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Table 1 Trials about MSCs in RA, SLE, IBD

From: Research progress of the application of mesenchymal stem cells in chronic inflammatory systemic diseases

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)
[42, 102]
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 12 weeks
20% (combined remission), 70% (clinical response)
At 48 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]
  1. Bold indicates a decrease, italic indicates no significant change, and bold italic indicates an increase