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Wang G, Jiang YB, Liu ZB, Li MH, Niu WJ, Lei ZC, Wang BW, Lu DY, Zhu YW. Benefits of liquid dressings in postoperative wound dressing of diabetic foot ulcer. Curr Probl Surg 2025; 65:101730. [PMID: 40128000 DOI: 10.1016/j.cpsurg.2025.101730] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Revised: 01/29/2025] [Accepted: 01/30/2025] [Indexed: 03/26/2025]
Affiliation(s)
- Gang Wang
- Department of Ulcer and Peripheral Vascular Surgery, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research; Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China.
| | - Yi-Biao Jiang
- Department of Ulcer and Peripheral Vascular Surgery, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research; Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
| | - Zhen-Bin Liu
- Department of Ulcer and Peripheral Vascular Surgery, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research; Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
| | - Meng-Hu Li
- Department of Ulcer and Peripheral Vascular Surgery, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research; Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
| | - Wen-Jing Niu
- Department of Ulcer and Peripheral Vascular Surgery, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research; Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
| | - Zhang-Cheng Lei
- Department of Ulcer and Peripheral Vascular Surgery, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research; Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
| | - Bo-Wen Wang
- Department of Ulcer and Peripheral Vascular Surgery, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research; Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
| | - Dong-Ya Lu
- Department of Ulcer and Peripheral Vascular Surgery, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research; Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
| | - Yang-Wen Zhu
- Department of Ulcer and Peripheral Vascular Surgery, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research; Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
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Zhou C, Jiao L, Qiao X, Zhang W, Chen S, Yang C, Meng M. Combined treatment of umbilical cord Wharton's jelly-derived mesenchymal stem cells and platelet-rich plasma for a surgical patient with hospital-acquired pressure ulcer: a case report and literature review. Front Bioeng Biotechnol 2024; 12:1424941. [PMID: 39045540 PMCID: PMC11263083 DOI: 10.3389/fbioe.2024.1424941] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 06/10/2024] [Indexed: 07/25/2024] Open
Abstract
Hospital-acquired pressure ulcers (HAPUs) are still an important worldwide issue related to the safety and quality of patient care, which are among the top five adverse events reported. Patients who develop HAPUs have longer stays in the hospital than necessary, are at a greater risk of infections, and are more likely to die. Surgical patients are prone to developing PUs because they often remain immobile for extended periods of time, and their surgical procedures may limit the flow of blood oxygen and nutrition and lead to a decrease in muscle tone. Mesenchymal stem cells (MSCs) represent an attractive stem cell source for tissue regeneration in clinical applications, which have been demonstrated to improve wound healing through re-epithelialization, increased angiogenesis, and granulation tissue formation. Here, we present the case of an emergency surgical patient who developed an ulcer on the right heel during hospitalization. The human umbilical cord Wharton's jelly-derived MSCs (WJ-MSCs) re-suspended in platelet-rich plasma (PRP) were injected into ulcer margins. Four days after the WJ-MSC application, the patient showed progressive healing of the PU. From days 4 to 33, granulation tissue formation and re-epithelialization were clearly observed. The ulcer was almost healed completely on day 47, and the pain in the patient's wound area also decreased. Thus, intradermal transplantation of WJ-MSCs and PRP was safe and effective for treatment in patients with pressure ulcers. WJ-MSCs, together with PRP, may offer a promising treatment option for wound healing.
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Affiliation(s)
- Changhui Zhou
- Department of Central Laboratory, Liaocheng People’s Hospital, Liaocheng, China
| | - Linlin Jiao
- Nursing Department, Liaocheng People’s Hospital, Liaocheng, China
| | - Xiaoping Qiao
- Department of Traditional Chinese Medicine, Liaocheng People’s Hospital, Liaocheng, China
| | - Weiwei Zhang
- Department of Central Laboratory, Liaocheng People’s Hospital, Liaocheng, China
| | - Shuangfeng Chen
- Department of Central Laboratory, Liaocheng People’s Hospital, Liaocheng, China
| | - Chunling Yang
- Nursing Department, Liaocheng People’s Hospital, Liaocheng, China
| | - Min Meng
- Department of Central Laboratory, Liaocheng People’s Hospital, Liaocheng, China
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Wang F, Zhang X, Zhang J, Xu Q, Yu X, Xu A, Yi C, Bian X, Shao S. Recent advances in the adjunctive management of diabetic foot ulcer: Focus on noninvasive technologies. Med Res Rev 2024; 44:1501-1544. [PMID: 38279968 DOI: 10.1002/med.22020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2022] [Revised: 12/15/2023] [Accepted: 01/10/2024] [Indexed: 01/29/2024]
Abstract
Diabetic foot ulcer (DFU) is one of the most costly and serious complications of diabetes. Treatment of DFU is usually challenging and new approaches are required to improve the therapeutic efficiencies. This review aims to update new and upcoming adjunctive therapies with noninvasive characterization for DFU, focusing on bioactive dressings, bioengineered tissues, mesenchymal stem cell (MSC) based therapy, platelet and cytokine-based therapy, topical oxygen therapy, and some repurposed drugs such as hypoglycemic agents, blood pressure medications, phenytoin, vitamins, and magnesium. Although the mentioned therapies may contribute to the improvement of DFU to a certain extent, most of the evidence come from clinical trials with small sample size and inconsistent selections of DFU patients. Further studies with high design quality and adequate sample sizes are necessitated. In addition, no single approach would completely correct the complex pathogenesis of DFU. Reasonable selection and combination of these techniques should be considered.
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Affiliation(s)
- Fen Wang
- Division of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Branch of National Clinical Research Center for Metabolic Diseases, Hubei, China
| | - Xiaoling Zhang
- Division of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Branch of National Clinical Research Center for Metabolic Diseases, Hubei, China
| | - Jing Zhang
- Division of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Branch of National Clinical Research Center for Metabolic Diseases, Hubei, China
| | - Qinqin Xu
- Division of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Branch of National Clinical Research Center for Metabolic Diseases, Hubei, China
| | - Xuefeng Yu
- Division of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Branch of National Clinical Research Center for Metabolic Diseases, Hubei, China
| | - Anhui Xu
- Division of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Chengla Yi
- Division of Trauma Surgery, Tongji Hospital, Tongji Medical College, Wuhan, China
| | - Xuna Bian
- Division of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Branch of National Clinical Research Center for Metabolic Diseases, Hubei, China
| | - Shiying Shao
- Division of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Branch of National Clinical Research Center for Metabolic Diseases, Hubei, China
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Torabi E, Omidvari S, Azimzadeh Z, Darabi S, Keramatinia A, Asghari MA, Abbaszadeh HA, Rashnoo F. Exploring Photobiomodulation Therapy and Regenerative Medicine for Diabetic Foot Ulcers: Pathogenesis and Multidisciplinary Treatment Approach. J Lasers Med Sci 2024; 15:e18. [PMID: 39050998 PMCID: PMC11267415 DOI: 10.34172/jlms.2024.18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2023] [Accepted: 03/09/2024] [Indexed: 07/27/2024]
Abstract
Introduction: Diabetes is associated with several debilitating complications, including the development of diabetic foot ulcers (DFUs), which can have serious consequences. This study emphasizes a multidisciplinary approach, providing a thorough overview of DFU pathogenesis and available treatments. Methods: An extensive literature review, covering studies published between 2000 and 2023, was conducted to gather data on DFU pathophysiology and treatments, including wound dressings, photobiomodulation, off-loading devices, adjunct medicines, and stem cell therapy. Results: DFUs are complicated due to infection, ischemia, and neuropathy. Sufficient wound dressings maintain a moist environment, promoting autolytic debridement and facilitating the healing process. Through cellular mechanisms, photobiomodulation therapy (PBM) was observed to expedite the healing process. Additionally, off-loading devices were invented to reduce ulcer pressure and promote healing. Adjunct therapies such as negative pressure wound therapy and hyperbaric oxygen therapy were identified as valuable tools for enhancing healing outcomes. Furthermore, autologous and allogeneic stem cell treatments exhibited the potential for promoting tissue regeneration and expediting the healing process. Conclusion: The complex pathophysiology of DFUs necessitates a multimodal treatment approach. Essential components include PBM, wound dressings, off-loading devices, adjunct treatments, and stem cell therapy.
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Affiliation(s)
- Elahe Torabi
- Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Samareh Omidvari
- Rayan Stem Cells and Regenerative Medicine Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zahra Azimzadeh
- Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shahram Darabi
- Cellular and Molecular Research Center, Research Institute for Non-Communicable Diseases, Qazvin University of Medical Sciences, Qazvin, Iran
| | - Aliasghar Keramatinia
- Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Ali Asghari
- Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hojjat Allah Abbaszadeh
- Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Rayan Stem Cells and Regenerative Medicine Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fariborz Rashnoo
- Department of General Surgery, School of Medicine, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Wang XQ, Pu DL, Leng WL, Lei XT, Juan J, La Z, Yao D, Xi JZ, Jian L, Miao T, Wu QN. Efficacy of Huangma Ding or autologous platelet-rich gel for the diabetic lower extremity arterial disease patients with foot ulcers. World J Diabetes 2024; 15:923-934. [PMID: 38766441 PMCID: PMC11099365 DOI: 10.4239/wjd.v15.i5.923] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2023] [Revised: 02/01/2024] [Accepted: 03/19/2024] [Indexed: 05/10/2024] Open
Abstract
BACKGROUND Diabetes foot is one of the most serious complications of diabetes and an important cause of death and disability, traditional treatment has poor efficacy and there is an urgent need to develop a practical treatment method. AIM To investigate whether Huangma Ding or autologous platelet-rich gel (APG) treatment would benefit diabetic lower extremity arterial disease (LEAD) patients with foot ulcers. METHODS A total of 155 diabetic LEAD patients with foot ulcers were enrolled and divided into three groups: Group A (62 patients; basal treatment), Group B (38 patients; basal treatment and APG), and Group C (55 patients; basal treatment and Huangma Ding). All patients underwent routine follow-up visits for six months. After follow-up, we calculated the changes in all variables from baseline and determined the differences between groups and the relationships between parameters. RESULTS The infection status of the three groups before treatment was the same. Procalcitonin (PCT) improved after APG and Huangma Ding treatment more than after traditional treatment and was significantly greater in Group C than in Group B. Logistic regression analysis revealed that PCT was positively correlated with total amputation, primary amputation, and minor amputation rates. The ankle-brachial pressure and the transcutaneous oxygen pressure in Groups B and C were greater than those in Group A. The major amputation rate, minor amputation rate, and total amputation times in Groups B and C were lower than those in Group A. CONCLUSION Our research indicated that diabetic foot ulcers (DFUs) lead to major amputation, minor amputation, and total amputation through local infection and poor microcirculation and macrocirculation. Huangma Ding and APG were effective attreating DFUs. The clinical efficacy of Huangma Ding was better than that of autologous platelet gel, which may be related to the better control of local infection by Huangma Ding. This finding suggested that in patients with DFUs combined with coinfection, controlling infection is as important as improving circulation.
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Affiliation(s)
- Xue-Qin Wang
- Endocrinology Department, The People’s Hospital of Yubei District of Chongqing City, Chongqing 401120, China
| | - Dan-Lan Pu
- Department of Endocrinology, Chongqing Yubei District People’s Hospital, Chongqing 400030, China
| | - Wei-Ling Leng
- Endocrinology Department, The First Affiliated Hospital of the Army Medical University, Chongqing 400038, China
| | - Xiao-Tian Lei
- Endocrinology Department, The First Affiliated Hospital of the Army Medical University, Chongqing 400038, China
| | - Jiang Juan
- Endocrinology and Nephrology Department, Chongqing University Cancer Hospital and Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing 400016, China
| | - Zou La
- Endocrinology and Nephrology Department, Chongqing University Cancer Hospital and Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing 400016, China
| | - Ding Yao
- Endocrinology and Nephrology Department, Chongqing University Cancer Hospital and Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing 400016, China
| | - Jia-Zhuang Xi
- Department of Endocrinology, Dazu Hospital of Chongqing Medical University, The People’s Hospital of Dazu, Chongqing 402360, China
| | - Li Jian
- Department of Endocrinology, Dazu Hospital of Chongqing Medical University, The People’s Hospital of Dazu, Chongqing 402360, China
| | - Teng Miao
- Endocrinology Department, The People’s Hospital of Yubei District of Chongqing City, Chongqing 401120, China
| | - Qi-Nan Wu
- Department of Endocrinology, Dazu Hospital of Chongqing Medical University, The People’s Hospital of Dazu, Chongqing 402360, China
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Torres-Guzman RA, Avila FR, Maita K, Garcia JP, De Sario GD, Borna S, Eldaly AS, Quinones-Hinojosa A, Zubair AC, Ho OA, Forte AJ. Mesenchymal Stromal Cell Healing Outcomes in Clinical and Pre-Clinical Models to Treat Pressure Ulcers: A Systematic Review. J Clin Med 2023; 12:7545. [PMID: 38137625 PMCID: PMC10743704 DOI: 10.3390/jcm12247545] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Revised: 11/26/2023] [Accepted: 11/29/2023] [Indexed: 12/24/2023] Open
Abstract
BACKGROUND Despite numerous measures used to prevent pressure ulcers, their growing prevalence in recent years is expected to continue as the population ages. This review aims to report the outcomes of the regenerative potential of MSCs in treating pressure ulcers, assessing the effectiveness of MSCs in treating pressure ulcers. METHODS A computerized search for articles on animal models that use MSCs as primary therapy to treat pressure ulcers, published from conception to present, was conducted using PubMed, MEDLINE, Embase, and CINAHL. Our search yielded 52 articles, narrowed to 44 after excluding duplicates. RESULTS Out of 52 articles collected from four databases, 11 met the inclusion criteria. A total of 11 articles published between 2008 and 2020 met the inclusion criteria. Eight studies were observational descriptive papers in animal models, and three were prospective. Six studies used autologous MSCs, while five used allogenic MSCs. Three studies were conducted in humans, and the remaining eight were conducted in animals. The most common method of cell delivery was an intradermal injection in the margins of the ulcer. All studies reported positive results, including improved wound healing, reduced inflammation, and improved tissue regeneration. CONCLUSIONS MSCs have shown promising results in treating pressure ulcers in animal and clinical trials. The combination of MSCs and scaffold materials has also been studied and found to be effective in wound healing. A standardized human wound model has been proposed further to investigate the efficacy of cell-based therapies for chronic wounds. However, more research is needed to determine the best quantity of cells to apply for pressure ulcers and to ensure the safety and efficacy of these treatments in clinical settings.
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Affiliation(s)
| | | | - Karla Maita
- Division of Plastic Surgery, Mayo Clinic, Jacksonville, FL 32224, USA
| | - John P. Garcia
- Division of Plastic Surgery, Mayo Clinic, Jacksonville, FL 32224, USA
| | | | - Sahar Borna
- Division of Plastic Surgery, Mayo Clinic, Jacksonville, FL 32224, USA
| | | | | | - Abba C. Zubair
- Department of Laboratory Medicine and Pathology, Transfusion Medicines and Stem Cell Therapy, Mayo Clinic, Jacksonville, FL 32224, USA
| | - Olivia A. Ho
- Division of Plastic Surgery, Mayo Clinic, Jacksonville, FL 32224, USA
| | - Antonio J. Forte
- Division of Plastic Surgery, Mayo Clinic, Jacksonville, FL 32224, USA
- Department of Neurosurgery, Mayo Clinic, Jacksonville, FL 32224, USA
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Zhang HM, Yang ML, Xi JZ, Yang GY, Wu QN. Mesenchymal stem cells-based drug delivery systems for diabetic foot ulcer: A review. World J Diabetes 2023; 14:1585-1602. [DOI: 10.4239/wjd.v14.i11.1585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2023] [Revised: 07/16/2023] [Accepted: 09/11/2023] [Indexed: 11/14/2023] Open
Abstract
The complication of diabetes, which is known as diabetic foot ulcer (DFU), is a significant concern due to its association with high rates of disability and mortality. It not only severely affects patients’ quality of life, but also imposes a substantial burden on the healthcare system. In spite of efforts made in clinical practice, treating DFU remains a challenging task. While mesenchymal stem cell (MSC) therapy has been extensively studied in treating DFU, the current efficacy of DFU healing using this method is still inadequate. However, in recent years, several MSCs-based drug delivery systems have emerged, which have shown to increase the efficacy of MSC therapy, especially in treating DFU. This review summarized the application of diverse MSCs-based drug delivery systems in treating DFU and suggested potential prospects for the future research.
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Affiliation(s)
- Hong-Min Zhang
- Department of Endocrinology, People’s Hospital of Chongqing Liangjiang New Area, Chongqing 400030, China
| | - Meng-Liu Yang
- Department of Endocrinology, The Second Affiliated Hospital of The Chongqing Medical University, Chongqing 400030, China
| | - Jia-Zhuang Xi
- Department of Endocrinology, Dazu Hospital of Chongqing Medical University, The People’s Hospital of Dazu, Chongqing 406230, China
| | - Gang-Yi Yang
- Department of Endocrinology, The Second Affiliated Hospital of The Chongqing Medical University, Chongqing 400030, China
| | - Qi-Nan Wu
- Department of Endocrinology, Dazu Hospital of Chongqing Medical University, The People’s Hospital of Dazu, Chongqing 406230, China
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Yin XL, Hu L, Li T, Zou Y, Li HL. A meta-analysis on the efficacy of vacuum sealing drainage combined with autologous platelet-rich plasma in the treatment of Grade 2 and Grade 3 diabetic foot ulcers. Int Wound J 2023; 20:1033-1041. [PMID: 36111514 PMCID: PMC10031232 DOI: 10.1111/iwj.13956] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 08/25/2022] [Accepted: 08/26/2022] [Indexed: 11/29/2022] Open
Abstract
This meta-analysis aims to systemically evaluate the efficacy of vacuum sealing drainage (VSD) combined with autologous platelet-rich plasma (PRP) in the treatment of diabetic foot ulcers (DFU). The China HowNet, China Biomedical Literature, VIP periodical resource integration service platform, Wanfang, Embase, Cochrane Central, and PubMed databases were retrieved using the computer. The retrieval period was up to July 2021. Randomised controlled trials on VSD combined with PRP in the treatment of DFU were collected. Those trials that met the inclusion criteria were included for meta-analysis using RevMan 5.3 software. A total of 13 articles were included. In the trial group, 477 patients with DFU were treated with VSD combined with PRP, while in the control group, 482 patients with DFU were treated with conventional dressings and/or VSD. The meta-analysis showed that, compared with the control group, VSD combined with PRP has significant advantages in shortening healing time (standardised mean difference [SMD] = -0.87, 95% confidence interval [CI]: -1.07 to -0.67, P < .00001), improving ulcer healing rates (odds ratio = 4.01, 95% CI: 2.95 ~ 5.46, P < .00001), and reducing hospital stays (mean difference = -15.29, 95% CI: -16.05 to -14.54, P < .00001), but the differences in dressing change times (SMD = -1.27, 95% CI: -2.71 to 0.17, P = .08) and hospitalisation expenses (SMD = -0.16, 95% CI: -13.40 to 13.07, P = .98) were not statistically significant. VSD combined with autologous PRP has good curative efficacy in the treatment of DFU and is a better treatment option. However, this treatment is limited in patients with platelet dysfunction, thrombocytopenia, leukaemia, and poor general condition.
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Affiliation(s)
- Xiao-Ling Yin
- Department of Endocrinology, The First Hospital of Nanchang (The Third Affiliated Hospital of Nanchang University), Nanchang, Jiangxi, China
| | - Ling Hu
- Department of Endocrinology, The First Hospital of Nanchang (The Third Affiliated Hospital of Nanchang University), Nanchang, Jiangxi, China
| | - Ting Li
- Department of Endocrinology, The First Hospital of Nanchang (The Third Affiliated Hospital of Nanchang University), Nanchang, Jiangxi, China
| | - Yi Zou
- Department of Endocrinology, The First Hospital of Nanchang (The Third Affiliated Hospital of Nanchang University), Nanchang, Jiangxi, China
| | - Hong-Lin Li
- Department of Biochemistry, Medical College of Georgia, Augusta, Georgia, USA
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Raja JM, Maturana MA, Kayali S, Khouzam A, Efeovbokhan N. Diabetic foot ulcer: A comprehensive review of pathophysiology and management modalities. World J Clin Cases 2023; 11:1684-1693. [PMID: 36970004 PMCID: PMC10037283 DOI: 10.12998/wjcc.v11.i8.1684] [Citation(s) in RCA: 37] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Revised: 01/08/2023] [Accepted: 02/17/2023] [Indexed: 03/07/2023] Open
Abstract
Diabetic foot ulcer (DFU) is a debilitating and severe manifestation of uncontrolled and prolonged diabetes that presents as ulceration, usually located on the plantar aspect of the foot. Approximately 15% of individuals with diabetes will eventually develop DFU, and 14%-24% of them will require amputation of the ulcerated foot due to bone infection or other ulcer-related complications. The pathologic mechanisms underlying DFU are comprise a triad: Neuropathy, vascular insufficiency, and secondary infection due to trauma of the foot. Standard local and invasive care along with novel approaches like stem cell therapy pave the way to reduce morbidity, decrease amputations, and prevent mortality from DFU. In this manuscript, we review the current literature with focus on the pathophysiology, preventive options, and definitive management of DFU.
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Affiliation(s)
- Joel M Raja
- Department of Internal Medicine, University of Tennessee Health Science Center, Memphis, TN 38119, United States
| | - Miguel A Maturana
- Department of Internal Medicine, University of Tennessee Health Science Center, Memphis, TN 38119, United States
| | - Sharif Kayali
- Department of Internal Medicine, University of Tennessee Health Science Center, Memphis, TN 38119, United States
| | - Amir Khouzam
- Department of Internal Medicine, University of Tennessee Health Science Center, Memphis, TN 38119, United States
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Yang L, Rong GC, Wu QN. Diabetic foot ulcer: Challenges and future. World J Diabetes 2022; 13:1014-1034. [PMID: 36578870 PMCID: PMC9791573 DOI: 10.4239/wjd.v13.i12.1014] [Citation(s) in RCA: 46] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 10/07/2022] [Accepted: 11/28/2022] [Indexed: 12/15/2022] Open
Abstract
Diabetic foot ulcers (DFUs) have become one of the important causes of mortality and morbidity in patients with diabetes, and they are also a common cause of hospitalization, which places a heavy burden on patients and society. The prevention and treatment of DFUs requires multidisciplinary management. By controlling various risk factors, such as blood glucose levels, blood pressure, lipid levels and smoking cessation, local management of DFUs should be strengthened, such as debridement, dressing, revascularization, stem cell decompression and oxygen therapy. If necessary, systemic anti-infection treatment should be administered. We reviewed the progress in the clinical practice of treating DFUs in recent years, such as revascularization, wound repair, offloading, stem cell transplantation, and anti-infection treatment. We also summarized and prospectively analyzed some new technologies and measurements used in the treatment of DFUs and noted the future challenges and directions for the development of DFU treatments.
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Affiliation(s)
- Li Yang
- Department of Endocrinology, Dazu Hospital of Chongqing Medical University, The People's Hospital of Dazu, Chongqing 402360, China
| | - Gui-Chuan Rong
- Department of Gynaecology, Dazu Hospital of Chongqing Medical University, The People's Hospital of Dazu, Chongqing 402360, China
| | - Qi-Nan Wu
- Department of Endocrinology, Dazu Hospital of Chongqing Medical University, The People's Hospital of Dazu, Chongqing 402360, China
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Li W, Wang QY, Bai XG, Xu J. Autologous platelet-rich gel in the treatment of diabetic foot ulcers: A retrospective study. Medicine (Baltimore) 2022; 101:e31701. [PMID: 36401364 PMCID: PMC9678626 DOI: 10.1097/md.0000000000031701] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
This study retrospectively investigated the effectiveness and safety of autologous platelet-rich gel (APRG) for the treatment of diabetic foot ulcers (DFU). In this retrospective study, we reviewed the electronic medical records (EMR) of 72 patients with DFU. The patients were allocated to a treatment group (n = 36) or a control group (n = 36). The patients in both groups received standard care (SC) and dressing change. In addition, patients in the treatment group also received APRG. Patients in both groups were treated for 12 weeks. The outcomes were DFU healing time (days), length of hospital stay (days), healing rate of DFU, DFU surface area reduction (cm2), and adverse events. We assessed and analyzed the outcomes before and after the 12-week treatment period. After treatment, there were significant differences in DFU healing time (P = .04), length of hospital stay (P = .04), DFU healing rate, and DFU surface area reduction (P < .01). Regarding safety, no EMR reported adverse events in this study. The results of this study showed that the APRG may benefit patients with DFU. However, high-quality prospective randomized controlled trials are required to verify these findings.
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Affiliation(s)
- Wei Li
- Department of Endocrine and Metabolism, Yanan University Affiliated Hospital, Yan’an, China
| | - Qiao-Yun Wang
- Department of Ultrasound Diagnosis, Yanan University Affiliated Hospital, Yan’an, China
| | - Xiao-Gang Bai
- Department of Endocrine and Metabolism, Yanan University Affiliated Hospital, Yan’an, China
| | - Jie Xu
- Department of Endocrine and Metabolism, Yanan University Affiliated Hospital, Yan’an, China
- *Correspondence: Jie Xu, Department of Endocrine and Metabolism, Yanan University Affiliated Hospital, No. 43 North Street, Baota District, Yan’an, 716000, China (e-mail: )
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12
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Potential of stem cells for treating infected Diabetic Foot Wounds and Ulcers: a systematic review. Mol Biol Rep 2022; 49:10925-10934. [PMID: 36008608 DOI: 10.1007/s11033-022-07721-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Revised: 06/14/2022] [Accepted: 06/16/2022] [Indexed: 02/01/2023]
Abstract
Infected diabetic foot ulcers (iDFUs) cause great concern, as they generally heal poorly and are precursive of diabetic-related foot amputation and even death. Scientists have tested various techniques in attempts to ascertain the best treatment for iDFUs; however, the results have remained inconclusive. Stem cell therapy (SCT) appears to improve iDFU through its antimicrobial impacts, yet cogent information regarding the repair of iDFUs with SCT is lacking. Herein, published articles are evaluated to report coherent information about the antimicrobial effects of SCT on the repair of iDFUs in diabetic animals and humans. In this systematic review, we searched the Scopus, Medline, Google Scholar, and Web of Science databases for relevant full-text English language articles published from 2000 to 2022 that described stem cell antimicrobial treatments, infected diabetic wounds, or ulcers. Ultimately, six preclinical and five clinical studies pertaining to the effectiveness of SCT on healing infected diabetic wounds or ulcers were selected. Some of the human studies confirmed that SCT is a promising therapy for diabetic wounds and ulcers. Notably, more controlled studies performed on animal models revealed that stem cells combined with a biostimulator such as photobiomodulation decreased colony forming units and hastened healing in infected diabetic wounds. Moreover, stem cells alone had lower therapeutic impact than when combined with a biostimulant.
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13
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Lin CW, Hung CM, Chen WJ, Chen JC, Huang WY, Lu CS, Kuo ML, Chen SG. New Horizons of Macrophage Immunomodulation in the Healing of Diabetic Foot Ulcers. Pharmaceutics 2022; 14:pharmaceutics14102065. [PMID: 36297499 PMCID: PMC9606988 DOI: 10.3390/pharmaceutics14102065] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 09/22/2022] [Accepted: 09/23/2022] [Indexed: 11/16/2022] Open
Abstract
Diabetic foot ulcers (DFUs) are one of the most costly and troublesome complications of diabetes mellitus. The wound chronicity of DFUs remains the main challenge in the current and future treatment of this condition. Persistent inflammation results in chronic wounds characterized by dysregulation of immune cells, such as M1 macrophages, and impairs the polarization of M2 macrophages and the subsequent healing process of DFUs. The interactive regulation of M1 and M2 macrophages during DFU healing is critical and seems manageable. This review details how cytokines and signalling pathways are co-ordinately regulated to control the functions of M1 and M2 macrophages in normal wound repair. DFUs are defective in the M1-to-M2 transition, which halts the whole wound-healing machinery. Many pre-clinical and clinical innovative approaches, including the application of topical insulin, CCL chemokines, micro RNAs, stem cells, stem-cell-derived exosomes, skin substitutes, antioxidants, and the most recent Phase III-approved ON101 topical cream, have been shown to modulate the activity of M1 and M2 macrophages in DFUs. ON101, the newest clinically approved product in this setting, is designed specifically to down-regulate M1 macrophages and further modulate the wound microenvironment to favour M2 emergence and expansion. Finally, the recent evolution of macrophage modulation therapies and techniques will improve the effectiveness of the treatment of diverse DFUs.
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Affiliation(s)
| | | | | | | | | | | | - Ming-Liang Kuo
- Microbio Co., Ltd., Taipei 115, Taiwan
- Correspondence: (M.-L.K.); or (S.-G.C.); Tel.: +886-2-27031298 (ext. 550) (M.-L.K.); +886-2-27031098 (ext. 551) (S.-G.C.)
| | - Shyi-Gen Chen
- Oneness Biotech Co., Ltd., Taipei 106, Taiwan
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan
- Correspondence: (M.-L.K.); or (S.-G.C.); Tel.: +886-2-27031298 (ext. 550) (M.-L.K.); +886-2-27031098 (ext. 551) (S.-G.C.)
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14
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Du L, Zeng D, Hu X, Ren X, He D. The efficacy of autologous platelet-rich gel and traditional Chinese medicine in diabetic foot treatment: a parallel randomized controlled clinical trial. Ann Vasc Surg 2022; 87:529-537. [PMID: 36064130 DOI: 10.1016/j.avsg.2022.07.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2022] [Revised: 06/30/2022] [Accepted: 07/18/2022] [Indexed: 11/26/2022]
Abstract
INTRODUCTION Diabetic Foot (DF) is a prevalent metabolic infection. DF wounds are the basis for all cases of non-traumatic lower limbs amputations in diabetes. DF care approaches include debridement of wound, pressure relief in the wounded area, proper wound, infection and ischemia management. However, there is a need for research to develop more effective therapeutic approaches. This study investigated the effectivity and safety of autologous platelet-rich gel combined with conventional treatment and traditional Chinese medicine (TCM) in diabetic foot ulcers therapy. METHODS Sixty diabetic foot ulcer patients were divided into treatment and control groups of 30 patients each. The treatment group involved a combination of autologous platelet-rich gel, conventional treatment, and TCM. The control group was only treated with a combination of conventional therapy and TCM. Laboratory variables, including platelets, hemoglobin, albumin, and HbA1c, were analyzed and compared between treatment and control groups at baseline and end-point. Healing area, volume, and rates were compared in both groups. RESULTS basic patients' data and the wound conditions had no significant difference between treatment and control group. The treatment and control groups cure rates were 93.3% vs. 50%, respectively. The healing rate per two weeks was significantly higher in the treatment than in control group (0.78±0.05 vs. 0.43±0.04). There was no statistically significant difference in the platelets, hemoglobin, albumin, and HbA1c levels in the treatment and control groups. CONCLUSION Autologous platelet-rich gel combined with conventional treatment and traditional Chinese medicine (TCM) is effective and safe for diabetic foot ulcers treatment.
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Affiliation(s)
- Liangliang Du
- Department of Endocrinology, Yueyang Hospital of Traditional Chinese Medicine, No.269 Fengqiao Lake Road, Yueyang City, Hunan Province
| | - Douyun Zeng
- Department of Endocrinology, Yueyang Hospital of Traditional Chinese Medicine, No.269 Fengqiao Lake Road, Yueyang City, Hunan Province
| | - Xian Hu
- Department of Endocrinology, Yueyang Hospital of Traditional Chinese Medicine, No.269 Fengqiao Lake Road, Yueyang City, Hunan Province
| | - Xi Ren
- Department of Endocrinology, Yueyang Hospital of Traditional Chinese Medicine, No.269 Fengqiao Lake Road, Yueyang City, Hunan Province
| | - Dazhi He
- Department of Endocrinology, Yueyang Hospital of Traditional Chinese Medicine, No.269 Fengqiao Lake Road, Yueyang City, Hunan Province.
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15
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El Hage R, Knippschild U, Arnold T, Hinterseher I. Stem Cell-Based Therapy: A Promising Treatment for Diabetic Foot Ulcer. Biomedicines 2022; 10:1507. [PMID: 35884812 PMCID: PMC9312797 DOI: 10.3390/biomedicines10071507] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 06/17/2022] [Accepted: 06/21/2022] [Indexed: 11/16/2022] Open
Abstract
Diabetic foot ulcer (DFU) is a severe complication of diabetes and a challenging medical condition. Conventional treatments for DFU have not been effective enough to reduce the amputation rates, which urges the need for additional treatment. Stem cell-based therapy for DFU has been investigated over the past years. Its therapeutic effect is through promoting angiogenesis, secreting paracrine factors, stimulating vascular differentiation, suppressing inflammation, improving collagen deposition, and immunomodulation. It is controversial which type and origin of stem cells, and which administration route would be the most optimal for therapy. We reviewed the different types and origins of stem cells and routes of administration used for the treatment of DFU in clinical and preclinical studies. Diabetes leads to the impairment of the stem cells in the diseased patients, which makes it less ideal to use autologous stem cells, and requires looking for a matching donor. Moreover, angioplasty could be complementary to stem cell therapy, and scaffolds have a positive impact on the healing process of DFU by stem cell-based therapy. In short, stem cell-based therapy is promising in the field of regenerative medicine, but more studies are still needed to determine the ideal type of stem cells required in therapy, their safety, proper dosing, and optimal administration route.
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Affiliation(s)
- Racha El Hage
- Department of Vascular Surgery, Universitätsklinikum Ruppin-Brandenburg, Medizinische Hochschule Branderburg Theodor Fontane, Fehrbelliner Str. 38, 16816 Neuruppin, Germany;
| | - Uwe Knippschild
- Department of General and Visceral Surgery, Surgery Center, Ulm University, Albert-Einstein-Allee 23, 89081 Ulm, Germany; (U.K.); (T.A.)
| | - Tobias Arnold
- Department of General and Visceral Surgery, Surgery Center, Ulm University, Albert-Einstein-Allee 23, 89081 Ulm, Germany; (U.K.); (T.A.)
| | - Irene Hinterseher
- Department of Vascular Surgery, Universitätsklinikum Ruppin-Brandenburg, Medizinische Hochschule Branderburg Theodor Fontane, Fehrbelliner Str. 38, 16816 Neuruppin, Germany;
- Berlin Institute of Health, Vascular Surgery Clinic, Charité-Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany
- Fakultät für Gesundheitswissenschaften Brandenburg, Gemeinsame Fakultät der Universität Potsdam, der Medizinischen Hochschule Brandenburg Theodor Fontane und der Brandenburgischen Technischen Universität Cottbus—Senftenberg, Karl-Liebknecht-Str. 24-25, 14476 Potsdam, Germany
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16
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Lin ZH, Wang J, Liang ZH, Pan YC. [Research advances on stem cell therapy for diabetic foot wounds]. ZHONGHUA SHAO SHANG YU CHUANG MIAN XIU FU ZA ZHI 2022; 38:281-286. [PMID: 35325974 DOI: 10.3760/cma.j.cn501120-20210828-00292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Diabetic foot wound repair is a challenging issue in clinical practice. Due to the influence of multiple factors including the damage and regeneration failure of local tissue, the impaired pathways of wound repairing through blood vessels and nerve nutrition, and disorders of a variety of cellular factors, traditional treatment methods are often difficult to achieve good therapeutic effects. Stem cells are a type of cells with potentials of multidirectional differentiation, which also possess functions such as regulating immunity and paracrine to facilitate the comprehensive wound repair, so they have promising application prospect at present for the treatment of diabetic foot wounds. Because the relevant parameters of stem cell treatment are in the exploratory phase, there were no standardized data. This paper reviews the application of stem cells in the research of diabetic foot wound treatment over the past 6 years, analyzing and summarizing the contents in focused aspects including the types and sources of stem cells, effects of donor age and gender on stem cells, mode of administration, transplantation survival rate and safety, which may provide a reference for further application of stem cells in the clinical treatment of diabetic foot wound.
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Affiliation(s)
- Z H Lin
- Department of Burn and Skin Repair, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou 570311, China
| | - J Wang
- Department of Burn and Skin Repair, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou 570311, China
| | - Z H Liang
- Department of Burn and Skin Repair, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou 570311, China
| | - Y C Pan
- Department of Burn and Skin Repair, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou 570311, China
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17
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Chia-Jui H, Yu L, Jiang YQ, Tan W, Gao GM, Li HB, Han L. Negative pressure wound therapy, artificial skin and autogenous skin implantation in diabetic foot ulcers. J Wound Care 2022; 31:40-46. [PMID: 35077212 DOI: 10.12968/jowc.2022.31.1.40] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
OBJECTIVE Diabetic foot ulcers (DFUs) are one of the most serious diabetic consequences, leading to amputations. Various therapies have been used to treat DFUs; however, a combination of negative pressure suction, artificial skin and autogenous skin implantation have never been investigated. This study aimed to evaluate the effectiveness of a novel three-step therapy protocol using negative pressure wound therapy (NPWT), artificial skin and autogenous skin implantation in patients with DFUs. METHOD At a single tertiary university hospital between 2015 and 2018, the three-step therapy protocol was applied to patients with DFUs and its safety and efficacy was investigated. RESULTS A total of 21 patients took part in the study. The majority of the patients were female (62%), with a mean age of 65 years and a mean body mass index of 21kg/m2. A third (n=7) of operative sites experienced minor complications, with two requiring re-operation. At a median follow up of 24 months, the average time of complete wound healing was 46 days, and the wound healing rate was 71%. The first-stage wound healing rate was 90%. All patients had achieved remission without any further recurrence of disease. CONCLUSION This comprehensive surgical technique for managing DFUs achieved a high local cure rate, minimal functional morbidity, and acceptable wound complication rates. The three-step therapy protocol has the potential to promote the healing process of DFUs, which is expected to serve as a new method for the treatment and cure of DFUs.
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Affiliation(s)
- Hu Chia-Jui
- Department of Orthopedics, Xiamen ChangGung Hospital, Xiamen City, Fujian Province, China
| | - Lai Yu
- Department of Orthopedics, Xiamen ChangGung Hospital, Xiamen City, Fujian Province, China
| | - Yu-Qing Jiang
- Department of Orthopedics, Xiamen ChangGung Hospital, Xiamen City, Fujian Province, China
| | - Wen Tan
- Department of Orthopedics, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou City, Jiangsu Province, China
| | - Gong-Ming Gao
- Department of Orthopedics, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou City, Jiangsu Province, China
| | - Hai-Bo Li
- Department of Orthopedics, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou City, Jiangsu Province, China
| | - Long Han
- Department of Orthopedics, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou City, Jiangsu Province, China
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18
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Meamar R, Ghasemi-Mobarakeh L, Norouzi MR, Siavash M, Hamblin MR, Fesharaki M. Improved wound healing of diabetic foot ulcers using human placenta-derived mesenchymal stem cells in gelatin electrospun nanofibrous scaffolds plus a platelet-rich plasma gel: A randomized clinical trial. Int Immunopharmacol 2021; 101:108282. [PMID: 34737130 DOI: 10.1016/j.intimp.2021.108282] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Revised: 10/16/2021] [Accepted: 10/17/2021] [Indexed: 01/13/2023]
Abstract
AIM The effectiveness of nanofibers containing human placenta-derived mesenchymal stem cells (hPDMSCs) plus platelet-rich plasma (PRP) for healing of diabetic foot ulcers (DFUs) was investigated. METHODS hPDMSCs were isolated from human donor placentas, and cultured in electrospun gelatin nanofibrous scaffolds (GNS). Twenty-eight patients with DFUs were randomized into three groups in a 12-week trial: (A) Treated with hPDMSCs; (B) Treated with hPDMSCs after coating the ulcer with PRP gel; (C) Control group received standard wound care. Wound area and pain freewalkingdistance were measured every 2 weeks. RESULTS Flow cytometry showed the expression of mesenchymal markers. SEM images and DAPI staining indicated significantly higher levels of hPDMSC proliferation on GNS after 3 and 7 days of culture. The MTS assay showed a significant increase in proliferation on GNS, compared to controls. Wound size reduction was 66% in group A, 71% in group B, and 36% in control group C. A significant difference in wound closure and pain-free walking distance was observed between groups A and B, compared to control group C (p < 0.05), but no difference between groups A and B. Biopsy of the implanted tissue showed the development of new capillary formation in groups A and B. CONCLUSION Implantation of hPDMSCs in GNS accelerated wound healing and improved clinical parameters in DFU patients.
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Affiliation(s)
- Rokhsareh Meamar
- Isfahan Clinical Toxicology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Laleh Ghasemi-Mobarakeh
- Department of Textile Engineering, Isfahan University of Technology, Isfahan 84156-83111, Iran
| | - Mohammad-Reza Norouzi
- Department of Textile Engineering, Isfahan University of Technology, Isfahan 84156-83111, Iran
| | - Mansour Siavash
- Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Michael R Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein 2028, South Africa
| | - Mehrafarin Fesharaki
- Isfahan Clinical Toxicology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
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19
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Jiang X, Yuan Y, Ma Y, Zhong M, Du C, Boey J, Armstrong DG, Deng W, Duan X. Pain Management in People with Diabetes-Related Chronic Limb-Threatening Ischemia. J Diabetes Res 2021; 2021:6699292. [PMID: 34046505 PMCID: PMC8128546 DOI: 10.1155/2021/6699292] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Revised: 04/19/2021] [Accepted: 05/03/2021] [Indexed: 12/24/2022] Open
Abstract
Management of neuropathic pain in people with diabetes has been widely investigated. However, little attention was paid to address ischemic-related pain in patients with diabetes mellitus who suffered from chronic limb-threatening ischemia (CLTI), the end stage of lower extremity arterial disease (LEAD). Pain management has a tremendous influence on patients' quality of life and prognosis. Poor management of this type of pain owing to the lack of full understanding undermines patients' physical and mental quality of life, which often results in a grim prognosis, such as depression, myocardial infarction, lower limb amputation, and even mortality. In the present article, we review the current strategy in the pain management of diabetes-related CLTI. The endovascular therapy, pharmacological therapies, and other optional methods could be selected following comprehensive assessments to mitigate ischemic-related pain, in line with our current clinical practice. It is very important for clinicians and patients to strengthen the understanding and build intervention strategy in ischemic pain management and possible adverse consequence.
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Affiliation(s)
- Xiaoyan Jiang
- Department of Endocrinology, Diabetic Foot Center, Chongqing University Central Hospital, Chongqing Emergency Medical Center, Chongqing 400014, China
| | - Yi Yuan
- Department of Endocrinology, Diabetic Foot Center, Chongqing University Central Hospital, Chongqing Emergency Medical Center, Chongqing 400014, China
| | - Yu Ma
- Department of Endocrinology, Diabetic Foot Center, Chongqing University Central Hospital, Chongqing Emergency Medical Center, Chongqing 400014, China
| | - Miao Zhong
- Department of Endocrinology, Diabetic Foot Center, Chongqing University Central Hospital, Chongqing Emergency Medical Center, Chongqing 400014, China
| | - Chenzhen Du
- Department of Endocrinology, Diabetic Foot Center, Chongqing University Central Hospital, Chongqing Emergency Medical Center, Chongqing 400014, China
| | - Johnson Boey
- Department of Podiatry, National University of Hospital Singapore, Singapore 169608
| | - David G. Armstrong
- Keck School of Medicine of University of Southern California, Los Angeles, CA 90033, USA
| | - Wuquan Deng
- Department of Endocrinology, Diabetic Foot Center, Chongqing University Central Hospital, Chongqing Emergency Medical Center, Chongqing 400014, China
| | - Xiaodong Duan
- Department of Rehabilitation, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
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Shafiee S, Heidarpour M, Sabbagh S, Amini E, Saffari H, Dolati S, Meamar R. Stem cell transplantation therapy for diabetic foot ulcer: a narrative review. ASIAN BIOMED 2021; 15:3-18. [PMID: 37551298 PMCID: PMC10388749 DOI: 10.2478/abm-2021-0002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Diabetes mellitus is a chronic metabolic disease associated with high cardiovascular risk. A vascular complication of diabetes is foot ulcers. Diabetic foot ulcers are prevalent and substantially reduce the quality of life of patients who have them. Currently, diabetic foot ulcer is a major problem for wound care specialists, and its treatment requires considerable health care resources. So far, various therapeutic modalities have been proposed to treat diabetic foot ulcers and one of them is stem cell-based therapy. Stem cell-based therapy has shown great promise for the treatment of diabetic foot ulcers. This strategy has been shown to be safe and effective in both preclinical and clinical trials. In this review, we provide an overview of the stem cell types and possible beneficial effects of stem cell transplantation therapy for diabetic foot ulcers, and an overview of the current status of stem cell research in both preclinical and clinical trial stages of treatment strategies for diabetic foot ulcers.
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Affiliation(s)
- Sahar Shafiee
- Isfahan Clinical Toxicology Research Center, Isfahan University of Medical Sciences, Isfahan81746-73461, Iran
- Clinical Development Research Center, Islamic Azad University, Najafabad Branch, Isfahan81737-35131, Iran
| | - Maryam Heidarpour
- Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan81737-35131, Iran
| | - Sima Sabbagh
- Isfahan Clinical Toxicology Research Center, Isfahan University of Medical Sciences, Isfahan81746-73461, Iran
- Clinical Development Research Center, Islamic Azad University, Najafabad Branch, Isfahan81737-35131, Iran
| | - Elham Amini
- Isfahan Clinical Toxicology Research Center, Isfahan University of Medical Sciences, Isfahan81746-73461, Iran
- Clinical Development Research Center, Islamic Azad University, Najafabad Branch, Isfahan81737-35131, Iran
| | - Hanieh Saffari
- Clinical Development Research Center, Islamic Azad University, Najafabad Branch, Isfahan81737-35131, Iran
| | - Sara Dolati
- Clinical Development Research Center, Islamic Azad University, Najafabad Branch, Isfahan81737-35131, Iran
| | - Rokhsareh Meamar
- Isfahan Clinical Toxicology Research Center, Isfahan University of Medical Sciences, Isfahan81746-73461, Iran
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21
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Combined Transplantation of Mesenchymal Stem Cells and Endothelial Colony-Forming Cells Accelerates Refractory Diabetic Foot Ulcer Healing. Stem Cells Int 2020; 2020:8863649. [PMID: 33061991 PMCID: PMC7545465 DOI: 10.1155/2020/8863649] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 07/19/2020] [Accepted: 08/26/2020] [Indexed: 12/17/2022] Open
Abstract
Background This study is aimed at investigating the effect of combined transplantation of umbilical cord mesenchymal stem cells (UCMSCs) and umbilical cord blood-derived endothelial colony-forming cells (ECFCs) on diabetic foot ulcer healing and at providing a novel therapy for chronic diabetic foot ulcer. Methods We reported the treatment of refractory diabetic foot ulcers in twelve patients. Among them, five patients had two or more wounds; thus, one wound in the same patient was treated with cell injection, and other wounds were regarded as self-controls. The remaining seven patients had only one wound; therefore, the difference between the area of wound before and after treatment was estimated. The UCMSCs and ECFCs were injected into the wound along with topically applied hyaluronic acid (HA). Results In this report, we compared the healing rate of multiple separate wounds in the same foot of the same patient: one treated with cell injection combined with topically applied HA-based hydrogel and was later covered by the hydrocolloid dressings, while the self-control wounds were only treated with conventional therapy and covered by the hydrocolloid dressings. The wound underwent cell injection showed accelerated healing in comparison to control wound within the first week after treatment. In other diabetic patients with only one refractory wound, the healing rate after cell transplantation was significantly faster than that before injection. Two large wounds healed without needing skin grafts after combination therapy of cell injection and HA. After four weeks of combination treatment, wound closure was reached in six patients, and the wounds of the other six patients were significantly reduced in size. Conclusions Our study suggests that the combination of UCMSCs, ECFCs, and HA can safely synergize the accelerated healing of refractory diabetic foot ulcers.
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22
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Zhao X, Guo J, Zhang F, Zhang J, Liu D, Hu W, Yin H, Jin L. Therapeutic application of adipose-derived stromal vascular fraction in diabetic foot. Stem Cell Res Ther 2020; 11:394. [PMID: 32928305 PMCID: PMC7488783 DOI: 10.1186/s13287-020-01825-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 05/15/2020] [Accepted: 07/10/2020] [Indexed: 02/06/2023] Open
Abstract
Diabetic foot is one of the severest complications of diabetes. In severe cases, this disease may be lead to amputation or even death due to secondary infection and ischemic necrosis. Since the ineffectiveness of traditional therapy, autologous stem cell transplantation has been used to treat diabetic foot. This simple, safe, and effective therapy is expected to be applied and promoted in the future.In this review, we described the detailed pathogenesis of diabetic foot and the common clinical treatments currently used. We also revealed vascular remodeling as the potential mechanism of therapeutic functions of adipose-derived stromal vascular fraction (SVF) in treating diabetic foot.
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Affiliation(s)
- Xiansheng Zhao
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, 211198, Jiangsu Province, China
| | - Jiamin Guo
- Irell & Manella Graduate School of Biological Sciences, City of Hope National Medical Center, California, 91010, USA
| | - Fangfang Zhang
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, 211198, Jiangsu Province, China
| | - Jue Zhang
- Department of Endocrinology, The Affiliated ZhongDa Hospital of Southeast University, Nanjing, 210009, Jiangsu Province, China
| | - Delin Liu
- Department of Endocrinology, The Affiliated ZhongDa Hospital of Southeast University, Nanjing, 210009, Jiangsu Province, China
| | - Wenjun Hu
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, 211198, Jiangsu Province, China.
| | - Han Yin
- Department of Endocrinology, The Affiliated ZhongDa Hospital of Southeast University, Nanjing, 210009, Jiangsu Province, China.
| | - Liang Jin
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, 211198, Jiangsu Province, China.
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23
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Xu J, Wang QY, Li W. Autologous platelet-rich gel and continuous vacuum sealing drainage for the treatment of patients with diabetic foot ulcer: Study Protocol. Medicine (Baltimore) 2019; 98:e17928. [PMID: 31725645 PMCID: PMC6867736 DOI: 10.1097/md.0000000000017928] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Research focusing on the efficacy of autologous platelet-rich gel (APRG) and continuous vacuum sealing drainage (CVSD) for diabetic foot ulcer (DFU) is increasing. Despite increasing knowledge on this theme, its results remain inconsistent. Thus, we will provide insight into the efficacy of APRG and CVSD for patients with DFU. METHODS We will search electronic databases of MEDILINE, EMBASE, Cochrane Library, CINAHL, AMED, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure from inception to October 1, 2019. No language limitation is utilized to these databases. Two authors will independently perform study selection, data extraction, and risk of bias assessment. Disagreements between 2 authors will be solved through discussion with a third author. RESULTS The efficacy and safety of APRG and CVSD for patients with DFU will be assessed by the time to complete healing, proportion of ulcers healed within trial period, change of size of ulcer, health-related quality of life, patient length of hospital stay, and adverse events. CONCLUSION The results of this study will provide helpful evidence of APRG and CVSD for patients with DFU. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42019153289.
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Affiliation(s)
- Jie Xu
- Department of Endocrine and Metabolism
| | - Qiao-Yun Wang
- Department of Ultrasound Diagnosis, Yan’an University Affiliated Hospital, Yan’an, China
| | - Wei Li
- Department of Endocrine and Metabolism
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Pu D, Lei X, Leng W, Zheng Y, Chen L, Liang Z, Chen B, Wu Q. Lower limb arterial intervention or autologous platelet-rich gel treatment of diabetic lower extremity arterial disease patients with foot ulcers. ANNALS OF TRANSLATIONAL MEDICINE 2019; 7:485. [PMID: 31700921 PMCID: PMC6803174 DOI: 10.21037/atm.2019.07.87] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/31/2019] [Accepted: 07/24/2019] [Indexed: 11/06/2022]
Abstract
BACKGROUND To investigate whether lower limb vascular intervention or autologous platelet-rich gel (APG) treatment would benefit diabetic lower extremity arterial disease (LEAD) patients with foot ulcers. METHODS A total of 82 diabetic LEAD patients with foot ulcers were recruited and divided into three groups: group A (30 patients received basal treatment), group B (21 patients received basal and APG treatment), and group C (31 patients received basal and lower limb vascular intervention treatment). All patients underwent routine follow-up visits for 6 months. The baseline characteristics and parameters were examined. After treatment, changes in all parameters from baseline were recorded. The differences between groups and the relationship among each parameter were determined. RESULTS There were no differences in the ankle brachial index (ABI) or major amputation between groups A and B (P>0.05). Compared with groups A and B, the ABI and major amputation rate of group C were improved (P<0.05). There were no significant differences in transcutaneous oxygen partial pressure (TcPO2), the heal rate or minor amputation between groups A and C (P>0.05). Compared with groups A and C, TcPO2, the heal rate and minor amputation of group B were improved (P<0.05). The logistic regression analysis indicated that major amputation was mainly associated with the ABI, and minor amputation was mainly associated with TcPO2. Lower limb vascular intervention improves the ABI and reduces major amputation, and APG improves TcPO2 and reduces minor amputation. CONCLUSIONS In diabetic LEAD patients with foot ulcers, major amputation was mainly associated with the ABI, while minor amputation was mainly associated with TcPO2. Interventional surgery (angioplasty) mainly improves the ABI, reduces the incidence of major amputation and improves the macrovasculature, and APG mainly improves local TcPO2, reduces the incidence of minor amputation and improves the microcirculation.
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Affiliation(s)
- Danlan Pu
- Endocrinology and Nephrology Department, Chongqing University Cancer Hospital and Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing 400030, China
| | - Xiaotian Lei
- Endocrinology Department, the First Affiliated Hospital of the Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Weiling Leng
- Endocrinology Department, the First Affiliated Hospital of the Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Yanling Zheng
- Endocrinology Department, the First Affiliated Hospital of the Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Liu Chen
- Endocrinology Department, the First Affiliated Hospital of the Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Ziwen Liang
- Endocrinology Department, the First Affiliated Hospital of the Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Bing Chen
- Endocrinology Department, the First Affiliated Hospital of the Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Qinan Wu
- Endocrinology and Nephrology Department, Chongqing University Cancer Hospital and Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing 400030, China
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Han Y, Li X, Zhang Y, Han Y, Chang F, Ding J. Mesenchymal Stem Cells for Regenerative Medicine. Cells 2019; 8:E886. [PMID: 31412678 PMCID: PMC6721852 DOI: 10.3390/cells8080886] [Citation(s) in RCA: 716] [Impact Index Per Article: 119.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Revised: 08/05/2019] [Accepted: 08/06/2019] [Indexed: 02/06/2023] Open
Abstract
In recent decades, the biomedical applications of mesenchymal stem cells (MSCs) have attracted increasing attention. MSCs are easily extracted from the bone marrow, fat, and synovium, and differentiate into various cell lineages according to the requirements of specific biomedical applications. As MSCs do not express significant histocompatibility complexes and immune stimulating molecules, they are not detected by immune surveillance and do not lead to graft rejection after transplantation. These properties make them competent biomedical candidates, especially in tissue engineering. We present a brief overview of MSC extraction methods and subsequent potential for differentiation, and a comprehensive overview of their preclinical and clinical applications in regenerative medicine, and discuss future challenges.
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Affiliation(s)
- Yu Han
- Department of Orthopedics, The Second Hospital of Jilin University, 218 Ziqiang Street, Changchun 130041, China
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun 130022, China
| | - Xuezhou Li
- Department of Orthopedics, The Second Hospital of Jilin University, 218 Ziqiang Street, Changchun 130041, China
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun 130022, China
| | - Yanbo Zhang
- Department of Orthopedics, China-Japan Union Hospital of Jilin University, 126 Xiantai Street, Changchun 130033, China.
| | - Yuping Han
- Department of Urology, China-Japan Union Hospital of Jilin University, 126 Xiantai Street, Changchun 130033, China.
| | - Fei Chang
- Department of Orthopedics, The Second Hospital of Jilin University, 218 Ziqiang Street, Changchun 130041, China.
| | - Jianxun Ding
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun 130022, China
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Wu M, Leng W, Pan H, Lei X, Chen L, Ouyang X, Liang Z. The Reduced Expression of EOLA1 May Be Related to Refractory Diabetic Foot Ulcer. Mediators Inflamm 2019; 2019:6705424. [PMID: 31007603 PMCID: PMC6441532 DOI: 10.1155/2019/6705424] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2018] [Revised: 01/02/2019] [Accepted: 01/14/2019] [Indexed: 12/02/2022] Open
Abstract
BACKGROUND Chronic diabetic foot ulcer (DFU) is one of the most intractable complications of diabetes mellitus (DM). Its pathogenesis is complex, and uncontrolled chronic inflammation is an important factor. Endothelial overexpressed lipopolysaccharide-associated factor 1 (EOLA1) discovered in our laboratory is an intracellular protein with the function of inflammatory regulation. This study was aimed at observing the expression of EOLA1 in DFU skin tissues and its relationship with inflammation and at exploring the possible role of EOLA1 in DFU and its mechanism. METHODS The patients with DFU were divided into 2 groups based on the formation time of ulcer: the acute wound (AW) group with the course of disease ≤ 4 weeks and the chronic wound (CW) group with the course of disease > 4 weeks. The relevant clinical data of patients were collected, and the skin tissues around the ulcer were used for immunofluorescence detection and immunohistochemical staining to observe inflammation. The expression levels of EOLA1, metallothionein 2A (MT2A), nuclear factor-κB (NF-κB), and interleukin-6 (IL-6) were detected by western blot. RESULTS A total of 79 patients were enrolled in the study. The results of immunofluorescence and immunohistochemistry showed that EOLA1 was expressed in the epithelial tissues of DFU. However, the expression of EOLA1 in the CW group was significantly lower than that in the AW group (P < 0.05), and the expression of NF-κB and IL-6 was obviously increased (P < 0.05). CONCLUSION The refractory wounds in patients with DFU may be closely related to the uncontrolled activation of inflammatory pathways in cells caused by the reduced expression of negative regulators of inflammation (e.g., EOLA1), and such decreased expression may be also strongly linked to the persistent state of inflammation.
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Affiliation(s)
- Mingxia Wu
- Health Management Center, First Affiliated Hospital of Army Medical University (Third Military Medical University), Chongqing 400038, China
| | - Weiling Leng
- Department of Endocrinology, First Affiliated Hospital of Army Medical University (Third Military Medical University), Chongqing 400038, China
| | - Hang Pan
- Department of Endocrinology, First Affiliated Hospital of Army Medical University (Third Military Medical University), Chongqing 400038, China
| | - Xiaotian Lei
- Department of Endocrinology, First Affiliated Hospital of Army Medical University (Third Military Medical University), Chongqing 400038, China
| | - Liu Chen
- Department of Endocrinology, First Affiliated Hospital of Army Medical University (Third Military Medical University), Chongqing 400038, China
| | - Xinshou Ouyang
- Department of Internal Medicine, Section of Digestive Diseases, Yale University of Medicine, New Haven, CT 06520, USA
| | - Ziwen Liang
- Department of Endocrinology, First Affiliated Hospital of Army Medical University (Third Military Medical University), Chongqing 400038, China
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