Table 3.
Allogeneic MSC-based clinical trials.
| MSC source | DM type | Age | Time of DM | Number of patients | Number of injections/route of delivery | Number of cells injected | Follow-up (m) | Results | Adverse events | Ref |
|---|---|---|---|---|---|---|---|---|---|---|
| AT-ISC-MSC+HSC ∗Conditioning |
1 | 13-43 y (21 y) | 1-24 y (8.2 y) | 11 | Single dose, omental vein | Mean total cell quantum transplanted: 96.3 ml (92-118 ml) HSC: 28 × 103/μl (12.2- 62.7 × 103/μl) MSC: 1.2 × 103/μl (0.5-2.1 × 103/μl) |
23 | ↓ Insulin requirement, HbA1C ↑C-peptide |
None | [156] |
| Placental | 2 | 45-82 y (66 y) | 3-20 y (11 y) | 10 | Single dose, IV | 1.35 × 106/kg (1.22-1.51 × 106/kg) | 3 | ↓ Insulin requirement, HbA1c ↑ C-peptide, insulin |
None | [165] |
| Wharton's jelly-MSC | 1 | Group 1 (MSC): 17.6 ± 8.7 y Group 2 (saline): 18.2 ± 7.9 y |
Newly onset | 29 Group 1: n = 15 Group 2: n = 14 |
Two doses (4 weeks apart), IV | 2.6 ± 1.2 × 107 (1.5-3.2 × 107) | 21 | ↔ FBG, GAD antibody ↓ Insulin requirement, postprandial glucose, HbA1c ↑ C-peptide, C-peptide/glucose ratio |
None | [166] |
| Wharton's jelly-MSC | 2 | 52.9 ± 10.5 y | 8.7 ± 4.3 y | 22 | One dose IV and one dose intrapancreatic | 1 × 106/kg | 12 | ↓ FBG, postprandial glucose, HbA1c, insulin requirement ↑ C-peptide, HOMA-β ↓ Serum CD3+ and CD4+ lymphocytes ↔ Serum CD8+ lymphocytes ↓ Serum IL-6, IL-1β ↔ Serum TNF-α and IL-10 |
Fever (n = 3), hematoma (n = 1), nausea, vomiting, headache (n = 1) | [167] |
| BM (rexlemestrocel-L) ∗eGFR: 20-50 ml/min/1.73 m2 |
2 | Placebo: 74.8 ± 7.9 y Lower dose MSCs: 70.5 ± 7.4 y Higher dose MSCs: 64.8 ± 10.1 y |
Time of DM: N/A | 30 (n = 10 each) | Single dose, IV | 150 × 106/kg (lower dose) or 300 × 106/kg (higher dose) | 12 | ↔ eGFR, albuminuria ↔ Lipid profile ↔ Blood pressure ↔ Serum C-reactive protein, TNF-α ↓ Serum IL-6 |
None | [155] |
| UC+autologous BM-MNC | 1 | Standard care: 13-27 y (20.4 y) Cell therapy: 5-28 y (18.3 y) |
Standard care: 2-13 y (7.0 y) Cell therapy: 2-16 y (9.2 y) |
42 (n = 21 each) | Single dose of each cell, dorsal pancreatic artery | UCB: 1.1 × 106/kg BM-MNCs: 106.8 × 106/kg |
12 | Cell therapy versus standard care: ↑ AUC of C-peptide ↑ AUC of insulin ↓ FBG, HbA1c ↓ Fasting C-peptide ↓ Insulin requirement ↓ Anxiety score ↓ Depression score ↑ Quality of life |
Upper respiratory tract infection (n = 7), bleeding (n = 1), abdominal pain (n = 1) | [168] |
AT-ISC-MSC: adipose-derived insulin-secreting mesenchymal stem cells; AUC: area under the curve; BM-HSCs: bone marrow-derived hematopoietic stem cells; BM-MNCs: bone marrow-derived mononuclear cells; FBG: fasting blood glucose; eGFR: estimated glomerular filtration rate; HbA1c: glycated haemoglobin; IV: intravenous; IU: International Units; m: month; NPR: nonproliferative retinopathy; PR: proliferative retinopathy; SC: subcutaneous; ZO-1: zonula occludens-1; y: years.