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Miricescu D, Badoiu SC, Stanescu-Spinu II, Totan AR, Stefani C, Greabu M. Growth Factors, Reactive Oxygen Species, and Metformin-Promoters of the Wound Healing Process in Burns? Int J Mol Sci 2021; 22:ijms22179512. [PMID: 34502429 PMCID: PMC8431501 DOI: 10.3390/ijms22179512] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Revised: 08/26/2021] [Accepted: 08/30/2021] [Indexed: 12/19/2022] Open
Abstract
Burns can be caused by various factors and have an increased risk of infection that can seriously delay the wound healing process. Chronic wounds caused by burns represent a major health problem. Wound healing is a complex process, orchestrated by cytokines, growth factors, prostaglandins, free radicals, clotting factors, and nitric oxide. Growth factors released during this process are involved in cell growth, proliferation, migration, and differentiation. Reactive oxygen species are released in acute and chronic burn injuries and play key roles in healing and regeneration. The main aim of this review is to present the roles of growth factors, reactive oxygen species, and metformin in the healing process of burn injuries.
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Affiliation(s)
- Daniela Miricescu
- Department of Biochemistry, Faculty of Dental Medicine, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Blvd, 050474 Bucharest, Romania; (D.M.); (A.R.T.); (M.G.)
| | - Silviu Constantin Badoiu
- Department of Anatomy and Embriology, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Blvd, 050474 Bucharest, Romania
- Department of Plastic and Reconstructive Surgery, Life Memorial Hospital, 365 Grivitei Street, 010719 Bucharest, Romania
- Correspondence: (S.C.B.); (I.-I.S.-S.)
| | - Iulia-Ioana Stanescu-Spinu
- Department of Biochemistry, Faculty of Dental Medicine, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Blvd, 050474 Bucharest, Romania; (D.M.); (A.R.T.); (M.G.)
- Correspondence: (S.C.B.); (I.-I.S.-S.)
| | - Alexandra Ripszky Totan
- Department of Biochemistry, Faculty of Dental Medicine, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Blvd, 050474 Bucharest, Romania; (D.M.); (A.R.T.); (M.G.)
| | - Constantin Stefani
- Department of Family Medicine and Clinical Base, Dr. Carol Davila Central Military Emergency University Hospital, 010825 Bucharest, Romania;
| | - Maria Greabu
- Department of Biochemistry, Faculty of Dental Medicine, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Blvd, 050474 Bucharest, Romania; (D.M.); (A.R.T.); (M.G.)
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Li W, Jiao X, Song J, Sui B, Guo Z, Zhao Y, Li J, Shi S, Huang Q. Therapeutic potential of stem cells from human exfoliated deciduous teeth infusion into patients with type 2 diabetes depends on basal lipid levels and islet function. Stem Cells Transl Med 2021; 10:956-967. [PMID: 33660433 PMCID: PMC8235136 DOI: 10.1002/sctm.20-0303] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Revised: 01/02/2021] [Accepted: 02/06/2021] [Indexed: 12/12/2022] Open
Abstract
Mesenchymal stem cells (MSCs) hold great potential in treating patients with diabetes, but the therapeutic effects are not always achieved. Particularly, the clinical factors regulating MSC therapy in this setting are largely unknown. In this study, 24 patients with type 2 diabetes mellitus (T2DM) treated with insulin were selected to receive three intravenous infusions of stem cells from human exfoliated deciduous teeth (SHED) over the course of 6 weeks and were followed up for 12 months. We observed a significant reduction of glycosylated serum albumin level (P < .05) and glycosylated hemoglobin level (P < .05) after SHED transplantation. The total effective rate was 86.36% and 68.18%, respectively, at the end of treatment and follow‐up periods. Three patients ceased insulin injections after SHED transplantation. A steamed bread meal test showed that the serum levels of postprandial C‐peptide at 2 hours were significantly higher than those at the baseline (P < .05). Further analysis showed that patients with a high level of blood cholesterol and a low baseline level of C‐peptide had poor response to SHED transplantation. Some patients experienced a transient fever (11.11%), fatigue (4.17%), or rash (1.39%) after SHED transplantation, which were easily resolved. In summary, SHED infusion is a safe and effective therapy to improve glucose metabolism and islet function in patients with T2DM. Blood lipid levels and baseline islet function may serve as key factors contributing to the therapeutic outcome of MSC transplantation in patients with T2DM.
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Affiliation(s)
- Wenwen Li
- Department of Endocrinology, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China
| | - Xuan Jiao
- Department of Endocrinology, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China
| | - Jingyun Song
- Department of Endocrinology, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China
| | - Bingdong Sui
- South China Center of Craniofacial Stem Cell Research, Guanghua School and Hospital of Stomatology, Sun Yat-sen University, Guangzhou, People's Republic of China.,Research and Development Center for Tissue Engineering, School of Stomatology, Air Force Medical University, People's Republic of China
| | - Zhili Guo
- Department of Dermatology, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China
| | - Yingji Zhao
- South China Center of Craniofacial Stem Cell Research, Guanghua School and Hospital of Stomatology, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Jun Li
- Easter Greenland Hospital, People's Republic of China
| | - Songtao Shi
- South China Center of Craniofacial Stem Cell Research, Guanghua School and Hospital of Stomatology, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Qin Huang
- Department of Endocrinology, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China
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Deng L, Du C, Song P, Chen T, Rui S, Armstrong DG, Deng W. The Role of Oxidative Stress and Antioxidants in Diabetic Wound Healing. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:8852759. [PMID: 33628388 PMCID: PMC7884160 DOI: 10.1155/2021/8852759] [Citation(s) in RCA: 289] [Impact Index Per Article: 72.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Accepted: 12/29/2020] [Indexed: 12/16/2022]
Abstract
Foot ulcers are one of the most common and severe complication of diabetes mellitus with significant resultant morbidity and mortality. Multiple factors impair wound healing include skin injury, diabetic neuropathy, ischemia, infection, inadequate glycemic control, poor nutritional status, and severe morbidity. It is currently believed that oxidative stress plays a vital role in diabetic wound healing. An imbalance of free radicals and antioxidants in the body results in overproduction of reactive oxygen species which lead to cell, tissue damage, and delayed wound healing. Therefore, decreasing ROS levels through antioxidative systems may reduce oxidative stress-induced damage to improve healing. In this context, we provide an update on the role of oxidative stress and antioxidants in diabetic wound healing through following four perspectives. We then discuss several therapeutic strategies especially dietary bioactive compounds by targeting oxidative stress to improve wounds healing.
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Affiliation(s)
- Liling Deng
- Department of Endocrinology, Multidisciplinary Diabetic Foot Medical Center, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing 400014, China
| | - Chenzhen Du
- Department of Endocrinology, Multidisciplinary Diabetic Foot Medical Center, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing 400014, China
| | - Peiyang Song
- Department of Endocrinology, Multidisciplinary Diabetic Foot Medical Center, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing 400014, China
| | - Tianyi Chen
- Department of Endocrinology, Multidisciplinary Diabetic Foot Medical Center, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing 400014, China
| | - Shunli Rui
- Department of Endocrinology, Multidisciplinary Diabetic Foot Medical Center, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing 400014, China
| | - David G. Armstrong
- Department of Surgery, Keck School of Medicine of the University of Southern California, CA, USA
| | - Wuquan Deng
- Department of Endocrinology, Multidisciplinary Diabetic Foot Medical Center, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing 400014, China
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Jiang LL, Liu L. Effect of metformin on stem cells: Molecular mechanism and clinical prospect. World J Stem Cells 2020; 12:1455-1473. [PMID: 33505595 PMCID: PMC7789120 DOI: 10.4252/wjsc.v12.i12.1455] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 09/28/2020] [Accepted: 10/23/2020] [Indexed: 02/06/2023] Open
Abstract
Metformin is a first-line medication for type II diabetes. Numerous studies have shown that metformin not only has hypoglycemic effects, but also modulates many physiological and pathological processes ranging from aging and cancer to fracture healing. During these different physiological activities and pathological changes, stem cells usually play a core role. Thus, many studies have investigated the effects of metformin on stem cells. Metformin affects cell differentiation and has promising applications in stem cell medicine. It exerts anti-aging effects and can be applied to gerontology and regenerative medicine. The potential anti-cancer stem cell effect of metformin indicates that it can be an adjuvant therapy for cancers. Furthermore, metformin has beneficial effects against many other diseases including cardiovascular and autoimmune diseases. In this review, we summarize the effects of metformin on stem cells and provide an overview of its molecular mechanisms and clinical prospects.
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Affiliation(s)
- Lin-Li Jiang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Lei Liu
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China.
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Raghavan S, Malayaperumal S, Mohan V, Balasubramanyam M. A comparative study on the cellular stressors in mesenchymal stem cells (MSCs) and pancreatic β-cells under hyperglycemic milieu. Mol Cell Biochem 2020; 476:457-469. [PMID: 32997307 DOI: 10.1007/s11010-020-03922-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Accepted: 09/19/2020] [Indexed: 12/30/2022]
Abstract
β-cell dysfunction is a critical determinant for both type 1 diabetes and type 2 diabetes and β-cells are shown to be highly susceptible to cellular stressors. Mesenchymal stem cells (MSCs) on the other hand are known to have immunomodulatory potential and preferred in clinical applications. However, there is paucity of a comparative study on these cells in relation to several cellular stressors in response to hyperglycemia and this forms the rationale for the present study. INS1 β-cells and MSCs were subjected to high-glucose treatment without and with Metformin, Lactoferrin, or TUDCA and assessed for stress signaling alterations using gene expression, protein expression, as well as functional read-outs. Compared to the untreated control cells, INS1 β-cells or MSCs treated with high glucose showed significant increase in mRNA expressions of ER stress, senescence, and proinflammation. This was accompanied by increased miR146a target genes and decreased levels of SIRT1, NRF2, and miR146a in both the cell types. Consistent with the mRNA results, protein expression levels do reflect the same alterations. Notably, the alterations are relatively less extent in MSCs compared to INS1 β-cells. Interestingly, three different agents, viz., Metformin, Lactoferrin, or TUDCA, were found to overcome the high glucose-induced cellular stresses in a concerted and inter-linked way and restored the proliferation and migration capacity in MSCs as well as normalized the glucose-stimulated insulin secretion in INS1 β-cells. While our study gives a directionality for potential supplementation of metformin/lactoferrin/TUDCA in optimization protocols of MSCs, we suggest that in vitro preconditioning of MSCs with such factors should be further explored with in-depth investigations to harness and enhance the therapeutic capacity/potential of MSCs.
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Affiliation(s)
- Srividhya Raghavan
- Department of Cell and Molecular Biology, Dr. Mohan's Diabetes Specialties Centre, ICMR- Centre for Advanced Research On Diabetes, Madras Diabetes Research Foundation, Gopalapuram, Chennai, 600 086, India
| | - Sarubala Malayaperumal
- Department of Cell and Molecular Biology, Dr. Mohan's Diabetes Specialties Centre, ICMR- Centre for Advanced Research On Diabetes, Madras Diabetes Research Foundation, Gopalapuram, Chennai, 600 086, India
| | - Viswanathan Mohan
- Department of Cell and Molecular Biology, Dr. Mohan's Diabetes Specialties Centre, ICMR- Centre for Advanced Research On Diabetes, Madras Diabetes Research Foundation, Gopalapuram, Chennai, 600 086, India
| | - Muthuswamy Balasubramanyam
- Department of Cell and Molecular Biology, Dr. Mohan's Diabetes Specialties Centre, ICMR- Centre for Advanced Research On Diabetes, Madras Diabetes Research Foundation, Gopalapuram, Chennai, 600 086, India. .,Medical and Health Sciences (MHS), SRM Institute of Science and Technology (SRMIST), SRM Nagar, Kattankulathur, Kanchipuram, Chennai, 603 203, India.
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