Mesenchymal Stem Cells as a Prospective Therapy for the Diabetic Foot

Wu, Qinan; Chen, Bing; Liang, Ziwen

doi:10.1155/2016/4612167

Cited by 29 publications

(22 citation statements)

References 166 publications

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“…Compared to the hydrogel group, the addition of GMSC-derived exosomes significantly promoted the nerve density, which suggests that the GMSC-derived exosomes could facilitate neuronal ingrowth to the wound bed. Previous studies have found that MSCs could promote nerve growth, restoration of neuropathic morphology and nerve function in diabetic rats, and the main mechanism is the secretion of nerve growth factor (NGF) by the MSCs, which can in turn promote the regeneration of nerve fibers (Sun et al, 2012 ; Xia et al, 2015 ; Wu et al, 2016 ). However, to our knowledge, there are no studies focused on the effects of MSC-derived exosomes on neuronal growth in diabetic rat skin defect model at present, and our results provide new evidence that the use of MSC-derived exosomes may be a promising method to promote the healing of chronic wounds in DM patients.…”

Section: Discussionmentioning

confidence: 99%

GMSC-Derived Exosomes Combined with a Chitosan/Silk Hydrogel Sponge Accelerates Wound Healing in a Diabetic Rat Skin Defect Model

et al. 2017

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Background: Delayed wound healing in diabetic patients is one of the most challenging complications in clinical medicine, as it poses a greater risk of gangrene, amputation and even death. Therefore, a novel method to promote diabetic wound healing is of considerable interest at present. Previous studies showed that injection of MSC-derived exosomes has beneficial effects on wound healing. In current studies, we aimed to isolate exosomes derived from gingival mesenchymal stem cells (GMSCs) and then loading them to the chitosan/silk hydrogel sponge to evaluate the effects of this novel non-invasive method on skin defects in diabetic rats.Methods: GMSCs were isolated from human gingival connective tissue and characterized by surface antigen analysis and in vitro multipotent differentiation. The cell supernatant was collected to isolate the exosomes. The exosomes were characterized by transmission electron microscopy, Western blot and size distribution analysis. The chitosan/silk-based hydrogel sponge was prepared using the freeze-drying method and then structural and physical properties were characterized. Then, the exosomes were added to the hydrogel and tested in a diabetic rat skin defect model. The effects were evaluated by wound area measurement, histological, immunohistochemical and immunofluorescence analysis.Results: We have successfully isolated GMSCs and exosomes with a mean diameter of 127 nm. The chitosan/silk hydrogel had the appropriate properties of swelling and moisture retention capacity. The in vivo studies showed that the incorporating of GMSC-derived exosomes to hydrogel could effectively promote healing of diabetic skin defects. The histological analysis revealed more neo-epithelium and collagen in the hydrogel-exosome group. In addition, the hydrogel-exosome group had the highest microvessel density and nerve density.Conclusions: The combination of GMSC-derived exosomes and hydrogel could effectively promote skin wound healing in diabetic rats by promoting the re-epithelialization, deposition and remodeling of collagen and by enhancing angiogenesis and neuronal ingrowth. These findings not only provide new information on the role of the GMSC-derived exosomes in wound healing but also provide a novel non-invasive application method of exosomes with practical value for skin repair.

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Section: Discussionmentioning

confidence: 99%

GMSC-Derived Exosomes Combined with a Chitosan/Silk Hydrogel Sponge Accelerates Wound Healing in a Diabetic Rat Skin Defect Model

et al. 2017

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“…22,23 Having such a perivascular location, MSCs have been shown to promote blood and lymphatic vessel formation and stability as support niche cells for vascular regeneration, by recruiting circulating vascular progenitor cells or by releasing pro-angiogenic factors. 10,[23][24][25] The effects of MSCs on vascular regeneration have been found to be beneficial for wound healing, [26][27][28] attenuation of limb ischemia, 29 or reperfusion of infarcted heart. 30 Apart from their effects on vascular cells, MSCs can modulate various immune cells including monocytes/macrophages.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stromal Cells Inhibit Inflammatory Lymphangiogenesis in the Cornea by Suppressing Macrophage in a TSG-6-Dependent Manner

Song

Park

et al. 2018

Molecular Therapy

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The cornea is a transparent tissue devoid of blood and lymphatic vessels. However, various inflammatory conditions can cause hemangiogenesis and lymphangiogenesis in the cornea, compromising transparency and visual acuity. Mesenchymal stem/stromal cells (MSCs) have therapeutic potentials in a variety of diseases because of anti-inflammatory properties. Herein, we investigated the effects of MSCs on corneal angiogenesis using a model of suture-induced inflammatory corneal neovascularization. Data demonstrated that an intravenous administration of MSCs suppressed corneal inflammation and neovascularization, inhibiting both hemangiogenesis and lymphangiogenesis. MSCs reduced the levels of vascular endothelial growth factor (VEGF)-C, VEGF-D, Tek, MRC1, and MRC2 in the cornea, which are expressed by pro-angiogenic macrophages. Moreover, the number of CD11b monocytes/macrophages in the cornea, spleen, peripheral blood, and draining lymph nodes was decreased by MSCs. Depletion of circulating CD11b monocytes by blocking antibodies replicated the effects of MSCs. Importantly, knockdown of tumor necrosis factor alpha (TNF-α)-stimulated gene/protein 6 (TSG-6) in MSCs abrogated the effects of MSCs in inhibiting corneal hemangiogenesis and lymphangiogenesis and monocyte/macrophage infiltration. Together, the results suggest that MSCs inhibit inflammatory neovascularization in the cornea by suppressing pro-angiogenic monocyte/macrophage recruitment in a TSG-6-dependent manner.

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“…As such, the novel cell therapy was assigned to this patient to eradicate its potential recurrence. Since 2005, our team has been dedicated to the therapeutic use of different stem cells for diabetic wound repair and limb salvage [ 6 , 7 , 12 – 14 ]. Both BMMSCs and bone marrow-derived mononuclear cells have been used for diabetics with critical limb ischemia and foot ulcer, the former producing better clinical outcomes [ 6 ].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and long-term longitudinal follow-up of bone marrow mesenchymal cell transplantation therapy in a diabetic patient with recurrent lower limb bullosis diabeticorum

Chen

et al. 2018

Stem Cell Res Ther

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Bullosis diabeticorum is a rare presentation of cutaneous manifestation most commonly affecting the lower limbs in patients with diabetes. The appearance, often as insidious as its resolution, is characterized by tense blisters on the skin surfaces of the lower limbs and the feet. The cause still remains unclear, but it may relate to microangiopathy and neuropathy. In this report, we present a case of a 64-year-old male with multiple episodes of blistering in the left lateral lower limb after a traumatic fall who was subsequently diagnosed with type 2 diabetes mellitus. The patient had a history of poorly controlled blood glucose and subsequently developed vasculopathy and peripheral neuropathy. Despite appropriate glycemic control and antibiotics therapy, the patient developed recurrent bullosis diabeticorum on five separate occasions during a 2-year span from 2005 to 2007. Building on our success with ischemic diabetic foot, we used bone marrow mesenchymal stem cell (BMMSC) transplantation therapy for bullosis diabeticorum. After a 9-month treatment, this patient developed another episode of cellulitis in the same lower limb which was successfully treated with antibacterial therapy. It is interesting that the patient reported no recurrence in the next 10-year follow-up span. This study demonstrates that bullosis diabeticorum could appear even before the onset of diabetes, and vascular insufficiency predisposes to the occurrence of bullosis diabeticorum. Our findings suggest that autologous BMMSC transplantation therapy may be an effective measure for recurrent bullosis diabeticorum; however, this will require further investigation to be conclusive. Early identification of diabetes and its complications and appropriate treatment may improve clinical outcomes and prevent lower limb amputation.Trial registration: ClinicalTrials.gov Identifier: NCT00955669. Registered on August 10, 2009.

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Mesenchymal Stem Cells as a Prospective Therapy for the Diabetic Foot

Cited by 29 publications

References 166 publications

GMSC-Derived Exosomes Combined with a Chitosan/Silk Hydrogel Sponge Accelerates Wound Healing in a Diabetic Rat Skin Defect Model

GMSC-Derived Exosomes Combined with a Chitosan/Silk Hydrogel Sponge Accelerates Wound Healing in a Diabetic Rat Skin Defect Model

Mesenchymal Stromal Cells Inhibit Inflammatory Lymphangiogenesis in the Cornea by Suppressing Macrophage in a TSG-6-Dependent Manner

Efficacy and long-term longitudinal follow-up of bone marrow mesenchymal cell transplantation therapy in a diabetic patient with recurrent lower limb bullosis diabeticorum

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