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Yang HA, Hsu RJ, Jheng WL, Weng FJ, Lee JJ. Comparative Efficacy of Regenerative Therapies for Diabetic Foot Ulcers: A Network Meta-analysis. Ann Plast Surg 2025; 94:S24-S32. [PMID: 39996539 DOI: 10.1097/sap.0000000000004192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/26/2025]
Abstract
BACKGROUND Diabetic foot ulcer (DFU) is one of the most dreaded complications of diabetes mellitus and is associated with a high risk of lower limb amputation and mortality. Because the efficacy of conventional treatments for DFUs is often limited, regenerative medicine therapy, such as growth factors and stem cells, may provide a solution to chronic wound healing. In this study, we compared several kinds of regenerative therapy for treating DFUs in terms of efficacy. METHODS We systemically searched relevant studies on PubMed, Cochrane Library, and EMBASE. Randomized clinical trials on conventional treatment combined with platelet-rich plasma (PRP), epidermal growth factor (EGF), or stem cell therapy, compared with conventional treatment alone in patients with DFUs, were included in this study. RESULTS A total of 1454 patients from 23 randomized controlled trials (RCTs) were included in the network meta-analysis. In terms of the number of completely healed ulcers, no significant difference was noted between PRP, stem cell therapy, and EGF group. We also performed surface under the cumulative ranking curve analyses to predict the rank of each intervention by the number of completely healed ulcers. The predicted ranking was as follows: stem cell, PRP, EGF, and the control group (conventional treatment alone). Furthermore, when we compared the mean of the wound healing time of DFUs among these four interventions, we found that the PRP group achieved significantly earlier ulcer healing than the stem cell, EGF, and control groups. No significant difference was observed in the time needed for wound healing between the stem cell and EGF groups. Funnel plot analysis demonstrated no publication bias. CONCLUSIONS PRP combined with conventional treatment significantly accelerates wound healing for DFUs. The mean wound healing time was similar between the stem cell and EGF groups. However, additional reviews of rigorous, large, well-designed RCTs are warranted for further validation of our findings.
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Affiliation(s)
| | | | | | | | - Jian-Jr Lee
- Department of Plastic and Reconstructive Surgery, China Medical University Hospital, Taichung City, Taiwan
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Lee HM, Ryu H. Bioresorbable Materials for Wound Management. Biomimetics (Basel) 2025; 10:108. [PMID: 39997131 PMCID: PMC11852938 DOI: 10.3390/biomimetics10020108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Revised: 02/10/2025] [Accepted: 02/10/2025] [Indexed: 02/26/2025] Open
Abstract
Chronic wounds pose a significant healthcare challenge due to their risk of severe complications, necessitating effective management strategies. Bioresorbable materials have emerged as an innovative solution, offering advantages such as eliminating the need for secondary surgical removal, reducing infection risks, and enabling time-delayed drug delivery. This review examines recent advancements in bioresorbable wound healing materials, focusing on a systematic review of bioresorbable materials, systems incorporating electrical stimulation, and drug delivery technologies to accelerate tissue repair. The discussion encompasses the fundamental principles of bioresorbable materials, including their resorption mechanisms and key properties, alongside preclinical applications that demonstrate their practical potential. Critical challenges impeding widespread adoption are addressed, and prospects for integrating these cutting-edge systems into clinical practice are outlined. Together, these insights underscore the promise of bioresorbable materials in revolutionizing chronic wound care.
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Affiliation(s)
- Hye-Min Lee
- Department of Advanced Materials Engineering, Chung-Ang University, Anseong-si 17546, Gyeonggi-do, Republic of Korea
| | - Hanjun Ryu
- Department of Advanced Materials Engineering, Chung-Ang University, Anseong-si 17546, Gyeonggi-do, Republic of Korea
- Department of Intelligence Energy and Industry, Chung-Ang University, Seoul 06974, Republic of Korea
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Zhao S, Hu X, Zhao Y, Zhang Y, Jin Y, Hua F, Xu Y, Ding W. Hydrogel-based therapies for diabetic foot ulcers: recent developments and clinical implications. BURNS & TRAUMA 2025; 13:tkae084. [PMID: 39917278 PMCID: PMC11801273 DOI: 10.1093/burnst/tkae084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Revised: 12/03/2024] [Accepted: 12/06/2024] [Indexed: 02/09/2025]
Abstract
The diabetic foot ulcer is among the most serious diabetes-associated complications, with a long disease course considerably increasing the pain and economic burden of patients, leading to amputation and even death. High blood sugar is characteristic of diabetic foot ulcers, with insufficient blood supply, oxidative stress disorder, and high-risk bacterial infection posing great challenges for disease treatment. Advances in hydrogel dressings have shown potential for the management of diabetic foot ulcers involving multisystem lesions. This study comprehensively reviews the pathogenesis of diabetic foot ulcers and advances in hydrogel dressings in treating diabetic foot ulcers, providing innovative perspectives for assessing the nursing care requirements and associated clinical applications.
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Affiliation(s)
- Shuao Zhao
- Department of Traumatic Orthopaedics, Third Affiliated Hospital of Soochow University, Soochow University, No. 185 Juqian Road, Changzhou 213003, Jiangsu, China
- Orthopaedic Institute, Suzhou Medical College, Soochow University, No. 178 East Ganjiang Road, Suzhou 215000, Jiangsu, China
| | - Xinyu Hu
- Department of Traumatic Orthopaedics, Third Affiliated Hospital of Soochow University, Soochow University, No. 185 Juqian Road, Changzhou 213003, Jiangsu, China
| | - Yiwen Zhao
- Department of Traumatic Orthopaedics, Third Affiliated Hospital of Soochow University, Soochow University, No. 185 Juqian Road, Changzhou 213003, Jiangsu, China
| | - Yige Zhang
- Department of Traumatic Orthopaedics, Third Affiliated Hospital of Soochow University, Soochow University, No. 185 Juqian Road, Changzhou 213003, Jiangsu, China
| | - Yesheng Jin
- Orthopaedic Institute, Suzhou Medical College, Soochow University, No. 178 East Ganjiang Road, Suzhou 215000, Jiangsu, China
- Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou Medical College, Soochow University, No. 899 Pinghai Road, Suzhou 215000, Jiangsu, China
| | - Fei Hua
- Department of Endocrine, Third Affiliated Hospital of Soochow University, No. 185 Juqian Road, Changzhou 213003, Jiangsu, China
| | - Yong Xu
- Orthopaedic Institute, Suzhou Medical College, Soochow University, No. 178 East Ganjiang Road, Suzhou 215000, Jiangsu, China
- Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou Medical College, Soochow University, No. 899 Pinghai Road, Suzhou 215000, Jiangsu, China
| | - Wenge Ding
- Department of Traumatic Orthopaedics, Third Affiliated Hospital of Soochow University, Soochow University, No. 185 Juqian Road, Changzhou 213003, Jiangsu, China
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Tong L, Tang L, Tang B, Zhang J. Impacts of stem cells from different sources on wound healing rate in diabetic foot ulcers: a systematic review and meta-analysis. Front Genet 2025; 15:1541992. [PMID: 39935694 PMCID: PMC11811113 DOI: 10.3389/fgene.2024.1541992] [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: 12/09/2024] [Accepted: 12/31/2024] [Indexed: 02/13/2025] Open
Abstract
Background Diabetic foot ulcers (DFU) are a significant complication of diabetes, with huge implications on patient morbidity and healthcare costs. The objective of this meta-analysis was to evaluate the impacts of stem cells from different sources on wound healing rate in DFU patients. Methods We systematically retrieved records via key databases PubMed, Cochrane Library, Web of Science, Embase, China National Knowledge Infrastructure (CNKI) and Wanfang from the inception to October 2024. The Stata 16.0 (Stata Corp, TX) software was used to perform the meta-analysis. Risk of bias in all included studies was evaluated by Cochrane Risk of Bias version 2. Results A total of 24 studies involving 1,321 patients were included. There was an increased likelihood of wound healing with peripheral blood-derived stem cells, the most effective cells (odds ratios (OR) = 7.31, 95% CI: 2.90-18.47), followed by adipose-derived stem cells (OR = 5.23, 95% CI: 2.76-9.90), umbilical cord-derived stem cells (OR = 4.94, 95% CI: 0.61-40.03), bone-derived stem cells (OR = 4.36, 95% CI: 2.43-7.85) and other sources stem cells (OR = 3.16, 95% CI: 1.83-5.45). Nevertheless, only umbilical cord-derived stem cells showed statistical significance (p < 0.05). The heterogeneity ranged from non-existent in the adipose and peripheral blood groups (I2 = 0.00%) to moderate in the bone groups (I2 = 26.31%) and other groups (I2 = 30.62%), and substantial in the umbilical cord groups (I2 = 88.37%). Asymmetrical funnel plots pointed to publication bias, but the trim-and-fill method to correct for this brought the effect estimates even lower: based on the pooled OR, corrected OR was 3.40 (95% CI 2.39-4.84). Stem cell therapy was also associated with improvements in several secondary outcomes, suggesting its potential to influence the progression of DFU. Conclusion Our study suggested that stem cells from different sources showed potential in promoting wound healing in DFU, although with some variation in effectiveness. Despite some publication bias and moderate heterogeneity, the overall therapeutic effect remained positive. These findings indicated that stem cell therapy might influence the progression of DFU.
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Affiliation(s)
- Le Tong
- Department of Emergency Medicine, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, China
- Disaster Medical Center, Sichuan University, Chengdu, China
- Nursing Key Laboratory of Sichuan Province, Chengdu, China
| | - Lin Tang
- Department of Emergency Medicine, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, China
- Disaster Medical Center, Sichuan University, Chengdu, China
- Nursing Key Laboratory of Sichuan Province, Chengdu, China
| | - Bangli Tang
- Department of Dermatology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China
| | - Jianna Zhang
- Department of Emergency Medicine, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, China
- Disaster Medical Center, Sichuan University, Chengdu, China
- Nursing Key Laboratory of Sichuan Province, Chengdu, China
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Yang R, Zhou Y, Hu Y, Liu S. Periosteal distraction as a new surgical technique for the treatment of senile diabetic foot: A retrospective case analysis. Medicine (Baltimore) 2025; 104:e41183. [PMID: 40184093 PMCID: PMC11709152 DOI: 10.1097/md.0000000000041183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 12/09/2024] [Accepted: 12/13/2024] [Indexed: 04/05/2025] Open
Abstract
This study investigates the clinical effect and safety of periosteal distraction in the treatment of senile diabetic foot. The clinical data of 45 patients with diabetic foot treated with periosteal distraction in the Central Hospital of Dalian University of Technology from January 2020 to May 2024 were retrospectively analyzed. Finally, 42 patients were followed up, and 3 patients were lost to follow-up, including 29 males and 13 females, aged (71.17 ± 6.43), (62-84) years respectively. The Wagner grade of the ulcer surface of the affected foot was grade 2 in 25 cases, grade 3 in 13 cases, and grade 4 in 4 cases; the ulcer sites were toes in 18 cases, soles in 14 cases, dorsum of the foot in 8 cases, heels in 1 case, and ankles in 1 case. The toe oxygen saturation, ankle-brachial index (ABI), skin temperature and visual analogue score (VAS) were recorded before operation and at 1 day, 7 days, 14 days, 1 month, 2 months, and 3 months after operation. The therapeutic effect was observed and evaluated in combination with Michigan neurological sign score and lower limb computed tomography angiography. The wound ulcer healing rate, amputation rate and ulcer recurrence were also counted. The toe oxygen saturation, ABI, skin temperature, VAS score and Michigan neurological sign score of all patients were significantly improved after operation compared with those before operation, and the differences were statistically significant (P < .05); After a 3-month post-surgery period, 37 patients were observed to have microcirculation formation in the affected limb, as well as increased and thickened lower extremity arterioles in comparison to pre-surgery conditions, forming an interwoven network. During the follow-up period, 21 patients exhibited healed foot ulcers at 2 months post-surgery, while by the end of the follow-up period, 38 patients had healed foot ulcers, 5 patients had experienced a significant reduction in wound ulcer area, and the overall ulcer healing rate was 90%. Notably, no instances of amputation or ulcer recurrence were observed during treatment. Periosteal distraction is a new surgical method for the treatment of senile diabetic foot ulcer, which can obtain satisfactory short-term efficacy and is worthy of clinical promotion.
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Affiliation(s)
- Rui Yang
- School of Graduates, Dalian Medical University, Dalian City, Liaoning Province, China
- Department of Orthopedics, Central Hospital of Dalian University of Technology, Dalian City, Liaoning Province, China
| | - Yue Zhou
- Department of Orthopedics, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P.R. China
| | - Yunxiang Hu
- Department of Orthopedics, The Second Affiliated Hospital, Dalian Medical University, Dalian, Liaoning, P.R. China
| | - Sanmao Liu
- Department of Orthopedics, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P.R. China
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Cheng X, Li YL, Wang H, Zhang RJ, Fan KY, Qi XT, Zheng GP, Dong HL. Mesenchymal stem cell therapy in atherosclerosis: A bibliometric and visual analysis. World J Stem Cells 2024; 16:1062-1085. [PMID: 39734478 PMCID: PMC11669984 DOI: 10.4252/wjsc.v16.i12.1062] [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: 05/03/2024] [Revised: 10/15/2024] [Accepted: 11/18/2024] [Indexed: 12/13/2024] Open
Abstract
BACKGROUND Mesenchymal stem cells (MSCs) are capable of self-renewal and differentiation, and extensive studies have demonstrated their therapeutic potential in atherosclerosis (AS). AIM To conduct a bibliometric analysis of studies on the use of MSC therapy for AS over the past two decades, assess key trends and provide insights for future research directions. METHODS We systematically searched the Web of Science Core Collection database for articles published between 1999 and 2023, yielding a total of 556 articles. Visual representation and bibliometric analysis of information and trends were facilitated using CiteSpace, the R package 'bibliometrix' and VOSviewer. RESULTS The analyzed articles were predominantly from 52 countries/regions, with prominent contributions from China and the United States. A cohort of 3057 authors contributed to these publications, with the works of Libby P distinguished by their influence and citation count. Int J Mol Sci has emerged as the journal with the highest publication volume, prominently disseminating influential papers and identifying citation outbreaks. Furthermore, our analysis identified current research hotspots within the field, focusing on vascular progenitor cells, inflammatory mechanisms, and extracellular vesicles. Emerging research frontiers, such as extracellular vesicles and oxidative stress, have been highlighted as areas of burgeoning interest. Finally, we offer perspectives on the status of research and future directions of MSC therapy in AS. CONCLUSION This comprehensive analysis provides valuable insights for advancing scientific research on MSC therapy for AS. By elucidating pivotal trends and research directions, this study aimed to foster innovation and promote the progress of disciplines in this field, thereby contributing to advancing scientific knowledge and clinical practice.
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Affiliation(s)
- Xing Cheng
- Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
| | - Ya-Ling Li
- Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
| | - Heng Wang
- Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney 2145, New South Wales, Australia
| | - Rui-Jing Zhang
- Department of Nephrology, The Second Hospital of Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
| | - Ke-Yi Fan
- Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
| | - Xiao-Tong Qi
- Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
| | - Guo-Ping Zheng
- Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
- Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney 2145, New South Wales, Australia
| | - Hong-Lin Dong
- Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan 030000, Shanxi Province, China.
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Zhang R, Mu X, Liu D, Chen C, Meng B, Qu Y, Liu J, Wang R, Li C, Mao X, Wang Q, Zhang Q. Apoptotic vesicles rescue impaired mesenchymal stem cells and their therapeutic capacity for osteoporosis by restoring miR-145a-5p deficiency. J Nanobiotechnology 2024; 22:580. [PMID: 39304875 PMCID: PMC11414301 DOI: 10.1186/s12951-024-02829-2] [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: 05/14/2024] [Accepted: 09/01/2024] [Indexed: 09/22/2024] Open
Abstract
Apoptotic vesicles (apoVs) play a vital role in various physiological and pathological conditions. However, we have yet to fully understand their precise biological effects in rescuing impaired mesenchymal stem cells (MSCs). Here, we proved that systemic infusion of MSCs derived from wild-type (WT) mice rather than from ovariectomized (OVX) mice effectively improved the osteopenia phenotype and rescued the impaired recipient MSCs in osteoporotic mice. Meanwhile, apoVs derived from WT MSCs (WT apoVs) instead of OVX apoVs efficiently restored the impaired biological function of OVX MSCs and their ability to improve osteoporosis. Mechanistically, the reduced miR-145a-5p expression hindered the osteogenic differentiation and immunomodulatory capacity of OVX MSCs by affecting the TGF-β/Smad 2/3-Wnt/β-catenin signaling axis, resulting in the development of osteoporosis. WT apoVs directly transferred miR-145a-5p to OVX MSCs, which were then reused to restore their impaired biological functions. The differential expression of miR-145a-5p is responsible for the distinct efficacy between the two types of apoVs. Overall, our findings unveil the remarkable potential of apoVs, as a novel nongenetic engineering approach, in rescuing the biological function and therapeutic capability of MSCs derived from patients. This discovery offers a new avenue for exploring apoVs-based stem cell engineering and expands the application scope of stem cell therapy, contributing to the maintenance of bone homeostasis through a previously unrecognized mechanism.
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Affiliation(s)
- Rong Zhang
- Department of Temporomandibular Joint, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction & Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou, Guangdong, 510180, China
- Department of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA
- Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, Guangdong, 510055, China
| | - Xiaodan Mu
- Department of Stomatology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Dawei Liu
- Department of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA
- Department of Orthodontics, Peking University School & Hospital of Stomatology, Beijing, 100081, China
| | - Chider Chen
- Department of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA
| | - Bowen Meng
- Hospital of Stomatology, Guanghua School of Stomatology, Center of Craniofacial Stem Cell Research, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, 510055, China
| | - Yan Qu
- Hospital of Stomatology, Guanghua School of Stomatology, Center of Craniofacial Stem Cell Research, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, 510055, China
| | - Jin Liu
- Department of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA
- Lab of Aging Research and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Runci Wang
- Department of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA
| | - Chuanjie Li
- Department of Temporomandibular Joint, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction & Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou, Guangdong, 510180, China
| | - Xueli Mao
- Department of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA
- Hospital of Stomatology, Guanghua School of Stomatology, Center of Craniofacial Stem Cell Research, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, 510055, China
| | - Qintao Wang
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Air Force Medical University, Xi'an, Shaanxi, 710032, China.
| | - Qingbin Zhang
- Department of Temporomandibular Joint, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction & Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou, Guangdong, 510180, China.
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Xia Y, Wu P, Chen H, Chen Z. Advances in stem cell therapy for diabetic foot. Front Genet 2024; 15:1427205. [PMID: 39290985 PMCID: PMC11405205 DOI: 10.3389/fgene.2024.1427205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Accepted: 08/14/2024] [Indexed: 09/19/2024] Open
Abstract
Diabetic Foot Ulcers (DFU) represent a grave complication often encountered in the advanced stages of diabetes mellitus. They frequently lead to recurrent hospitalizations and, in severe cases, can result in life-threatening conditions such as infections, gangrene, and even amputation Diabetic foot ulcers (DFU), as a serious complication in the late stage of diabetes mellitus, are prone to lead to repeated hospitalization, and in severe cases, infection, gangrene, and even amputation. Although there are many methods for treating diabetic foot, there is no clear and effective method to reduce the amputation rate of diabetic foot patients. In recent years, advancements in the understanding of stem cell therapy for the treatment of DFU have shed light on its potential as a novel therapeutic approach. In recent years, as the research on stem cell therapy for diabetic foot is gradually deepening, stem cells are expected to become a new therapeutic method for treating DFU in the future. Their therapeutic effects are through promoting angiogenesis, secreting paracrine factors, controlling inflammation, promoting collagen deposition, and regulating immunity, etc. Despite numerous studies confirming the efficacy of stem cell therapy in treating DFU, there is still a need for the establishment of standardized treatment protocols. Although numerous studies have shown that stem cell therapy for DFU is real and effective, there has not yet been a standardized treatment protocol. This article reviews studies related to stem cell therapy for DFU, looking at the mechanism of action, types of stem cells, and modes of administration.
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Affiliation(s)
- Yinfeng Xia
- Department of Burn and Plastic Surgery, Chongqing University Fuling Hospital, Chongqing University, Chongqing, China
| | - Ping Wu
- Department of Burn and Plastic Surgery, Chongqing University Fuling Hospital, Chongqing University, Chongqing, China
| | - Hong Chen
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing MedicalUniversity, Chongqing, China
| | - Zhiyong Chen
- Department of Burn and Plastic Surgery, Chongqing University Fuling Hospital, Chongqing University, Chongqing, China
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Ren Y, Wang H, Song X, Wu Y, Lyu Y, Zeng W. Advancements in diabetic foot insoles: a comprehensive review of design, manufacturing, and performance evaluation. Front Bioeng Biotechnol 2024; 12:1394758. [PMID: 39076210 PMCID: PMC11284111 DOI: 10.3389/fbioe.2024.1394758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2024] [Accepted: 05/24/2024] [Indexed: 07/31/2024] Open
Abstract
The escalating prevalence of diabetes has accentuated the significance of addressing the associated diabetic foot problem as a major public health concern. Effectively offloading plantar pressure stands out as a crucial factor in preventing diabetic foot complications. This review comprehensively examines the design, manufacturing, and evaluation strategies employed in the development of diabetic foot insoles. Furthermore, it offers innovative insights and guidance for enhancing their performance and facilitating clinical applications. Insoles designed with total contact customization, utilizing softer and highly absorbent materials, as well as incorporating elliptical porous structures or triply periodic minimal surface structures, prove to be more adept at preventing diabetic foot complications. Fused Deposition Modeling is commonly employed for manufacturing; however, due to limitations in printing complex structures, Selective Laser Sintering is recommended for intricate insole designs. Preceding clinical implementation, in silico and in vitro testing methodologies play a crucial role in thoroughly evaluating the pressure-offloading efficacy of these insoles. Future research directions include advancing inverse design through machine learning, exploring topology optimization for lightweight solutions, integrating flexible sensor configurations, and innovating new skin-like materials tailored for diabetic foot insoles. These endeavors aim to further propel the development and effectiveness of diabetic foot management strategies. Future research avenues should explore inverse design methodologies based on machine learning, topology optimization for lightweight structures, the integration of flexible sensors, and the development of novel skin-like materials specifically tailored for diabetic foot insoles. Advancements in these areas hold promise for further enhancing the effectiveness and applicability of diabetic foot prevention measures.
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Affiliation(s)
- Yuanfei Ren
- The First Department of Hand and Foot Surgery, Central Hospital of Dalian University of Technology, Dalian, China
| | - Hao Wang
- Department of Engineering Mechanics, School of Mechanics and Aerospace Engineering, Dalian University of Technology, Dalian, China
| | - Xiaoshuang Song
- Department of Engineering Mechanics, School of Mechanics and Aerospace Engineering, Dalian University of Technology, Dalian, China
| | - Yanli Wu
- Department of Engineering Mechanics, School of Mechanics and Aerospace Engineering, Dalian University of Technology, Dalian, China
| | - Yongtao Lyu
- Department of Engineering Mechanics, School of Mechanics and Aerospace Engineering, Dalian University of Technology, Dalian, China
- DUT-BSU Joint Institute, Dalian University of Technology, Dalian, China
| | - Wei Zeng
- Department of Mechanical Engineering, New York Institute of Technology, New York, NY, United States
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10
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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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11
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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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12
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Memarpour S, Raoufinia R, Saburi E, Razavi MS, Attaran M, Fakoor F, Rahimi HR. The future of diabetic wound healing: unveiling the potential of mesenchymal stem cell and exosomes therapy. AMERICAN JOURNAL OF STEM CELLS 2024; 13:87-100. [PMID: 38765803 PMCID: PMC11101987 DOI: 10.62347/ovbk9820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Accepted: 03/18/2024] [Indexed: 05/22/2024]
Abstract
Diabetes mellitus (DM) is a significant public health problem and is one of the most challenging medical conditions worldwide. It is the severe complications that make this disease more intricate. A diabetic wound is one of these complications. Patients with diabetes are at higher risk of developing diabetic foot ulcers (DFU). Due to the ineffectiveness of Conventional treatments, growth in limb amputation, morbidity, and mortality have been recognized, which indicates the need for additional treatment. Mesenchymal stem cells (MSCs) can significantly improve wound healing. However, there are some risks related to stem cell therapy. Exosome therapy is a new treatment option for diabetic wounds that has shown promising results. However, an even more advanced form called cell-free therapy using exosomes has emerged. This upgraded version of stem cell therapy offers improved efficacy and eliminates the risk of cancer progression. Exosome therapy promotes wound healing from multiple angles, unlike traditional methods that primarily rely on the body's self-healing ability and only provide wound protection. Therefore, exosome therapy has the potential to replace conventional treatments effectively. However, further research is necessary to distinguish the optimal type of stem cells for therapy, ensure their safety, establish appropriate dosing, and identify the best management trail. The present study focused on the current literature on diabetic wound ulcers, their treatment, and mesenchymal stem cell and exosome therapy potential in DFU.
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Affiliation(s)
- Sara Memarpour
- Medical Genetics Research Center, Mashhad University of Medical SciencesMashhad, Iran
| | - Ramin Raoufinia
- Medical Genetics Research Center, Mashhad University of Medical SciencesMashhad, Iran
- Department of Basic Medical Sciences, Neyshabur University of Medical SciencesNeyshabur, Iran
| | - Ehsan Saburi
- Medical Genetics Research Center, Mashhad University of Medical SciencesMashhad, Iran
| | - Masoud Sharifian Razavi
- Department of Internal Medicine, Ghaem Hospital, Mashhad University of Medical SciencesMashhad, Iran
| | - Matin Attaran
- Department of Obstetrics and Gynecology, Mashhad University of Medical SciencesMashhad, Iran
| | - Farhad Fakoor
- Department of Paramedical Sciences, Iran University of Medical SciencesTehran, Iran
| | - Hamid Reza Rahimi
- Vascular and Endovascular Surgery Research Center, Mashhad University of Medical SciencesMashhad, Iran
- Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical SciencesMashhad, Iran
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13
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Zhang Y, Li J, Liu M. Efficacy of stem cell therapy for diabetic foot: Clinical evidence from meta-analyses. Int Wound J 2024; 21:e14632. [PMID: 38156706 PMCID: PMC10961866 DOI: 10.1111/iwj.14632] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Revised: 12/13/2023] [Accepted: 12/14/2023] [Indexed: 01/03/2024] Open
Abstract
To assess the clinical data on the effectiveness of stem cell therapy for diabetic foot (DF) based on recent systematic reviews and meta-analyses (SRs/MAs). SRs/MAs that evaluate the clinical evidence on the efficacy of stem cell therapy for DF were identified through a systematic search in public databases. The methodological quality and evidence quality of the included SRs/MAs were assessed separately by two researchers. Eight SRs/MAs were included in this analysis. Since there were no registered protocol or exclusion criteria for the included SRs/MAs, the methodological quality was rated as critically low. There was no high-quality evidence available for the outcomes, and the evidence quality ranged from critically low to moderate. Evidence degradation was most commonly caused by the risk of bias, followed by imprecision, publication bias and inconsistency. In conclusion, stem cell therapy may be effective for DF. However, this conclusion should be approached with caution, considering the quality of the supporting SRs/MAs.
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Affiliation(s)
- Yao Zhang
- The First Clinical Medical SchoolGuangzhou University of Chinese MedicineGuangzhouChina
| | - Jing Li
- Shangqiu Institute of TechnologyShangqiuChina
| | - Min Liu
- The First Affiliated HospitalGuangzhou University of Chinese MedicineGuangzhouChina
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14
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Hetta HF, Elsaghir A, Sijercic VC, Akhtar MS, Gad SA, Moses A, Zeleke MS, Alanazi FE, Ahmed AK, Ramadan YN. Mesenchymal stem cell therapy in diabetic foot ulcer: An updated comprehensive review. Health Sci Rep 2024; 7:e2036. [PMID: 38650719 PMCID: PMC11033295 DOI: 10.1002/hsr2.2036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Revised: 02/06/2024] [Accepted: 03/19/2024] [Indexed: 04/25/2024] Open
Abstract
Background Diabetes has evolved into a worldwide public health issue. One of the most serious complications of diabetes is diabetic foot ulcer (DFU), which frequently creates a significant financial strain on patients and lowers their quality of life. Up until now, there has been no curative therapy for DFU, only symptomatic relief or an interruption in the disease's progression. Recent studies have focused attention on mesenchymal stem cells (MSCs), which provide innovative and potential treatment candidates for several illnesses as they can differentiate into various cell types. They are mostly extracted from the placenta, adipose tissue, umbilical cord (UC), and bone marrow (BM). Regardless of their origin, they show comparable features and small deviations. Our goal is to investigate MSCs' therapeutic effects, application obstacles, and patient benefit strategies for DFU therapy. Methodology A comprehensive search was conducted using specific keywords relating to DFU, MSCs, and connected topics in the databases of Medline, Scopus, Web of Science, and PubMed. The main focus of the selection criteria was on English-language literature that explored the relationship between DFU, MSCs, and related factors. Results and Discussion Numerous studies are being conducted and have demonstrated that MSCs can induce re-epithelialization and angiogenesis, decrease inflammation, contribute to immunological modulation, and subsequently promote DFU healing, making them a promising approach to treating DFU. This review article provides a general snapshot of DFU (including clinical presentation, risk factors and etiopathogenesis, and conventional treatment) and discusses the clinical progress of MSCs in the management of DFU, taking into consideration the side effects and challenges during the application of MSCs and how to overcome these challenges to achieve maximum benefits. Conclusion The incorporation of MSCs in the management of DFU highlights their potential as a feasible therapeutic strategy. Establishing a comprehensive understanding of the complex relationship between DFU pathophysiology, MSC therapies, and related obstacles is essential for optimizing therapy outcomes and maximizing patient benefits.
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Affiliation(s)
- Helal F. Hetta
- Division of Microbiology, Immunology and Biotechnology, Department of Natural Products and Alternative MedicineFaculty of Pharmacy, University of TabukTabukSaudi Arabia
- Department of Medical Microbiology and ImmunologyFaculty of Medicine, Assiut UniversityAssiutEgypt
| | - Alaa Elsaghir
- Department of Microbiology and ImmunologyFaculty of Pharmacy, Assiut UniversityAssiutEgypt
| | | | | | - Sayed A. Gad
- Faculty of Medicine, Assiut UniversityAssiutEgypt
| | | | - Mahlet S. Zeleke
- Menelik II Medical and Health Science College, Kotebe Metropolitan UniversityAddis AbabaEthiopia
| | - Fawaz E. Alanazi
- Department of Pharmacology and ToxicologyFaculty of Pharmacy, University of TabukTabukSaudi Arabia
| | | | - Yasmin N. Ramadan
- Department of Microbiology and ImmunologyFaculty of Pharmacy, Assiut UniversityAssiutEgypt
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15
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Wang Y, Li F, Mao L, Liu Y, Chen S, Liu J, Huang K, Chen Q, Wu J, Lu L, Zheng Y, Shen W, Ying T, Dai Y, Shen Y. Promoting collateral formation in type 2 diabetes mellitus using ultra-small nanodots with autophagy activation and ROS scavenging. J Nanobiotechnology 2024; 22:85. [PMID: 38429826 PMCID: PMC10908163 DOI: 10.1186/s12951-024-02357-z] [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: 01/03/2024] [Accepted: 02/20/2024] [Indexed: 03/03/2024] Open
Abstract
BACKGROUND Impaired collateral formation is a major factor contributing to poor prognosis in type 2 diabetes mellitus (T2DM) patients with atherosclerotic cardiovascular disease. However, the current pharmacological treatments for improving collateral formation remain unsatisfactory. The induction of endothelial autophagy and the elimination of reactive oxygen species (ROS) represent potential therapeutic targets for enhancing endothelial angiogenesis and facilitating collateral formation. This study investigates the potential of molybdenum disulfide nanodots (MoS2 NDs) for enhancing collateral formation and improving prognosis. RESULTS Our study shows that MoS2 NDs significantly enhance collateral formation in ischemic tissues of diabetic mice, improving effective blood resupply. Additionally, MoS2 NDs boost the proliferation, migration, and tube formation of endothelial cells under high glucose/hypoxia conditions in vitro. Mechanistically, the beneficial effects of MoS2 NDs on collateral formation not only depend on their known scavenging properties of ROS (H2O2, •O2-, and •OH) but also primarily involve a molecular pathway, cAMP/PKA-NR4A2, which promotes autophagy and contributes to mitigating damage in diabetic endothelial cells. CONCLUSIONS Overall, this study investigated the specific mechanism by which MoS2 NDs mediated autophagy activation and highlighted the synergy between autophagy activation and antioxidation, thus suggesting that an economic and biocompatible nano-agent with dual therapeutic functions is highly preferable for promoting collateral formation in a diabetic context, thus, highlighting their therapeutic potential.
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Affiliation(s)
- Yixuan Wang
- Department of Cardiovascular Medicine, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
- Shanghai Clinical Research Center for Interventional Medicine, Shanghai, 200025, China
| | - Feifei Li
- Department of Cardiovascular Medicine, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
- Shanghai Clinical Research Center for Interventional Medicine, Shanghai, 200025, China
| | - Linshuang Mao
- Department of Cardiovascular Medicine, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
- Shanghai Clinical Research Center for Interventional Medicine, Shanghai, 200025, China
| | - Yu Liu
- Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Medicine and Engineering, Beihang University, Beijing, 100191, China
| | - Shuai Chen
- Department of Cardiovascular Medicine, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
- Shanghai Clinical Research Center for Interventional Medicine, Shanghai, 200025, China
| | - Jingmeng Liu
- Department of Cardiovascular Medicine, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
- Shanghai Clinical Research Center for Interventional Medicine, Shanghai, 200025, China
| | - Ke Huang
- Department of Cardiovascular Medicine, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
- Shanghai Clinical Research Center for Interventional Medicine, Shanghai, 200025, China
| | - Qiujing Chen
- Department of Cardiovascular Medicine, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
- Shanghai Clinical Research Center for Interventional Medicine, Shanghai, 200025, China
| | - Jianrong Wu
- Department of Ultrasound in Medicine, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
| | - Lin Lu
- Department of Cardiovascular Medicine, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
- Shanghai Clinical Research Center for Interventional Medicine, Shanghai, 200025, China
| | - Yuanyi Zheng
- Department of Ultrasound in Medicine, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
| | - Weifeng Shen
- Department of Cardiovascular Medicine, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
- Shanghai Clinical Research Center for Interventional Medicine, Shanghai, 200025, China
| | - Tao Ying
- Department of Ultrasound in Medicine, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.
| | - Yang Dai
- Department of Cardiovascular Medicine, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
- Shanghai Clinical Research Center for Interventional Medicine, Shanghai, 200025, China.
| | - Ying Shen
- Department of Cardiovascular Medicine, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
- Shanghai Clinical Research Center for Interventional Medicine, Shanghai, 200025, China.
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16
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Mert S, Heidekrueger PI, Fuchs B, Nuernberger T, Haas-Lützenberger EM, Giunta RE, Ehrl D, Demmer W. Microvascular Muscle vs. Fascio-Cutaneous Free Flaps for Reconstruction of Plantar Load-Bearing Foot Defects-An International Survey. J Clin Med 2024; 13:1287. [PMID: 38592127 PMCID: PMC10932295 DOI: 10.3390/jcm13051287] [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: 01/20/2024] [Revised: 02/18/2024] [Accepted: 02/21/2024] [Indexed: 04/10/2024] Open
Abstract
Background: The reconstruction of plantar load-bearing foot defects faces many plastic surgeons with a major challenge. The optimal patient- and defect-oriented reconstructive strategy must be selected. Methods: To analyze the current trends and recommendations in reconstruction of plantar load-bearing foot defects, we conducted an international survey among plastic surgeons querying them about their recommendations and experiences. Results: The survey revealed that the most common strategies for reconstruction of the foot sole are locoregional and microvascular free flaps, emphasizing the relevance of plastic surgery. Among microvascular free flaps, muscle and fascio-cutaneous free flaps are by far the most frequently used. The target qualities of the reconstructed tissue to be considered are manifold, with adherence being the most frequently mentioned. We observed a noteworthy correlation between the utilization of muscle flaps and a preference for adherence. In addition, we identified a substantial correlation between the usage of fascio-cutaneous free flaps and further target qualities, such as good skin quality and sensitivity. Conclusions: Our findings provide insights into the clinical reality and highlight important aspects that must be considered in reconstruction of the weight-bearing areas of the foot providing support in the selection of the appropriate therapy.
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Affiliation(s)
- Sinan Mert
- Division of Hand, Plastic and Aesthetic Surgery, LMU University Hospital, LMU Munich, 80336 Munich, Germany (W.D.)
| | - Paul I. Heidekrueger
- Centre of Plastic, Aesthetic, Hand and Reconstructive Surgery, University of Regensburg, 93053 Regensburg, Germany
| | - Benedikt Fuchs
- Division of Hand, Plastic and Aesthetic Surgery, LMU University Hospital, LMU Munich, 80336 Munich, Germany (W.D.)
| | - Tim Nuernberger
- Division of Hand, Plastic and Aesthetic Surgery, LMU University Hospital, LMU Munich, 80336 Munich, Germany (W.D.)
| | | | - Riccardo E. Giunta
- Division of Hand, Plastic and Aesthetic Surgery, LMU University Hospital, LMU Munich, 80336 Munich, Germany (W.D.)
| | - Denis Ehrl
- Division of Hand, Plastic and Aesthetic Surgery, LMU University Hospital, LMU Munich, 80336 Munich, Germany (W.D.)
- Department of Plastic, Reconstructive and Hand Surgery, Burn Centre for Severe Burn Injuries, Nuremberg Clinics, University Hospital Paracelsus Medical University, 90419 Nuremberg, Germany
| | - Wolfram Demmer
- Division of Hand, Plastic and Aesthetic Surgery, LMU University Hospital, LMU Munich, 80336 Munich, Germany (W.D.)
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17
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Zhu D, Wei W, Zhang J, Zhao B, Li Q, Jin P. Mechanism of damage of HIF-1 signaling in chronic diabetic foot ulcers and its related therapeutic perspectives. Heliyon 2024; 10:e24656. [PMID: 38318060 PMCID: PMC10839564 DOI: 10.1016/j.heliyon.2024.e24656] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Revised: 01/11/2024] [Accepted: 01/11/2024] [Indexed: 02/07/2024] Open
Abstract
Diabetic foot ulcer (DFU) is a chronic complication of diabetes. Wound healing in patients with DFU is generally very slow, with a high recurrence rate even after the ulcer healed. The DFU remains a major clinical challenge due to a lack of understanding of its pathogenesis. Given the significant impact of DFU on patient health and medical costs, enhancing our understanding of pathophysiological alterations and wound healing in DFU is critical. A growing body of research has shown that impaired activation of the HIF-1 pathway in diabetics, which weakens HIF-1 mediated responses to hypoxia and leads to down-regulation of its downstream target genes, leading to incurable diabetic foot ulcers. By analyzing and summarizing the literature in recent years, this review summarizes the mechanism of HIF-1 signaling pathway damage in the development of DFU, analyzes and compares the application of PHD inhibitors, VHL inhibitors, biomaterials and stem cell therapy in chronic wounds of diabetes, and proposes a new treatment scheme mediated by participation in the HIF-1 signaling pathway, which provides new ideas for the treatment of DFU.
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Affiliation(s)
- Dong Zhu
- Department of Plastic Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Wuhan Wei
- Department of Plastic Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Jingyu Zhang
- Department of Plastic Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Bingkun Zhao
- Department of Plastic Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Qiang Li
- Department of Plastic Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Peisheng Jin
- Department of Plastic Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
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18
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Mudgal SK, Kumar S, Gaur R, Singh H, Saikia D, Varshney S, Gupta P, Grover A, Varikasuvu SR. Effectiveness of Stem Cell Therapy for Diabetic Foot Ulcers: A Systematic Review and GRADE Compliant Bootstrapped Meta-Analysis of Randomized Clinical Trials. INT J LOW EXTR WOUND 2024:15347346241227530. [PMID: 38298002 DOI: 10.1177/15347346241227530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2024]
Abstract
Diabetic foot (DF) represents a severe complication of diabetes mellitus, imposing substantial psychological and economic burdens on affected individuals. This investigation sought to assess the therapeutic efficacy of stem cell interventions in the management of DF complications. A comprehensive systematic search across PubMed, Embase, CINAHL, Scopus, and the Cochrane library databases was conducted to identify pertinent studies for meta-analysis. Outcome measures encompassed ulcer or wound healing rates, amputation rates, angiogenesis, ankle-brachial index (ABI), and pain-free walking distance. Dichotomous outcomes were expressed as risk differences (RDs) with 95% confidence intervals (CIs), while continuous data were articulated as standardized mean differences (SMDs) with corresponding 95% CIs. Statistical analyses were executed using RevMan 5.3 and Open Meta, with bootstrapped meta-analysis conducted through OpenMEE software. A total of 20 studies, comprising 24 arms and involving 1304 participants, were incorporated into the meta-analysis. The findings revealed that stem cell therapy exhibited superior efficacy compared to conventional interventions in terms of ulcer or wound healing rate [RD = 0.36 (0.28, 0.43)], pain-free walking distance [SMD = 1.27 (0.89, 1.65)], ABI [SMD = 0.61 (0.33, 0.88)], and new vessel development [RD = 0.48 (0.23, 0.78)], while concurrently reducing the amputation rate significantly [RD = -0.19 (-0.25, -0.12)]. Furthermore, no statistically significant difference in adverse events was observed [RD -0.07 (-0.16, 0.02)]. The Grading of Recommendations, Assessment, Development, and Evaluation assessment indicated varying levels of evidence certainty, ranging from very low to moderate, for different outcomes. Bootstrapping analysis substantiated the precision of the results. The meta-analysis underscores the significant superiority of stem cell therapy over conventional approaches in treating DF complications. Future investigations should prioritize large-scale, randomized, double-blind, placebo-controlled, multicenter trials, incorporating rigorous long-term follow-up protocols. These studies are essential for elucidating the optimal cell types and therapeutic parameters that contribute to the most effective treatment strategies for DF management.
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Affiliation(s)
- Shiv Kumar Mudgal
- All India Institute of Medical Sciences (AIIMS), Deoghar, Jharkhand, India
| | - Subodh Kumar
- All India Institute of Medical Sciences (AIIMS), Deoghar, Jharkhand, India
| | - Rakhi Gaur
- All India Institute of Medical Sciences (AIIMS), Deoghar, Jharkhand, India
| | - Harminder Singh
- All India Institute of Medical Sciences (AIIMS), Deoghar, Jharkhand, India
| | - Dibyajyoti Saikia
- All India Institute of Medical Sciences (AIIMS), Guwahati, Assam, India
| | - Saurabh Varshney
- All India Institute of Medical Sciences (AIIMS), Deoghar, Jharkhand, India
| | - Pratima Gupta
- All India Institute of Medical Sciences (AIIMS), Deoghar, Jharkhand, India
| | - Ashoo Grover
- Indian Council of Medical Research (ICMR), Head Quarters, New Delhi, India
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19
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Shi HS, Yuan X, Wu FF, Li XY, Fan WJ, Yang X, Hu XM, Liu GB. Research progress and challenges in stem cell therapy for diabetic foot: Bibliometric analysis and perspectives. World J Stem Cells 2024; 16:33-53. [PMID: 38292441 PMCID: PMC10824042 DOI: 10.4252/wjsc.v16.i1.33] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Revised: 12/06/2023] [Accepted: 12/28/2023] [Indexed: 01/22/2024] Open
Abstract
BACKGROUND Stem cell therapy has shown great potential for treating diabetic foot (DF). AIM To conduct a bibliometric analysis of studies on the use of stem cell therapy for DF over the past two decades, with the aim of depicting the current global research landscape, identifying the most influential research hotspots, and providing insights for future research directions. METHODS We searched the Web of Science Core Collection database for all relevant studies on the use of stem cell therapy in DF. Bibliometric analysis was carried out using CiteSpace, VOSviewer, and R (4.3.1) to identify the most notable studies. RESULTS A search was conducted to identify publications related to the use of stem cells for DF treatment. A total of 542 articles published from 2000 to 2023 were identified. The United States had published the most papers on this subject. In this field, Iran's Shahid Beheshti University Medical Sciences demonstrated the highest productivity. Furthermore, Dr. Bayat from the same university has been an outstanding researcher in this field. Stem Cell Research & Therapy is the journal with the highest number of publications in this field. The main keywords were "diabetic foot ulcers," "wound healing," and "angiogenesis." CONCLUSION This study systematically illustrated the advances in the use of stem cell therapy to treat DF over the past 23 years. Current research findings suggested that the hotspots in this field include stem cell dressings, exosomes, wound healing, and adipose-derived stem cells. Future research should also focus on the clinical translation of stem cell therapies for DF.
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Affiliation(s)
- Hong-Shuo Shi
- Department of Peripheral Vascular Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 250021, China
| | - Xin Yuan
- Department of Peripheral Vascular Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 250021, China
| | - Fang-Fang Wu
- Department of Peripheral Vascular Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 250021, China
| | - Xiao-Yu Li
- Department of Peripheral Vascular Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 250021, China
| | - Wei-Jing Fan
- Department of Peripheral Vascular Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 250021, China
| | - Xiao Yang
- Department of Peripheral Vascular Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 250021, China
| | - Xiao-Ming Hu
- Department of Peripheral Vascular Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 250021, China
| | - Guo-Bin Liu
- Department of Peripheral Vascular Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 250021, China.
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20
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Panda D, Nayak S. Stem Cell-Based Tissue Engineering Approaches for Diabetic Foot Ulcer: a Review from Mechanism to Clinical Trial. Stem Cell Rev Rep 2024; 20:88-123. [PMID: 37867186 DOI: 10.1007/s12015-023-10640-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/05/2023] [Indexed: 10/24/2023]
Abstract
Diabetic foot ulcer (DFU) is a complication from incomplete or prolonged wound healing, at times requires amputation, putting substantial health and socioeconomic burden. Wound healing is a dynamic overlapping process that can be regulated by arrays of molecular factors showing redundancy in function. However, dysregulation in the mechanism of angiogenesis, extra cellular matrix (ECM) formation and immune modulation are the major causes for impair wound healing in hyperglycaemic patients. Despite development of wound care research, there is a lack of well-accepted targeted therapy with multidisciplinary approach for DFU treatment. Stem cell therapy holds a promising outcome both in preclinical and clinical trials because of its ability to promote healing via regeneration and specialized tissue differentiation. Among different types of stem cells, regenerative potential of mesenchymal stem cell (MSC) is well demonstrated in both experimental and clinical trial. Still there is a huge knowledge gap among medical practitioners for deciding the best stem cell source, administration route, and safety. This review strengthens the fact that why stem cell therapy is a promising candidate to treat DFU and cited multiple tissue engineering and biomaterial-based approaches for delivering stem cells and their aftermath paracrine events. Based on the pre-clinical and clinical studies, the review tried to come up with optimum stem cell source and delivery route for the treatment of DFU. At last, the review glances on possible direction to enhance therapeutics strategy for the same, including different approaches like: phytocompounds, exosomes, scaffold geometry, cell preconditioning and licensing etc.
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Affiliation(s)
- Debarchan Panda
- Department of Integrative Biology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, 632014, India
| | - Sunita Nayak
- Department of Integrative Biology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, 632014, India.
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Karpov DS, Sosnovtseva AO, Pylina SV, Bastrich AN, Petrova DA, Kovalev MA, Shuvalova AI, Eremkina AK, Mokrysheva NG. Challenges of CRISPR/Cas-Based Cell Therapy for Type 1 Diabetes: How Not to Engineer a "Trojan Horse". Int J Mol Sci 2023; 24:17320. [PMID: 38139149 PMCID: PMC10743607 DOI: 10.3390/ijms242417320] [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: 11/03/2023] [Revised: 12/04/2023] [Accepted: 12/07/2023] [Indexed: 12/24/2023] Open
Abstract
Type 1 diabetes mellitus (T1D) is an autoimmune disease caused by the destruction of insulin-producing β-cells in the pancreas by cytotoxic T-cells. To date, there are no drugs that can prevent the development of T1D. Insulin replacement therapy is the standard care for patients with T1D. This treatment is life-saving, but is expensive, can lead to acute and long-term complications, and results in reduced overall life expectancy. This has stimulated the research and development of alternative treatments for T1D. In this review, we consider potential therapies for T1D using cellular regenerative medicine approaches with a focus on CRISPR/Cas-engineered cellular products. However, CRISPR/Cas as a genome editing tool has several drawbacks that should be considered for safe and efficient cell engineering. In addition, cellular engineering approaches themselves pose a hidden threat. The purpose of this review is to critically discuss novel strategies for the treatment of T1D using genome editing technology. A well-designed approach to β-cell derivation using CRISPR/Cas-based genome editing technology will significantly reduce the risk of incorrectly engineered cell products that could behave as a "Trojan horse".
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Affiliation(s)
- Dmitry S. Karpov
- Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia; (D.S.K.); (A.O.S.); (M.A.K.); (A.I.S.)
| | - Anastasiia O. Sosnovtseva
- Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia; (D.S.K.); (A.O.S.); (M.A.K.); (A.I.S.)
| | - Svetlana V. Pylina
- Endocrinology Research Centre, 115478 Moscow, Russia; (S.V.P.); (A.N.B.); (D.A.P.); (A.K.E.)
| | - Asya N. Bastrich
- Endocrinology Research Centre, 115478 Moscow, Russia; (S.V.P.); (A.N.B.); (D.A.P.); (A.K.E.)
| | - Darya A. Petrova
- Endocrinology Research Centre, 115478 Moscow, Russia; (S.V.P.); (A.N.B.); (D.A.P.); (A.K.E.)
| | - Maxim A. Kovalev
- Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia; (D.S.K.); (A.O.S.); (M.A.K.); (A.I.S.)
| | - Anastasija I. Shuvalova
- Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia; (D.S.K.); (A.O.S.); (M.A.K.); (A.I.S.)
| | - Anna K. Eremkina
- Endocrinology Research Centre, 115478 Moscow, Russia; (S.V.P.); (A.N.B.); (D.A.P.); (A.K.E.)
| | - Natalia G. Mokrysheva
- Endocrinology Research Centre, 115478 Moscow, Russia; (S.V.P.); (A.N.B.); (D.A.P.); (A.K.E.)
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Isildar B, Ozkan S, Koyuturk M. Therapeutic Potential of Mesenchymal Stem Cell‐Derived Conditioned Medium for Diabetes Mellitus and Related Complications. ADVANCED THERAPEUTICS 2023; 6. [DOI: 10.1002/adtp.202300216] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Indexed: 01/06/2025]
Abstract
AbstractDiabetes mellitus (DM) is one of the most life‐threatening metabolic disorders, with 9% of the global prevalence, and it is estimated to be rising to 12.2% in 2045. Currently, there is no definitive treatment for DM. Although life‐saving, insulin administration to control blood sugar is not a cure for DM and is insufficient to prevent DM‐related complications such as nephropathy, neuropathy, or retinopathy. For this reason, studies are continuing to develop treatments that will provide β‐cell regeneration while suppressing autoimmunity. Mesenchymal stem cells (MSCs) are multipotent stem cells with a high proliferation capacity, immunosuppression, and immunomodulation ability. MSCs have gained therapeutic importance with these properties besides their differentiation ability. The immunosuppressive and immunomodulatory properties of the cells arise from the soluble and insoluble factors they secrete into the extracellular environment. Therefore, the culture medium where these cells grow has therapeutic value and is named conditioned medium (CM). In this context, CM obtained from MSCs can provide a similar therapeutic effect with fewer safety concerns. Furthermore, preconditioning of MSCs can improve the effectiveness of these cells and associated cellular products. So, this review summarizes the recent advances in MSC‐derived CMs and their therapeutic potential for DM and related complications.
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Affiliation(s)
- Basak Isildar
- Balikesir University Faculty of Medicine Histology and Embryology Department Balikesir 10185 Turkey
| | - Serbay Ozkan
- Izmir Katip Celebi University Faculty of Medicine Histology and Embryology Department Izmir 35620 Turkey
| | - Meral Koyuturk
- Istanbul University‐Cerrahpasa Cerrahpasa Faculty of Medicine Histology and Embryology Department Istanbul 34098 Turkey
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Wang H, Duan C, Keate RL, Ameer GA. Panthenol Citrate Biomaterials Accelerate Wound Healing and Restore Tissue Integrity. Adv Healthc Mater 2023; 12:e2301683. [PMID: 37327023 PMCID: PMC11468745 DOI: 10.1002/adhm.202301683] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2023] [Indexed: 06/17/2023]
Abstract
Impaired wound healing is a common complication for diabetic patients and effective diabetic wound management remains a clinical challenge. Furthermore, a significant problem that contributes to patient morbidity is the suboptimal quality of healed skin, which often leads to reoccurring chronic skin wounds. Herein, a novel compound and biomaterial building block, panthenol citrate (PC), is developed. It has interesting fluorescence and absorbance properties, and it is shown that PC can be used in soluble form as a wash solution and as a hydrogel dressing to address impaired wound healing in diabetes. PC exhibits antioxidant, antibacterial, anti-inflammatory, and pro-angiogenic properties, and promotes keratinocyte and dermal fibroblast migration and proliferation. When applied in a splinted excisional wound diabetic rodent model, PC improves re-epithelialization, granulation tissue formation, and neovascularization. It also reduces inflammation and oxidative stress in the wound environment. Most importantly, it improves the regenerated tissue quality with enhanced mechanical strength and electrical properties. Therefore, PC could potentially improve wound care management for diabetic patients and play a beneficial role in other tissue regeneration applications.
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Affiliation(s)
- Huifeng Wang
- Department of Biomedical EngineeringNorthwestern UniversityEvanstonIL60208USA
- Center for Advanced Regenerative EngineeringNorthwestern UniversityEvanstonIL60208USA
| | - Chongwen Duan
- Department of Biomedical EngineeringNorthwestern UniversityEvanstonIL60208USA
- Center for Advanced Regenerative EngineeringNorthwestern UniversityEvanstonIL60208USA
| | - Rebecca L. Keate
- Department of Biomedical EngineeringNorthwestern UniversityEvanstonIL60208USA
- Center for Advanced Regenerative EngineeringNorthwestern UniversityEvanstonIL60208USA
| | - Guillermo A. Ameer
- Department of Biomedical EngineeringNorthwestern UniversityEvanstonIL60208USA
- Center for Advanced Regenerative EngineeringNorthwestern UniversityEvanstonIL60208USA
- Department of SurgeryFeinberg School of MedicineNorthwestern UniversityChicagoIL60611USA
- Chemistry of Life Processes InstituteNorthwestern UniversityEvanstonIL60208USA
- Simpson Querrey InstituteNorthwestern UniversityChicagoIL60611USA
- International Institute for NanotechnologyNorthwestern UniversityEvanstonIL60208USA
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24
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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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Li K, Zhu Z, Zhai Y, Chen S. Recent Advances in Electrospun Nanofiber-Based Strategies for Diabetic Wound Healing Application. Pharmaceutics 2023; 15:2285. [PMID: 37765254 PMCID: PMC10535965 DOI: 10.3390/pharmaceutics15092285] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 08/30/2023] [Accepted: 08/30/2023] [Indexed: 09/29/2023] Open
Abstract
Diabetic ulcers are the second largest complication caused by diabetes mellitus. A great number of factors, including hyperchromic inflammation, susceptible microbial infection, inferior vascularization, the large accumulation of free radicals, and other poor healing-promoting microenvironments hold back the healing process of chronic diabetic ulcer in clinics. With the increasing clinical cases of diabetic ulcers worldwide, the design and development of advanced wound dressings are urgently required to accelerate the treatment of skin wounds caused by diabetic complications. Electrospinning technology has been recognized as a simple, versatile, and cost-reasonable strategy to fabricate dressing materials composed of nanofibers, which possess excellent extracellular matrix (ECM)-mimicking morphology, structure, and biological functions. The electrospinning-based nanofibrous dressings have been widely demonstrated to promote the adhesion, migration, and proliferation of dermal fibroblasts, and further accelerate the wound healing process compared with some other dressing types like traditional cotton gauze and medical sponges, etc. Moreover, the electrospun nanofibers are commonly harvested in the structure of nonwoven-like mats, which possess small pore sizes but high porosity, resulting in great microbial barrier performance as well as excellent moisture and air permeable properties. They also serve as good carriers to load various bioactive agents and/or even living cells, which further impart the electrospinning-based dressings with predetermined biological functions and even multiple functions to significantly improve the healing outcomes of different chronic skin wounds while dramatically shortening the treatment procedure. All these outstanding characteristics have made electrospun nanofibrous dressings one of the most promising dressing candidates for the treatment of chronic diabetic ulcers. This review starts with a brief introduction to diabetic ulcer and the electrospinning process, and then provides a detailed introduction to recent advances in electrospinning-based strategies for the treatment of diabetic wounds. Importantly, the synergetic application of combining electrospinning with bioactive ingredients and/or cell therapy was highlighted. The review also discussed the advantages of hydrogel dressings by using electrospun nanofibers. At the end of the review, the challenge and prospects of electrospinning-based strategies for the treatment of diabetic wounds are discussed in depth.
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Affiliation(s)
- Kun Li
- College of Textile & Clothing, Qingdao University, Qingdao 266071, China;
| | - Zhijun Zhu
- College of Chemistry & Chemical Engineering, Qingdao University, Qingdao 266071, China; (Z.Z.); (Y.Z.)
| | - Yanling Zhai
- College of Chemistry & Chemical Engineering, Qingdao University, Qingdao 266071, China; (Z.Z.); (Y.Z.)
| | - Shaojuan Chen
- College of Textile & Clothing, Qingdao University, Qingdao 266071, China;
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26
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Yu X, Liu P, Li Z, Zhang Z. Function and mechanism of mesenchymal stem cells in the healing of diabetic foot wounds. Front Endocrinol (Lausanne) 2023; 14:1099310. [PMID: 37008908 PMCID: PMC10061144 DOI: 10.3389/fendo.2023.1099310] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Accepted: 03/06/2023] [Indexed: 03/18/2023] Open
Abstract
Diabetes has become a global public health problem. Diabetic foot is one of the most severe complications of diabetes, which often places a heavy economic burden on patients and seriously affects their quality of life. The current conventional treatment for the diabetic foot can only relieve the symptoms or delay the progression of the disease but cannot repair damaged blood vessels and nerves. An increasing number of studies have shown that mesenchymal stem cells (MSCs) can promote angiogenesis and re-epithelialization, participate in immune regulation, reduce inflammation, and finally repair diabetic foot ulcer (DFU), rendering it an effective means of treating diabetic foot disease. Currently, stem cells used in the treatment of diabetic foot are divided into two categories: autologous and allogeneic. They are mainly derived from the bone marrow, umbilical cord, adipose tissue, and placenta. MSCs from different sources have similar characteristics and subtle differences. Mastering their features to better select and use MSCs is the premise of improving the therapeutic effect of DFU. This article reviews the types and characteristics of MSCs and their molecular mechanisms and functions in treating DFU to provide innovative ideas for using MSCs to treat diabetic foot and promote wound healing.
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Affiliation(s)
- Xiaoping Yu
- School of Medicine and Nursing, Chengdu University, Chengdu, Sichuan, China
| | - Pan Liu
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Zheng Li
- People’s Hospital of Jiulongpo District, Chongqing, China
| | - Zhengdong Zhang
- School of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, China
- Department of Orthopedics, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China
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27
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Fang WC, Lan CCE. The Epidermal Keratinocyte as a Therapeutic Target for Management of Diabetic Wounds. Int J Mol Sci 2023; 24:4290. [PMID: 36901720 PMCID: PMC10002069 DOI: 10.3390/ijms24054290] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Revised: 02/13/2023] [Accepted: 02/20/2023] [Indexed: 02/24/2023] Open
Abstract
Diabetes mellitus (DM) is an important cause of chronic wounds and non-traumatic amputation. The prevalence and number of cases of diabetic mellitus are increasing worldwide. Keratinocytes, the outermost layer of the epidermis, play an important role in wound healing. A high glucose environment may disrupt the physiologic functions of keratinocytes, resulting in prolonged inflammation, impaired proliferation, and the migration of keratinocytes and impaired angiogenesis. This review provides an overview of keratinocyte dysfunctions in a high glucose environment. Effective and safe therapeutic approaches for promoting diabetic wound healing can be developed if molecular mechanisms responsible for keratinocyte dysfunction in high glucose environments are elucidated.
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Affiliation(s)
- Wei-Cheng Fang
- Department of Dermatology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Cheng-Che E. Lan
- Department of Dermatology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Department of Dermatology, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
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28
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Li Y, Ju S, Li X, Li W, Zhou S, Wang G, Cai Y, Dong Z. Characterization of the microenvironment of diabetic foot ulcers and potential drug identification based on scRNA-seq. Front Endocrinol (Lausanne) 2023; 13:997880. [PMID: 36686438 PMCID: PMC9845942 DOI: 10.3389/fendo.2022.997880] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Accepted: 12/02/2022] [Indexed: 01/05/2023] Open
Abstract
Background Diabetes foot ulcers (DFUs) are a type of foot infection, ulcer, and/or deep tissue destruction caused by neuropathy and vascular disease in the distal extremities of diabetic patients. Its pathogenesis and its microenvironment are not entirely understood. Methods Initially, the GSE165816 data set from the GEO database was utilized for single cell analysis to reveal the microenvironment and functional status of DFUs. The GSE199939 RNA-seq data set was utilized for external validation. On the basis of the logistic regression machine learning algorithm (OCLR), pseudo time series analysis, dryness index analysis, and drug target gene analysis were then performed. By constructing drug-gene and gene-gene networks, we can locate the most recent DFUs treatments. Finally, immunofluorescence technology was used to detect the cell-related markers of the DFUs microenvironment, and qPCR was used to detect the expression of drug targets in DFUs. Results Firstly, we used the Cell Maker database to obtain information about human cells and related gene markers, and manually reviewed a total of 45 kinds of cells and maker information that may appear in the DFUs microenvironment, which were divided into 17 cell clusters after annotation. Subsequently, we counted the proportions of DM and DFUs in different types of cells, and the results showed that the proportions of macrophages, white blood cells, and monocytes were higher in patients with DFUs, while the proportions of pluripotent stem cells and stromal cells were higher in patients with DM. The Pseudo-time series analysis of cells in DFUs showed that the differentiation pathways of immune cells, mesenchymal cells and stem cells were similar in the three states, while the other cells were distributed in different stages. At the level of a single cell, the scores of both multipotential stem cells and hematopoietic stem cells were significantly lower in DFU healing and non-healing than in DM. Additionally, the highly expressed genes in DFU were chosen as drug targets. We identified seven potential target genes and discovered twenty drugs with high significance. Finally, the colocalization relationship between CD19, ITGAM, and HLA-DR expression in monocytes and macrophages of DFU skin tissue and healthy subjects was analyzed by laser confocal microscopy with the immunofluorescence triple labeling method. The results showed that the expressions of CD19, ITGAM, and HLA-DR in the skin of DFUs were significantly higher than those in the skin of healthy subjects, and the co-localization relationship was significant in DFUs. Conclusion This study can serve as a resource for the treatment of DFUs.
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Affiliation(s)
- Yao Li
- Vascular and wound center, Jinshan Hospital, Fudan University, Shanghai, China
| | - Shuai Ju
- Vascular and wound center, Jinshan Hospital, Fudan University, Shanghai, China
| | - Xiaoyan Li
- Vascular and wound center, Jinshan Hospital, Fudan University, Shanghai, China
| | - Wenqiang Li
- Vascular and wound center, Jinshan Hospital, Fudan University, Shanghai, China
| | - Siyuan Zhou
- Vascular and wound center, Jinshan Hospital, Fudan University, Shanghai, China
- Shanghai Medical College, Fudan University, Shanghai, China
| | - Guili Wang
- Vascular and wound center, Jinshan Hospital, Fudan University, Shanghai, China
- Shanghai Medical College, Fudan University, Shanghai, China
| | - Yunmin Cai
- Vascular and wound center, Jinshan Hospital, Fudan University, Shanghai, China
| | - Zhihui Dong
- Vascular and wound center, Jinshan Hospital, Fudan University, Shanghai, China
- Department of vascular surgery, Zhongshan Hospital, Fudan University, Shanghai, China
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29
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Mahmoudvand G, Karimi Rouzbahani A, Razavi ZS, Mahjoor M, Afkhami H. Mesenchymal stem cell therapy for non-healing diabetic foot ulcer infection: New insight. Front Bioeng Biotechnol 2023; 11:1158484. [PMID: 37122856 PMCID: PMC10133463 DOI: 10.3389/fbioe.2023.1158484] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Accepted: 03/31/2023] [Indexed: 05/02/2023] Open
Abstract
Diabetic foot ulcer (DFU) is considered the most catastrophic complication of diabetes mellitus (DM), leading to repeated hospitalizations, infection, gangrene, and finally amputation of the limb. In patients suffering from diabetes mellitus, the wound-healing process is impaired due to various factors such as endothelial dysfunction and synthesis of advanced glycation end-products, hence, conventional therapeutic interventions might not be effective. With increasing therapeutic applications of mesenchymal stem cells (MSCs) in recent years, their potential as a method for improving the wound-healing process has gained remarkable attention. In this field, mesenchymal stem cells exert their beneficial effects through immunomodulation, differentiation into the essential cells at the site of ulcers, and promoting angiogenesis, among others. In this article, we review cellular and molecular pathways through which mesenchymal stem cell therapy reinforces the healing process in non-healing Diabetic foot ulcers.
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Affiliation(s)
- Golnaz Mahmoudvand
- Student Research Committee, USERN Office, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Arian Karimi Rouzbahani
- Student Research Committee, USERN Office, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Zahra Sadat Razavi
- Physiology Research Center, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mohamad Mahjoor
- Department of Immunology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Hamed Afkhami
- Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran
- Department of Medical Microbiology, Faculty of Medicine, Shahed University, Tehran, Iran
- *Correspondence: Hamed Afkhami,
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30
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Wu J, Chen LH, Sun SY, Li Y, Ran XW. Mesenchymal stem cell-derived exosomes: The dawn of diabetic wound healing. World J Diabetes 2022; 13:1066-1095. [PMID: 36578867 PMCID: PMC9791572 DOI: 10.4239/wjd.v13.i12.1066] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 11/04/2022] [Accepted: 11/23/2022] [Indexed: 12/15/2022] Open
Abstract
Chronic wound healing has long been an unmet medical need in the field of wound repair, with diabetes being one of the major etiologies. Diabetic chronic wounds (DCWs), especially diabetic foot ulcers, are one of the most threatening chronic complications of diabetes. Although the treatment strategies, drugs, and dressings for DCWs have made great progress, they remain ineffective in some patients with refractory wounds. Stem cell-based therapies have achieved specific efficacy in various fields, with mesenchymal stem cells (MSCs) being the most widely used. Although MSCs have achieved good feedback in preclinical studies and clinical trials in the treatment of cutaneous wounds or other situations, the potential safety concerns associated with allogeneic/autologous stem cells and unknown long-term health effects need further attention and supervision. Recent studies have reported that stem cells mainly exert their trauma repair effects through paracrine secretion, and exosomes play an important role in intercellular communication as their main bioactive component. MSC-derived exosomes (MSC-Exos) inherit the powerful inflammation and immune modulation, angiogenesis, cell proliferation and migration promotion, oxidative stress alleviation, collagen remodeling imbalances regulation of their parental cells, and can avoid the potential risks of direct stem cell transplantation to a large extent, thus demonstrating promising performance as novel "cell-free" therapies in chronic wounds. This review aimed to elucidate the potential mechanism and update the progress of MSC-Exos in DCW healing, thereby providing new therapeutic directions for DCWs that are difficult to be cured using conventional therapy.
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Affiliation(s)
- Jing Wu
- Innovation Center for Wound Repair, Diabetic Foot Care Center, Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Li-Hong Chen
- Innovation Center for Wound Repair, Diabetic Foot Care Center, Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Shi-Yi Sun
- Innovation Center for Wound Repair, Diabetic Foot Care Center, Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Yan Li
- Innovation Center for Wound Repair, Diabetic Foot Care Center, Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Xing-Wu Ran
- Innovation Center for Wound Repair, Diabetic Foot Care Center, Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
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31
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Huang JN, Cao H, Liang KY, Cui LP, Li Y. Combination therapy of hydrogel and stem cells for diabetic wound healing. World J Diabetes 2022; 13:949-961. [PMID: 36437861 PMCID: PMC9693739 DOI: 10.4239/wjd.v13.i11.949] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2022] [Revised: 09/25/2022] [Accepted: 11/02/2022] [Indexed: 11/11/2022] Open
Abstract
Diabetic wounds (DWs) are a common complication of diabetes mellitus; DWs have a low cure rate and likely recurrence, thus affecting the quality of patients’ lives. As traditional therapy cannot effectively improve DW closure, DW has become a severe clinical medical problem worldwide. Unlike routine wound healing, DW is difficult to heal because of its chronically arrested inflammatory phase. Although mesenchymal stem cells and their secreted cytokines can alleviate oxidative stress and stimulate angiogenesis in wounds, thereby promoting wound healing, the biological activity of mesenchymal stem cells is compromised by direct injection, which hinders their therapeutic effect. Hydro-gels form a three-dimensional network that mimics the extracellular matrix, which can provide shelter for stem cells in the inflammatory microenvironment with reactive oxygen species in DW, and maintains the survival and viability of stem cells. This review summarizes the mechanisms and applications of stem cells and hydrogels in treating DW; additionally, it focuses on the different applications of therapy combining hydrogel and stem cells for DW treatment.
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Affiliation(s)
- Jia-Na Huang
- School of Biomedical Engineering, Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, Guangdong Province, China
- Guangdong Provincial Key Laboratory of Sensor Technology and Biomedical Instrument, Sun Yat-sen University, Guangzhou 510006, Guangdong Province, China
| | - Hao Cao
- School of Biomedical Engineering, Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, Guangdong Province, China
- Guangdong Provincial Key Laboratory of Sensor Technology and Biomedical Instrument, Sun Yat-sen University, Guangzhou 510006, Guangdong Province, China
| | - Kai-Ying Liang
- School of Biomedical Engineering, Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, Guangdong Province, China
- Guangdong Provincial Key Laboratory of Sensor Technology and Biomedical Instrument, Sun Yat-sen University, Guangzhou 510006, Guangdong Province, China
| | - Li-Ping Cui
- Endocrinology Department, Panyu Central Hospital, Guangzhou 511400, Guangdong Province, China
| | - Yan Li
- School of Biomedical Engineering, Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, Guangdong Province, China
- Guangdong Provincial Key Laboratory of Sensor Technology and Biomedical Instrument, Sun Yat-sen University, Guangzhou 510006, Guangdong Province, China
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Mesenchymal Stem Cell-Derived Extracellular Vesicles: A Potential Therapy for Diabetes Mellitus and Diabetic Complications. Pharmaceutics 2022; 14:pharmaceutics14102208. [PMID: 36297643 PMCID: PMC9607185 DOI: 10.3390/pharmaceutics14102208] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 10/10/2022] [Accepted: 10/13/2022] [Indexed: 12/02/2022] Open
Abstract
As a novel cell-free strategy, mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) inherit the therapeutic potential of donor cells, and are widely used for the treatment of many diseases. Increasing studies have shown that MSC-EVs transfer various bioactive molecules to create a beneficial microenvironment, thus exerting protective roles in diabetic mellitus (DM) and diabetic complications. To overcome the limitations of natural MSC-EVs such as heterogeneity and insufficient function, several modification methods have been established for constructing engineered MSC-EVs with elevated repairing efficiency. In this review, the PubMed library was searched from inception to August 2022, using a combination of Medical Subject Headings (MeSH) and keywords related to MSC-EVs, DM, and diabetic complications. We provide an overview of the major characteristics of MSC-EVs and summarize the recent advances of MSC-EV-based therapy for hyperglycemia-induced tissue damage with an emphasis on MSC-EV-mediated delivery of functional components. Moreover, the potential applications of engineered MSC-EVs in DM-related diseases therapy are discussed by presenting examples, and the opportunities and challenges for the clinical translation of MSC-EVs, especially engineered MSC-EVs, are evaluated.
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Lu L, Xiong Y, Lin Z, Chu X, Panayi AC, Hu Y, Zhou J, Mi B, Liu G. Advances in the therapeutic application and pharmacological properties of kinsenoside against inflammation and oxidative stress-induced disorders. Front Pharmacol 2022; 13:1009550. [PMID: 36267286 PMCID: PMC9576948 DOI: 10.3389/fphar.2022.1009550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Accepted: 09/13/2022] [Indexed: 11/19/2022] Open
Abstract
Extensive research has implicated inflammation and oxidative stress in the development of multiple diseases, such as diabetes, hepatitis, and arthritis. Kinsenoside (KD), a bioactive glycoside component extracted from the medicinal plant Anoectochilus roxburghii, has been shown to exhibit potent anti-inflammatory and anti-oxidative abilities. In this review, we summarize multiple effects of KD, including hepatoprotection, pro-osteogenesis, anti-hyperglycemia, vascular protection, immune regulation, vision protection, and infection inhibition, which are partly responsible for suppressing inflammation signaling and oxidative stress. The protective action of KD against dysfunctional lipid metabolism is also associated with limiting inflammatory signals, due to the crosstalk between inflammation and lipid metabolism. Ferroptosis, a process involved in both inflammation and oxidative damage, is potentially regulated by KD. In addition, we discuss the physicochemical properties and pharmacokinetic profiles of KD. Advances in cultivation and artificial synthesis techniques are promising evidence that the shortage in raw materials required for KD production can be overcome. In addition, novel drug delivery systems can improve the in vivo rapid clearance and poor bioavailability of KD. In this integrated review, we aim to offer novel insights into the molecular mechanisms underlying the therapeutic role of KD and lay solid foundations for the utilization of KD in clinical practice.
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Affiliation(s)
- Li Lu
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, China
| | - Yuan Xiong
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, China
| | - Ze Lin
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, China
| | - Xiangyu Chu
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, China
| | - Adriana C. Panayi
- Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
- Department of Hand-, Plastic and Reconstructive Surgery, Microsurgery, Burn Trauma Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Ludwigshafen, Germany
| | - Yiqiang Hu
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, China
| | - Juan Zhou
- Department of Cardiology, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China
| | - Bobin Mi
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, China
- *Correspondence: Bobin Mi, ; Guohui Liu,
| | - Guohui Liu
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, China
- *Correspondence: Bobin Mi, ; Guohui Liu,
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Jiao Y, Chen X, Nong B, Luo M, Niu Y, Huang S, Zhang J, Wei A, Huang J. Transplantation of Wharton's jelly mesenchymal stem cells encapsulated with Hydroactive® Gel promotes diabetic wound antifibrotic healing in type 2 diabetic rats. J Mater Chem B 2022; 10:8330-8346. [PMID: 36168995 DOI: 10.1039/d2tb01649d] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Diabetic cutaneous ulcers (DCU) are a complication for diabetes patients, mostly occurring in the foot and causing non-healing diabetic foot ulcers. Mesenchymal stem cell (MSC)-based therapy is currently being investigated as a therapeutic avenue for chronic diabetic ulcers. However, poor engraftment, short retention, and low survival still limit the treatment effectiveness. Hydroactive® Gel is a sterile transparent gel made of natural hydrocolloid, which has been widely used for wound management. Whether transplantation of Wharton's jelly mesenchymal stem cells (WJMSCs) encapsulated with Hydroactive® Gel is helpful to diabetic ulcers wound healing remains to be explored. The biocompatibility experiments showed that WJMSCs embedded in Hydroactive® Gel did not influence the cell viability, survival, proliferation, and apoptosis of WJMSCs in vitro. RNA-seq results also implied that Hydroactive® Gel + WJMSCs transplantation activated the "cytokine-cytokine receptor interaction", "mononuclear cell differentiation", "regulation of cell-cell adhesion", and "chemokine receptor activity" to accelerate the inflammatory reaction and epidermis regeneration in diabetic wounds. Histological analysis results demonstrated that Hydroactive® Gel encapsulated WJMSCs transplantation promoted diabetic wound healing and regeneration, indicating improved dermis regeneration, sebaceous gland formation, and type III collagen fiber deposition. Besides, immunohistochemical analysis results showed that Hydroactive® Gel + WJMSCs transplantation also facilitated the transformation of pro-inflammatory M1 macrophages to anti-inflammatory M2 macrophages, cell proliferation, and neovascularization at the wound site. Hydroactive® Gel encapsulation further prolonged the retention time of WJMSCs at the diabetic wound site. Above all, Hydroactive® Gel accelerates WJMSCs-mediated diabetic wound healing by promoting macrophage transformation, facilitating cell proliferation and angiogenesis, and prolonging cell retention time. Our findings may potentially provide a useful therapeutic strategy based on the combination of WJMSCs and biomedical materials for patients with diabetic cutaneous ulcers.
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Affiliation(s)
- Yiren Jiao
- MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China.
| | - Xiaolin Chen
- MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China.
| | - Baoting Nong
- MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China.
| | - Mingxun Luo
- MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China.
| | - Yongxia Niu
- MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China.
| | - Sunxing Huang
- Key Laboratory of Reproductive Medicine of Guangdong Province, The First Affiliated Hospital and School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China
| | - Jue Zhang
- Department of Endocrinology, Foshan Hospital of Traditional Chinese Medicine, Foshan 528000, China.
| | - Aisheng Wei
- Department of Endocrinology, Foshan Hospital of Traditional Chinese Medicine, Foshan 528000, China.
| | - Junjiu Huang
- MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China. .,Key Laboratory of Reproductive Medicine of Guangdong Province, The First Affiliated Hospital and School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China
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Gao CC, Chen JA, Wang AP. [Research progress of induced pluripotent stem cells in promoting wound healing of diabetic foot ulcers]. ZHONGHUA SHAO SHANG YU CHUANG MIAN XIU FU ZA ZHI 2022; 38:864-869. [PMID: 36177592 DOI: 10.3760/cma.j.cn501120-20210630-00230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Chronic wounds such as diabetic foot ulcers are epidemic, which bring huge burdens to both the patients and the society. However, with current treatment methods, diabetic foot ulcers often heal poorly and recur frequently, so it is urgent and important to find new and advanced therapies. Stem cell therapy has been proved by a large number of pre-clinical and clinical studies as a potential treatment for chronic wounds. However, the acquisition of stem cells often depends on invasive techniques, and immunogenicity and limited cell survival in vivo also limit the large-scale application and promotion of stem cell therapy. In the recent years, with the development and advance of induced pluripotent stem cell (iPSC) technology, it has shown a strong translational potential in the treatment of chronic wounds such as diabetic foot ulcers. This article reviews the applications and prospect of iPSCs in animal wound healing models including diabetic ulcers and limb ischemia, the limitations of their clinical application, and the methods to improve their safety.
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Affiliation(s)
- C C Gao
- Department of Endocrinology, Air Force Hospital of Eastern Theater Command, Diabetic Foot Center, Nanjing 210002, China
| | - J A Chen
- Department of Endocrinology, Air Force Hospital of Eastern Theater Command, Diabetic Foot Center, Nanjing 210002, China
| | - A P Wang
- Department of Endocrinology, Air Force Hospital of Eastern Theater Command, Diabetic Foot Center, Nanjing 210002, China
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Chakraborty R, Borah P, Dutta PP, Sen S. Evolving spectrum of diabetic wound: Mechanistic insights and therapeutic targets. World J Diabetes 2022; 13:696-716. [PMID: 36188143 PMCID: PMC9521443 DOI: 10.4239/wjd.v13.i9.696] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2022] [Revised: 06/12/2022] [Accepted: 08/18/2022] [Indexed: 02/05/2023] Open
Abstract
Diabetes mellitus is a chronic metabolic disorder resulting in an increased blood glucose level and prolonged hyperglycemia, causes long term health conse-quences. Chronic wound is frequently occurring in diabetes patients due to compromised wound healing capability. Management of wounds in diabetic patients remains a clinical challenge despite many advancements in the field of science and technology. Increasing evidence indicates that alteration of the biochemical milieu resulting from alteration in inflammatory cytokines and matrix metalloproteinase, decrease in fibroblast and keratinocyte functioning, neuropathy, altered leukocyte functioning, infection, etc., plays a significant role in impaired wound healing in diabetic people. Apart from the current pharmacotherapy, different other approaches like the use of conventional drugs, antidiabetic medication, antibiotics, debridement, offloading, platelet-rich plasma, growth factor, oxygen therapy, negative pressure wound therapy, low-level laser, extracorporeal shock wave bioengineered substitute can be considered in the management of diabetic wounds. Drugs/therapeutic strategy that induce angiogenesis and collagen synthesis, inhibition of MMPs, reduction of oxidative stress, controlling hyperglycemia, increase growth factors, regulate inflammatory cytokines, cause NO induction, induce fibroblast and keratinocyte proliferation, control microbial infections are considered important in controlling diabetic wound. Further, medicinal plants and/or phytoconstituents also offer a viable alternative in the treatment of diabetic wound. The focus of the present review is to highlight the molecular and cellular mechanisms, and discuss the drug targets and treatment strategies involved in the diabetic wound.
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Affiliation(s)
- Raja Chakraborty
- Institute of Pharmacy, Assam Don Bosco University, Kamrup 782402, Assam, India
| | - Pobitra Borah
- School of Pharmacy, Graphic Era Hill University, Dehradun 248002, Uttarakhand, India
| | - Partha Pratim Dutta
- Faculty of Pharmaceutical Science, Assam down town University, Guwahati 781026, Assam, India
| | - Saikat Sen
- Faculty of Pharmaceutical Science, Assam down town University, Guwahati 781026, Assam, India
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Sun Y, Zhao J, Zhang L, Li Z, Lei S. Effectiveness and safety of stem cell therapy for diabetic foot: a meta-analysis update. Stem Cell Res Ther 2022; 13:416. [PMID: 35964145 PMCID: PMC9375292 DOI: 10.1186/s13287-022-03110-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Accepted: 08/02/2022] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND Diabetic foot (DF) is one of the most common and serious complications of diabetes mellitus (DM), which brings great psychological and economic pressure to patients. This study aimed to evaluate the efficacy of stem cells in the treatment of diabetic foot. METHODS All relevant studies in Cochrane, Embase, PubMed, Web of Science, China National Knowledge Infrastructure, and WanFang databases were systematically searched for meta-analysis. The outcomes consisted of ulcer or wound healing rate, amputation rate, new vessels, ankle-brachial index (ABI), transcutaneous oxygen pressure (TcPO2), pain-free walking distance, and rest pain score. Dichotomous outcomes were described as risk ratios (RR) with 95% confidence intervals (CIs), while continuous data were presented as standardized mean differences (SMDs) with 95% CIs. Statistical analysis was performed with RevMan 5.3 software. RESULTS A total of 14 studies with 683 participants were included in the meta-analysis. Meta-analysis showed that stem cell therapy was more effective than conventional therapy in terms of ulcer or wound healing rate [OR = 8.20 (5.33, 12.62)], improvement in lower extremity ischemia(new vessels) [OR = 16.48 (2.88, 94.18)], ABI [MD = 0.13 (0.04, 0.08)], TcO2[MD = 4.23 (1.82, 6.65)], pain-free walking distance [MD = 220.79 (82.10, 359.48)], and rest pain score [MD = - 1.94 (- 2.50, - 1.39)], while the amputation rate was significantly decreased [OR = 0.19 (0.10, 0.36)]. CONCLUSIONS The meta-analysis of the current studies has shown that stem cells are significantly more effective than traditional methods in the treatment of diabetic foot and can improve the quality of life of patients after treatment. Future studies should conduct large-scale, randomized, double-blind, placebo-controlled, multicenter trials with high-quality long-term follow-up to demonstrate the most effective cell types and therapeutic parameters for the treatment of diabetic foot.
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Affiliation(s)
- Yuming Sun
- Department of Plastic and Cosmetic Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan Province, China
| | - Jinhong Zhao
- School of Health Policy and Management, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China
| | - Lifang Zhang
- Department of Plastic and Cosmetic Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan Province, China
| | - Zhexuan Li
- Department of Plastic and Cosmetic Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan Province, China.
| | - Shaorong Lei
- Department of Plastic and Cosmetic Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan Province, China.
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Rai V, Moellmer R, Agrawal DK. Stem Cells and Angiogenesis: Implications and Limitations in Enhancing Chronic Diabetic Foot Ulcer Healing. Cells 2022; 11:2287. [PMID: 35892584 PMCID: PMC9330772 DOI: 10.3390/cells11152287] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2022] [Revised: 07/21/2022] [Accepted: 07/22/2022] [Indexed: 01/27/2023] Open
Abstract
Nonhealing diabetic foot ulcers (DFUs) are a continuing clinical issue despite the improved treatment with wound debridement, off-loading the ulcer, medication, wound dressings, and preventing infection by keeping the ulcer clean. Wound healing is associated with granulation tissue formation and angiogenesis favoring the wound to enter the resolution phase of healing followed by healing. However, chronic inflammation and reduced angiogenesis in a hyperglycemic environment impair the normal healing cascade and result in chronically non-healing diabetic foot ulcers. Promoting angiogenesis is associated with enhanced wound healing and using vascular endothelial growth factors has been proven beneficial to promote neo-angiogenesis. However, still, nonhealing DFUs persist with increased risks of amputation. Regenerative medicine is an evolving branch applicable in wound healing with the use of stem cells to promote angiogenesis. Various studies have reported promising results, but the associated limitations need in-depth research. This article focuses on summarizing and critically reviewing the published literature since 2021 on the use of stem cells to promote angiogenesis and enhance wound healing in chronic non-healing DFUs.
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Affiliation(s)
- Vikrant Rai
- Department of Translational Research, Western University of Health Sciences, Pomona, CA 91766, USA;
| | - Rebecca Moellmer
- College of Podiatric Medicine, Western University of Health Sciences, Pomona, CA 91766, USA;
| | - Devendra K. Agrawal
- Department of Translational Research, Western University of Health Sciences, Pomona, CA 91766, USA;
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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: 7] [Impact Index Per Article: 2.3] [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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40
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Kandregula B, Narisepalli S, Chitkara D, Mittal A. Exploration of Lipid-Based Nanocarriers as Drug Delivery Systems in Diabetic Foot Ulcer. Mol Pharm 2022; 19:1977-1998. [PMID: 35481377 DOI: 10.1021/acs.molpharmaceut.1c00970] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Diabetes mellitus is a chronic manifestation characterized by high levels of glucose in the blood resulting in several complications including diabetic wounds and ulcers, which predominantly require a longer duration of treatment and adversely affect the quality of life of the patients. Nanotechnology-based therapeutics (both intrinsic and extrinsic types) have emerged as a promising treatment in diabetic foot ulcer/chronic wounds owing to their unique characteristics and specific functional properties. In this review, we have focused on the significance of the use of lipids in the healing of diabetic ulcers, their interaction with the injured skin, and recent trends in lipid-based nanocarriers for the healing of diabetic wounds. Lipid nanocarriers are also being investigated for gene therapy in diabetic wound healing to encapsulate nucleic acids such as siRNA and miRNA, which could silence the expression of inflammatory cytokines overexpressed in chronic wounds. Additionally, these are also being explored for encapsulating proteins, peptides, growth factors, and other biological genetic material as therapeutic agents. Lipid-based nanocarriers encompassing a wide variety of carriers such as liposomes, niosomes, ethosomes, solid lipid nanoparticles, and lipidoid nanoparticles that are explored for the treatment of foot ulcers supplemented with relevant research studies have been discussed in the present review. Lipid-based nanodrug delivery systems have demonstrated promising wound healing potential, particularly in diabetic conditions due to the enhanced efficacy of the entrapped active molecules.
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Affiliation(s)
- Bhaskar Kandregula
- Department of Pharmacy, Birla Institute of Technology and Science, Pilani 333031, Rajasthan, India
| | - Saibhargav Narisepalli
- Department of Pharmacy, Birla Institute of Technology and Science, Pilani 333031, Rajasthan, India
| | - Deepak Chitkara
- Department of Pharmacy, Birla Institute of Technology and Science, Pilani 333031, Rajasthan, India
| | - Anupama Mittal
- Department of Pharmacy, Birla Institute of Technology and Science, Pilani 333031, Rajasthan, India.,Department of Cellular and Molecular Biology, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan
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D'Amico R, Malucelli C, Uccelli A, Grosso A, Di Maggio N, Briquez PS, Hubbell JA, Wolff T, Gürke L, Mujagic E, Gianni-Barrera R, Banfi A. Therapeutic arteriogenesis by factor-decorated fibrin matrices promotes wound healing in diabetic mice. J Tissue Eng 2022; 13:20417314221119615. [PMID: 36093431 PMCID: PMC9452813 DOI: 10.1177/20417314221119615] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Accepted: 07/28/2022] [Indexed: 11/16/2022] Open
Abstract
Chronic wounds in type-2 diabetic patients present areas of severe local skin ischemia despite mostly normal blood flow in deeper large arteries. Therefore, restoration of blood perfusion requires the opening of arterial connections from the deep vessels to the superficial skin layer, that is, arteriogenesis. Arteriogenesis is regulated differently from microvascular angiogenesis and is optimally stimulated by high doses of Vascular Endothelial Growth Factor-A (VEGF) together with Platelet-Derived Growth Factor-BB (PDGF-BB). Here we found that fibrin hydrogels decorated with engineered versions of VEGF and PDGF-BB proteins, to ensure protection from degradation and controlled delivery, efficiently accelerated wound closure in diabetic and obese db/db mice, promoting robust microvascular growth and a marked increase in feeding arterioles. Notably, targeting the arteriogenic factors to the intact arterio-venous networks in the dermis around the wound was more effective than the routine treatment of the inflamed wound bed. This approach is readily translatable to a clinical setting.
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Affiliation(s)
- Rosalinda D'Amico
- Cell and Gene Therapy, Department of Biomedicine, Basel University Hospital and University of Basel, Basel, Switzerland.,Vascular Surgery, Department of Surgery, Basel University Hospital and University of Basel, Basel, Switzerland
| | - Camilla Malucelli
- Cell and Gene Therapy, Department of Biomedicine, Basel University Hospital and University of Basel, Basel, Switzerland
| | - Andrea Uccelli
- Cell and Gene Therapy, Department of Biomedicine, Basel University Hospital and University of Basel, Basel, Switzerland
| | - Andrea Grosso
- Cell and Gene Therapy, Department of Biomedicine, Basel University Hospital and University of Basel, Basel, Switzerland
| | - Nunzia Di Maggio
- Cell and Gene Therapy, Department of Biomedicine, Basel University Hospital and University of Basel, Basel, Switzerland
| | - Priscilla S Briquez
- Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, USA
| | - Jeffrey A Hubbell
- Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, USA
| | - Thomas Wolff
- Vascular Surgery, Department of Surgery, Basel University Hospital and University of Basel, Basel, Switzerland
| | - Lorenz Gürke
- Vascular Surgery, Department of Surgery, Basel University Hospital and University of Basel, Basel, Switzerland
| | - Edin Mujagic
- Vascular Surgery, Department of Surgery, Basel University Hospital and University of Basel, Basel, Switzerland
| | - Roberto Gianni-Barrera
- Cell and Gene Therapy, Department of Biomedicine, Basel University Hospital and University of Basel, Basel, Switzerland
| | - Andrea Banfi
- Cell and Gene Therapy, Department of Biomedicine, Basel University Hospital and University of Basel, Basel, Switzerland.,Vascular Surgery, Department of Surgery, Basel University Hospital and University of Basel, Basel, Switzerland
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