Haifeng Wang1, Lianyu Chen2, Yang Liu1, Bangzhen Luo1, Nanzi Xie1, Tao Tan3, Lige Song4, Pei Erli5, Ming Luo1. 1. Division of Geriatrics, Tongji Hospital, School of Medicine, Tongji University Shanghai 200065, China. 2. Department of Integrative Oncology, Fudan University Shanghai Cancer CenterShanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan UniversityShanghai 200032, China. 3. Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center Columbus, Ohio 43210, USA. 4. Department of Endocrinology, Tongji Hospital, Tongji University School of Medicine Shanghai 200065, China. 5. Department of General Surgery, Tongji University Yangpu Hospital, Institute of Gastrointestinal Surgery and Translational Medicine, Tongji University School of Medicine Shanghai 200065, China.
Abstract
BACKGROUND: Diabetic foot ulcer (DFU) is a major complication of diabetes mellitus. Although previous studies have established that inflammation, ischemia and neuropathy contribute to the development of DFU, it is still an unmet medical need due to lack knowledge of cellular and molecular mechanisms associated with DFU. In the present study, we tested our hypothesis that subcutaneous application of human placental mesenchymal stem cells (PMSCs) can accelerate diabetic dermal wound healing by modulating immunoresponse. METHODS AND RESULTS: By using an in vivo excisional wound healing model in Goto-Kakizaki (GK) rats, we found that injection of PMSCs accelerates wound closure. Further studies revealed that application of PMSCs can regulate inflammation associated with wound healing by controlling secretion of pro- and anti-inflammatory factors, the beneficial effects can be partially blocked by application of antibodies against interleukin-10 (IL-10). Furthermore, in vitro experiments suggested that co-culture of PMSCs with human dermal fibroblasts can significantly inhibit activation of NF-ĸB induced by lipopolysaccharides (LPS), indicating the molecular mechanism of PMSCs mediated immunomodulation. CONCLUSION: Taken together, our study suggested that the immunomodulation of PMSCs play an important role on diabetic dermal wound healing process, thus PMSCs might represent an attractive choice for treatment of diabetes dermal wound and DFU.
BACKGROUND:Diabetic foot ulcer (DFU) is a major complication of diabetes mellitus. Although previous studies have established that inflammation, ischemia and neuropathy contribute to the development of DFU, it is still an unmet medical need due to lack knowledge of cellular and molecular mechanisms associated with DFU. In the present study, we tested our hypothesis that subcutaneous application of human placental mesenchymal stem cells (PMSCs) can accelerate diabetic dermal wound healing by modulating immunoresponse. METHODS AND RESULTS: By using an in vivo excisional wound healing model in Goto-Kakizaki (GK) rats, we found that injection of PMSCs accelerates wound closure. Further studies revealed that application of PMSCs can regulate inflammation associated with wound healing by controlling secretion of pro- and anti-inflammatory factors, the beneficial effects can be partially blocked by application of antibodies against interleukin-10 (IL-10). Furthermore, in vitro experiments suggested that co-culture of PMSCs with human dermal fibroblasts can significantly inhibit activation of NF-ĸB induced by lipopolysaccharides (LPS), indicating the molecular mechanism of PMSCs mediated immunomodulation. CONCLUSION: Taken together, our study suggested that the immunomodulation of PMSCs play an important role on diabetic dermal wound healing process, thus PMSCs might represent an attractive choice for treatment of diabetes dermal wound and DFU.
Authors: M P De Miguel; S Fuentes-Julián; A Blázquez-Martínez; C Y Pascual; M A Aller; J Arias; F Arnalich-Montiel Journal: Curr Mol Med Date: 2012-06 Impact factor: 2.222
Authors: J B Ricco; L Thanh Phong; F Schneider; G Illuminati; R Belmonte; A Valagier; G Régnault De La Mothe Journal: J Cardiovasc Surg (Torino) Date: 2013-12 Impact factor: 1.888
Authors: Ji Hyun Kim; Denethia S Green; Young Min Ju; Mollie Harrison; J William Vaughan; Anthony Atala; Sang Jin Lee; John D Jackson; Cory Nykiforuk; James J Yoo Journal: Front Bioeng Biotechnol Date: 2022-07-22