Combined Transplantation of Mesenchymal Stem Cells and Endothelial Colony-Forming Cells Accelerates Refractory Diabetic Foot Ulcer Healing

Background. This study is aimed at investigating the effect of combined transplantation of umbilical cord mesenchymal stem cells (UCMSCs) and umbilical cord blood-derived endothelial colony-forming cells (ECFCs) on diabetic foot ulcer healing and at providing a novel therapy for chronic diabetic foot ulcer. Methods. We reported the treatment of refractory diabetic foot ulcers in twelve patients. Among them, five patients had two or more wounds; thus, one wound in the same patient was treated with cell injection, and other wounds were regarded as self-controls. The remaining seven patients had only one wound; therefore, the difference between the area of wound before and after treatment was estimated. The UCMSCs and ECFCs were injected into the wound along with topically applied hyaluronic acid (HA). Results. In this report, we compared the healing rate of multiple separate wounds in the same foot of the same patient: one treated with cell injection combined with topically applied HA-based hydrogel and was later covered by the hydrocolloid dressings, while the self-control wounds were only treated with conventional therapy and covered by the hydrocolloid dressings. The wound underwent cell injection showed accelerated healing in comparison to control wound within the first week after treatment. In other diabetic patients with only one refractory wound, the healing rate after cell transplantation was significantly faster than that before injection. Two large wounds healed without needing skin grafts after combination therapy of cell injection and HA. After four weeks of combination treatment, wound closure was reached in six patients, and the wounds of the other six patients were significantly reduced in size. Conclusions. Our study suggests that the combination of UCMSCs, ECFCs, and HA can safely synergize the accelerated healing of refractory diabetic foot ulcers.

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PHASE 1, OPEN-LABEL SAFETY STUDY OF UMBILICAL CORD LINING MESENCHYMAL STEM CELLS (CORLICYTE®) TO HEAL CHRONIC DIABETIC FOOT ULCERS

Case Medical Research ◽

10.31525/ct1-nct04104451 ◽

2019 ◽

Author(s):

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Umbilical Cord ◽

Diabetic Foot ◽

Phase 1 ◽

Foot Ulcers ◽

Diabetic Foot Ulcers ◽

Open Label ◽

Safety Study

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Emerging Diabetic Foot Ulcer Microbiome Analysis using Cutting Edge Technologies

Journal of Diabetes Science and Technology ◽

10.1177/1932296821990097 ◽

2021 ◽

pp. 193229682199009

Author(s):

Brian M. Schmidt

Keyword(s):

Diabetic Foot ◽

Foot Ulcer ◽

Diabetic Foot Ulcer ◽

Standard Of Care ◽

Molecular Techniques ◽

Foot Ulcers ◽

Care Practice ◽

Antibiotic Administration ◽

Diabetic Foot Ulcers ◽

Conventional Culture

One of the most prevalent complications of diabetes mellitus are diabetic foot ulcers (DFU). Diabetic foot ulcers represent a complex condition placing individuals at-risk for major lower extremity amputations and are an independent predictor of patient mortality. DFU heal poorly when standard of care therapy is applied. In fact, wound healing occurs only approximately 30% within 12 weeks and only 45% regardless of time when standard of care is utilized. Similarly, diabetic foot infections occur in half of all DFU and conventional microbiologic cultures can take several days to process before a result is known. DFU represent a significant challenge in this regard because DFU often demonstrate polymicrobial growth, become resistant to preferred antibiotic therapy, and do not inform providers about long-term prognosis. In addition, conventional culture yields may be affected by the timing of antibiotic administration and collection of tissue for analysis. This may lead to suboptimal antibiotic administration or debilitating amputations. The microbiome of DFU is a new frontier to better understand the interactions between host organisms and pathogenic ones. Newer molecular techniques are readily available to assist in analyzing the constituency of the microbiome of DFU. These emerging techniques have already been used to study the microbiome of DFU and have clinical implications that may alter standard of care practice in the near future. Here emerging molecular techniques that can provide clinicians with rapid DFU-related-information and help prognosticate outcomes in this vulnerable patient population are presented.

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Security and efficacy of intradermal injection of mesenchymal stem cells derivatives on chronic diabetic foot ulcers: a randomized controlled clinical trial

Cytotherapy ◽

10.1016/s1465324921002814 ◽

2021 ◽

Vol 23 (5) ◽

pp. S22

Author(s):

S.M. Becerra-Bayona ◽

V.A. Solarte-David ◽

C.L. Sossa ◽

L.C. Mateus ◽

J. Pereira ◽

...

Keyword(s):

Clinical Trial ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Diabetic Foot ◽

Intradermal Injection ◽

Foot Ulcers ◽

Controlled Clinical Trial ◽

Diabetic Foot Ulcers ◽

Randomized Controlled Clinical Trial ◽

Randomized Controlled

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The Influence of Arterial Calcification on Clinical Outcomes in Patients with Diabetic Foot Ulcer Complicated by Osteomyelitis Treated by Surgery

The International Journal of Lower Extremity Wounds ◽

10.1177/15347346211022587 ◽

2021 ◽

pp. 153473462110225

Author(s):

Marta Carmena-Pantoja ◽

Francisco Javier Álvaro-Afonso ◽

Esther García-Morales ◽

Yolanda García-Álvarez ◽

Aroa Tardáguila-García ◽

...

Keyword(s):

Clinical Outcomes ◽

Diabetic Foot ◽

Foot Ulcer ◽

Diabetic Foot Ulcer ◽

Arterial Calcification ◽

Foot Ulcers ◽

Diabetic Foot Ulcers ◽

Time To Recurrence ◽

Artery Disease ◽

Clinical Records

The aim of our study was to analyze the influence of radiographic arterial calcification (RAC) on clinical outcomes and wound healing in patients with diabetic foot ulcers complicated by osteomyelitis treated by surgery. We analyzed retrospectively the clinical records of 102 patients with diabetic foot osteomyelitis who underwent surgery at a specialized diabetic foot unit between January 2014 and December 2016. The clinical data of evolution until its complete epithelialization and a follow-up 1 year were reviewed, and after reviewing the radiological images, patients were classified into 2 groups: those with RAC and those without RAC. We analyzed several clinical features in both groups. The presence of RAC was associated with a greater time of healing (10.68 ± 7.24 vs 8.11 ± 4.50 weeks; P = .029) and shorter time to recurrence and reulceration (13.30 ± 9.25 vs 18.81 ± 11.63 weeks; P = .036). However, this association was not found for patients with mild and moderate peripheral artery disease (PAD), whose time of healing was 8.97 ± 4.51 weeks compared to 9.16 ± 6.39 weeks for patients without PAD; P = .864. The time of healing of diabetic foot ulcers complicated by osteomyelitis treated by surgery can be negatively affected by the presence of RAC even more than by the presence of mild and moderate ischemia. The presence of RAC may offer clinical guidance at the level of primary care though this would need thorough validation in future studies.

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The Diabetic Foot Ulcer Scale-Short Form (DFS-SF) comprehensively measures the impact of diabetic foot ulcers on patients' QOL

PharmacoEconomics & Outcomes News ◽

10.1007/bf03277107 ◽

2003 ◽

Vol 440 (1) ◽

pp. 10-10

Keyword(s):

Diabetic Foot ◽

Short Form ◽

Foot Ulcer ◽

Diabetic Foot Ulcer ◽

Foot Ulcers ◽

Diabetic Foot Ulcers ◽

The Impact

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Characterization Of Phyto-Synthesized Silver Nanoparticles And Their Antimicrobial Activity Against Diabetic Foot Ulcer Bacterial Isolates

International Journal of Pharma and Bio Sciences ◽

10.22376/ijpbs/lpr.2021.11.6.l88-96 ◽

2021 ◽

Vol 11 (6) ◽

pp. 88-96

Author(s):

Chhajed Shweta ◽

Arora Asha

Keyword(s):

Antimicrobial Activity ◽

Silver Nanoparticles ◽

Diabetic Foot ◽

Foot Ulcer ◽

Diabetic Foot Ulcer ◽

Lower Limbs ◽

Diffusion Method ◽

Foot Ulcers ◽

Diabetic Foot Ulcers ◽

Bacterial Isolates

Diabetic Foot Ulcer (DFU) is one of the major complications of Diabetes. Patients with Diabetic Foot ulcers have a high susceptibility to microbial infections and are the leading cause of hospitalization and amputation of lower limbs. In the era of increased prevalence of bacterial resistance and outbreak of resistant infectious diseases, it is very essential to develop effective therapeutic strategies towards multi-drug resistant pathogens. The antimicrobial properties of silver nanoparticles have been well studied, therefore their use in biomedicine and pharmacology is a trend. Herein we present the use of Phyto-mediated synthesized AgNPs for the treatment of diabetic foot ulcers by topical administration. The nanoparticles were synthesized by reducing silver nitrate using Terminalia chebula fruit extract. The nanoparticles were analyzed and characterized using UV-Visible Spectrophotometer, FTIR, XRD, SEM with EDAX, TEM, and DLS. The synthesized silver nanoparticles were assayed for antimicrobial activity against five Diabetic Foot Ulcer bacterial isolates i.e. Escherichia coli, Klebsiella Pneumoniae, Pseudomonas aeruginosa, Streptococcus aureus, and Bacillus subtilis. The bactericidal property of synthesized nanoparticles was analyzed by the Agar well diffusion method, which revealed the remarkable antimicrobial effects against all the selective pathogenic bacterial isolates of Diabetic foot ulcers in the present study. These results constituted the basis for further studies on the use of plant-based silver nanoparticles for the treatment of Diabetic Foot ulcers from different origins

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Role and effect of vein-transplanted human umbilical cord mesenchymal stem cells in the repair of diabetic foot ulcers in rats

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gmaa039 ◽

2020 ◽

Vol 52 (6) ◽

pp. 620-630 ◽

Cited By ~ 1

Author(s):

Rongfeng Shi ◽

Weishuai Lian ◽

Yinpeng Jin ◽

Chuanwu Cao ◽

Shilong Han ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Umbilical Cord ◽

Diabetic Foot ◽

Femoral Vein ◽

Foot Ulcer ◽

Diabetic Foot Ulcer ◽

Multipotent Mesenchymal Stromal Cells ◽

Diabetic Rat ◽

Human Umbilical Cord

Abstract Diabetic foot ulcer (DFU) is one of diabetic complications, which is frequently present and tormented in diabetes mellitus. Most multipotent mesenchymal stromal cells (MSCs) are capable of immune evasion, providing an allogeneic, ready-to-use, cell product option for therapeutic applications. The beneficial effect of MSCs for the treatment of a variety of traumatic injuries, such as open wounds, has been extensively explored. In this study, a rat DFU model was used to simulate the pathophysiology of clinical patients and to investigate the localization of human umbilical cord mesenchymal stem cells (hUC-MSCs) after intravenous transplantation and its role in DFU healing, so as to evaluate the potential of hUC-MSCs in the treatment of DFU. The diabetic rat model was established by streptozotocin injection, which was used to create full-thickness foot dorsal skin wounds to mimic DFU by a 6-mm skin biopsy punch and a Westcott scissor. The hUC-MSCs were transplanted through femoral vein, and the ulcer cicatrization situation and the fate of hUC-MSCs were evaluated. Our data suggest that intravenously transplantated hUC-MSCs have the ability to migrate and locate to the wound tissue and are helpful to wound healing in DFU rats, partly by regulating inflammation, trans-differentiation and providing growth factors that promote angiogenesis, cell proliferation and collagen deposition. Herein, we demonstrate that hUC-MSC transplantation is able to accelerate DFU healing in rats and transplantation of exogenous stem cells may be a potential strategy for clinical application in DFUs.

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Adipose-Derived Mesenchymal Stem Cells in the Treatment of Diabetic Foot Ulcers: A Review of Preclinical and Clinical Studies

Angiology ◽

10.1177/0003319720939467 ◽

2020 ◽

Vol 71 (9) ◽

pp. 853-863 ◽

Cited By ~ 2

Author(s):

Francisco Javier Álvaro-Afonso ◽

Irene Sanz-Corbalán ◽

José Luis Lázaro-Martínez ◽

Despoina Kakagia ◽

Nikolaos Papanas

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Diabetic Foot ◽

Clinical Studies ◽

Optimal Dose ◽

Arterial Disease ◽

Therapeutic Angiogenesis ◽

Foot Ulcers ◽

Diabetic Foot Ulcers ◽

Safe Alternative

This review provides an outline of the use of adipose-derived mesenchymal stem cells (AMSCs) in the treatment of diabetic foot ulcers (DFUs). A systematic search of PubMed and the Cochrane database was performed on October 2, 2019. Eighteen studies were identified (14 preclinical and 4 clinical). Studies in animal models have demonstrated that AMSCs enhance diabetic wound healing, accelerate granulation tissue formation, and increase reepithelialization and neovascularization. Only 1 randomized control trial has been published so far. Patients (n = 25) with DFUs were treated using an allogeneic AMSC directly on the wound bed as a primary dressing, and improvements were found in complete wound closure in the treatment group (n = 16). Three clinical studies showed that autologous AMSC might be a safe alternative to achieve therapeutic angiogenesis in patients with diabetes and peripheral arterial disease. Based on the available evidence, AMSCs hold promise in the treatment of DFUs. However, this evidence requires confirmation by well-designed trials. Additional studies are also required to understand some issues regarding this treatment for DFUs. For example, the potential application of autologous or allogeneic AMSCs in different types of DFUs, optimal dose/infusion schedules, safety evaluations, and cost-effectiveness.

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Prevention and treatment of diabetic foot ulcers

Journal of the Royal Society of Medicine ◽

10.1177/0141076816688346 ◽

2017 ◽

Vol 110 (3) ◽

pp. 104-109 ◽

Cited By ~ 40

Author(s):

Jonathan Zhang Ming Lim ◽

Natasha Su Lynn Ng ◽

Cecil Thomas

Keyword(s):

Diabetic Foot ◽

Healthcare Access ◽

Foot Ulcer ◽

Diabetic Foot Ulcer ◽

Foot Ulcers ◽

Diabetic Patients ◽

Diabetic Foot Ulcers ◽

Foot Care ◽

Healthcare Provision ◽

Foot Complications

The rising prevalence of diabetes estimated at 3.6 million people in the UK represents a major public health and socioeconomic burden to our National Health Service. Diabetes and its associated complications are of a growing concern. Diabetes-related foot complications have been identified as the single most common cause of morbidity among diabetic patients. The complicating factor of underlying peripheral vascular disease renders the majority of diabetic foot ulcers asymptomatic until latter evidence of non-healing ulcers become evident. Therefore, preventative strategies including annual diabetic foot screening and diabetic foot care interventions facilitated through a multidisciplinary team have been implemented to enable early identification of diabetic patients at high risk of diabetic foot complications. The National Diabetes Foot Care Audit reported significant variability and deficiencies of care throughout England and Wales, with emphasis on change in the structure of healthcare provision and commissioning, improvement of patient education and availability of healthcare access, and emphasis on preventative strategies to reduce morbidities and mortality of this debilitating disease. This review article aims to summarise major risk factors contributing to the development of diabetic foot ulcers. It also considers the key evidence-based strategies towards preventing diabetic foot ulcer. We discuss tools used in risk stratification and classifications of foot ulcer.

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