Management of lower extremity neuropathic ulcers in diabetic patients has changed little in the past decade. The healing rate is poor, risk of amputations relatively high, and there is a paucity of objective methods for choosing treatments. We will carry out a multi-center clinical cohort study of circulating and wound margin vasculogenic stem/progenitor cells (SPCs) in diabetic patients undergoing treatment for lower extremity neuropathic ulcers. The goal is to develop simple, quantitative methods that provide guidance on effective treatment choices. Our hypothesis is that an analysis of SPCs number and their biochemical characteristics can predict whether diabetic foot ulcers will heal. The experimental approach is built on the very productive framework used in our preliminary R21 project and recent publication. The four specific aims center on SPCs and their association with traditional methods for assessing diabetic control and wound characteristics.
Aims are as follows: (1) Determine whether SPCs mobilization/wound recruitment and hypoxia inducible factor-related processes are associated with wound repair, (2) Assess if wound care practices are associated with SPCs mobilization and SPCs homing to wounds, (3) Determine if variations in SPCs are associated with healing, and (4) Assess whether SPCs differences observed between a healing acute biopsy wound versus the foot ulcer are related to clinical issues such as metabolic status. We will evaluate whether SPCs number and content of several intracellular proteins correlate with wound and disease-related factors and whether these measurements can be used to predict diabetic wound healing.
We plan to carry out a multi-center clinical cohort study of circulating and wound margin vasculogenic stem/progenitor cells in diabetic patients undergoing treatment for limb-threatening lower extremity neuropathic ulcers. The goal is to develop simple, quantitative methods to assess ulcers that provide guidance on effective treatment choices. Our hypothesis is that an analysis of stem/progenitor cell number and their biochemical characteristics can predict whether diabetic foot ulcers will heal.
|Thom, Stephen R; Bhopale, Veena M; Yu, Kevin et al. (2017) Neutrophil microparticle production and inflammasome activation by hyperglycemia due to cytoskeletal instability. J Biol Chem 292:18312-18324|
|Margolis, David J; Hampton, Michelle; Hoffstad, Ole et al. (2017) NOS1AP genetic variation is associated with impaired healing of diabetic foot ulcers and diminished response to healing of circulating stem/progenitor cells. Wound Repair Regen 25:733-736|
|Bhullar, Jasjeet; Bhopale, Veena M; Yang, Ming et al. (2016) Microparticle formation by platelets exposed to high gas pressures - An oxidative stress response. Free Radic Biol Med 101:154-162|
|Thom, Stephen R; Hampton, Michelle; Troiano, Michael A et al. (2016) Measurements of CD34+/CD45-dim Stem Cells Predict Healing of Diabetic Neuropathic Wounds. Diabetes 65:486-97|
|Gould, Lisa; Abadir, Peter; Brem, Harold et al. (2015) Chronic wound repair and healing in older adults: current status and future research. Wound Repair Regen 23:1-13|
|Margolis, David J; Hampton, Michelle; Hoffstad, Ole et al. (2015) Health literacy and diabetic foot ulcer healing. Wound Repair Regen 23:299-301|
|Fosen, Katina M; Thom, Stephen R (2014) Hyperbaric oxygen, vasculogenic stem cells, and wound healing. Antioxid Redox Signal 21:1634-47|
|Heyboer 3rd, Marvin; Milovanova, Tatyana N; Wojcik, Susan et al. (2014) CD34+/CD45-dim stem cell mobilization by hyperbaric oxygen - changes with oxygen dosage. Stem Cell Res 12:638-45|
|Margolis, David J; Gupta, Jayanta; Hoffstad, Ole et al. (2013) Response to Comments on: Margolis et al. Lack of effectiveness of hyperbaric oxygen therapy for the treatment of diabetic foot ulcer and the prevention of amputation: a cohort study. Diabetes Care 2013;36:1961-1966. Diabetes Care 36:e132-3|
|Margolis, David J; Gupta, Jayanta; Thom, Stephen R et al. (2013) Diabetes, lower extremity amputation, loss of protective sensation, and neuronal nitric oxide synthase associated protein in the chronic renal insufficiency cohort study. Wound Repair Regen 21:17-24|
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