC-MSCs | 35 SLE | 1 × 106 cells/kg intravenous infusion | 24 months | no adverse events | SLEDAI, Th17 WBC, platelet, Hb, Tregs, Treg/Th17 | [79] |
hBM-MSCs | NZB/W mice | 1 × 106 cells/mouse/injection at 17, 19, and 21 weeks of age etro-orbital injection of the venous sinus |  |  | anti-dsDNA urinary albumin, Th 1Th2, Th17, Tregs | [27] |
UC-MSCs | 30SLE | 1 × 106 cells/kg intravenous infusion | 12 months |  | Th17,IL-17,TNF-α, IL-6, IL-17A Treg, Foxp3, TGF-β | [21] |
adMSC/iMSC | DSS | 1 × 106 cells at 10, 13, 16 day tail vein infusion |  |  | F4/80+, CD11b+macrophages CD103+monocytes CD3+T cells, CD4+T cells Ki-67+intestinal epithelial cells LGR5+intestinal stem cells CD31+endothelium FOXP3+Tregs (in tissue) | [41] |
hBM-MSCs | IL-10 − / − mice | 5 × 105 cells 0, 1 week tail vein infusion |  |  | ROS, lipid MDA formation, INF-γ, TNF-α, IL-4, CD8, p-NF-kB, type I collagen, CD4, SOD2 Catalase, SOD1 (in tissue) | [99] |
hBM-MSCs | DSS | 5 × 106 cells 1, 2, 3 day tail vein infusion |  |  | IL17A+ Th17, IFN-γ+ Th1 FOXP3+Tregs, IL4+Th2 (in PB, tissue) Ki-67+intestinal epithelial cells LGR5+intestinal stem cells CD31+endothelium (in tissue) | [38] |
IBM-MSCs | DSS | 1 × 106 cells 7 day injected intraperitoneally |  |  | IL-6, TNF-α, IFN-γ, IL-17A IL-10 (in tissue) | [13] |
IBM-MSCs | TNBS | 1 × 106 cells 7 day injected intraperitoneally |  |  | SAA, TNF-α, IL-6, IFN-γ IL-17A, IL-10 (in tissue) | [13] |
adMSCs | TNBS | 1 × 106 cells 1, 2 day injected intraperitoneally |  |  | TNF-α, IFN-γ, IL-6, IL-1β, and IL-12, RANTES, macrophage inhibitory protein 2,Th1 IL-10, Treg (in tissue) | [100] |
adMSCs | TNBS | 3 to 5 × 106 cells injected intraperitoneally |  |  | TNF-α, IL-12, IL-6, IL-23, IL-21, IFN-γ IL-17A IL-10, TGF-β (in serum) Th1, Th17 Th2 CD5+Breg (in spleen, MLN) | [101] |
P-MSCs | EF | 1 × 106 cells intralesional injection |  |  | IL-1β, IL-6, TNF-α, IFN-γ, ROS IL-10, TGF-β, VEGF, Ang-2 (in tissue) | [98] |
adMSCs | 24 CD with fistulas | 2 × 107 cells intralesional injection | At 24 weeks 69.2% (response) 56.3% (some fistulas close) 30% (all fistula close) | anal abscess (12.5%) pyrexia (4.17%) uterine leiomyoma (4.17%) | MSS, PDAI CDAI | [103] |
BM-MSCs | 15 CD with fistulas | 1 × 107, 3 × 107, 9 × 107 cells intralesional injection | At 12 weeks 40.0%, 80.0%, 20.0% (all fistula close) At 24 weeks 80.0% (1 × 107) Follow-up by 4 years 63.0%, 100%, 43.0% (closed fistula) | Fever anal pain pus blood from the fistula or anus | PDAI, IL-8, IL-1β, IL-6 IL- 10, TNF, IL-12p70 (cannot be detected) | |
autologous MSC | 12 CD with fistulas | 2 × 107 cells intralesional injection | At 24 weeks 83% (all fistula close) | no related adverse events |  | [105] |
autologous ADSVF | 10 CD with fistulas | intralesional injection | At 12Â weeks 20% (combined remission), 70% (clinical response) At 48Â weeks 60% (combined remission), 80% (clinical response) | Flares fistula tract | PDAI CRP, fibrinogen, WBC SIBDQ | [106] |
adMSCs | 212CD with fistulas | 1.2 × 108 cells intralesional injection | 50% (remission) 17% (adverse events) | anal abscess proctalgia | PDAI IBDQ, CDAI, time to combined remission, relapse, time to relapse, van Assche score | [104] |
BM-MSCs | 12CD | 2 × 106, 5 × 106, 10 × 106 cells/kg intravenous infusion | 12-weeks | acute appendicitis, C. difficile colitis |  | [43] |
UC-MSCs | 82 CDAI 220–450 | 1 × 106 cells/kg intravenous infusion | No patient achieved complete remission (CDAI < 150) | upper respiratory tract infection | CDAI, HBI, and corticosteroid dosage Blood cell count. Liver and renal function | [107] |
BM-MSCs | 13 CDAI 220–450 | 1.5 to 2.0 × 106 cells/kg at weeks 0 and 4 intravenous infusion | At week 12 15.4% (clinical response) 7.7%(remission) | no related adverse events | CDAI, CRP, FC, Treg, CD4+T, CD8+T, B, IgA/G/M NK%, NKT% | [96] |