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

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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An open‐label trial of cryopreserved human umbilical cord in the treatment of complex diabetic foot ulcers complicated by osteomyelitis

Wound Repair and Regeneration ◽

10.1111/wrr.12754 ◽

2019 ◽

Vol 27 (6) ◽

pp. 680-686 ◽

Cited By ~ 4

Author(s):

William A. Marston ◽

John C. Lantis ◽

Stephanie C. Wu ◽

Aksone Nouvong ◽

Tommy D. Lee ◽

...

Keyword(s):

Umbilical Cord ◽

Diabetic Foot ◽

Foot Ulcers ◽

Human Umbilical Cord ◽

Diabetic Foot Ulcers ◽

Open Label ◽

Open Label Trial

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

Stem Cells International ◽

10.1155/2020/8863649 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Liling Zhao ◽

Zi Guo ◽

Ke Chen ◽

Wenjun Yang ◽

Xinxing Wan ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Diabetic Foot ◽

Healing Rate ◽

Foot Ulcer ◽

Diabetic Foot Ulcer ◽

Foot Ulcers ◽

Diabetic Foot Ulcers ◽

Cell Injection ◽

Endothelial Colony Forming Cells

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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Transplantation of Bone Marrow-Derived Mesenchymal Stem Cells Promotes Delayed Wound Healing in Diabetic Rats

Journal of Diabetes Research ◽

10.1155/2013/647107 ◽

2013 ◽

Vol 2013 ◽

pp. 1-11 ◽

Cited By ~ 25

Author(s):

Jiangbo Wan ◽

Liulu Xia ◽

Wenjia Liang ◽

Yi Liu ◽

Qian Cai

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Wound Healing ◽

Mesenchymal Stem Cells ◽

Diabetic Foot ◽

Diabetic Rats ◽

Foot Ulcers ◽

Allogeneic Bone ◽

Diabetic Foot Ulcers ◽

Delayed Wound Healing

In this paper, we established a delayed wound healing model on diabetic rat to mimic the pathophysiology of clinical patients who suffered from diabetic foot ulcers. We also evaluated if transplantation of allogeneic bone marrow-derived mesenchymal stem cells could promote the delayed wound healing and investigated the possible underlying biological mechanisms and stem cell behavior involved in this process. The results showed that bone marrow-derived mesenchymal stem cells had a positive effect on delayed wound healing in diabetic rats. Intramuscular transplantation demonstrated the best efficacy. This effect is associated with granulation tissue formation, angiogenesis, cellular proliferation, and high vascular endothelial growth factor expression in wound tissues. In addition, bone marrow-derived mesenchymal stem cells have been shown to mobilize and find home for ischemic and wounded tissues to participate in the process of wound healing. Intramuscular transplantation of exogenous isogeneic stem cells may be suitable for clinical application in the treatment of diabetic foot ulcers although the safety of this therapy should be considered.

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Mesenchymal stem cells derivatives as a novel and potential therapeutic approach to treat diabetic foot ulcers

Endocrinology Diabetes and Metabolism Case Reports ◽

10.1530/edm-19-0164 ◽

2020 ◽

Vol 2020 ◽

Author(s):

Silvia M Becerra-Bayona ◽

Víctor Alfonso Solarte-David ◽

Claudia L Sossa ◽

Ligia C Mateus ◽

Martha Villamil ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Diabetic Foot ◽

Conventional Treatment ◽

Wound Closure ◽

Diabetic Mouse ◽

Foot Ulcers ◽

Diabetic Foot Ulcers ◽

Marrow Mesenchymal Stem Cells

Summary Diabetic foot ulcer morbidity and mortality are dramatically increasing worldwide, reinforcing the urgency to propose more effective interventions to treat such a devastating condition. Previously, using a diabetic mouse model, we demonstrated that administration of bone marrow mesenchymal stem cells derivatives is more effective than the use of bone marrow mesenchymal stem cells alone. Here, we used the aforementioned treatments on three patients with grade 2 diabetic foot ulcers and assessed their beneficial effects, relative to the conventional approach. In the present study, two doses of cell derivatives, one dose of mesenchymal stem cells or one dose of vehicle (saline solution with 5% of human albumin), were intradermally injected around wounds. Wound healing process and changes on re-epithelialization were macroscopically evaluated until complete closure of the ulcers. All ulcers were simultaneously treated with conventional treatment (PolyMen® dressing). Patients treated with either cell derivatives or mesenchymal stem cells achieved higher percentages of wound closure in shorter times, relative to the patient treated with the conventional treatment. The cell derivative and mesenchymal stem cells approaches resulted in complete wound closure and enhanced skin regeneration at some point between days 35 and 42, although no differences between these two treatments were observed. Moreover, wounds treated with the conventional treatment healed after 161 days. Intradermal administration of cell derivatives improved wound healing to a similar extent as mesenchymal stem cells. Thus, our results suggest that mesenchymal stem cell derivatives may serve as a novel and potential therapeutic approach to treat diabetic foot ulcers. Learning points: In diabetic mouse models, the administration of mesenchymal stem cells derivatives have been demonstrated to be more effective than the use of marrow mesenchymal stem cells alone. Mesenchymal stem cells have been explored as an attractive therapeutic option to treat non-healing ulcers. Mesenchymal stem cells derivatives accelerate the re-epithelialization on diabetic foot ulcers.

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