Table 1
Human studies using stem cell transplantation for the treatment of diabetic foot ulcer
| Reference, country | Number of patients | Administration route | Follow-up duration | Treatment duration | Cell type | Dosage | Outcome |
|---|---|---|---|---|---|---|---|
| Vojtaššák et al. [35] 2006, Slovakia | A 77-year-old diabetic patient | Injected into the edges of the wound | 29 days | 7 days and 17 days | BM-MSCs with autologous skin fibroblasts on biodegradable collagen membrane | (3 × 106 of cells) were set onto a surface (25 mm × 50 mm) | Improved:
|
| Debin et al. [30] 2008, China | Patients were randomized into 22 cases (transplanted group) 23 controls | Intramuscular injections | 12 weeks | 3 weeks | BM-MSCs | 7.32 × 108 to 5.61 × 109 at 3 cm × 3 cm long and 1–1.5 cm deep | Improved:
|
| Dash et al. [20] 2009, India | Patients were randomized into 3 cases and 3 controls | Around ulcer, covered by a dressing | 12 weeks | Every 2 weeks | Autologous BM-MSCs | >1 × 106 cells from 5.04 ± 0.70 cm2 to 1.48 ± 0.56 cm2 | Improved:
|
| Lu et al. [34] 2011, China | Patients were randomized into 20 patients (BM-MSC group), 21 patients (BM-MNC group), and both groups have a 1 normal saline group as control (double-blind) | Intramuscular into the inferior limb (20 sites, 3 cm long, 1–1.5 cm deep, and 0.5–1 mL BM-MSCs or BM-MNCs in each site) | 24 weeks | 6 weeks | BM-MSCs | 0.5–1 mL BM-MSCs (20 sites, 3 cm × 3 cm in lengths, 1–1.5 cm in fundus) | Improved:
|
| Jain et al. [31] 2011, India | Patients randomized into 25 cases and 23 controls | Borders of the wound in 4 distant sites from the middle and 4 additional intermediate equal positions between previous positions | 3 months | 2 weeks | Autologous BM-MSC | 5 mL in 39.6–43.4 cm2 | Improved:
|
| Kirana et al. [33] 2012, Germany | Patients were randomized to receive either BM-MNC (12) or BM-MSC enriched in CD90+ cells (12) | Intramuscular injection | 52 weeks | 16 weeks | Autologous BM-MSC | 50 × 106 cells a 3 cm × 5 cm area, 4 cm deep | Improved:
|
| Wu et al. [36] 2018, China | A 54-year-old woman | Subcutaneous injection of BM-MSCs and autologous platelet-rich gel | Once every 5–7 days | 30 days | Autologous BM-MSCs | Cell: 2 × 108/L at 2.5 cm × 1.5 cm | Improved:
|
| Li et al. [37] 2013, China | 15 patients | Intramuscular injections | 4 weeks | 12 weeks | HUC-MSCs | 10 mL (1.6–2.4 × 106/mL 20 sites, 3 cm × 3 cm in intervals, 1–1.5 cm in-depth, 0.5–1 mL per site). 2 mL was also delivered into the basilar portions of foot ulcers and the surrounding subcutaneous tissues (2 × 106 cells in each point) | Improved:
|
| Qin et al. [38] 2013, China | 28 cases and 12 controls | Intravenously injected | 3 month | 2 months | HUC-MSCs | Stem cells 4.8 × 107 to 8.6 × 107 Injected into the diseased limb from multipoint, 0.5–1.0 mL per point, 3 cm × 3 cm area | Improved:
|
| Qin et al. [14] 2016, China | 28 cases and 25 controls | Endovascular injection and infusion encircling the foot ulcer | 2 weeks | 1–3 months | HUC-MSCs | 4.8 × 107 to 8.6 × 107 cells in a 3 cm × 3 cm area | Improved:
|
| Han et al. [39] 2010, Korea | 28 cases and 26 controls Total 54 single-blinded | Same-day procedure. Dispersed onto the wound and sealed with fibrinogen, thrombin, and Tegaderm | 8 weeks | 17.3 ± 8.5 days | Through applying collagenase and centrifugation, the ADSC pellet was isolated (freshly isolated stem cells) | Autografts 4.0 × 106 to 8.0 × 106 cells Donor site: abdomen | Improved:
|
| Lee et al. [40] 2012, Korea | 3 diabetic patients | 60 intramuscular injections under spinal anesthesia. The interval between harvest and injection is not noted | 6 months | 7 days | Subcutaneous adipose used and digested using collagenase and centrifugation | 3 × 108 ADSC (0.5 mL each, included 5 × 106 in 60 points) | Improved:
|
| Masłowski [41] 2013, Poland | 22 cases | – | 6 months | – | ADSC | 5 mL | Improved:
|
| Marino et al. [42] 2013, Italy | 18 patients | Using a 10 mL syringe with a 21 gauge needle at the edges of the ulcer; cells were injected at a depth of 1 cm | 3 months | 1 day | ADSC | 5 mL (3 × 105 cells/mL) | Improved:
|
| Moon et al. [43] 2019, Korea | 30 cases (ADSC treatment group) and 29 controls (treated with polyurethane film) | Applied directly to the wound bed | 2 years | 12 weeks | Allogeneic ADSC | 5 cm × 5 cm hydrogel sheet containing allogeneic ADSC (the number of ADSCs reached about 1 × 106 cells/sheet) | Improved:
|
| Viswanathan et al. [44] 2013, India | 5 patients with PAD and 4 diabetic ulcers | Intramuscular approximately 10 separated sites with 5–8 cm space from each other | 14 months | 3 months | (HSCs, CD34+) and UC-MSCs from the HUC blood | Total calculated UC-MSCs and CD34+ at 2 million/kg body weight in an 80:20 ratio Injection 1–1.5 mL was injected in each site | Improved:
|
| Tanaka et al. [45] 2014, Japan | 5 patients | Intramuscularly | 3 years | 12–26 weeks, average 18.8 weeks (131.6 days); 12 weeks post-therapy, if complete wound closure did not occur follow up continued every 4 weeks | Autologous G-CSF mobilized peripheral blood CD34+ cells | 2 × 107 CD34+ cells/patient was administered 20 injections, each injection containing 1 × 106 cells/0.25 mL saline (0.25 mL × 20 sites, 1.5–2.0 cm deep) | Improved:
|
| Xu and Liang [46] 2016, China | 127 patients | Subcutaneous injections | 3 years | Group A (n = 63), 16, 17, 16, and 14 patients were treated for 4, 5, 6, and 7 days, respectively. Group B (n = 64), 10 mg/kg/day Filgrastim through subcutaneous injections, 16, 17, 16, and 15 patients were treated for 4, 5, 6, and 7 days, respectively | Autologous peripheral blood stem cell | 2 mL stem cell suspension fluid per marker point | Improved:
|
[i] ABI, ankle-brachial index; ADSC, adipose-derived stem cell; BM-MNC, bone marrow mononuclear cell; BM-MSC, bone marrow mesenchymal stem cell; DFU, diabetic foot ulcer; G-CSF, granulocyte colony-stimulating factor; HSC, hematopoietic stem cell; HUC, human umbilical cord; HUC-MSC, human umbilical cord blood mesenchymal stem cell; TcPO2, transcutaneous oxygen pressure; UC-MSC, umbilical cord-derived mesenchymal stem cell.