The role of stem cells in the treatment of diabetic foot ulcers

Blumberg, Sheila; Berger, Alexandra; Hwang, Lisa; Pastar, Irena; Warren, Stephen M.; Chen, Weiliam

doi:10.1016/j.diabres.2011.10.032

Cited by 91 publications

(72 citation statements)

References 104 publications

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“…Chronic wounds, such as venous and arterial ulcers, pressure ulcers, and diabetic ulcers, are often associated with advanced age, compromised blood circulation, patient immobility, and systemic illnesses. 1,2 Each year, nearly 4 million individuals in the United States experience some form of chronic skin ulcer. 3 These wounds are painful, unsightly, and can require limb amputation if left unattended.…”

Section: Introductionmentioning

confidence: 99%

“…Biocompatible collagen-based wound dressings or tissue substitutes contribute to local haemostatic and chemotactic stimuli, while supplying a structural support scaffold upon which neotissue can be formed at enhanced rates. 14,19 In addition, 1 CollPlant Ltd., Ness-Ziona, Israel. collagen dressings have other advantages over conventional dressings in terms of ease of application and being natural, nonimmunogenic, nonpyrogenic, hypoallergenic, and pain free.…”

Section: Introductionmentioning

confidence: 99%

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Cutaneous Wound Healing After Treatment with Plant-Derived Human Recombinant Collagen Flowable Gel

Shilo

Roth

Amzel

et al. 2013

Tissue Engineering Part A

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Chronic wounds, particularly diabetic ulcers, represent a main public health concern with significant costs. Ulcers often harbor an additional obstacle in the form of tunneled or undermined wounds, requiring treatments that can reach the entire wound tunnel, because bioengineered grafts are typically available only in a sheet form. While collagen is considered a suitable biodegradable scaffold material, it is usually extracted from animal and human cadaveric sources, and accompanied by potential allergic and infectious risks. The purpose of this study was to test the performance of a flowable gel made of human recombinant type I collagen (rhCollagen) produced in transgenic tobacco plants, indicated for the treatment of acute, chronic, and tunneled wounds. The performance of the rhCollagen flowable gel was tested in an acute full-thickness cutaneous wound-healing rat model and compared to saline treatment and two commercial flowable gel control products made of bovine collagen and cadaver human skin collagen. When compared to the three control groups, the rhCollagen-based gel accelerated wound closure and triggered a significant jumpstart to the healing process, accompanied by enhanced re-epithelialization. In a cutaneous full-thickness wound pig model, the rhCollagen-based flowable gel induced accelerated wound healing compared to a commercial product made of bovine tendon collagen. By day 21 post-treatment, 95% wound closure was observed with the rhCollagen product compared to 68% closure in wounds treated with the reference product. Moreover, rhCollagen treatment induced an early angiogenic response and induced a significantly lower inflammatory response than in the control group. In summary, rhCollagen flowable gel proved to be efficacious in animal wound models and is expected to be capable of reducing the healing time of human wounds.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cutaneous Wound Healing After Treatment with Plant-Derived Human Recombinant Collagen Flowable Gel

Shilo

Roth

Amzel

et al. 2013

Tissue Engineering Part A

View full text Add to dashboard Cite

show abstract

“…MSCs are a promising source of cells for multiple regenerative processes, including patches used for myocardial infarction and skin regeneration [10][11][12][13][14]. MSCs give rise to mesodermal lineages including muscle, fat and pericytes and can transdifferentiate into epidermal cells [15,16]; MSCs also enhance angiogenesis via multiple cytokines that ameliorate ischemic environments, including VEGF, MCP-1 and MIP-1α [17,18].…”

mentioning

confidence: 99%

Delivery of Mesenchymal Stem Cells in Biomimetic Engineered Scaffolds Promotes Healing of Diabetic Ulcers

Assi

Foster

et al. 2016

Regen. Med.

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Aim:We hypothesized that delivery of mesenchymal stem cells (MSCs) in a biomimetic collagen scaffold improves wound healing in a diabetic mouse model. Materials & methods:Rolled collagen scaffolds containing MSCs were implanted or applied topically to diabetic C57BL/6 mice with excisional wounds. Results: Rolled scaffolds were hypoxic, inducing MSC synthesis and secretion of VEGF. Diabetic mice with wounds treated with rolled scaffolds containing MSCs showed increased healing compared with controls. Histologic examination showed increased cellular proliferation, increased VEGF expression and capillary density, and increased numbers of macrophages, fibroblasts and smooth muscle cells. Addition of laminin to the collagen scaffold enhanced these effects. Conclusion: Activated MSCs delivered in a biomimetic-collagen scaffold enhanced wound healing in a translationally relevant diabetic mouse model.

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“…Cell-based therapy has emerged as a new application for the treatment of ulcers (8,9). In particular, mesenchymal stem cells (MSCs) exhibit an excellent potential for increasing the rate of wound healing given their selfrenewal capacity, immunomodulatory effects, and ability to differentiate into various cell lineages (10).…”

mentioning

confidence: 99%

Allogeneic Transplantation of an Adipose-Derived Stem Cell Sheet Combined With Artificial Skin Accelerates Wound Healing in a Rat Wound Model of Type 2 Diabetes and Obesity

et al. 2015

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One of the most common complications of diabetes is diabetic foot ulcer. Diabetic ulcers do not heal easily due to diabetic neuropathy and reduced blood flow, and nonhealing ulcers may progress to gangrene, which necessitates amputation of the patient's foot. This study attempted to develop a new cell-based therapy for nonhealing diabetic ulcers using a full-thickness skin defect in a rat model of type 2 diabetes and obesity. Allogeneic adipose-derived stem cells (ASCs) were harvested from the inguinal fat of normal rats, and ASC sheets were created using cell sheet technology and transplanted into full-thickness skin defects in Zucker diabetic fatty rats. The results indicate that the transplantation of ASC sheets combined with artificial skin accelerated wound healing and vascularization, with significant differences observed 2 weeks after treatment. The ASC sheets secreted large amounts of several angiogenic growth factors in vitro, and transplanted ASCs were observed in perivascular regions and incorporated into the newly constructed vessel structures in vivo. These results suggest that ASC sheets accelerate wound healing both directly and indirectly in this diabetic wound-healing model. In conclusion, allogeneic ASC sheets exhibit potential as a new therapeutic strategy for the treatment of diabetic ulcers.

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The role of stem cells in the treatment of diabetic foot ulcers

Cited by 91 publications

References 104 publications

Cutaneous Wound Healing After Treatment with Plant-Derived Human Recombinant Collagen Flowable Gel

Cutaneous Wound Healing After Treatment with Plant-Derived Human Recombinant Collagen Flowable Gel

Delivery of Mesenchymal Stem Cells in Biomimetic Engineered Scaffolds Promotes Healing of Diabetic Ulcers

Allogeneic Transplantation of an Adipose-Derived Stem Cell Sheet Combined With Artificial Skin Accelerates Wound Healing in a Rat Wound Model of Type 2 Diabetes and Obesity

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