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Ma T, Liu Q, Zhang Z, Nan J, Liu G, Yang Y, Hu Y, Xie J. Fused exosomal targeted therapy in periprosthetic osteolysis through regulation of bone metabolic homeostasis. Bioact Mater 2025; 50:171-188. [PMID: 40248188 PMCID: PMC12005309 DOI: 10.1016/j.bioactmat.2025.04.006] [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: 11/04/2024] [Revised: 03/18/2025] [Accepted: 04/03/2025] [Indexed: 04/19/2025] Open
Abstract
The onset of periprosthetic osteolysis is mediated by wear particles following artificial arthroplasty. This manifests as a disturbed bone metabolism microenvironment, characterized by insufficient osteogenesis and angiogenesis, and enhanced osteoclastic activity. To target and remodel the homeostatic environment of bone metabolism in the sterile region around the prosthesis, we successfully pioneered the proposal and construction of a fused exosome (f-exo) system with M2 macrophage-derived exosomes (M2-exo) and urine-derived stem cell exosomes (USC-exo). The results demonstrate that f-exo effectively combines the osteolysis region-targeting capabilities of M2-exo with the bone metabolic homeostasis modulation effects of two exosomes (M2-exo and USC-exo), thereby achieving a significantly enhanced bone metabolic homeostasis targeting effect in the periprosthetic osteolysis region. The proteomic analysis of M2-exo, USC-exo, and f-exo revealed the potential mechanism of f-exo in targeting-regulation of bone metabolic homeostasis. Our study employs an innovative approach utilizing the fused exosome system for exosome targeted delivery, which offers a novel intervention strategy for the clinical management of periprosthetic osteolysis. Furthermore, it provides a novel conceptual framework for the development of exosome-based drug-targeting delivery systems.
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Affiliation(s)
| | | | - Zheyu Zhang
- Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, No.79 Qingchun Road, Hangzhou, Zhejiang, 310003, China
| | - Jiangyu Nan
- Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, No.79 Qingchun Road, Hangzhou, Zhejiang, 310003, China
| | - Guanzhi Liu
- Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, No.79 Qingchun Road, Hangzhou, Zhejiang, 310003, China
| | - Yute Yang
- Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, No.79 Qingchun Road, Hangzhou, Zhejiang, 310003, China
| | - Yihe Hu
- Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, No.79 Qingchun Road, Hangzhou, Zhejiang, 310003, China
| | - Jie Xie
- Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, No.79 Qingchun Road, Hangzhou, Zhejiang, 310003, China
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Yao F, Bao Y, Meng Q, Chen Y, Zhao L, Wang P, Zhou B. Periprosthetic osteolysis: Mechanisms and potential treatment strategies. Cell Signal 2025; 131:111758. [PMID: 40132773 DOI: 10.1016/j.cellsig.2025.111758] [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: 12/11/2024] [Revised: 02/26/2025] [Accepted: 03/19/2025] [Indexed: 03/27/2025]
Abstract
Periprosthetic osteolysis is a common bone-related disorder that often occurs after total hip arthroplasty. The implants can cause damage to bone and bone-related cells due to mechanical stress and micromotions, resulting in the generation of a large number of wear particles. These wear particles trigger inflammation and oxidative stress in the surrounding tissues, disrupting the delicate balance maintained by osteoblasts and osteoclasts, ultimately leading to bone loss around the implant. Clinical investigations have demonstrated that Epimedium prenylflavonoids, miR-19a-3p, stem cell-derived exosomes, and certain non-PPO category pharmaceuticals have regulatory effects on bone homeostasis through distinct molecular pathways. Notably, this phenomenon reflects inherent biological rationality rather than stochastic occurrence. Extensive research has revealed that multiple natural compounds, non-coding RNAs, exosomes, and non-PPO therapeutics not only exert modulatory influences on critical pathophysiological processes including inflammatory cascades, oxidative stress responses, and tissue regeneration mechanisms, but also effectively regulate bone-related cellular functions to inhibit PPO progression. Therefore, this review comprehensively and systematically summarizes the main pathogenic mechanisms of periprosthetic osteolysis. Furthermore, it delves deeper into the research progress on the applications of currently reported natural products, ncRNAs, exosomes, and non-PPO medications in the treatment of periprosthetic osteolysis. Based on this, we hope that this paper can provide new perspectives and references for the future development of drugs targeting periprosthetic osteolysis.
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Affiliation(s)
- Fang Yao
- Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, China
| | - Yue Bao
- Department of Nursing, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, China
| | - Qian Meng
- Outpatient Department, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, China
| | - Yanrong Chen
- Department of Orthopaedics, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, China
| | - Luxi Zhao
- Department of Anesthesiology, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, China
| | - Pingmei Wang
- Department of Orthopaedics, The People's Hospital of Shimen County, Shimen 415399, China
| | - Bin Zhou
- Department of Orthopaedics, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, China.
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Wang B, Lyu FJ, Deng Z, Zheng Q, Ma Y, Peng Y, Guo S, Lei G, Lai Y, Li Q. Therapeutic potential of stem cell-derived exosomes for bone tissue regeneration around prostheses. J Orthop Translat 2025; 52:85-96. [PMID: 40291635 PMCID: PMC12023751 DOI: 10.1016/j.jot.2025.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Revised: 03/09/2025] [Accepted: 03/14/2025] [Indexed: 04/30/2025] Open
Abstract
Artificial joint replacement is a widely recognized treatment for arthritis and other severe joint conditions. However, one of the primary causes of failure in joint replacements is the loosening of the prosthesis. After implantation, wear particles between the implant and the adjacent bone tissue are the principal contributors to this loosening. Recently, exosomes have garnered significant interest due to their low immunogenicity and effective membrane binding. They have shown potential in promoting bone regeneration via the paracrine pathway. This review examines the role and mechanisms of exosomes derived from mesenchymal stem cells (MSCs) in bone regeneration, their impact on the integration of various implants into surrounding bone tissue and current challenges and future directions for the clinical application of exosomes. The Translational Potential of this Article: Emerging evidence suggests that mesenchymal stem cell-derived exosomes may offer a promising therapeutic strategy for aseptic prosthesis loosening, potentially mediated through mechanisms such as modulation of inflammatory responses, suppression of osteoclastogenesis, enhancement of osteogenic differentiation and facilitation of bone regeneration. Preclinical studies further indicate that the therapeutic potential of these extracellular vesicles could be optimized through bioengineering strategies, including surface modification and cargo-loading techniques, warranting further investigation to advance their clinical translation.
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Affiliation(s)
- Biwu Wang
- Department of Orthopedics, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China
- Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, China
| | - Feng-Juan Lyu
- The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, 510000, China
- South China University of Technology-The University of Western Australia Joint Center for Regenerative Medicine Research, School of Medicine, South China University of Technology, Guangzhou, 510006, China
| | - Zhantao Deng
- Department of Orthopedics, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China
| | - Qiujian Zheng
- Department of Orthopedics, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China
| | - Yuanchen Ma
- Department of Orthopedics, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China
| | - Yujie Peng
- Department of Orthopedics, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China
- Shantou University Medical College, Xinling Road 22, Shantou, 515041, China
| | - Shujun Guo
- South China University of Technology-The University of Western Australia Joint Center for Regenerative Medicine Research, School of Medicine, South China University of Technology, Guangzhou, 510006, China
| | - Guihua Lei
- South China University of Technology-The University of Western Australia Joint Center for Regenerative Medicine Research, School of Medicine, South China University of Technology, Guangzhou, 510006, China
| | - Yonggang Lai
- South China University of Technology-The University of Western Australia Joint Center for Regenerative Medicine Research, School of Medicine, South China University of Technology, Guangzhou, 510006, China
| | - Qingtian Li
- Department of Orthopedics, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China
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Atia GA, Abdal Dayem A, Taher ES, Alghonemy WY, Cho SG, Aldarmahi AA, Haque MA, Alshambky A, Taymour N, Ibrahim AM, Zaghamir DE, Elmorsy EM, Hetta HF, Mohamed ME, Abass KS, Khanday S, Abdeen A. Urine-derived stem cells: a sustainable resource for advancing personalized medicine and dental regeneration. Front Bioeng Biotechnol 2025; 13:1571066. [PMID: 40357329 PMCID: PMC12066649 DOI: 10.3389/fbioe.2025.1571066] [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: 02/05/2025] [Accepted: 04/07/2025] [Indexed: 05/15/2025] Open
Abstract
Urine-based therapy, an ancient practice, has been utilized across numerous civilizations to address a wide range of ailments. Urine was considered a priceless resource in numerous traditional therapeutic applications due to its reported medicinal capabilities. While the utilization of urine treatment is contentious and lacks significant support from modern healthcare, the discovery of urine-derived stem cells (UDSCs) has introduced a promising avenue for cell-based therapy. UDSCs offer a noninvasive and easily repeatable collection method, making them a practical and viable option for therapeutic applications. Research has shown that UDSCs contribute to organ preservation by promoting revascularization and decreasing inflammatory reactions in many diseases and conditions. This review will outline the contemporary status of UDSCs research and explore their potential applications in both fundamental science and medical practice.
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Affiliation(s)
- Gamal A. Atia
- Department of Oral Medicine, Periodontology, and Diagnosis, Faculty of Dentistry, Suez Canal University, Ismailia, Egypt
| | - Ahmed Abdal Dayem
- Department of Stem Cell and Regenerative Biotechnology, School of Advanced Biotechnology, Molecular & Cellular Reprogramming Center, Institute of Advanced Regenerative Science, and Institute of Health, Aging & Society, Konkuk University, Seoul, Republic of Korea
| | - Ehab S. Taher
- Department of Basic and Clinical Medical Sciences, Faculty of Dentistry, Zarqa University, Zarqa, Jordan
| | - Wafaa Y. Alghonemy
- Department of Basic and Clinical Medical Sciences, Faculty of Dentistry, Zarqa University, Zarqa, Jordan
| | - Ssang-Goo Cho
- Department of Stem Cell and Regenerative Biotechnology, School of Advanced Biotechnology, Molecular & Cellular Reprogramming Center, Institute of Advanced Regenerative Science, and Institute of Health, Aging & Society, Konkuk University, Seoul, Republic of Korea
- R&D Team, StemExOne Co., Ltd., Seoul, Republic of Korea
| | - Ahmed A. Aldarmahi
- Department of Basic Science, College of Science and Health Professions, King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
- National Guard- Health Affairs, King Abdullah International Medical Research Centre, Jeddah, Saudi Arabia
| | - Md Azizul Haque
- Department of Biotechnology, Yeungnam University, Gyeongsan, Republic of Korea
| | - Abeer Alshambky
- Molecular Therapeutics Program, Fox Chase Cancer Center, Temple University, Philadelphia, PA, United States
- Department of Biochemistry, Animal Health Research Institute, Cairo, Egypt
| | - Noha Taymour
- Department of Substitutive Dental Sciences, College of Dentistry, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Ateya M. Ibrahim
- College of Nursing, Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi Arabia
| | - Donia E. Zaghamir
- College of Nursing, Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi Arabia
| | - Ekramy M. Elmorsy
- Center for Health Research, Northern Border University, Arar, Saudi Arabia
| | - Helal F. Hetta
- Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia
| | - Mohamed E. Mohamed
- Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh, Saudi Arabia
| | - Kasim S. Abass
- Department of Physiology, Biochemistry, and Pharmacology, College of Veterinary Medicine, University of Kirkuk, Kirkuk, Iraq
| | - Shifan Khanday
- Department of Biomedical Sciences, Dubai Medical College for Girls, Dubai Medical University, Dubai, United Arab Emirates
| | - Ahmed Abdeen
- Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Benha University, Toukh, Egypt
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Yu X, Jiang J, Li C, Wang Y, Ren Z, Hu J, Yuan T, Wu Y, Wang D, Sun Z, Wu Q, Chen B, Fang P, Ding H, Meng J, Jiang H, Zhao J, Bao N. Osthole ameliorates wear particle-induced osteogenic impairment by mitigating endoplasmic reticulum stress via PERK signaling cascade. Mol Med 2024; 30:266. [PMID: 39707212 DOI: 10.1186/s10020-024-01034-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: 09/11/2024] [Accepted: 12/06/2024] [Indexed: 12/23/2024] Open
Abstract
BACKGROUND Periprosthetic osteolysis and subsequent aseptic loosening are the leading causes of failure following total joint arthroplasty. Osteogenic impairment induced by wear particles is regarded as a crucial contributing factor in the development of osteolysis, with endoplasmic reticulum (ER) stress identified as a key underlying mechanism. Therefore, identifying potential therapeutic targets and agents that can regulate ER stress adaption in osteoblasts is necessary for arresting aseptic loosening. Osthole (OST), a natural coumarin derivative, has demonstrated promising osteogenic properties and the ability to modulate ER stress adaption in various diseases. However, the impact of OST on ER stress-mediated osteogenic impairment caused by wear particles remains unclear. METHODS TiAl6V4 particles (TiPs) were sourced from the prosthesis of patients who underwent revision hip arthroplasty due to aseptic loosening. A mouse calvarial osteolysis model was utilized to explore the effects of OST on TiPs-induced osteogenic impairment in vivo. Primary mouse osteoblasts were employed to investigate the impact of OST on ER stress-mediated osteoblast apoptosis and osteogenic inhibition induced by TiPs in vitro. The mechanisms underlying OST-modulated alleviation of ER stress induced by TiPs were elucidated through Molecular docking, immunochemistry, PCR, and Western blot analysis. RESULTS In this study, we found that OST treatment effectively mitigated TiAl6V4 particles (TiPs)-induced osteolysis by enhancing osteogenesis in a mouse calvarial model. Furthermore, we observed that OST could attenuate ER stress-mediated apoptosis and osteogenic reduction in osteoblasts exposed to TiPs in vitro and in vivo. Mechanistically, we demonstrated that OST exerts bone-sparing effects on stressed osteoblasts upon TiPs exposure by specifically suppressing the ER stress-dependent PERK signaling cascade. CONCLUSION Osthole ameliorates wear particle-induced osteogenic impairment by mitigating endoplasmic reticulum stress via PERK signaling cascade. These findings suggest that OST may serve as a potential therapeutic agent for combating wear particle-induced osteogenic impairment, offering a novel alternative strategy for managing aseptic prosthesis loosening.
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Affiliation(s)
- Xin Yu
- Department of Orthopedics, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Juan Jiang
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China
| | - Cheng Li
- Department of Orthopedics, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Yang Wang
- Department of Orthopedics, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Zhengrong Ren
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China
| | - Jianlun Hu
- State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, China
| | - Tao Yuan
- Department of Orthopedics, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Yongjie Wu
- State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China
| | - Dongsheng Wang
- Department of Spine Surgery, Center of Orthopedics, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Ziying Sun
- Department of Orthopedics, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Qi Wu
- Department of Vascular Surgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Bin Chen
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Julius Wolff Institute, Berlin, Germany
| | - Peng Fang
- Department of Orthopedics, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Hao Ding
- Department of Orthopedics, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Jia Meng
- Department of Orthopedics, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
| | - Hui Jiang
- Department of Orthopedics, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
| | - Jianning Zhao
- Department of Orthopedics, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
- Department of Orthopedics, Nanjing Hospital of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
| | - Nirong Bao
- Department of Orthopedics, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
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Liu H, Li M, Xiang B, Yang Z, Cao S, Gong W, Li J, Zhou W, Ding L, Tang Q, Wang S, Tang J, Fan Z, He K, Jiang X, Shen Z, Chen W, Hui J. An integrated "Engage & Evasion" approach for mononuclear phagocyte system escape and efficient extracellular vesicle therapy. J Nanobiotechnology 2024; 22:770. [PMID: 39696354 DOI: 10.1186/s12951-024-03032-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: 05/23/2024] [Accepted: 11/21/2024] [Indexed: 12/20/2024] Open
Abstract
Ischemic diseases are major contributors to global morbidity and mortality, posing a substantial threat to human health. Extracellular vesicles (EVs) play an essential role in enhancing neovascularization in ischemic tissues, thereby facilitating tissue repair and regeneration. However, the utilization of EVs is hindered by their rapid uptake and clearance by the mononuclear phagocyte system (MPS), which markedly impedes their therapeutic efficacy and organ-specific accumulation. Notably, CD47, upon binding to signal regulatory protein alpha, initiates a "don't eat me" signal, enabling immune evasion from the MPS. Our research has demonstrated that phagocytes predominantly engulf CD47low dendritic DC2.4 cell-derived EVs (DV), while engineered CD47high EVs (MV47) experience minimal ingestion. Leveraging these findings, we have developed a dual-faceted "Engage & Evasion" strategy. Initially, DVs were employed to saturate the MPS, serving as the "engage" component. Subsequently, MV47, fortified with CD47, was introduced for "evasion" purposes. This approach effectively minimized entrapment by the liver and spleen, boosted serum concentration, and enhanced final accumulation in non-MPS organs. In summary, our "Engage & Evasion" therapeutic strategy offers a promising avenue to enhance EV therapeutic potential against ischemic challenges through improved systemic distribution.
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Affiliation(s)
- Hongman Liu
- Department of Cardiovascular Surgery of The First Affiliated Hospital & Institute for Cardiovascular Science, Suzhou Medical College, Soochow University, Suzhou, China
- Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, China
- Department of Cardiovascular Medicine, The Affiliated Taian City Central Hospital of Qingdao University, Taian, China
| | - Mengting Li
- Department of Cardiovascular Surgery of The First Affiliated Hospital & Institute for Cardiovascular Science, Suzhou Medical College, Soochow University, Suzhou, China
| | - Bing Xiang
- Department of Cardiovascular Medicine, The Affiliated Taian City Central Hospital of Qingdao University, Taian, China
| | - Ziying Yang
- Department of Cardiovascular Surgery of The First Affiliated Hospital & Institute for Cardiovascular Science, Suzhou Medical College, Soochow University, Suzhou, China
| | - Shiyu Cao
- Department of Cardiovascular Surgery of The First Affiliated Hospital & Institute for Cardiovascular Science, Suzhou Medical College, Soochow University, Suzhou, China
| | - Wen Gong
- Department of Cardiovascular Medicine, The Affiliated Taian City Central Hospital of Qingdao University, Taian, China
| | - Jingjing Li
- Department of Cardiovascular Surgery of The First Affiliated Hospital & Institute for Cardiovascular Science, Suzhou Medical College, Soochow University, Suzhou, China
| | - Wenjing Zhou
- School of Life Sciences, Faculty of Medicine, Tianjin University, Tianjin, China
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China
| | - Liang Ding
- Department of Cardiovascular Surgery of The First Affiliated Hospital & Institute for Cardiovascular Science, Suzhou Medical College, Soochow University, Suzhou, China
| | - Qingsong Tang
- Department of Cardiovascular Surgery of The First Affiliated Hospital & Institute for Cardiovascular Science, Suzhou Medical College, Soochow University, Suzhou, China
| | - Shengnan Wang
- Department of Cardiovascular Surgery of The First Affiliated Hospital & Institute for Cardiovascular Science, Suzhou Medical College, Soochow University, Suzhou, China
| | - Jin Tang
- Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine, Sun Yat-Sen University, Shenzhen, China
| | - Zixuan Fan
- Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine, Sun Yat-Sen University, Shenzhen, China
| | - Ke He
- Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine, Sun Yat-Sen University, Shenzhen, China
| | - Xuan Jiang
- Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine, Sun Yat-Sen University, Shenzhen, China.
| | - Zhenya Shen
- Department of Cardiovascular Surgery of The First Affiliated Hospital & Institute for Cardiovascular Science, Suzhou Medical College, Soochow University, Suzhou, China.
| | - Weiqian Chen
- Department of Cardiovascular Surgery of The First Affiliated Hospital & Institute for Cardiovascular Science, Suzhou Medical College, Soochow University, Suzhou, China.
| | - Jie Hui
- Department of Cardiovascular Surgery of The First Affiliated Hospital & Institute for Cardiovascular Science, Suzhou Medical College, Soochow University, Suzhou, China.
- Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, China.
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Marinho A, Reis S, Nunes C. On the design of cell membrane-coated nanoparticles to treat inflammatory conditions. NANOSCALE HORIZONS 2024; 10:38-55. [PMID: 39499543 DOI: 10.1039/d4nh00457d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/07/2024]
Abstract
Biomimetic-based drug delivery systems (DDS) attempt to recreate the complex interactions that occur naturally between cells. Cell membrane-coated nanoparticles (CMCNPs) have been one of the main strategies in this area to prevent opsonization and clearance. Moreover, coating nanoparticles with cell membranes allows them to acquire functions and properties inherent to the mother cells. In particular, cells from bloodstream show to have specific advantages depending on the cell type to be used for that application, specifically in cases of chronic inflammation. Thus, this review focuses on the biomimetic strategies that use membranes from blood cells to target and treat inflammatory conditions.
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Affiliation(s)
- Andreia Marinho
- LAQV, REQUIMTE, Faculdade de Farmácia, Universidade do Porto, R. Jorge de Viterbo Ferreira 228, 4500-313 Porto, Portugal.
- LAQV, REQUIMTE, Faculdade de Ciências, Universidade do Porto, R. Campo Alegre s/n, 4169-007 Porto, Portugal
| | - Salette Reis
- LAQV, REQUIMTE, Faculdade de Farmácia, Universidade do Porto, R. Jorge de Viterbo Ferreira 228, 4500-313 Porto, Portugal.
| | - Cláudia Nunes
- LAQV, REQUIMTE, Faculdade de Farmácia, Universidade do Porto, R. Jorge de Viterbo Ferreira 228, 4500-313 Porto, Portugal.
- LAQV, REQUIMTE, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, R. Jorge de Viterbo Ferreira 228, 4500-313 Porto, Portugal
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8
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Liao R, Dewey MJ, Rong J, Johnson SA, D’Angelo WA, Hussey GS, Badylak SF. Matrix-bound nanovesicles alleviate particulate-induced periprosthetic osteolysis. SCIENCE ADVANCES 2024; 10:eadn1852. [PMID: 39423278 PMCID: PMC11488533 DOI: 10.1126/sciadv.adn1852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Accepted: 09/16/2024] [Indexed: 10/21/2024]
Abstract
Aseptic loosening of orthopedic implants is an inflammatory disease characterized by immune cell activation, chronic inflammation, and destruction of periprosthetic bone, and is one of the leading reasons for prosthetic failure, affecting 12% of total joint arthroplasty patients. Matrix-bound nanovesicles (MBVs) are a subclass of extracellular vesicle recently shown to mitigate inflammation in preclinical models of rheumatoid arthritis and influenza-mediated "cytokine storm." The molecular mechanism of these anti-inflammatory properties is only partially understood. The objective of the present study was to investigate the effects of MBV on RANKL-induced osteoclast formation in vitro and particulate-induced osteolysis in vivo. Results showed that MBV attenuated osteoclast differentiation and activity by suppressing the NF-κB signaling pathway and downstream NFATc1, DC-STAMP, c-Src, and cathepsin K expression. In vivo, local administration of MBV attenuated ultrahigh molecular weight polyethylene particle-induced osteolysis, bone reconstruction, and periosteal inflammation. The results suggest that MBV may be a therapeutic option for preventing periprosthetic loosening.
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Affiliation(s)
- Runzhi Liao
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA
- Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA
| | - Marley J. Dewey
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA
- Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA
| | - Jiayang Rong
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA
| | - Scott A. Johnson
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA
| | - William A. D’Angelo
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA
| | - George S. Hussey
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA
- Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA
| | - Stephen F. Badylak
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA
- Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15219, USA
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9
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Yang HS, Zheng YX, Bai X, He XY, Wang TH. Application prospects of urine-derived stem cells in neurological and musculoskeletal diseases. World J Orthop 2024; 15:918-931. [PMID: 39473520 DOI: 10.5312/wjo.v15.i10.918] [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: 04/24/2024] [Revised: 08/25/2024] [Accepted: 09/09/2024] [Indexed: 10/11/2024] Open
Abstract
Urine-derived stem cells (USCs) are derived from urine and harbor the potential of proliferation and multidirectional differentiation. Moreover, USCs could be reprogrammed into pluripotent stem cells [namely urine-derived induced pluripotent stem cells (UiPSCs)] through transcription factors, such as octamer binding transcription factor 4, sex determining region Y-box 2, kruppel-like factor 4, myelocytomatosis oncogene, and Nanog homeobox and protein lin-28, in which the first four are known as Yamanaka factors. Mounting evidence supports that USCs and UiPSCs possess high potential of neurogenic, myogenic, and osteogenic differentiation, indicating that they may play a crucial role in the treatment of neurological and musculoskeletal diseases. Therefore, we summarized the origin and physiological characteristics of USCs and UiPSCs and their therapeutic application in neurological and musculoskeletal disorders in this review, which not only contributes to deepen our understanding of hallmarks of USCs and UiPSCs but also provides the theoretical basis for the treatment of neurological and musculoskeletal disorders with USCs and UiPSCs.
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Affiliation(s)
- Hui-Si Yang
- Department of Neurology and National Traditional Chinese Medicine Clinical Research Base, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
| | - Yue-Xiang Zheng
- Department of Neurology and National Traditional Chinese Medicine Clinical Research Base, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
| | - Xue Bai
- Department of Neurology and National Traditional Chinese Medicine Clinical Research Base, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
| | - Xiu-Ying He
- Department of Anesthesiology, Institute of Neurological Disease, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Ting-Hua Wang
- Department of Neurology and National Traditional Chinese Medicine Clinical Research Base, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
- Department of Anesthesiology, Institute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
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10
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Wagener N, Pumberger M, Hardt S. Impact of fixation method on femoral bone loss: a retrospective evaluation of stem loosening in first-time revision total hip arthroplasty among two hundred and fifty five patients. INTERNATIONAL ORTHOPAEDICS 2024; 48:2339-2350. [PMID: 38822836 PMCID: PMC11347471 DOI: 10.1007/s00264-024-06230-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Accepted: 05/22/2024] [Indexed: 06/03/2024]
Abstract
PURPOSE Implant loosening represent the most common indication for stem revision in hip revision arthroplasty. This study compares femoral bone loss and the risk of initial revisions between cemented and uncemented loosened primary stems, investigating the impact of fixation method at primary implantation on femoral bone defects. METHODS This retrospective study reviewed 255 patients who underwent their first revision for stem loosening from 2010 to 2022, receiving either cemented or uncemented stem implants. Femoral bone loss was preoperatively measured using the Paprosky classification through radiographic evaluations. Kaplan-Meier analysis estimated the survival probability of the original stem, and the hazard ratio assessed the relative risk of revision for uncemented versus cemented stems in the first postoperative year and the following two to ten years. RESULTS Cemented stems showed a higher prevalence of significant bone loss (type 3b and 4 defects: 32.39% vs. 2.72%, p < .001) compared to uncemented stems, which more commonly had type 1 and 2 defects (82.07% vs. 47.89%, p < .001). In our analysis of revision cases, primary uncemented stems demonstrated a 20% lower incidence of stem loosening in the first year post-implantation compared to cemented stems (HR 0.8; 95%-CI 0.3-2.0). However, the incidence in uncemented stems increased by 20% during the subsequent years two to ten (HR 1.2; 95%-CI 0.7-1.8). Septic loosening was more common in cemented stems (28.17% vs. 10.87% in uncemented stems, p = .001). Kaplan-Meier analysis indicated a modestly longer revision-free period for cemented stems within the first ten years post-implantation (p < .022). CONCLUSION During first-time revision, cemented stems show significantly larger femoral bone defects than uncemented stems. Septic stem loosening occurred 17.30% more in cemented stems.
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Affiliation(s)
- Nele Wagener
- Center for Musculoskeletal Surgery, Department of Orthopaedic Surgery, Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117, Berlin, Germany.
| | - Matthias Pumberger
- Center for Musculoskeletal Surgery, Department of Orthopaedic Surgery, Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117, Berlin, Germany
| | - Sebastian Hardt
- Center for Musculoskeletal Surgery, Department of Orthopaedic Surgery, Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117, Berlin, Germany
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11
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Wang J, Liang S, Chen S, Ma T, Chen M, Niu C, Leng Y, Wang L. Bacterial outer membrane vesicle-cancer cell hybrid membrane-coated nanoparticles for sonodynamic therapy in the treatment of breast cancer bone metastasis. J Nanobiotechnology 2024; 22:328. [PMID: 38858780 PMCID: PMC11165797 DOI: 10.1186/s12951-024-02619-w] [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: 03/11/2024] [Accepted: 06/05/2024] [Indexed: 06/12/2024] Open
Abstract
Breast cancer bone metastasis is a terminal-stage disease and is typically treated with radiotherapy and chemotherapy, which causes severe side effects and limited effectiveness. To improve this, Sonodynamic therapy may be a more safe and effective approach in the future. Bacterial outer membrane vesicles (OMV) have excellent immune-regulating properties, including modulating macrophage polarization, promoting DC cell maturation, and enhancing anti-tumor effects. Combining OMV with Sonodynamic therapy can result in synergetic anti-tumor effects. Therefore, we constructed multifunctional nanoparticles for treating breast cancer bone metastasis. We fused breast cancer cell membranes and bacterial outer membrane vesicles to form a hybrid membrane (HM) and then encapsulated IR780-loaded PLGA with HM to produce the nanoparticles, IR780@PLGA@HM, which had tumor targeting, immune regulating, and Sonodynamic abilities. Experiments showed that the IR780@PLGA@HM nanoparticles had good biocompatibility, effectively targeted to 4T1 tumors, promoted macrophage type I polarization and DC cells activation, strengthened anti-tumor inflammatory factors expression, and presented the ability to effectively kill tumors both in vitro and in vivo, which showed a promising therapeutic effect on breast cancer bone metastasis. Therefore, the nanoparticles we constructed provided a new strategy for effectively treating breast cancer bone metastasis.
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Affiliation(s)
- Jiahao Wang
- The School of Medicine, Nankai University, Tianjin, 300071, China
- Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Shuailong Liang
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, China
- Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Sijie Chen
- Department of Ultrasound Diagnosis, Second Xiangya Hospital, Central South University, Changsha, China
| | - Tianliang Ma
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, China
- Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Mingyu Chen
- Department of Ultrasound Diagnosis, Second Xiangya Hospital, Central South University, Changsha, China
| | - Chengcheng Niu
- Department of Ultrasound Diagnosis, Second Xiangya Hospital, Central South University, Changsha, China
| | - Yi Leng
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, China
- Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Department of Rehabilitation, Xiangya Hospital, Central South University, Changsha, China
| | - Long Wang
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, China.
- Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
- Hunan Key Laboratary of Aging Biology, Xiangya Hospital, Central South University, 87 Xiangya Road, Kaifu District, Changsha, Hunan, 410008, China.
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12
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Ming L, Wu H, Fan Q, Dong Z, Huang J, Xiao Z, Xiao N, Huang H, Liu H, Li Z. Bio-inspired drug delivery systems: A new attempt from bioinspiration to biomedical applications. Int J Pharm 2024; 658:124221. [PMID: 38750980 DOI: 10.1016/j.ijpharm.2024.124221] [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: 04/11/2024] [Revised: 05/06/2024] [Accepted: 05/08/2024] [Indexed: 05/19/2024]
Abstract
Natural organisms have evolved sophisticated and multiscale hierarchical structures over time to enable survival. Currently, bionic design is revolutionizing drug delivery systems (DDS), drawing inspiration from the structure and properties of natural organisms that offer new possibilities to overcome the challenges of traditional drug delivery systems. Bionic drug delivery has contributed to a significant improvement in therapeutic outcomes, providing personalized regimens for patients with various diseases and enhancing both their quality of life and drug efficacy. Therefore, it is important to summarize the progress made so far and to discuss the challenges and opportunities for future development. Herein, we review the recent advances in bio-inspired materials, bio-inspired drug vehicles, and drug-loading platforms of biomimetic structures and properties, emphasizing the importance of adapting the structure and function of organisms to meet the needs of drug delivery systems. Finally, we highlight the delivery strategies of bionics in DDS to provide new perspectives and insights into the research and exploration of bionics in DDS. Hopefully, this review will provide future insights into utilizing biologically active vehicles, bio-structures, and bio-functions, leading to better clinical outcomes.
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Affiliation(s)
- Liangshan Ming
- Institute for Advanced Study, Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Chinese Medicine, Jiangxi, Nanchang 330004, China
| | - Hailian Wu
- Institute for Advanced Study, Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Chinese Medicine, Jiangxi, Nanchang 330004, China
| | - Qimeng Fan
- Institute for Advanced Study, Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Chinese Medicine, Jiangxi, Nanchang 330004, China
| | - Zishu Dong
- Institute for Advanced Study, Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Chinese Medicine, Jiangxi, Nanchang 330004, China
| | - Jia Huang
- Institute for Advanced Study, Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Chinese Medicine, Jiangxi, Nanchang 330004, China
| | - Zijian Xiao
- Institute for Advanced Study, Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Chinese Medicine, Jiangxi, Nanchang 330004, China
| | - Nan Xiao
- Institute for Advanced Study, Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Chinese Medicine, Jiangxi, Nanchang 330004, China
| | - Hao Huang
- National Engineering Research Center for Modernization of Traditional Chinese Medicine-Hakka Medical Resources Branch, College of Pharmacy, Gannan Medical, University, Jiangxi, Ganzhou 341000, China.
| | - Hongning Liu
- Institute for Advanced Study, Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Chinese Medicine, Jiangxi, Nanchang 330004, China.
| | - Zhe Li
- Institute for Advanced Study, Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Chinese Medicine, Jiangxi, Nanchang 330004, China.
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13
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Sun Y, Zhao H, Yang S, Wang G, Zhu L, Sun C, An Y. Urine-derived stem cells: Promising advancements and applications in regenerative medicine and beyond. Heliyon 2024; 10:e27306. [PMID: 38509987 PMCID: PMC10951541 DOI: 10.1016/j.heliyon.2024.e27306] [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: 09/23/2023] [Revised: 02/27/2024] [Accepted: 02/27/2024] [Indexed: 03/22/2024] Open
Abstract
Currently, stem cells are a prominent focus of regenerative engineering research. However, due to the limitations of commonly used stem cell sources, their application in therapy is often restricted to the experimental stage and constrained by ethical considerations. In contrast, urine-derived stem cells (USCs) offer promising advantages for clinical trials and applications. The noninvasive nature of the collection process allows for repeated retrieval within a short period, making it a more feasible option. Moreover, studies have shown that USCs have a protective effect on organs, promoting vascular regeneration, inhibiting oxidative stress, and reducing inflammation in various acute and chronic organ dysfunctions. The application of USCs has also been enhanced by advancements in biomaterials technology, enabling better targeting and controlled release capabilities. This review aims to summarize the current state of research on USCs, providing insights for future applications in basic and clinical settings.
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Affiliation(s)
| | | | - Shuguang Yang
- Department of Critical Care Medicine, Peking University People's Hospital, PR China
| | - Guangjie Wang
- Department of Critical Care Medicine, Peking University People's Hospital, PR China
| | - Leijie Zhu
- Department of Critical Care Medicine, Peking University People's Hospital, PR China
| | - Chang Sun
- Department of Critical Care Medicine, Peking University People's Hospital, PR China
| | - Youzhong An
- Department of Critical Care Medicine, Peking University People's Hospital, PR China
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14
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Chen S, Ma T, Wang J, Liang S, Liao H, Tan W, Chen M, Zhou X, Xu Y, Wang L, Niu C. Macrophage-derived biomimetic nanoparticles enhanced SDT combined with immunotherapy inhibited tumor growth and metastasis. Biomaterials 2024; 305:122456. [PMID: 38184961 DOI: 10.1016/j.biomaterials.2023.122456] [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: 08/31/2023] [Revised: 12/27/2023] [Accepted: 12/28/2023] [Indexed: 01/09/2024]
Abstract
Combination therapy based on sonodynamic therapy (SDT) combined with immune checkpoint blockers anti-PD-L1 provides effective anti-tumor effects. We designed a combination therapy based on M1/PLGA@IR780/CAT NPs of SDT-enhanced immunity combined with immune checkpoint blockers against PD-L1, which was based on M1 macrophage membrane-encapsulated poly (lactic-co-glycolic acid) (PLGA) nanoparticles loaded with the acoustic sensitizer IR780 and catalase (CAT) to successfully realize it. SDT based on M1/PLGA@IR780/CAT NPs could induce tumor cell death by promoting dendritic cell (DC) maturation and modulating the tumor immune microenvironment. In particular, the systemic anti-tumor immune response and potent immune memory induced upon combination with anti-PD-L1 checkpoint blockade not only alleviated the progression of mammary cancer in 4T1 mice and effectively blocked distant metastasis, but also prevented tumor recurrence, providing a promising new therapeutic strategy for clinical tumor therapy.
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Affiliation(s)
- Sijie Chen
- Department of Ultrasound Diagnosis, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Research Center of Ultrasonography, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Clinical Research Center for Ultrasound Diagnosis and Treatment in Hunan Province, China
| | - Tianliang Ma
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, China
| | - Jiahao Wang
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, China
| | - Shuailong Liang
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, China
| | - Haiqin Liao
- Department of Ultrasound Diagnosis, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Research Center of Ultrasonography, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Clinical Research Center for Ultrasound Diagnosis and Treatment in Hunan Province, China
| | - Wanlin Tan
- Department of Ultrasound Diagnosis, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Research Center of Ultrasonography, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Clinical Research Center for Ultrasound Diagnosis and Treatment in Hunan Province, China
| | - Mingyu Chen
- Department of Ultrasound Diagnosis, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Research Center of Ultrasonography, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Clinical Research Center for Ultrasound Diagnosis and Treatment in Hunan Province, China
| | - Xiaohui Zhou
- Department of Ultrasound Diagnosis, Changsha Central Hospital, Nanhua University, Changsha, Hunan 410014, China
| | - Yan Xu
- Department of Ultrasound Diagnosis, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Research Center of Ultrasonography, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Clinical Research Center for Ultrasound Diagnosis and Treatment in Hunan Province, China
| | - Long Wang
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, China
| | - Chengcheng Niu
- Department of Ultrasound Diagnosis, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Research Center of Ultrasonography, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Clinical Research Center for Ultrasound Diagnosis and Treatment in Hunan Province, China.
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15
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Yu L, Zhou A, Jia J, Wang J, Ji X, Deng Y, Lin X, Wang F. Immunoactivity of a hybrid membrane biosurface on nanoparticles: enhancing interactions with dendritic cells to augment anti-tumor immune responses. Biomater Sci 2024; 12:1016-1030. [PMID: 38206081 DOI: 10.1039/d3bm01628e] [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: 01/12/2024]
Abstract
Nano-biointerfaces play a pivotal role in determining the functionality of engineered therapeutic nanoparticles, particularly in the context of designing nanovaccines to effectively activate immune cells for cancer immunotherapy. Unlike involving chemical reactions by conventional surface decorating strategies, cell membrane-coating technology offers a straightforward approach to endow nanoparticles with natural biosurfaces, enabling them to mimic and integrate into the intricate biosystems of the body to interact with specific cells under physiological conditions. In this study, cell membranes, in a hybrid formulation, derived from cancer and activated macrophage cells were found to enhance the interaction of nanoparticles (HMP) with dendritic cells (DCs) and T cells among the mixed immune cells from lymph nodes (LNs), which could be leveraged in the development of nanovaccines for anti-tumor therapy. After loading with an adjuvant (R837), the nanoparticles coated with a hybrid membrane (HMPR) demonstrated effectiveness in priming DCs both in vitro and in vivo, resulting in amplified anti-tumor immune responses compared to those of nanoparticles coated with a single type of membrane or those lacking a membrane coating. The elevated immunoactivity of nanoparticles achieved by incorporating a hybrid membrane biosurface provides us a more profound comprehension of the nano-immune interaction, which may significantly benefit the development of bioactive nanomaterials for advanced therapy.
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Affiliation(s)
- Luying Yu
- Key Laboratory of Nanomedical Technology (Education Department of Fujian Province), Nanomedical Technology Research Institute, School of Pharmacy, Fujian Medical University, Fuzhou 350122, China.
| | - Ao Zhou
- Key Laboratory of Nanomedical Technology (Education Department of Fujian Province), Nanomedical Technology Research Institute, School of Pharmacy, Fujian Medical University, Fuzhou 350122, China.
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China.
| | - Jingyan Jia
- Key Laboratory of Nanomedical Technology (Education Department of Fujian Province), Nanomedical Technology Research Institute, School of Pharmacy, Fujian Medical University, Fuzhou 350122, China.
| | - Jieting Wang
- Key Laboratory of Nanomedical Technology (Education Department of Fujian Province), Nanomedical Technology Research Institute, School of Pharmacy, Fujian Medical University, Fuzhou 350122, China.
| | - Xueyang Ji
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China.
| | - Yu Deng
- Key Laboratory of Nanomedical Technology (Education Department of Fujian Province), Nanomedical Technology Research Institute, School of Pharmacy, Fujian Medical University, Fuzhou 350122, China.
| | - Xinhua Lin
- Key Laboratory of Nanomedical Technology (Education Department of Fujian Province), Nanomedical Technology Research Institute, School of Pharmacy, Fujian Medical University, Fuzhou 350122, China.
| | - Fang Wang
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China.
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16
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Ma T, Chen S, Wang J, Liang S, Chen M, Liu Q, Zhang Z, Liu G, Yang Y, Hu Y, Xie J. Enhanced Osteolysis Targeted Therapy through Fusion of Exosomes Derived from M2 Macrophages and Bone Marrow Mesenchymal Stem Cells: Modulating Macrophage Polarization. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2024; 20:e2303506. [PMID: 37806770 DOI: 10.1002/smll.202303506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 08/30/2023] [Indexed: 10/10/2023]
Abstract
Aseptic loosening of prostheses is a highly researched topic, and wear particle-induced macrophage polarization is a significant cause of peri-prosthetic osteolysis. Exosomes derived from bone marrow mesenchymal stem cells (BMSCs-Exos) promote M2 polarization and inhibit M1 polarization of macrophages. However, clinical application problems such as easy clearance and lack of targeting exist. Exosomes derived from M2 macrophages (M2-Exos) have good biocompatibility, immune escape ability, and natural inflammatory targeting ability. M2-Exos and BMSCs-Exos fused exosomes (M2-BMSCs-Exos) are constructed, which targeted the osteolysis site and exerted the therapeutic effect of both exosomes. M2-BMSCs-Exos achieved targeted osteolysis after intravenous administration inhibiting M1 polarization and promoting M2 polarization to a greater extent at the targeted site, ultimately playing a key role in the prevention and treatment of aseptic loosening of prostheses. In conclusion, M2-BMSCs-Exos can be used as a precise and reliable molecular drug for peri-prosthetic osteolysis. Fused exosomes M2-BMSCs-Exos were originally proposed and successfully prepared, and exosome fusion technology provides a new theoretical basis and solution for the clinical application of therapeutic exosomes.
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Affiliation(s)
- Tianliang Ma
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Sijie Chen
- Department of Ultrasound Diagnosis, Second Xiangya Hospital, Central South University, Changsha, 410012, China
| | - Jiahao Wang
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Shuailong Liang
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Mingyu Chen
- Department of Ultrasound Diagnosis, Second Xiangya Hospital, Central South University, Changsha, 410012, China
| | - Qimeng Liu
- Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Zheyu Zhang
- Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Guanzhi Liu
- Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Yute Yang
- Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Yihe Hu
- Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Jie Xie
- Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
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Yin Z, Gong G, Liu X, Yin J. Mechanism of regulating macrophages/osteoclasts in attenuating wear particle-induced aseptic osteolysis. Front Immunol 2023; 14:1274679. [PMID: 37860014 PMCID: PMC10582964 DOI: 10.3389/fimmu.2023.1274679] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Accepted: 09/22/2023] [Indexed: 10/21/2023] Open
Abstract
Joint replacement surgery is the most effective treatment for end-stage arthritis. Aseptic loosening caused by periprosthetic osteolysis is a common complication after joint replacement. Inflammation induced by wear particles derived from prosthetic biomaterials is a major cause of osteolysis. We emphasize that bone marrow-derived macrophages and their fusion-derived osteoclasts play a key role in this pathological process. Researchers have developed multiple intervention approaches to regulate macrophage/osteoclast activation. Aiming at wear particle-induced periprosthetic aseptic osteolysis, this review separately discusses the molecular mechanism of regulation of ROS formation and inflammatory response through intervention of macrophage/osteoclast RANKL-MAPKs-NF-κB pathway. These molecular mechanisms regulate osteoclast activation in different ways, but they are not isolated from each other. There is also a lot of crosstalk among the different mechanisms. In addition, other bone and joint diseases related to osteoclast activation are also briefly introduced. Therefore, we discuss these new findings in the context of existing work with a view to developing new strategies for wear particle-associated osteolysis based on the regulation of macrophages/osteoclasts.
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Affiliation(s)
- Zhaoyang Yin
- Department of Orthopedics, The Affiliated Lianyungang Hospital of Xuzhou Medical University (The First People’s Hospital of Lianyungang), Lianyungang, China
| | - Ge Gong
- Department of Geriatrics, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Xinhui Liu
- Department of Orthopedics, The Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing, China
| | - Jian Yin
- Department of Orthopedics, The Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing, China
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18
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Chen P, Pan Y, Ning X, Shi X, Zhong J, Fan X, Li W, Teng Y, Liu X, Yu B, Yang Y, Li H, Ou C. Targeted heart repair by Tβ4-loaded cardiac-resident macrophage-derived extracellular vesicles modified with monocyte membranes. Acta Biomater 2023; 169:372-386. [PMID: 37597679 DOI: 10.1016/j.actbio.2023.08.022] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 08/08/2023] [Accepted: 08/11/2023] [Indexed: 08/21/2023]
Abstract
Recent studies have demonstrated the critical role of cardiac-resident macrophages (cMacs) in the maintenance of physiological homeostasis. However, recruitment of circulating monocyte-derived macrophages decreases cMac levels post-myocardial infarction (MI). Transplanting cMacs is not an ideal option due to their low survival rates and the risk of immunological rejection. However, extracellular vesicle therapy has the potential to provide a feasible and safe alternative for cardiac repair. In this study, cell membrane-modified extracellular vesicles (MmEVs) were developed for heart repair by modifying cMac-derived extracellular vesicles (mEVs) with monocyte membranes, resulting in immune evasion and sequential targeted localization to damaged regions through expression of CD47 on MmEVs and strong affinity between monocyte membrane proteins and CCL2. Additionally, to fully exploit the potential clinical application of MmEVs and achieve a better curative effect, thymosin β4 (Tβ4) was loaded into the nanoparticles, resulting in Tβ4-MmEVs. In vitro experiments indicated that both the MmEVs and Tβ4-MmEVs promoted cardiomyocyte proliferation and endothelial cell migration. Animal experiments suggested that MI mice treated with MmEVs and Tβ4-MmEVs exhibited reduced myocardial fibrosis and increased vascular density compared to the control group. Thus, we posit that these targeted nanoparticles hold significant potential for MI adjuvant therapy and may open new avenues for cardiac repair and regeneration. STATEMENT OF SIGNIFICANCE: Extracellular vesicles (EVs) derived from bioactive parent cell sources involved in pathological and repair processes for cardiovascular disease have emerged as a compelling strategy for regenerative therapy. In this study, we constructed monocyte membrane-modified extracellular vesicles loaded with a drug (Tβ4-MmEVs) for heart repair that exhibit extraordinary abilities of immune evasion and sequential localization to damaged regions owing to the presence of CD47 and the strong affinity between monocytes and damaged cardiomyocytes and endothelial cells. The bioactivities of Tβ4-MmEVs on enhancing cardiomyocyte and endothelial cell proliferation were validated both in vitro and in vivo. Effective development and implementation of therapeutically membrane-modified nanoparticles from homologous origins can provide a reference for adjuvant therapy in clinical MI management.
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Affiliation(s)
- Peier Chen
- Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Southern Medical University, Dongguan 523018, China
| | - Yuxuan Pan
- Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Southern Medical University, Dongguan 523018, China
| | - Xiaodong Ning
- Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Southern Medical University, Dongguan 523018, China
| | - Xu Shi
- Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Southern Medical University, Dongguan 523018, China
| | - Jianfeng Zhong
- Department of Cardiology, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524003, China
| | - Xianglin Fan
- Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Southern Medical University, Dongguan 523018, China
| | - Weirun Li
- Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Southern Medical University, Dongguan 523018, China
| | - Yintong Teng
- Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Southern Medical University, Dongguan 523018, China
| | - Xueting Liu
- Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Southern Medical University, Dongguan 523018, China
| | - Bin Yu
- Department of Rehabilitation Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China
| | - Yanhua Yang
- Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Southern Medical University, Dongguan 523018, China.
| | - Hekai Li
- Department of Cardiology, Laboratory of Heart Center, Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
| | - Caiwen Ou
- Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Southern Medical University, Dongguan 523018, China.
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Pan B, Zhang Z, Wu X, Xian G, Hu X, Gu M, Zheng L, Li X, Long L, Chen W, Sheng P. Macrophages-derived exosomes modulates wear particle-induced osteolysis via miR-3470b targeting TAB3/NF-κB signaling. Bioact Mater 2023; 26:181-193. [PMID: 36911207 PMCID: PMC9999169 DOI: 10.1016/j.bioactmat.2023.02.028] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 02/25/2023] [Accepted: 02/25/2023] [Indexed: 03/07/2023] Open
Abstract
Image 1.
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Key Words
- APL, Aseptic prothesis loosening
- Aseptic prothesis loosening
- Bglap, Osteocalcin
- CTSK, Cathepsin K
- Exosome
- Inflammatory osteolysis
- Macrophage
- NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells
- NFATc-1, Nuclear factor of activated T-cells, cytoplasmic 1
- Non-coding RNA
- OB, Osteoblast
- OC, Osteoclast
- P-P65, phospho-P65
- P65, NF-κB signaling
- Runx2, Runt-related transcription factor 2
- TAB3, TGF-β-activated kinase 1 (MAP3K7) binding protein 3
- ncRNA, non-coding RNA
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Affiliation(s)
- Baiqi Pan
- Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, China.,Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Sun Yat-Sen University, China
| | - Ziji Zhang
- Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, China.,Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Sun Yat-Sen University, China
| | - Xiaoyu Wu
- Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, China.,Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Sun Yat-Sen University, China
| | - Guoyan Xian
- Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, China.,Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Sun Yat-Sen University, China.,Université de Paris, CNRS, INSERM, B3OA, Paris, France
| | - Xuantao Hu
- Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, China.,Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Sun Yat-Sen University, China
| | - Minghui Gu
- Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, China.,Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Sun Yat-Sen University, China
| | - Linli Zheng
- Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, China.,Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Sun Yat-Sen University, China
| | - Xiang Li
- Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Sun Yat-Sen University, China.,Department of Spine Surgery, The first affiliated hospital of Sun Yat-sen University, China
| | - Lingli Long
- Research Center of Translational Medicine, The First Affiliated Hospital of Sun Yat-sen University, China
| | - Weishen Chen
- Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, China.,Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Sun Yat-Sen University, China
| | - Puyi Sheng
- Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, China.,Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Sun Yat-Sen University, China
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