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. 2023 Nov 7;24(22):16040. doi: 10.3390/ijms242216040

Table 4.

Clinical experience of MSCs transplantation in autoimmune diseases. A description of clinical studies of MSCs from different sources (including bone marrow (BM); umbilical cord (UC); adipose-tissue (AT)) and their application as a treatment of patients with autoimmune and autoinflammatory disorders using the following indicators of the efficacy: American College of Rheumatology 20% improvement criteria (ACR20);anti-cyclic citrullinated peptide (anti-CCP); anti-double-stranded DNA (anti-dsDNA); alkaline phosphatase (ALP); amyotrophic lateral sclerosis functional rating scale (ALSFRS); alanine transaminase (ALT); British Isles Lupus Assessment Group (BILAG); Derriford appearance scale (DAS24); 28-joint disease activity score (DAS28); Expanded Disability Status Scale (EDSS); gadolinium-enhancing lesions (GEL); gamma-glutamyl transferase (GGT); hospital anxiety and depression scale (HADS); health assessment questionnaire (HAQ); hepatitis B virus (HBV); hepatitis C virus (HCV); interleukin (IL); Model for End-Stage Liver Disease (MELD); magnetic resonance imaging (MRI); Systemic Lupus Erythematosus Disease Activity Index (SLEDAI); tumour necrosis factor-α (TNFα); visual analogue scales (VAS).

Disease Patients
(N)		 MSC Type Outcomes Reference
Steroid-refractory acute graft-versus-host disease 55 Allogeneic BM-MSCs

  • More than half of the patients responded to the treatment measured by improvement in symptoms of acute GVHD.

  • Patients had no side-effects.

 [144]
Acute graft-versus-host disease resistant to multiple immunosuppressive agents in children 75 Allogeneic BM-MSCs

  • The rate of overall response (complete and partial response) was 66.7% for GVHD grade B, 76.2% for grade C, and 53.3% for grade D.

  • Response for individual organs was 58.5% for the gastrointestinal system, 75.6% for the skin, and 44.4% for the liver.

  • Overall response for patients treated for severe refractory GVHD was 61.3%, and this response was correlated with statistically significant improved survival at day +100 after MSC infusion.

 [143]
Steroid-refractory acute graft-versus-host disease III/IV after hematopoietic stem cell transplantation 46 Allogeneic BM-MSCs

  • Clinical improvement in 50% (23/46) of patients: three patients (13%) had complete response, fourteen (61%) had partial response, and six (26%) had transient partial response.

  • The estimated probability of survival at 2 year was 17.4%.

  • Two patients (4.3%) presented acute transient side effects (nausea/vomiting and blurred vision) during cell infusion.

  • No late or severe side effects.

 [145]
Multiple sclerosis 20 Allogeneic UC-MSC

  • Improvement in EDSS scores (p < 0.03).

  • Reduction in bladder, bowel, and sexual. dysfunction (p < 0.01), in non-dominant hand average scores (p < 0.01), in walk times (p < 0.02).

  • MRI scans of the brain and the cervical spinal cord showed inactive lesions in 83.3% (15/18) patients after 1 year.

 [151]
Multiple sclerosis 9 patients received MSCs (N = 5) or placebo (N = 4) Autologous BM-MSCs

  • Patients treated with MSCs had lower mean cumulative numbers of GEL on MRI than in a placebo group after 6 months and reduced mean GEL after 12 months.

  • Non-significant decrease in the frequency of Th1 (CD4+IFNγ+) cells in blood of MSCs treated patients.

  • No serious adverse events.

 [152]
Secondary progressive multiple sclerosis 10 patients had low-dose (1 × 106 cells/kg) and 9 high-dose (4 × 106 cells/kg) Autologous AT-MSCs

  • One serious adverse event (one urinary infection—not related to study treatment).

  • Measures for 12 months of treatment effect based on EDSS score and MRI were non-significant.

 [153]
Amyotrophic lateral sclerosis 23 Autologous BM-MSCs

  • Reduction of ALSFRS decline at 3 months after application, in a few cases persisted for 6 months.

  • 80% of the patients had stable forced vital capacity for a time period of 9 months and 60% of patients at 12 months after application.

  • Weakness scales (WSs) remained stable in 75% of the patients at 3 months after application.

 [154]
Amyotrophic lateral sclerosis 20 Autologous BM-MSCs

  • Statistically significant improvement in ALSFRS score.

  • Improvement in forced vital capacity but insignificantly.

  • Thirteen patients showed a 25% improvement in the slope of progression of ALSFRS-R (mean improvement of 47.4%, p < 0.0038).

  • Three patients had an improvement of less than 25%.

  • Three patients had a deterioration.

  • No serious adverse events.

 [155]
Rheumatoid arthritis 53 Allogeneic AT-MSCs

  • Persistent clinical benefit measured by ACR20, ACR50, low disease activity.

 [156]
Rheumatoid arthritis 64 Allogeneic UC-MSC

  • The level of ESR, CRP, RF of 1 year and 3 years after treatment decreased.

  • Anti-CCP of 3 years after treatment decreased.

  • Health index (HAQ) and joint function index (DAS28) were lower 1 year and 3 years after treatment than before treatment.

  • Liver and kidney function and immunoglobulin examination were normal.

 [157]
Systemic lupus erythematosus with refractory cytopenia 35 BM-MSC

  • Significant improvement in leukopenia, anaemia, or thrombocytopenia.

  • Reduction in proteinuria, antinuclear antibodies, and anti-dsDNA antibodies.

  • Decline in disease activity according to SLEDAI score.

  • Increase Treg, decrease Th17.

 [158]
Systemic lupus erythematosus (severe and drug-refractory) 81 Allogeneic 22 BM-MSC,
59 UC-MSCs

  • 84% survival rate (68/81 patients) after MSC.

  • 27% of patients (22/81) in complete clinical remission.

  • 7% (6/81) in partial clinical remission.

  • 5-year overall rate of relapse of 24% (9/37).

  • Serum albumin, peripheral leucocytes, and platelet number levels improved during fifth year of follow up.

  • Decline in disease activity according to SLEDAI and remained significantly lower (p < 0.05) 5 years after MSC.

  • Serum levels of complement three significantly increased (p < 0.05).

  • 24-h proteinuria significantly decreased at 1-, 2-, 3-, 4-, and 5-year follow-up (all p < 0.05).

 [159]
Lupus nephritis 18 patients received MSCs (N = 12) or placebo (N = 6) Allogeneic UC-MSCs

  • Remission occurred in 75% of patients (9/12) in the UC-MSC group, in comparison to 83% of patients (5/6) in the placebo group.

  • Mean time to remission was 9 weeks for the UC-MSC group and 16 weeks for the placebo group.

  • 3.2-fold reduction in proteinuria at 6 months in the UC-MSC group compared with 1.4-fold reduction in proteinuria in the placebo group.

  • Improvement in the SLEDAI and BILAG scores, anti-dsDNA antibody, and ANA and serum C3 and C4 concentrations with no difference between groups.

  • Serum creatinine remained stable in both groups.

 [160]
Systemic sclerosis 14 Allogeneic UC-MSCs

  • Reduction of modified Rodnan skin score.

  • Improvement in lung function and computed tomography after 12 months of combined therapy.

  • Decrease in the anti-Scl70 autoantibody, TGFβ, and vascular endothelial growth factor.

 [161]
Systemic sclerosis 62 Autologous AT-MSCs

  • Significant 22% improvement in mouth function.

  • Improvement in the psychological status: 15% decrease in VAS and 22% decrease in DAS24 scores.

  • Decrease in the level of psychological distress related to physical appearance: 27% improvement in HADS-A score that measures levels of anxiety, 24% decrease in HADS-D score that measures levels of depression.

  • Reduction in SSc fibroblast viability and proliferation was significant after 14 days of co-culture with AT-MSCs.

  • Decrease in TGFβ1 and connective tissue growth factor in co-culturing SSc fibroblasts with AT-MSCs.

  • Decrease in Matrix metalloproteinase-8, Platelet derived growth factor-β, and Integrin Subunit Beta-6 in SSc co-culture with AT-MSCs compared to monoculture after 14 days.

 [162]
Liver cirrhosis caused by autoimmune diseases (mixed connective tissue disease, primary biliary cirrhosis, primary Sjögren’s syndrome, rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis) 26 Allogeneic
(23 patients received UC-MSCs, 2 received cord blood MSCs and 1—BM-MSCs)

  • ALT, ALP, GGT, and total bilirubin decreased.

  • Average serum albumin levels improved.

  • Improvement in Model for End-Stage Liver Disease (MELD) scores.

 [163]
Idiopathic pulmonary fibrosis 8 Allogeneic placenta-derived MSCs

  • Slight improvement in all spirometry tests.

  • Fibrosis scores were unchanged—no evidence of worsening fibrosis.

 [164]
Idiopathic pulmonary fibrosis 9 Allogeneic BM- MSCs

  • No serious adverse events.

  • Two nontreatment-related deaths occurred because of progression of IPF (disease worsening and/or acute exacerbation).

  • Recorded 3.0% mean decline in % predicted forced vital capacity and 5.4% mean decline in % predicted diffusing capacity of the lungs for carbon monoxide by 60 weeks after MSC transplantation.

 [165]
COVID-19 7 (1 critically severe type, 4 severe types and 2 common types) Autologous BM-MSCs

  • The pulmonary function and symptoms of all patients were significantly improved at 2 days after transplantation.

  • Two common and one severe patient were recovered.

  • Peripheral lymphocytes level increased.

  • CRP decreased.

  • Overactivated cytokine-secreting immune cells CXCR3+CD4+ T-cells, CXCR3+CD8+ T-cells, and CXCR3+ NK cells disappeared in 3–6 days.

  • CD14+CD11c+CD11bmid regulatory DC cell population increased.

  • The level of TNF-α decreased, while the level of IL10 increased.

 [166]