| 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:
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| 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:
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| 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:
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| 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:
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| 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:
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| 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:
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| 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:
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| 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:
Skin temperature
ABI
TcO2
Wound healing
Reduction in blood glucose and insulin requirement
Pain, weakness, feeling coldness, numbness, and intermittent limp
Normal blood pressure and blood lipid profile |
| 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 × 107Injected into the diseased limb from multipoint, 0.5–1.0 mL per point, 3 cm × 3 cm area | Improved:
ABI
Skin temperature
Claudication distance
Number of new vessels
Success rate of percutaneous transluminal angioplasty was 82%
Success rate for the treatment of stenosis was 88%
Success rate for the treatment of occlusion was 59% |
| 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:
Ulcer healing
ABI
TcPO2
Skin temperature
Claudication distance
New vessels
Not seen ulcer infection and sustain normal blood pressure, and heart function, blood glucose, and lipids
Treatment was not associated with any serious complications or adverse reactions |
| 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:
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| 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:
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| Masłowski [41] 2013, Poland | 22 cases | – | 6 months | – | ADSC | 5 mL | Improved:
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| 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:
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| 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:
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| 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:
Rest pains
Wound healing
Ulcer size |
| 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:
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| 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:
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