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Stem cell transplantation therapy for diabetic foot ulcer: a narrative review Cover

Stem cell transplantation therapy for diabetic foot ulcer: a narrative review

Open Access
|Feb 2021

Figures & Tables

Human studies using stem cell transplantation for the treatment of diabetic foot ulcer

Reference, countryNumber of patientsAdministration routeFollow-up durationTreatment durationCell typeDosageOutcome
Vojtaššák et al. [35] 2006, SlovakiaA 77-year-old diabetic patientInjected into the edges of the wound29 days7 days and 17 daysBM-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. [30] 2008, ChinaPatients were randomized into 22 cases (transplanted group) 23 controlsIntramuscular injections12 weeks3 weeksBM-MSCs7.32 × 108 to 5.61 × 109 at 3 cm × 3 cm long and 1–1.5 cm deepImproved:
  • Ulcer healing

  • ABI

  • Amputation rate

  • Rest pain

  • Angiogenesis

  • Intermittent claudication

Dash et al. [20] 2009, IndiaPatients were randomized into 3 cases and 3 controlsAround ulcer, covered by a dressing12 weeksEvery 2 weeksAutologous BM-MSCs>1 × 106 cells from 5.04 ± 0.70 cm2 to 1.48 ± 0.56 cm2Improved:
  • Walking interval without pain

  • Ulcer size decrease

  • No difference in the biochemical parameters

Lu et al. [34] 2011, ChinaPatients 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 weeks6 weeksBM-MSCs0.5–1 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. [31] 2011, IndiaPatients randomized into 25 cases and 23 controlsBorders of the wound in 4 distant sites from the middle and 4 additional intermediate equal positions between previous positions3 months2 weeksAutologous BM-MSC5 mL in 39.6–43.4 cm2Improved:
  • Wound healing

Kirana et al. [33] 2012, GermanyPatients were randomized to receive either BM-MNC (12) or BM-MSC enriched in CD90+ cells (12)Intramuscular injection52 weeks16 weeksAutologous BM-MSC50 × 106 cells a 3 cm × 5 cm area, 4 cm deepImproved:
  • 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. [36] 2018, ChinaA 54-year-old womanSubcutaneous injection of BM-MSCs and autologous platelet-rich gelOnce every 5–7 days30 daysAutologous BM-MSCsCell: 2 × 108/L at 2.5 cm × 1.5 cmImproved:
  • DFU healing

  • TcPO2

  • ABI

  • Biochemical evaluation and multiple tumor markers were normal

Li et al. [37] 2013, China15 patientsIntramuscular injections4 weeks12 weeksHUC-MSCs10 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, China28 cases and 12 controlsIntravenously injected3 month2 monthsHUC-MSCsStem 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 areaImproved:
  • 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, China28 cases and 25 controlsEndovascular injection and infusion encircling the foot ulcer2 weeks1–3 monthsHUC-MSCs4.8 × 107 to 8.6 × 107 cells in a 3 cm × 3 cm areaImproved:
  • 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, Korea28 cases and 26 controls Total 54 single-blindedSame-day procedure. Dispersed onto the wound and sealed with fibrinogen, thrombin, and Tegaderm8 weeks17.3 ± 8.5 daysThrough applying collagenase and centrifugation, the ADSC pellet was isolated (freshly isolated stem cells)Autografts 4.0 × 106 to 8.0 × 106 cells Donor site: abdomenImproved:
  • 100% of wounds in the case group and 62% in the control group healed in 8 weeks, with no adverse effects

Lee et al. [40] 2012, Korea3 diabetic patients60 intramuscular injections under spinal anesthesia. The interval between harvest and injection is not noted6 months7 daysSubcutaneous adipose used and digested using collagenase and centrifugation3 × 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 [41] 2013, Poland22 cases6 monthsADSC5 mLImproved:
  • 8 patients completely healed 9 patients with >50% reduction of ulcer area

  • No improvement in 5 patients

Marino et al. [42] 2013, Italy18 patientsUsing a 10 mL syringe with a 21 gauge needle at the edges of the ulcer; cells were injected at a depth of 1 cm3 months1 dayADSC5 mL (3 × 105 cells/mL)Improved:
  • Pain

  • 60% healing of the ulcer patient

Moon et al. [43] 2019, Korea30 cases (ADSC treatment group) and 29 controls (treated with polyurethane film)Applied directly to the wound bed2 years12 weeksAllogeneic ADSC5 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. [44] 2013, India5 patients with PAD and 4 diabetic ulcersIntramuscular approximately 10 separated sites with 5–8 cm space from each other14 months3 months(HSCs, CD34+) and UC-MSCs from the HUC bloodTotal 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 siteImproved:
  • Rest pains

  • Wound healing

  • Ulcer size

Tanaka et al. [45] 2014, Japan5 patientsIntramuscularly3 years12–26 weeks, average 18.8 weeks (131.6 days); 12 weeks post-therapy, if complete wound closure did not occur follow up continued every 4 weeksAutologous G-CSF mobilized peripheral blood CD34+ cells2 × 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 [46] 2016, China127 patientsSubcutaneous injections3 yearsGroup 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, respectivelyAutologous peripheral blood stem cell2 mL stem cell suspension fluid per marker pointImproved:
  • Collateral circulation

  • Blood supply to lower extremities

  • Pain in the affected limb

  • Cold sense of limbs

  • Clinical symptoms

  • Healing ulcers

  • Quality of life

DOI: https://doi.org/10.2478/abm-2021-0002 | Journal eISSN: 1875-855X | Journal ISSN: 1905-7415
Language: English
Page range: 3 - 18
Published on: Feb 21, 2021
Published by: Chulalongkorn University
In partnership with: Paradigm Publishing Services
Publication frequency: 6 issues per year

© 2021 Sahar Shafiee, Maryam Heidarpour, Sima Sabbagh, Elham Amini, Hanieh Saffari, Sara Dolati, Rokhsareh Meamar, published by Chulalongkorn University
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.