Table 2.
Autologous MSC-based clinical trials.
| MSC source | DM type | Age (years) | Time of DM | Number of patients | Number of injections/route of delivery | Number of cells injected | Follow-up (m) | Results | Adverse events | Ref |
|---|---|---|---|---|---|---|---|---|---|---|
| BM | 1 | <8 y | <2 m | 2 | Single dose, liver | 180 × 106/kg | 12 | ↑ C-peptide ↓ FBG, HbA1c Negative values of ICA, GAD and anti-insulin antibody levels |
None | [161] |
| BM | 1 | 18-40 y | <3 w | 10 treated with insulin and 10 treated with insulin+MSCs | Single dose, IV | 2.1-3.6 × 106/kg (median 2.75 × 106/kg) | 12 | ↑ C-peptide after mixed-meal tolerance test ↔ HbA1c, insulin dose, fasting C-peptide |
None | [162] |
| AT-ISC-MSC+BM-HSC ∗conditioning |
1 | Group 1: 20 ± 7 y Group 2: 20 ± 10 y |
Group 1: 8.1 ± 3.4 y Group 2: 9.9 ± 7.1 y |
Group 1: autologous AT-ISC-MSC+BM-HSC Group 2: allogeneic AT-ISC-MSC+BM-HSC from healthy nondiabetic donors (n = 10 each) |
Single dose, portal+intrathymus+SC | Group 1: AT-ISC-MSC-2.65 ± 0.8 × 104/kg Group 2: AT-ISC-MSC-2.07 ± 0.67 × 104/kg |
24 | Autologous versus allogeneic: (i) Allogeneic: ↓ insulin requirement up to 6 months and ↓ postprandial blood sugar from months 1-24 (ii) Autologous: ↑ C-peptide from months 15-24 (iii) Allogeneic = autologous: ↓ HbA1c, FBG, GAD antibody |
None | [157, 158] |
| BM | 2 | 30-60 y | ≥5 y | BM-MSC versus BM-MNCs versus control group (antidiabetic drugs) (n = 10 each) | Single dose, superior pancreatic-duodenal artery | MSCs: 1 × 106/kg MNCs: 1 × 107 |
12 | ↓ Insulin requirement ≥ 50% and HbA1c in 60% of individuals (BM-MSC and BM-MNC) ↔ HOMA indexes ↑ Insulin sensitivity index+insulin receptor substrate-1 gene expression in muscle (BM-MSC) ↑ Second phase C-peptide response during hyperglycaemic clamp (BM-MNCs) |
Nausea and vomiting (n = 2) | [163] |
| BM | 2 | 37-67 y (52.9 y) | 2-15 y (7.15 y) | NPR (n = 19) PR (n = 15) |
Single dose, IV | 3.0 × 106/kg | 6 | ↓ FBG, hypersensitivity C-reactive protein ↔ HbA1c, plasma IL-6 ↓ Macular thickness and improvement in best corrected visual acuity (proliferative retinopathy group) |
None | [164] |
AT-ISC-MSC: adipose-derived insulin-secreting mesenchymal stem cells; BM-HSCs: bone marrow-derived hematopoietic stem cells; BM-MNCs: bone marrow-derived mononuclear cells. Autoantibodies to β-cells: GAD65 (glutamic acid decarboxylase) and IA2 antibodies. FBG: fasting blood glucose; HbA1c: glycated haemoglobin; NPR: nonproliferative retinopathy; PR: proliferative retinopathy; SC: subcutaneous; IU: International Units; IV: intravenous; w: week; m: month; y: years.