Stem cell transplantation therapy for diabetic foot ulcer: a narrative review
, , , , , y | 21 feb 2021
Article Category: Review
Publicado en línea: 21 feb 2021
Páginas: 3 - 18
DOI: https://doi.org/10.2478/abm-2021-0002
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© 2021 Sahar Shafiee et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Human studies using stem cell transplantation for the treatment of diabetic foot ulcer
| Vojtaššák et al. [ |
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:
Vascularity of the dermis Dermal thickness of the wound Wound size |
| Debin et al. [ |
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:
Ulcer healing ABI Amputation rate Rest pain Angiogenesis Intermittent claudication |
| Dash et al. [ |
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:
Walking interval without pain Ulcer size decrease No difference in the biochemical parameters |
| Lu et al. [ |
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:
The ulcer healing rate of the BM-MSC group significantly higher than that of BM-MNCs Painless walking time ABI TcPO2 Increased collateral vessels with magnetic resonance angiography Lower limb perfusion Ulcer healing Blood pressure |
| Jain et al. [ |
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:
Wound healing |
| Kirana et al. [ |
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:
Wound healing 83% in the BM-MNC group and 80% in the BM-MSC group ABI TcPO2 Angiogenesis detected in 7 of the BM-MSC group |
| Wu et al. [ |
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:
DFU healing TcPO2 ABI Biochemical evaluation and multiple tumor markers were normal |
| Li et al. [ |
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). |
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. [ |
28 cases and 12 controls | Intravenously injected | 3 month | 2 months | HUC-MSCs | Stem cells 4.8 × 107 to 8.6 × 107 |
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. [ |
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. [ |
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:
100% of wounds in the case group and 62% in the control group healed in 8 weeks, with no adverse effects |
| Lee et al. [ |
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:
100% chronic wound healing Pain rating score Claudication walking distances (in 5 patients) |
| Masłowski [ |
22 cases | – | 6 months | – | ADSC | 5 mL | Improved:
8 patients completely healed 9 patients with >50% reduction of ulcer area No improvement in 5 patients |
| Marino et al. [ |
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:
Pain 60% healing of the ulcer patient |
| Moon et al. [ |
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:
Faster complete wound closure |
| Viswanathan et al. [ |
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. [ |
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:
Complete wound closure was observed for all patients with no major amputation No severe adverse events occurred during or after cell therapy |
| Xu and Liang [ |
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. |
Autologous peripheral blood stem cell | 2 mL stem cell suspension fluid per marker point | Improved:
Collateral circulation Blood supply to lower extremities Pain in the affected limb Cold sense of limbs Clinical symptoms Healing ulcers Quality of life |