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Nguyen MNH, Vu BT, Truong DM, Le TD, Vo TTT, Vo TV, Nguyen TH. Fabrication of 3-Dimensional-Printed Bilayered Scaffold Carboxymethyl Chitosan/Oxidized Xanthan Gum, Biphasic Calcium Phosphate for Osteochondral Regeneration. Biomater Res 2025; 29:0186. [PMID: 40207259 PMCID: PMC11979342 DOI: 10.34133/bmr.0186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Revised: 02/21/2025] [Accepted: 03/15/2025] [Indexed: 04/11/2025] Open
Abstract
Cartilage tissue regeneration remains challenging due to the tissue's poor self-healing capacity, attributed to its hypocellular and avascular nature, which limits nutrient delivery to the defect site and complicates healing. Traditional methods often utilize the subchondral tissue layer to improve nutrient exchange through its vascular network, although these approaches have limitations. To address these issues, 3-dimensional (3D) printing has been employed to create the bilayered scaffold that mimics the complex structure of osteochondral tissue. In this study, the N,O-carboxymethyl chitosan (NOCC) and oxidized xanthan gum (OXG) hydrogel was fabricated for the cartilage layer due to its similarity to the native cartilage structure, while the biphasic calcium phosphate (BCP) incorporation enhanced the osteoconductivity to promote new bone growth for osteochondral tissue regeneration. Various characterization tests, including compression strength, scanning electron microscopy analysis, and biological properties, were conducted to evaluate and balanced to achieve the highest regenerative capacity for implantation. No cytotoxicity was caused, while the in vitro testing highlighted that the addition of BCP considerably supported cellular behavior on the scaffold and improved the regeneration rate. With 60% BCP content, the 3D scaffold demonstrated a high osteochondral tissue regeneration rate, as evidenced by visual inspection, x-ray imaging, and histological analysis, outperforming other experimental models.
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Affiliation(s)
- My N.-H. Nguyen
- Tissue Engineering and Regenerative Medicine Department, School of Biomedical Engineering,
International University, Ho Chi Minh City, Vietnam
- Vietnam National University, Ho Chi Minh City, Vietnam
| | - Binh T. Vu
- Tissue Engineering and Regenerative Medicine Department, School of Biomedical Engineering,
International University, Ho Chi Minh City, Vietnam
- Vietnam National University, Ho Chi Minh City, Vietnam
| | - Dung M. Truong
- Biotechnology Center of Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Thanh D. Le
- Thong Nhat Hospital, Ho Chi Minh City, Vietnam
| | - Thanh-Tuyen T. Vo
- Tissue Engineering and Regenerative Medicine Department, School of Biomedical Engineering,
International University, Ho Chi Minh City, Vietnam
- Vietnam National University, Ho Chi Minh City, Vietnam
| | - Toi V. Vo
- Tissue Engineering and Regenerative Medicine Department, School of Biomedical Engineering,
International University, Ho Chi Minh City, Vietnam
- Vietnam National University, Ho Chi Minh City, Vietnam
| | - Thi-Hiep Nguyen
- Tissue Engineering and Regenerative Medicine Department, School of Biomedical Engineering,
International University, Ho Chi Minh City, Vietnam
- Vietnam National University, Ho Chi Minh City, Vietnam
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Shibahara K, Hayashi K, Nakashima Y, Ishikawa K. Controlling the pore size of carbonate apatite honeycomb scaffolds enhances orientation and strength of regenerated bone. BIOMATERIALS ADVANCES 2025; 166:214026. [PMID: 39299056 DOI: 10.1016/j.bioadv.2024.214026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Revised: 08/31/2024] [Accepted: 09/02/2024] [Indexed: 09/22/2024]
Abstract
To restore functions of long bones and avoid reconstruction failure, segmental defects should be quickly repaired using abundant amounts of regenerated bone with high mechanical strength and orientation along the bone axis. Although both bone volume and bone matrix orientation are important for faster restoration of long bones with segmental defects, researchers have primarily focused on the former. Artificial bone scaffolds with uniaxial channels, (e.g., honeycomb (HC) scaffolds), are considered adequate for regenerating bone oriented along the bone axis. The channel size may affect the orientation, amount, and strength of the regenerated bone. In this study, we investigated the effects of channel size in carbonate apatite HC scaffolds on the orientation of bones regenerated in segmental bone defects and determined the adequate channel size. Carbonate apatite HC scaffolds, with different channel sizes (350, 550, 730, and 890 μm in length on the side of the square aperture), were fabricated by extrusion molding of a mixture of calcium carbonate and organic binder, debinding, and subsequent phosphatization to convert the composition from calcium carbonate to carbonate apatite. No significant difference in the amounts of regenerated bones was observed for different channel sizes. However, bone along the bone axis was formed in the channels ≤550 μm in size but not in channels ≥730 μm. The HC scaffolds with a channel size of 350 μm regenerated bone with higher bending strength than those with a channel size of 890 μm. However, bone regenerated with the HC scaffolds having channel sizes of 350, 550, and 730 μm showed equal bending strength. Thus, the adequate channel size for fast regeneration of high-strength bone, oriented to the bone axis, is ≤730 μm. To the best of our knowledge, this is the first study to report the effect of channel size on bone orientation and strength. The findings of this study are relevant to the fast repair of segmental bone defects.
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Affiliation(s)
- Keigo Shibahara
- Department of Biomaterials, Faculty of Dental Science, Kyushu University 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
| | - Koichiro Hayashi
- Department of Biomaterials, Faculty of Dental Science, Kyushu University 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
| | - Yasuharu Nakashima
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
| | - Kunio Ishikawa
- Department of Biomaterials, Faculty of Dental Science, Kyushu University 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
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Kim E, Lee J, Kim SJ, Kim EM, Byun H, Huh SJ, Lee E, Shin H. Biomimetic composite gelatin methacryloyl hydrogels for improving survival and osteogenesis of human adipose-derived stem cells in 3D microenvironment. Mater Today Bio 2024; 29:101293. [PMID: 39483390 PMCID: PMC11525152 DOI: 10.1016/j.mtbio.2024.101293] [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: 05/25/2024] [Revised: 09/20/2024] [Accepted: 10/06/2024] [Indexed: 11/03/2024] Open
Abstract
Gelatin methacryloyl (GelMA) hydrogels are used for stem cell encapsulation in bone tissue engineering due to their fast and stable photo-crosslinking. However, cell viability and ability to induce osteogenesis are reduced by reactive oxygen species (ROS) produced during the crosslinking reaction. In this study, we developed biomimetic nanoparticles (TMNs) by combining tannic acid (TA) and simulated body fluid (SBF) minerals, and used them to synthesize GelMA-based composite hydrogels for addressing those limitations. The optimal concentrations of TA and SBF were investigated to create nanoparticles that can effectively scavenge ROS and induce osteogenesis. The incorporation of TMNs into composite hydrogels (G-TMN) significantly enhanced the survival and proliferation of encapsulated human adipose-derived stem cells (hADSCs) by providing resistance to oxidative conditions. In addition, the ions that were released, such as Ca2+ and PO4 3-, stimulated stem cell differentiation into bone cells. The hADSCs encapsulated in G-TMN had 2.0 ± 0.8-fold greater viability and 1.3 ± 1.8 times greater calcium deposition than those encapsulated in the hydrogel without nanoparticles. Furthermore, the in vivo transplantation of G-TMN into a subcutaneous mouse model demonstrated the rapid degradation of the gel-network while retaining the osteoinductive particles and cells in the transplanted area. The increased cellular activity observed in our multifunctional composite hydrogel can serve as a foundation for novel and effective therapies for bone deformities.
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Affiliation(s)
- Eunhyung Kim
- Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea
- BK21 FOUR, Education and Research Group for Biopharmaceutical Innovation Leader, Hanyang University, Seoul, 04763, Republic of Korea
| | - Jinkyu Lee
- Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea
| | - Se-Jeong Kim
- Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea
| | - Eun Mi Kim
- Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea
| | - Hayeon Byun
- Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea
| | - Seung Jae Huh
- Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea
- BK21 FOUR, Education and Research Group for Biopharmaceutical Innovation Leader, Hanyang University, Seoul, 04763, Republic of Korea
| | - Eunjin Lee
- Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea
- BK21 FOUR, Education and Research Group for Biopharmaceutical Innovation Leader, Hanyang University, Seoul, 04763, Republic of Korea
| | - Heungsoo Shin
- Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea
- BK21 FOUR, Education and Research Group for Biopharmaceutical Innovation Leader, Hanyang University, Seoul, 04763, Republic of Korea
- Institute of Nano Science and Technology, Hanyang University, Seoul, 04763, Republic of Korea
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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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Atia GA, Rashed F, Taher ES, Cho SG, Dayem AA, Soliman MM, Shalaby HK, Mohammed NA, Taymour N, El-Sherbiny M, Ebrahim E, Ramadan MM, Abdelkader A, Abdo M, Aldarmahi AA, Atwa AM, Bafail DA, Abdeen A. Challenges of therapeutic applications and regenerative capacities of urine based stem cells in oral, and maxillofacial reconstruction. Biomed Pharmacother 2024; 177:117005. [PMID: 38945084 DOI: 10.1016/j.biopha.2024.117005] [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: 03/31/2024] [Revised: 06/09/2024] [Accepted: 06/17/2024] [Indexed: 07/02/2024] Open
Abstract
Urine-derived stem cells (USCs) have gained the attention of researchers in the biomedical field in the past few years . Regarding the several varieties of cells that have been used for this purpose, USCs have demonstrated mesenchymal stem cell-like properties, such as differentiation and immunomodulation. Furthermore, they could be differentiated into several lineages. This is very interesting for regenerative techniques based on cell therapy. This review will embark on describing their separation, and profiling. We will specifically describe the USCs characteristics, in addition to their differentiation potential. Then, we will introduce and explore the primary uses of USCs. These involve thier utilization as a platform to produce stem cells, however, we shall concentrate on the utilization of USCs for therapeutic, and regenerative orofacial applications, providing an in-depth evaluation of this purpose. The final portion will address the limitations and challenges of their implementation in regenerative dentistry.
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Affiliation(s)
- Gamal A Atia
- Department of Oral Medicine, Periodontology, and Diagnosis, Faculty of Dentistry, Suez Canal University, Ismailia 41522, Egypt.
| | - Fatema Rashed
- Department of Basic Medical and Dental Sciences, Faculty of Dentistry, Zarqa University, Zarqa 13110, Jordan
| | - Ehab S Taher
- Department of Basic Medical and Dental Sciences, Faculty of Dentistry, Zarqa University, Zarqa 13110, Jordan
| | - Ssang-Goo Cho
- Department of Stem Cell and Regenerative Biotechnology and Institute of Advanced Regenerative Science, Konkuk University, Seoul 05029, South Korea.
| | - Ahmed Abdal Dayem
- Department of Stem Cell and Regenerative Biotechnology and Institute of Advanced Regenerative Science, Konkuk University, Seoul 05029, South Korea
| | - Magdalen M Soliman
- Department of Oral Medicine, Periodontology, and Diagnosis, Faculty of Dentistry, Badr University, Egypt
| | - Hany K Shalaby
- Department of Oral Medicine, Periodontology and Oral Diagnosis, Faculty of Dentistry, Suez University, Suez 43512, Egypt
| | - Nourelhuda A Mohammed
- Physiology and Biochemistry Department, Faculty of Medicine, Mutah University, Mutah, Al-Karak 61710, Jordan
| | - Noha Taymour
- Department of Substitutive Dental Sciences, College of Dentistry, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia
| | - Mohamed El-Sherbiny
- Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, 71666, Riyadh 11597, Saudi Arabia; Department of Anatomy, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
| | - Elturabi Ebrahim
- Department of Medical Surgical Nursing, Nursing College, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Mahmoud M Ramadan
- Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Afaf Abdelkader
- Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Benha University, Benha 13518, Egypt
| | - Mohamed Abdo
- Department of Animal Histology and Anatomy, School of Veterinary Medicine, Badr University in Cairo (BUC), Badr City, Egypt; Department of Anatomy and Embryology, Faculty Veterinary Medicine, University of Sadat City, Sadat City, Egypt
| | - Ahmed A Aldarmahi
- Department of Basic Science, College of Science and Health Professions, King Saud bin Abdulaziz University for Health Sciences, Jeddah 21582, Saudi Arabia; National Guard, Health Affairs, King Abdullah International Medical Research Centre, Jeddah 21582, Saudi Arabia
| | - Ahmed M Atwa
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Egyptian Russian University, Cairo 11829, Egypt
| | - Duaa A Bafail
- Department of Clinical Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah 11829, Saudi Arabia
| | - Ahmed Abdeen
- Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Benha University, Toukh 13736, Egypt.
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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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Balachandran Megha K, Syama S, Padmalayathil Sangeetha V, Vandana U, Oyane A, Valappil Mohanan P. Development of a 3D multifunctional collagen scaffold impregnated with peptide LL-37 for vascularised bone tissue regeneration. Int J Pharm 2024; 652:123797. [PMID: 38199447 DOI: 10.1016/j.ijpharm.2024.123797] [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: 10/18/2023] [Revised: 01/04/2024] [Accepted: 01/05/2024] [Indexed: 01/12/2024]
Abstract
Bone is a highly dynamic connective tissue that provides structural support, locomotion and acts as a shield for many vital organs from damage. Bone inherits the ability to heal after non-severe injury. In case of severe bone abnormalities due to trauma, infections, genetic disorders and tumors, there is a demand for a scaffold that can enhance bone formation and regenerate the lost bone tissue. In this study, a 3D collagen scaffold (CS) was functionalized and assessed under in vitro and in vivo conditions. For this, a collagen scaffold coated with hydroxyapatite (Ap-CS) was developed and loaded with a peptide LL-37. The physico-chemical characterisation confirmed the hydroxyapatite coating on the outer and inner surfaces of Ap-CS. In vitro studies confirmed that LL-37 loaded Ap-CS promotes osteogenic differentiation of human osteosarcoma cells without showing significant cytotoxicity. The efficacy of the LL-37 loaded Ap-CS for bone regeneration was evaluated at 4 and 12 weeks post-implantation by histopathological and micro-CT analysis in rabbit femur defect model. The implanted LL-37 loaded Ap-CS facilitated the new bone formation at 4 weeks compared with Ap-CS without LL-37. The LL-37 loaded Ap-CS incorporating apatite and peptide LL-37 would be useful as a multifunctional scaffold for bone tissue engineering.
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Affiliation(s)
- Kizhakkepurakkal Balachandran Megha
- Toxicology Division, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology (Govt. of India), Poojapura, Trivandrum 695 012, Kerala, India
| | - Santhakumar Syama
- Nanomaterials Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), AIST Tsukuba Central 5, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan
| | - Vijayan Padmalayathil Sangeetha
- Toxicology Division, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology (Govt. of India), Poojapura, Trivandrum 695 012, Kerala, India
| | - Unnikrishnan Vandana
- Toxicology Division, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology (Govt. of India), Poojapura, Trivandrum 695 012, Kerala, India
| | - Ayako Oyane
- Nanomaterials Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), AIST Tsukuba Central 5, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan
| | - Parayanthala Valappil Mohanan
- Toxicology Division, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology (Govt. of India), Poojapura, Trivandrum 695 012, Kerala, India.
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Xing F, Shen HY, Zhe M, Jiang K, Lei J, Xiang Z, Liu M, Xu JZ, Li ZM. Nano-Topographically Guided, Biomineralized, 3D-Printed Polycaprolactone Scaffolds with Urine-Derived Stem Cells for Promoting Bone Regeneration. Pharmaceutics 2024; 16:204. [PMID: 38399258 PMCID: PMC10892771 DOI: 10.3390/pharmaceutics16020204] [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: 11/30/2023] [Revised: 01/21/2024] [Accepted: 01/26/2024] [Indexed: 02/25/2024] Open
Abstract
Currently, biomineralization is widely used as a surface modification approach to obtain ideal material surfaces with complex hierarchical nanostructures, morphologies, unique biological functions, and categorized organizations. The fabrication of biomineralized coating for the surfaces of scaffolds, especially synthetic polymer scaffolds, can alter surface characteristics, provide a favorable microenvironment, release various bioactive substances, regulate the cellular behaviors of osteoblasts, and promote bone regeneration after implantation. However, the biomineralized coating fabricated by immersion in a simulated body fluid has the disadvantages of non-uniformity, instability, and limited capacity to act as an effective reservoir of bioactive ions for bone regeneration. In this study, in order to promote the osteoinductivity of 3D-printed PCL scaffolds, we optimized the surface biomineralization procedure by nano-topographical guidance. Compared with biomineralized coating constructed by the conventional method, the nano-topographically guided biomineralized coating possessed more mineral substances and firmly existed on the surface of scaffolds. Additionally, nano-topographically guided biomineralized coating possessed better protein adsorption and ion release capacities. To this end, the present work also demonstrated that nano-topographically guided biomineralized coating on the surface of 3D-printed PCL scaffolds can regulate the cellular behaviors of USCs, guide the osteogenic differentiation of USCs, and provide a biomimetic microenvironment for bone regeneration.
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Affiliation(s)
- Fei Xing
- Department of Orthopedic Surgery, Orthopedic Research Institute, Laboratory of Stem Cell and Tissue Engineering, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China; (F.X.); (Z.X.)
| | - Hui-Yuan Shen
- College of Polymer Science and Engineering and State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China; (H.-Y.S.); (K.J.); (J.L.); (Z.-M.L.)
| | - Man Zhe
- Animal Experiment Center, West China Hospital, Sichuan University, Chengdu 610041, China;
| | - Kai Jiang
- College of Polymer Science and Engineering and State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China; (H.-Y.S.); (K.J.); (J.L.); (Z.-M.L.)
| | - Jun Lei
- College of Polymer Science and Engineering and State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China; (H.-Y.S.); (K.J.); (J.L.); (Z.-M.L.)
| | - Zhou Xiang
- Department of Orthopedic Surgery, Orthopedic Research Institute, Laboratory of Stem Cell and Tissue Engineering, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China; (F.X.); (Z.X.)
| | - Ming Liu
- Department of Orthopedic Surgery, Orthopedic Research Institute, Laboratory of Stem Cell and Tissue Engineering, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China; (F.X.); (Z.X.)
| | - Jia-Zhuang Xu
- College of Polymer Science and Engineering and State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China; (H.-Y.S.); (K.J.); (J.L.); (Z.-M.L.)
| | - Zhong-Ming Li
- College of Polymer Science and Engineering and State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China; (H.-Y.S.); (K.J.); (J.L.); (Z.-M.L.)
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Wang X, Li L, Sun B, Hou X, Song S, Shi C, Chen W. Piezo1-ERK1/2-YAP Signaling Cascade Regulates the Proliferation of Urine-derived Stem Cells on Collagen Gels. Curr Stem Cell Res Ther 2024; 19:103-115. [PMID: 36999714 DOI: 10.2174/1574888x18666230331123540] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Revised: 12/30/2022] [Accepted: 01/26/2023] [Indexed: 04/01/2023]
Abstract
BACKGROUND Urine-derived stem cells (USCs) were considered to be an ideal source of stem cells for repairing urological diseases. However, the proliferative ability of USCs significantly decreased when cultured on plastic dishes, which limited their clinical application. It was found that collagen gels could promote the proliferation of USCs, but the underlying molecular mechanisms were unclear. OBJECTIVE The study aims to investigate the role of the mechanically activated cation channel Piezo1 and the transcriptional coactivator YAP in the regulation of proliferation of USCs on collagen gels. METHODS USCs were cultured on collagen gels (group COL), or plastic dishes (group NON). MTT assay, Scratch assay, EDU staining, and immunofluorescence (IF) of Ki67 were performed to evaluate the proliferation of USCs; IF of YAP was conducted to observe its nuclear localization; calcium imaging experiment was executed to evaluate the function of Piezo1; western blot was used to compare changes in protein expression of YAP, LATS1, ERK1/2, and p-ERK1/2. In addition, the regulatory effect of YAP on the proliferative capacity of USCs was confirmed by intervening YAP with its inhibitor verteporfin (VP); and the inhibitor or activator of Piezo1, GsMTx4 or Yoda1 was used to explore the effect of Piezo1 on the nuclear localization of YAP, the proliferation of USCs and the regeneration of injured bladder. RESULTS The results showed that cell proliferation was significantly enhanced in USCs in the COL group with the nuclear accumulation of YAP compared with the NON group and VP attenuated these effects. The expression and function of Piezo1 were higher in the COL group compared with the NON group. Blockage of Piezo1 by GsMTx4 decreased nuclear localization of YAP, the proliferation of USCs, and caused the failure of bladder reconstruction. Activation of Piezo1 by Yoda1 increased the nuclear expression of YAP, and the proliferation of USCs, which further improved the regeneration of the injured bladder. Finally, the ERK1/2 rather than LATS1 was revealed to participate in the Piezo1/YAP signal cascades of USCs proliferation. CONCLUSION Taken together, Piezo1-ERK1/2-YAP signal cascades were involved in regulating the proliferation ability of USCs in collagen gels which would be beneficial for the regeneration of the bladder.
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Affiliation(s)
- Xiaoya Wang
- Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Qingdao, Shandong Province, China
| | - Ling Li
- Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Qingdao, Shandong Province, China
| | - Bishao Sun
- Department of Urology, Xinqiao Hospital of Army Medical University, Chongqing, China
| | - Xianglin Hou
- Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
| | - Siqi Song
- Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Qingdao, Shandong Province, China
| | - Chunying Shi
- Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Qingdao, Shandong Province, China
| | - Wei Chen
- Department of Urology, Xinqiao Hospital of Army Medical University, Chongqing, China
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10
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Dvorakova J, Wiesnerova L, Chocholata P, Kulda V, Landsmann L, Cedikova M, Kripnerova M, Eberlova L, Babuska V. Human cells with osteogenic potential in bone tissue research. Biomed Eng Online 2023; 22:33. [PMID: 37013601 PMCID: PMC10069154 DOI: 10.1186/s12938-023-01096-w] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Accepted: 03/24/2023] [Indexed: 04/05/2023] Open
Abstract
Bone regeneration after injury or after surgical bone removal due to disease is a serious medical challenge. A variety of materials are being tested to replace a missing bone or tooth. Regeneration requires cells capable of proliferation and differentiation in bone tissue. Although there are many possible human cell types available for use as a model for each phase of this process, no cell type is ideal for each phase. Osteosarcoma cells are preferred for initial adhesion assays due to their easy cultivation and fast proliferation, but they are not suitable for subsequent differentiation testing due to their cancer origin and genetic differences from normal bone tissue. Mesenchymal stem cells are more suitable for biocompatibility testing, because they mimic natural conditions in healthy bone, but they proliferate more slowly, soon undergo senescence, and some subpopulations may exhibit weak osteodifferentiation. Primary human osteoblasts provide relevant results in evaluating the effect of biomaterials on cellular activity; however, their resources are limited for the same reasons, like for mesenchymal stem cells. This review article provides an overview of cell models for biocompatibility testing of materials used in bone tissue research.
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Affiliation(s)
- Jana Dvorakova
- Department of Medical Chemistry and Biochemistry, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1655/76, 323 00, Plzen, Czech Republic
| | - Lucie Wiesnerova
- Department of Medical Chemistry and Biochemistry, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1655/76, 323 00, Plzen, Czech Republic
| | - Petra Chocholata
- Department of Medical Chemistry and Biochemistry, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1655/76, 323 00, Plzen, Czech Republic
| | - Vlastimil Kulda
- Department of Medical Chemistry and Biochemistry, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1655/76, 323 00, Plzen, Czech Republic
| | - Lukas Landsmann
- Department of Medical Chemistry and Biochemistry, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1655/76, 323 00, Plzen, Czech Republic
| | - Miroslava Cedikova
- Biomedical Center, Laboratory of Tumor Biology and Immunotherapy, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1655/76, 323 00, Plzen, Czech Republic
| | - Michaela Kripnerova
- Department of Biology, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1655/76, 323 00, Plzen, Czech Republic
| | - Lada Eberlova
- Department of Anatomy, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1655/76, 323 00, Plzen, Czech Republic
| | - Vaclav Babuska
- Department of Medical Chemistry and Biochemistry, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1655/76, 323 00, Plzen, Czech Republic.
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11
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Zhang B, Xing F, Chen L, Zhou C, Gui X, Su Z, Fan S, Zhou Z, Jiang Q, Zhao L, Liu M, Fan Y, Zhang X. DLP fabrication of customized porous bioceramics with osteoinduction ability for remote isolation bone regeneration. BIOMATERIALS ADVANCES 2023; 145:213261. [PMID: 36577193 DOI: 10.1016/j.bioadv.2022.213261] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 11/20/2022] [Accepted: 12/16/2022] [Indexed: 12/24/2022]
Abstract
Currently, various bioceramics have been widely used in bone regeneration. However, it remains a huge challenge to remote isolation bone regeneration, such as severed finger regeneration. The remote isolation bone tissue has a poor regenerative microenvironment that lacks enough blood and nutrition supply. It is very difficult to repair and regenerate. In this study, well-controlled multi-level porous 3D-printed calcium phosphate (CaP) bioceramic scaffolds with precision customized structures were fabricated by high-resolution digital light projection (DLP) printing technology for remote isolation bone regeneration. In vitro results demonstrated that optimizing material processing procedures could achieve multi-level control of 3D-printed CaP bioceramic scaffolds and enhance the osteoinduction ability of bioceramics effectively. In vivo results indicated that 3D-printed CaP bioceramic scaffolds constructed by optimized processing procedure exhibited a promising ability of bone regeneration and osteoinduction in ectopic osteogenesis and in situ caudal vertebrae regeneration in beagles. This study provided a promising strategy based on 3D-printed CaP bioceramic scaffolds constructed by optimized processing procedures for remote isolation bone regeneration, such as severed finger regeneration.
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Affiliation(s)
- Boqing Zhang
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China; College of Biomedical Engineering, Sichuan University, Chengdu 610064, China
| | - Fei Xing
- Orthopedic Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Li Chen
- Analytical & Testing Center, Sichuan University, Chengdu, Sichuan 610064, China
| | - Changchun Zhou
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China; College of Biomedical Engineering, Sichuan University, Chengdu 610064, China
| | - Xingyu Gui
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China; College of Biomedical Engineering, Sichuan University, Chengdu 610064, China
| | - Zixuan Su
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China; College of Biomedical Engineering, Sichuan University, Chengdu 610064, China
| | - Shiqi Fan
- Schools of New Energy and Materials, Southwest Petroleum University, Chengdu 610500, China
| | - Zhigang Zhou
- Orthopedic Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Qing Jiang
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China; College of Biomedical Engineering, Sichuan University, Chengdu 610064, China
| | - Li Zhao
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
| | - Ming Liu
- Orthopedic Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu 610041, China.
| | - Yujiang Fan
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China; College of Biomedical Engineering, Sichuan University, Chengdu 610064, China
| | - Xingdong Zhang
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China; College of Biomedical Engineering, Sichuan University, Chengdu 610064, China
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12
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You Q, Lu M, Li Z, Zhou Y, Tu C. Cell Sheet Technology as an Engineering-Based Approach to Bone Regeneration. Int J Nanomedicine 2022; 17:6491-6511. [PMID: 36573205 PMCID: PMC9789707 DOI: 10.2147/ijn.s382115] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Accepted: 11/12/2022] [Indexed: 12/24/2022] Open
Abstract
Bone defects that are congenital or the result of infection, malignancy, or trauma represent a challenge to the global healthcare system. To address this issue, multiple research groups have been developing novel cell sheet technology (CST)-based approaches to promote bone regeneration. These methods hold promise for use in regenerative medicine because they preserve cell-cell contacts, cell-extracellular matrix interactions, and the protein makeup of cell membranes. This review introduces the concept and preparation system of the cell sheet (CS), explores the application of CST in bone regeneration, highlights the current states of the bone regeneration via CST, and offers perspectives on the challenges and future research direction of translating current knowledge from the lab to the clinic.
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Affiliation(s)
- Qi You
- Orthopedic Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China,Sichuan Model Worker and Craftsman Talent Innovation Research Studio, Chengdu, Sichuan Province, People’s Republic of China
| | - Minxun Lu
- Orthopedic Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China,Sichuan Model Worker and Craftsman Talent Innovation Research Studio, Chengdu, Sichuan Province, People’s Republic of China
| | - Zhuangzhuang Li
- Orthopedic Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China,Sichuan Model Worker and Craftsman Talent Innovation Research Studio, Chengdu, Sichuan Province, People’s Republic of China
| | - Yong Zhou
- Orthopedic Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China,Sichuan Model Worker and Craftsman Talent Innovation Research Studio, Chengdu, Sichuan Province, People’s Republic of China
| | - Chongqi Tu
- Orthopedic Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China,Sichuan Model Worker and Craftsman Talent Innovation Research Studio, Chengdu, Sichuan Province, People’s Republic of China,Correspondence: Chongqi Tu; Yong Zhou, Department of Orthopedics, West China Hospital, Sichuan University, No. 37, Guoxuexiang, Chengdu, 610041, Sichuan Province, People’s Republic of China, Email ;
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13
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Xing F, Yin HM, Zhe M, Xie JC, Duan X, Xu JZ, Xiang Z, Li ZM. Nanotopographical 3D-Printed Poly(ε-caprolactone) Scaffolds Enhance Proliferation and Osteogenic Differentiation of Urine-Derived Stem Cells for Bone Regeneration. Pharmaceutics 2022; 14:pharmaceutics14071437. [PMID: 35890332 PMCID: PMC9317219 DOI: 10.3390/pharmaceutics14071437] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Revised: 07/02/2022] [Accepted: 07/06/2022] [Indexed: 02/05/2023] Open
Abstract
3D-printing technology can be used to construct personalized bone substitutes with customized shapes, but it cannot regulate the topological morphology of the scaffold surface, which plays a vital role in regulating the biological behaviors of stem cells. In addition, stem cells are able to sense the topographical and mechanical cues of surface of scaffolds by mechanosensing and mechanotransduction. In our study, we fabricated a 3D-printed poly(ε-caprolactone) (PCL) scaffold with a nanotopographical surface and loaded it with urine-derived stem cells (USCs) for application of bone regeneration. The topological 3D-printed PCL scaffolds (TPS) fabricated by surface epiphytic crystallization, possessed uniformly patterned nanoridges, of which the element composition and functional groups of nanoridges were the same as PCL. Compared with bare 3D-printed PCL scaffolds (BPS), TPS have a higher ability for protein adsorption and mineralization in vitro. The proliferation, cell length, and osteogenic gene expression of USCs on the surface of TPS were significantly higher than that of BPS. In addition, the TPS loaded with USCs exhibited a good ability for bone regeneration in cranial bone defects. Our study demonstrated that nanotopographical 3D-printed scaffolds loaded with USCs are a safe and effective therapeutic strategy for bone regeneration.
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Affiliation(s)
- Fei Xing
- Orthopedic Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, No. 37 Guoxue Lane, Chengdu 610041, China; (F.X.); (Z.X.)
| | - Hua-Mo Yin
- College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China; (H.-M.Y.); (Z.-M.L.)
| | - Man Zhe
- Animal Experiment Center, West China Hospital, Sichuan University, Chengdu 610041, China;
| | - Ji-Chang Xie
- Laboratoire Roberval, FRE UTC-CNRS 2012, Sorbonne Universités, Université de Technologie de Compiègne, Centre de Recherche Royallieu, CS60319, CEDEX, 60203 Compiègne, France;
| | - Xin Duan
- Orthopedic Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, No. 37 Guoxue Lane, Chengdu 610041, China; (F.X.); (Z.X.)
- Correspondence: (X.D.); (J.-Z.X.)
| | - Jia-Zhuang Xu
- College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China; (H.-M.Y.); (Z.-M.L.)
- Correspondence: (X.D.); (J.-Z.X.)
| | - Zhou Xiang
- Orthopedic Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, No. 37 Guoxue Lane, Chengdu 610041, China; (F.X.); (Z.X.)
| | - Zhong-Ming Li
- College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China; (H.-M.Y.); (Z.-M.L.)
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14
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Unnikrishnan V, Venugopal A, Sivadasan SB, Boniface Fernandez F, Arumugam S, P R HV, Parayanthala Valappil M. Cellular and sub-chronic toxicity of hydroxyapatite porous beads loaded with antibiotic in rabbits, indented for chronic osteomyelitis. Int J Pharm 2022; 616:121535. [PMID: 35124118 DOI: 10.1016/j.ijpharm.2022.121535] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Revised: 12/14/2021] [Accepted: 01/28/2022] [Indexed: 10/19/2022]
Abstract
Bioceramics have emerged as a hopeful remedy for site-specific drug delivery in orthopaedic complications, especially in chronic osteomyelitis. The bioresorbable nature of bioceramic materials shaped them into a versatile class of local antibiotic delivery systems in the treatment of chronic osteomyelitis. Hydroxyapatite (HA) based bioceramics with natural bone mimicking chemical composition are of particular interest due to their excellent biocompatibility, better osteoconductive and osteointegrative properties. Although HA has been widely recognized as an efficient tool for local delivery of antibiotics, information regarding its subchronic systemic toxicity have not been explored yet. Moreover, a detailed investigation of in vivo subchronic systemic toxicity of HA is critical for understanding its biocompatibility and futuristic clinical applications of these materials as novel therapeutic system in its long haul. Evaluation of biocompatibility and sub-chronic systemic toxicity are significant determinants in ensuring biomedical device's long-term functionality and success. Sub-chronic systemic toxicity allows assessing the potential adverse effects caused by leachable and nanosized wear particles from the device materials under permissible human exposure to the distant organs that are not in direct contact with the devices. In this context, the present study evaluates the sub-chronic systemic toxicity of in-house developed Hydroxyapatite porous beads (HAPB), gentamicin-loaded HAPB (HAPB + G) and vancomycin- loaded HAPB (HAPB + V) through 4 and 26-week muscle implantation in New Zealand white rabbits, as per ISO 10993-6 and ISO 10993-11. Analysis of cellular responses of HAPB towards Human Osteosarcoma (HOS) cell line through MTT assay, direct contact cytotoxicity, live/dead assay based on Imaging Flow Cytometry (IFC) showed its non-cytotoxic behaviour. Histopathological analysis of muscle tissue, organs like heart, lungs, liver, kidney, spleen, adrenals, intestine, testes, ovaries, and uterus did not reveal any abnormal biological responses. Our study concludes that the HAPB, gentamicin-loaded HAPB (HAPB + G) and vancomycin-loaded HAPB (HAPB + V) are biocompatible and did not induce sub-chronic systemic toxicity and hence satisfies the criteria for regulatory approval of HAs as a plausible candidate for clinical applications.
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Affiliation(s)
- Vandana Unnikrishnan
- Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology (Govt. of India), Poojapura, Trivandrum 695 012, Kerala, India
| | - Akhil Venugopal
- Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology (Govt. of India), Poojapura, Trivandrum 695 012, Kerala, India
| | - Suresh Babu Sivadasan
- Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology (Govt. of India), Poojapura, Trivandrum 695 012, Kerala, India
| | - Francis Boniface Fernandez
- Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology (Govt. of India), Poojapura, Trivandrum 695 012, Kerala, India
| | - Sabareeswaran Arumugam
- Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology (Govt. of India), Poojapura, Trivandrum 695 012, Kerala, India
| | - Harikrishna Varma P R
- Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology (Govt. of India), Poojapura, Trivandrum 695 012, Kerala, India
| | - Mohanan Parayanthala Valappil
- Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology (Govt. of India), Poojapura, Trivandrum 695 012, Kerala, India.
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15
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Huang YZ, He T, Cui J, Jiang YL, Zeng JF, Zhang WQ, Xie HQ. Urine-Derived Stem Cells for Regenerative Medicine: Basic Biology, Applications, and Challenges. TISSUE ENGINEERING. PART B, REVIEWS 2022; 28:978-994. [PMID: 35049395 DOI: 10.1089/ten.teb.2021.0142] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Regenerative medicine based on stem cell research has the potential to provide advanced health care for human beings. Recent studies demonstrate that stem cells in human urine can serve as an excellent source of graft cells for regenerative therapy, mainly due to simple, low-cost, and noninvasive cell isolation. These cells, termed human urine-derived stem cells (USCs), are highly expandable and can differentiate into various cell lineages. They share many biological properties with mesenchymal stem cells, such as potent paracrine effects and immunomodulation ability. The advantage of USCs has motivated researchers to explore their applications in regenerative medicine, including genitourinary regeneration, musculoskeletal repair, skin wound healing, and disease treatment. Although USCs have showed many positive outcomes in preclinical studies, and although the possible applications of USCs for animal therapy have been reported, many issues need to be addressed before clinical translation. This article provides a comprehensive review of USC biology and recent advances in their application for tissue regeneration. Challenges in the clinical translation of USC-based therapy are also discussed. Impact statement Recently, stem cells isolated from urine, referred to as urine-derived stem cells (USCs), have gained much interest in the field of regenerative medicine. Many advantages of human USCs have been found for cell-based therapy: (i) the cell isolation procedure is simple and low cost; (ii) they have remarkable proliferation ability, multidifferentiation potential, and paracrine effects; and (iii) they facilitate tissue regeneration in many animal models. With the hope to facilitate the development of USC-based therapy, we describe the current understanding of USC biology, summarize recent advances in their applications, and discuss future challenges in clinical translation.
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Affiliation(s)
- Yi-Zhou Huang
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Tao He
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China.,Department of Breast Surgery, West China School of Medicine/West China Hospital, Sichuan University, Chengdu, China
| | - Jing Cui
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Yan-Lin Jiang
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Jun-Feng Zeng
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Wen-Qian Zhang
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Hui-Qi Xie
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
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16
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Sun J, Li L, Xing F, Yang Y, Gong M, Liu G, Wu S, Luo R, Duan X, Liu M, Zou M, Xiang Z. Graphene oxide-modified silk fibroin/nanohydroxyapatite scaffold loaded with urine-derived stem cells for immunomodulation and bone regeneration. Stem Cell Res Ther 2021; 12:591. [PMID: 34863288 PMCID: PMC8642892 DOI: 10.1186/s13287-021-02634-w] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Accepted: 10/22/2021] [Indexed: 02/08/2023] Open
Abstract
Background The invasive and complicated procedures involving the use of traditional stem cells limit their application in bone tissue engineering. Cell-free, tissue-engineered bones often have complex scaffold structures and are usually engineered using several growth factors (GFs), thus leading to costly and difficult preparations. Urine-derived stem cells (USCs), a type of autologous stem cell isolated noninvasively and with minimum cost, are expected to solve the typical problems of using traditional stem cells to engineer bones. In this study, a graphene oxide (GO)-modified silk fibroin (SF)/nanohydroxyapatite (nHA) scaffold loaded with USCs was developed for immunomodulation and bone regeneration. Methods The SF/nHA scaffolds were prepared via lyophilization and cross-linked with GO using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxy succinimide (NHS). Scaffolds containing various concentrations of GO were characterized using scanning electron microscopy (SEM), the elastic modulus test, Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectrometer (XPS). Examinations of cell adhesion, proliferation, viability, morphology, alkaline phosphatase activity, and osteogenesis-related gene expression were performed to compare the osteogenesis-related biological behaviors of USCs cultured on the scaffolds. The effect of USC-laden scaffolds on the differentiation of macrophages was tested using ELISA, qRT-PCR, and immunofluorescence staining. Subcutaneous implantations in rats were performed to evaluate the inflammatory response of the USC-laden scaffolds after implantation. The scaffolds loaded with USCs were implanted into a cranial defect model in rats to repair bone defects. Micro-computed tomography (μCT) analyses and histological evaluation were performed to evaluate the bone repair effects. Results GO modification enhanced the mechanical properties of the scaffolds. Scaffolds containing less than 0.5% GO had good biocompatibility and promoted USC proliferation and osteogenesis. The scaffolds loaded with USCs induced the M2-type differentiation and inhibited the M1-type differentiation of macrophages. The USC-laden scaffolds containing 0.1% GO exhibited the best capacity for promoting the M2-type differentiation of macrophages and accelerating bone regeneration and almost bridged the site of the rat cranial defects at 12 weeks after surgery. Conclusions This composite system has the capacity for immunomodulation and the promotion of bone regeneration and shows promising potential for clinical applications of USC-based, tissue-engineered bones. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-021-02634-w.
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Affiliation(s)
- Jiachen Sun
- Department of Orthopedics, West China Hospital, Sichuan University, Guoxue Lane 37, Chengdu, 610041, Sichuan Province, People's Republic of China
| | - Lang Li
- Department of Orthopedics, Hospital of Chengdu Office of People's Government of Tibetan Autonomous Region, Chengdu, 610041, Sichuan, People's Republic of China
| | - Fei Xing
- Department of Orthopedics, West China Hospital, Sichuan University, Guoxue Lane 37, Chengdu, 610041, Sichuan Province, People's Republic of China
| | - Yun Yang
- Department of Orthopedics, West China Hospital, Sichuan University, Guoxue Lane 37, Chengdu, 610041, Sichuan Province, People's Republic of China
| | - Min Gong
- Department of Orthopedics, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, Sichuan, People's Republic of China
| | - Guoming Liu
- Department of Orthopedics, Affiliated Hospital of Qingdao University, Qingdao, 266003, Shangdong, People's Republic of China
| | - Shuang Wu
- Department of Orthopedics, West China Hospital, Sichuan University, Guoxue Lane 37, Chengdu, 610041, Sichuan Province, People's Republic of China
| | - Rong Luo
- Department of Orthopedics, West China Hospital, Sichuan University, Guoxue Lane 37, Chengdu, 610041, Sichuan Province, People's Republic of China
| | - Xin Duan
- Department of Orthopedics, West China Hospital, Sichuan University, Guoxue Lane 37, Chengdu, 610041, Sichuan Province, People's Republic of China
| | - Ming Liu
- Department of Orthopedics, West China Hospital, Sichuan University, Guoxue Lane 37, Chengdu, 610041, Sichuan Province, People's Republic of China
| | - Min Zou
- Department of Orthopedics, Chengdu Second People's Hospital, Chengdu, 610017, Sichuan, People's Republic of China.
| | - Zhou Xiang
- Department of Orthopedics, West China Hospital, Sichuan University, Guoxue Lane 37, Chengdu, 610041, Sichuan Province, People's Republic of China.
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17
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Zhang W, Hu J, Huang Y, Wu C, Xie H. Urine-derived stem cells: applications in skin, bone and articular cartilage repair. BURNS & TRAUMA 2021; 9:tkab039. [PMID: 34859109 PMCID: PMC8633594 DOI: 10.1093/burnst/tkab039] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Revised: 09/18/2021] [Indexed: 02/05/2023]
Abstract
As an emerging type of adult stem cell featuring non-invasive acquisition, urine-derived stem cells (USCs) have shown great potential for applications in tissue engineering and regenerative medicine. With a growing amount of research on the topic, the effectiveness of USCs in various disease models has been shown and the underlying mechanisms have also been explored, though many aspects still remain unclear. In this review, we aim to provide an up-to-date overview of the biological characteristics of USCs and their applications in skin, bone and articular cartilage repair. In addition to the identification procedure of USCs, we also summarize current knowledge of the underlying repair mechanisms and application modes of USCs. Potential concerns and perspectives have also been summarized.
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Affiliation(s)
- Wenqian Zhang
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, Med-X Center for Materials, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Jungen Hu
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, Med-X Center for Materials, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Yizhou Huang
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, Med-X Center for Materials, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Chenyu Wu
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, Med-X Center for Materials, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Huiqi Xie
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, Med-X Center for Materials, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
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Zhang N, Zhao L, Liu D, Hu C, Wang Y, He T, Bi Y, He Y. Characterization of Urine-Derived Stem Cells from Patients with End-Stage Liver Diseases and Application to Induced Acute and Chronic Liver Injury of Nude Mice Model. Stem Cells Dev 2021; 30:1126-1138. [PMID: 34549601 DOI: 10.1089/scd.2021.0137] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Urine-derived stem cells (USCs) are adult stem cells isolated from urine with strong proliferative ability and differentiation potentials. Cell transplantation of USCs could partly repair liver injury. It has been reported that the proliferative ability of bone mesenchymal stem cells in patients with chronic liver failure is significantly lower than in patients without liver disease. The aim of this study was therefore to evaluate the biological characteristics of USCs from end-stage liver disease patients (LD-USCs, USCs from patients with liver disease) compared with those from normal healthy individuals (N-USCs, USCs from normal individuals), with a view to determining whether autologous USCs can be applied to the treatment of liver disease. In this study USCs were isolated from urine samples of male patients with end-stage liver disease. Adherent USCs exhibit a spindle- or rice grain-like morphology, and express CD24, CD29, CD73, CD90, and CD146 surface markers, but not CD31, CD34, CD45, and CD105. We observed no differences in cell morphology or cell surface marker profile between LD-USCs and N-USCs. LD-USCs exhibited similar proliferative, colony-forming, apoptotic, and migratory abilities to N-USCs. Both USCs demonstrated similar capacities for osteogenic, adipogenic, and chondrogenic differentiation. When USCs were transplanted into CCl4 treatment-induced acute and chronic liver fibrosis mouse models, we observed a decrease in liver index, recovery of alanine aminotransferase and aspartate aminotransferase levels, alleviation of liver tissue injury, and dramatic improvement of liver tissue structure. USC transplantation can effectively recover liver function and improve liver tissue damage in acute or chronic liver injury mouse models. According to the results, we concluded that the biological characteristics of LD-USCs are not affected by basic liver disease. This study provides further evidence of the stem cell characteristics and liver repair function of LD-USCs, which may serve as a theoretical and experimental foundation for autologous USC transplantation technology in the treatment of liver failure and end-stage liver diseases.
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Affiliation(s)
- Nannan Zhang
- Stem Cell Biology and Therapy Laboratory, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Li Zhao
- Stem Cell Biology and Therapy Laboratory, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Daijiang Liu
- Department of Gastroenterology, Chongqing Emergency Medical Center, Chongqing, China
| | - Chaoqun Hu
- Stem Cell Biology and Therapy Laboratory, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Yi Wang
- Stem Cell Biology and Therapy Laboratory, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Tongchuan He
- Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, Illinois, USA
| | - Yang Bi
- Stem Cell Biology and Therapy Laboratory, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Yun He
- Stem Cell Biology and Therapy Laboratory, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China
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Liu G, Sun J, Gong M, Xing F, Wu S, Xiang Z. Urine-derived stem cells loaded onto a chitosan-optimized biphasic calcium-phosphate scaffold for repairing large segmental bone defects in rabbits. J Biomed Mater Res B Appl Biomater 2021; 109:2014-2029. [PMID: 33979024 DOI: 10.1002/jbm.b.34850] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Revised: 03/28/2021] [Accepted: 03/31/2021] [Indexed: 02/05/2023]
Abstract
The treatment of large segmental bone defects can be challenging for orthopedic surgeons. The development of bone tissue engineering technology, including the selection of seeding cells and the construction of scaffolds, provides a promising solution. In this study, we investigated osteogenic differentiation of human urine-derived stem cells (hUSCs, a newly identified class of stem cells), and developed a novel porous hybrid scaffold using biphasic calcium phosphate (BCP) bioceramic ornamented with chitosan sponges (CS). We combined hUSCs with a CS/BCP hybrid scaffold to construct tissue-engineered bone and evaluated whether the combination promotes bone regeneration in large segmental bone defects in rabbits. The study showed that hUSCs can differentiate into osteoblasts, and the hUSCs adhered, proliferated, and differentiated on CS/BCP hybrid scaffolds. Micro-computed tomography measurements, biomechanical detection, and histological analyses revealed that the combination of hUSCs and the CS/BCP hybrid scaffold enhanced bone regeneration more effectively compared with conventional pure BCP scaffolds, indicating that hUSCs can be used as a cell source for bone tissue engineering and that cell-scaffold-based biomimetic bone may be a promising approach to the repair of bone defects.
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Affiliation(s)
- Guoming Liu
- Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, PR China.,Department of Orthopedics, Affiliated Hospital of Qingdao University, Qingdao, PR China
| | - Jiachen Sun
- Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, PR China
| | - Min Gong
- Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, PR China
| | - Fei Xing
- Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, PR China
| | - Shuang Wu
- Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, PR China
| | - Zhou Xiang
- Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, PR China.,Division of Stem Cell and Tissue Engineering, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, PR China
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Burdeyron P, Giraud S, Hauet T, Steichen C. Urine-derived stem/progenitor cells: A focus on their characterization and potential. World J Stem Cells 2020; 12:1080-1096. [PMID: 33178393 PMCID: PMC7596444 DOI: 10.4252/wjsc.v12.i10.1080] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 06/26/2020] [Accepted: 08/24/2020] [Indexed: 02/06/2023] Open
Abstract
Cell therapy, i.e., the use of cells to repair an affected tissue or organ, is at the forefront of regenerative and personalized medicine. Among the multiple cell types that have been used for this purpose [including adult stem cells such as mesenchymal stem cells or pluripotent stem cells], urine-derived stem cells (USCs) have aroused interest in the past years. USCs display classical features of mesenchymal stem cells such as differentiation capacity and immunomodulation. Importantly, they have the main advantage of being isolable from one sample of voided urine with a cheap and unpainful procedure, which is broadly applicable, whereas most adult stem cell types require invasive procedure. Moreover, USCs can be differentiated into renal cell types. This is of high interest for renal cell therapy-based regenerative approaches. This review will firstly describe the isolation and characterization of USCs. We will specifically present USC phenotype, which is not an object of consensus in the literature, as well as detail their differentiation capacity. In the second part of this review, we will present and discuss the main applications of USCs. These include use as a substrate to generate human induced pluripotent stem cells, but we will deeply focus on the use of USCs for cell therapy approaches with a detailed analysis depending on the targeted organ or system. Importantly, we will also focus on the applications that rely on the use of USC-derived products such as microvesicles including exosomes, which is a strategy being increasingly employed. In the last section, we will discuss the remaining barriers and challenges in the field of USC-based regenerative medicine.
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Affiliation(s)
- Perrine Burdeyron
- INSERM U1082 IRTOMIT, CHU de Poitiers, Poitiers 86021, France
- Faculté de Médecine et Pharmacie, Université de Poitiers, Poitiers 86021, France
| | - Sébastien Giraud
- INSERM U1082 IRTOMIT, CHU de Poitiers, Poitiers 86021, France
- Service de Biochimie, CHU de Poitiers, Poitiers 86021, France
| | - Thierry Hauet
- INSERM U1082 IRTOMIT, CHU de Poitiers, Poitiers 86021, France
- Faculté de Médecine et Pharmacie, Université de Poitiers, Poitiers 86021, France
- Service de Biochimie, CHU de Poitiers, Poitiers 86021, France
| | - Clara Steichen
- INSERM U1082 IRTOMIT, CHU de Poitiers, Poitiers 86021, France
- Faculté de Médecine et Pharmacie, Université de Poitiers, Poitiers 86021, France.
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