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Start Over Author "Auster, Michael E." Topic diabetes mellitus
3 results on '"Auster, Michael E."'

1. Alginate and DNA Gels Are Suitable Delivery Systems for Diabetic Wound Healing

Author

Tellechea, Ana, Silva, Eduardo A, Min, Jianghong, Leal, Ermelindo C, Auster, Michael E, Pradhan-Nabzdyk, Leena, Shih, William, Mooney, David J, and Veves, Aristidis

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Regenerative Medicine, Diabetes, Biotechnology, Bioengineering, Development of treatments and therapeutic interventions, 5.2 Cellular and gene therapies, Metabolic and endocrine, Alginates, Animals, Bandages, Biocompatible Materials, Diabetes Mellitus, Experimental, Diabetic Foot, Drug Carriers, Drug Delivery Systems, Gels, Glucuronic Acid, Hexuronic Acids, Mice, Mice, Inbred C57BL, Vascular Endothelial Growth Factor A, Wound Healing, biomaterials, diabetic foot ulcers, wound healing, neuropeptides, endothelial precursor cells, Dermatology & Venereal Diseases, Clinical sciences
Abstract

Diabetic foot ulcers (DFU) represent a severe health problem and an unmet clinical challenge. In this study, we tested the efficacy of novel biomaterials in improving wound healing in mouse models of diabetes mellitus (DM). The biomaterials are composed of alginate- and deoxyribonucleic acid (DNA)-based gels that allow incorporation of effector cells, such as outgrowth endothelial cells (OEC), and provide sustained release of bioactive factors, such as neuropeptides and growth factors, which have been previously validated in experimental models of DM wound healing or hind limb ischemia. We tested these biomaterials in mice and demonstrate that they are biocompatible and can be injected into the wound margins without major adverse effects. In addition, we show that the combination of OEC and the neuropeptide Substance P has a better healing outcome than the delivery of OEC alone, while subtherapeutic doses of vascular endothelial growth factor (VEGF) are required for the transplanted cells to exert their beneficial effects in wound healing. In summary, alginate and DNA scaffolds could serve as potential delivery systems for the next-generation DFU therapies.

Published
2015

2. Mast Cells Regulate Wound Healing in Diabetes

Author

Leena Pradhan-Nabzdyk, Dimitrios Baltzis, Antonios Kafanas, Smaro Panagiotidou, Janice M. Zabolotny, Sarada Kuchibhotla, Aristidis Veves, Michael E. Auster, Anastasia I. Petra, Yana Ostrovsky, Ana Tellechea, Yongjun Zheng, Francesco Tecilazich, Eugenia Carvalho, Arti B. Patel, Ermelindo C. Leal, Theoharis C. Theoharides, Zuyi Weng, Tellechea, Ana, Leal, Ermelindo C., Kafanas, Antonio, Auster, Michael E., Kuchibhotla, Sarada, Ostrovsky, Yana, Tecilazich, Francesco, Baltzis, Dimitrio, Zheng, Yongjun, Carvalho, Eugénia, Zabolotny, Janice M., Weng, Zuyi, Petra, Anastasia, Patel, Arti, Panagiotidou, Smaro, Pradhan Nabzdyk, Leena, Theoharides, Theoharis C., and Veves, Aristidis

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Complications, Endocrinology, Diabetes and Metabolism, Substance P, Internal Medicine, Diabetes Mellitus, Experimental, Mice, 03 medical and health sciences, chemistry.chemical_compound, Endocrinology, 0302 clinical medicine, Mediator, Diabetic Neuropathies, Forearm, Internal medicine, Diabetes mellitus, medicine, Animals, Humans, Mast Cells, Aged, Skin, Wound Healing, integumentary system, business.industry, Degranulation, Middle Aged, medicine.disease, 3. Good health, Diabetes and Metabolism, Vascular endothelial growth factor, Diabetes Mellitus, Type 1, 030104 developmental biology, medicine.anatomical_structure, chemistry, 030220 oncology & carcinogenesis, Immunology, Experimental pathology, Female, business, Wound healing
Abstract

Diabetic foot ulceration is a severe complication of diabetes that lacks effective treatment. Mast cells (MCs) contribute to wound healing, but their role in diabetes skin complications is poorly understood. Here we show that the number of degranulated MCs is increased in unwounded forearm and foot skin of patients with diabetes and in unwounded dorsal skin of diabetic mice (P < 0.05). Conversely, postwounding MC degranulation increases in nondiabetic mice, but not in diabetic mice. Pretreatment with the MC degranulation inhibitor disodium cromoglycate rescues diabetes-associated wound-healing impairment in mice and shifts macrophages to the regenerative M2 phenotype (P < 0.05). Nevertheless, nondiabetic and diabetic mice deficient in MCs have delayed wound healing compared with their wild-type (WT) controls, implying that some MC mediator is needed for proper healing. MCs are a major source of vascular endothelial growth factor (VEGF) in mouse skin, but the level of VEGF is reduced in diabetic mouse skin, and its release from human MCs is reduced in hyperglycemic conditions. Topical treatment with the MC trigger substance P does not affect wound healing in MC-deficient mice, but improves it in WT mice. In conclusion, the presence of nondegranulated MCs in unwounded skin is required for proper wound healing, and therapies inhibiting MC degranulation could improve wound healing in diabetes.

Published
2016
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3. Increased skin inflammation and blood vessel density in human and experimental diabetes

Author

Eugenia Carvalho, Francesco Tecilazich, Michael E. Auster, Sarada Kuchibhotla, Leena Pradhan Nabzdyk, Aristidis Veves, Iraklis Kontoes, Antonios Kafanas, Jacqueline Paolino, Ana Tellechea, Ermelindo C. Leal, Tellechea, Ana, Kafanas, Antonio, Leal, Ermelindo C., Tecilazich, Francesco, Kuchibhotla, Sarada, Auster, Michael E., Kontoes, Irakli, Paolino, Jacqueline, Carvalho, Eugenia, Nabzdyk, Leena Pradhan, and Veves, Aristidis

Subjects
Male, Pathology, Biopsy, diabetes, skin blood vessels, skin changes, skin inflammation, wound healing, Animals, Blood Vessels, Dermatitis, Diabetes Mellitus, Experimental, Diabetic Foot, Disease Progression, Female, Follow-Up Studies, Humans, Mice, Mice, Inbred BALB C, Middle Aged, Prospective Studies, Rabbits, Rats, Rats, Sprague-Dawley, Regional Blood Flow, Skin, Surgery, Rabbit, Systemic inflammation, skin change, Inbred BALB C, medicine.diagnostic_test, integumentary system, General Medicine, Diabetic foot ulcer, medicine.anatomical_structure, medicine.symptom, Blood vessel, Human, medicine.medical_specialty, Blood Vessel, Inflammation, Dermatiti, Article, Follow-Up Studie, Experimental, Diabetes mellitus, medicine, Diabetes Mellitus, business.industry, Animal, medicine.disease, Diabetic foot, Prospective Studie, diabete, Immunology, skin blood vessel, Rat, Sprague-Dawley, Wound healing, business
Abstract

Systemic inflammation is associated with impaired wound healing in diabetes mellitus (DM) patients. Using immunohistochemistry techniques, the authors investigated changes in skin inflammation and skin blood vessels in human and experimental diabetes. Comparing to the non-DM human subjects, the total number of inflammatory cells per biopsy and the number of inflammatory cells around blood vessels, a strong indication of inflammation, were higher in DM subjects irrespective of their risk for developing diabetic foot ulcer. Inflammatory cell infiltration was robustly increased in all DM animal models compared with their non-DM controls. The number and density of blood vessels and CD31 positive proliferating endothelial cells around preexisting skin vessels was also higher in the DM patients. However, there were no differences in the skin blood flow between the non-DM and DM subjects. The number of skin blood vessels was also increased in the DM animals; however, these differences were less obvious than the ones observed for inflammatory cells. We conclude that skin inflammation and skin blood vessel density is increased in diabetic human subjects and in rodent and rabbit models of diabetes.

Published
2013

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