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Bolideei M, Barzigar R, Gahrouei RB, Mohebbi E, Haider KH, Paul S, Paul MK, Mehran MJ. Applications of Gene Editing and Nanotechnology in Stem Cell-Based Therapies for Human Diseases. Stem Cell Rev Rep 2025; 21:905-934. [PMID: 40014250 DOI: 10.1007/s12015-025-10857-0] [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] [Accepted: 02/23/2025] [Indexed: 02/28/2025]
Abstract
Stem cell research is a dynamic and fast-advancing discipline with great promise for the treatment of diverse human disorders. The incorporation of gene editing technologies, including ZFNs, TALENs, and the CRISPR/Cas system, in conjunction with progress in nanotechnology, is fundamentally transforming stem cell therapy and research. These innovations not only provide a glimmer of optimism for patients and healthcare practitioners but also possess the capacity to radically reshape medical treatment paradigms. Gene editing and nanotechnology synergistically enhance stem cell-based therapies' precision, efficiency, and applicability, offering transformative potential for treating complex diseases and advancing regenerative medicine. Nevertheless, it is important to acknowledge that these technologies also give rise to ethical considerations and possible hazards, such as inadvertent genetic modifications and the development of genetically modified organisms, therefore creating a new age of designer infants. This review emphasizes the crucial significance of gene editing technologies and nanotechnology in the progress of stem cell treatments, particularly for degenerative pathologies and injuries. It emphasizes their capacity to restructure and comprehensively revolutionize medical treatment paradigms, providing fresh hope and optimism for patients and healthcare practitioners.
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Affiliation(s)
- Mansoor Bolideei
- Department of Respiratory and Critical Care Medicine, the Center for Biomedical Research, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, China
| | - Rambod Barzigar
- Department of Biotechnology, SJCE Technical Campus, JSS Research Foundation, University of Mysore, Mysore, 570006, Karnataka, India
| | - Razieh Bahrami Gahrouei
- Department of Pharmacy PES College, Rajiv Gandhi University of Health Sciences, Bangalore, Karnataka, India
| | - Elham Mohebbi
- Department of Medical Microbiology, Immunology, and Cell Biology, Southern Illinois School of Medicine, Springfield, IL, USA
| | - Khawaja Husnain Haider
- Sulaiman AlRajhi Medical School, Al Bukayriyah, AlQaseem, 52726, Kingdom of Saudi Arabia
| | - Sayan Paul
- Department of Biochemistry & Molecular Biology, University of Texas Medical Branch at Galveston, Galveston, TX, 77555, USA.
| | - Manash K Paul
- Department of Radiation Biology and Toxicology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India.
| | - Mohammad Javad Mehran
- Department of Biotechnology, SJCE Technical Campus, JSS Research Foundation, University of Mysore, Mysore, 570006, Karnataka, India.
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Xia Q, Zhou S, Zhou J, Zhao X, Saif MS, Wang J, Hasan M, Zhao M, Liu Q. Recent Advances and Challenges for Biological Materials in Micro/Nanocarrier Synthesis for Bone Infection and Tissue Engineering. ACS Biomater Sci Eng 2025; 11:1945-1969. [PMID: 40067283 DOI: 10.1021/acsbiomaterials.4c02118] [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] [Indexed: 04/15/2025]
Abstract
Roughly 1.71 billion people worldwide suffer from large bone abnormalities, which are the primary cause of disability. Traditional bone grafting procedures have several drawbacks that impair their therapeutic efficacy and restrict their use in clinical settings. A great deal of work has been done to create fresh, more potent strategies. Under these circumstances, a crucial technique for the regeneration of major lesions has emerged: bone tissue engineering (BTE). BTE involves the use of biomaterials that can imitate the natural design of bone. To yet, no biological material has been able to fully meet the parameters of the perfect implantable material, even though several varieties have been created and investigated for bone regeneration. Against this backdrop, researchers have focused a great deal of interest over the past few years on the subject of nanotechnology and the use of nanostructures in regenerative medicine. The ability to create nanoengineered particles that can overcome the current constraints in regenerative strategies─such as decreased cell proliferation and differentiation, insufficient mechanical strength in biological materials, and insufficient production of extrinsic factors required for effective osteogenesis has revolutionized the field of bone and tissue engineering. The effects of nanoparticles on cell characteristics and the application of biological materials for bone regeneration are the main topics of our review, which summarizes the most recent in vitro and in vivo research on the application of nanotechnology in the context of BTE.
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Affiliation(s)
- Qipeng Xia
- Yingtan People's Hospital, Nanchang University, Yingtan 335499, PR China
- Medical Faculty of Dalian University of Technology-Yingtan People's Hospital Joint Research Center, Yingtan 335499, PR China
| | - Shuyan Zhou
- School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang 330013, PR China
| | - Jingya Zhou
- Yingtan People's Hospital, Nanchang University, Yingtan 335499, PR China
- College of Acupuncture and Massage, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, PR China
| | - Xia Zhao
- Faculty of Medicine, Dalian University of Technology, Dalian 116024, PR China
| | - Muhammad Saqib Saif
- Department of Biochemistry, Faculty of Chemical and Biological Sciences, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan
| | - Jianping Wang
- Yingtan People's Hospital, Nanchang University, Yingtan 335499, PR China
- Medical Faculty of Dalian University of Technology-Yingtan People's Hospital Joint Research Center, Yingtan 335499, PR China
| | - Murtaza Hasan
- Department of Biotechnology, Faculty of Chemical and Biological Sciences, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan
| | - Min Zhao
- Yingtan People's Hospital, Nanchang University, Yingtan 335499, PR China
- Medical Faculty of Dalian University of Technology-Yingtan People's Hospital Joint Research Center, Yingtan 335499, PR China
| | - Qiang Liu
- Medical Faculty of Dalian University of Technology-Yingtan People's Hospital Joint Research Center, Yingtan 335499, PR China
- Faculty of Medicine, Dalian University of Technology, Dalian 116024, PR China
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Lin H, Zhou C, Li Q, Xie Q, Xia L, Liu L, Bao W, Xiong X, Zhang H, Zheng Z, Zhao J, Liang W. Nanotechnology-Assisted mesenchymal stem cells treatment for improved cartilage regeneration: A review of current practices. Biochem Pharmacol 2025; 237:116895. [PMID: 40154890 DOI: 10.1016/j.bcp.2025.116895] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Revised: 02/26/2025] [Accepted: 03/24/2025] [Indexed: 04/01/2025]
Abstract
Cartilage tissue does not promptly elicit an inflammatory response upon injury, hence constraining its capacity for healing and self-regeneration. Mesenchymal Stem Cells (MSC) therapy, enhanced by nanotechnology, offers promising advancements in cartilage repair. Injuries to cartilage often cause chronic pain, where current treatments are inadequate. As MSCs can readily differentiate into chondrocytes and secrete soluble factors, they are essential components in tissue engineering of cartilage repair. Although, like other stem cell applications, clinical applications are restricted by poor post implantation survival and differentiation. Recent studies show that nanoparticles (NPs) can further improve MSC outcomes by promoting cell adhesion, and chondrogenic differentiation allowing for sustained growth factor release. In addition, nanomaterials can improve the biological activity of MSCs, by also facilitating the composition of a conducive microenvironment for cartilage repair. In this review, the application of nanofibrous scaffolds, hydrogels and nanoscale particulate matter to improve mechanical properties in cartilage tissue engineering, are discussed. Moreover, the MSCs and nanotechnology synergistic effects present hope of overcoming the limitations of conventional treatments. Nanotechnology greatly enhances the MSC based cartilage regeneration strategies and could provide better treatment for cartilage related diseases in the future. Future research should be aimed at standardizing MSC harvesting and culturing protocols and contrasting their long-term efficacy.
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Affiliation(s)
- Hongming Lin
- Department of Orthopedics, Zhoushan Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Zhoushan 316000 Zhejiang Province, China
| | - Chao Zhou
- Department of Orthopedics, Zhoushan Guanghua hospital, Zhoushan 316000 Zhejiang Province, China
| | - Qingping Li
- Medical Research Center, Zhoushan Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Zhoushan 316000 Zhejiang Province, China
| | - Qiong Xie
- Medical Research Center, Zhoushan Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Zhoushan 316000 Zhejiang Province, China
| | - Linying Xia
- Medical Research Center, Zhoushan Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Zhoushan 316000 Zhejiang Province, China
| | - Lu Liu
- Medical Research Center, Zhoushan Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Zhoushan 316000 Zhejiang Province, China
| | - Wenwen Bao
- Medical Research Center, Zhoushan Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Zhoushan 316000 Zhejiang Province, China
| | - Xiaochun Xiong
- Department of Orthopedics, Zhoushan Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Zhoushan 316000 Zhejiang Province, China
| | - Hao Zhang
- Department of Orthopedics, Zhoushan Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Zhoushan 316000 Zhejiang Province, China
| | - Zeping Zheng
- Department of Orthopedics, Zhoushan Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Zhoushan 316000 Zhejiang Province, China
| | - Jiayi Zhao
- Department of Orthopedics, Zhoushan Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Zhoushan 316000 Zhejiang Province, China.
| | - Wenqing Liang
- Department of Orthopedics, Zhoushan Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Zhoushan 316000 Zhejiang Province, China.
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Wang J, Su Y, Wang F. Advances in the study of single-walled carbon nanotubes in ophthalmology. Hum Cell 2025; 38:76. [PMID: 40126731 DOI: 10.1007/s13577-025-01204-z] [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: 10/09/2024] [Accepted: 03/11/2025] [Indexed: 03/26/2025]
Abstract
With the rapid development of nanotechnology, the application of nanomaterials in the medical field shows unprecedented potential and innovative prospects. In particular, single-walled carbon nanotubes (SWCNTs), due to their unique physicochemical properties such as high surface area, excellent thermal and electrical properties, high surface/volume aspect ratio, and high tensile strength, show great potential for application in biomedical and biotechnological fields. Ophthalmology, as a branch of medicine that requires great precision and innovation, is gradually becoming one of the hotspots for nanotechnology applications. Although the research and application of nanomaterials in ophthalmology have made some progress, the potential of SWCNTs in ophthalmology has not yet been explored. This paper is a comprehensive review of the applications of nanomaterials in ophthalmology, including their use in drug delivery, antimicrobials, imaging, tissue repair, and photodynamic therapy, and further explores the similar roles of SWCNTs in other medical fields, thus speculating on their potentially important value in ophthalmic research.
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Affiliation(s)
- Junyu Wang
- Department of Ophthalmology, the Fourth Affiliated Hospital, Harbin Medical University, Harbin, China
| | - Ying Su
- Eye Hospital, the First Affiliated Hospital, Harbin Medical University, Harbin, China.
| | - Feng Wang
- Department of Ophthalmology, the Fourth Affiliated Hospital, Harbin Medical University, Harbin, China.
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5
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Zhang Y, Wang W, Chen L, Wang H, Dong D, Zhu J, Guo Y, Zhou Y, Liu T, Fu W. Human adipose-derived multipotent stromal cells enriched with IL-10 modRNA improve diabetic wound healing: Trigger the macrophage phenotype shift. Bioeng Transl Med 2025; 10:e10711. [PMID: 39801749 PMCID: PMC11711206 DOI: 10.1002/btm2.10711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Revised: 07/15/2024] [Accepted: 07/23/2024] [Indexed: 01/16/2025] Open
Abstract
Diabetic wounds present a significant challenge in regenerative medicine due to impaired healing, characterized by prolonged inflammation and deficient tissue repair, primarily caused by a skewed pro-inflammatory macrophage phenotype. This study investigates the therapeutic potential of interleukin-10 (IL-10) chemically modified mRNA (modRNA)-enriched human adipose-derived multipotent stromal cells (hADSCs) in a well-established murine model of diabetic wounds. The modRNAs used in this study were chemically modified using N1-methylpseudouridine-5'-triphosphate (m1Ψ) by substituting uridine-5-triphosphate. In vitro experiments demonstrated that IL-10 modRNA-transfected hADSCs effectively modulated macrophage polarization towards an anti-inflammatory phenotype. In vivo experiments with a well-established murine model demonstrated that transplantation of hADSCsmodIL-10 on postoperative day 5 (POD5) significantly improved wound healing outcomes, including accelerated wound closure, enhanced re-epithelialization, promoted M2 polarization, improved collagen deposition, and increased neovascularization. This study concludes that IL-10 modRNA-enriched hADSCs offer a promising therapeutic approach for diabetic wound healing, with the timing of IL-10 administration playing a crucial role in its effectiveness. These cells modulate macrophage polarization and promote tissue repair, demonstrating their potential for improving the management of diabetic wounds.
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Affiliation(s)
- Yuxin Zhang
- Shanghai Key Laboratory of Clinical Geriatric MedicineHuadong HospitalShanghaiChina
- Department of Plastic Surgery, Huadong Hospital, School of MedicineFudan UniversityShanghaiChina
| | - Wei Wang
- Shanghai Key Laboratory of Clinical Geriatric MedicineHuadong HospitalShanghaiChina
- Department of Plastic Surgery, Huadong Hospital, School of MedicineFudan UniversityShanghaiChina
| | - Liang Chen
- Department of Plastic Surgery, Huadong Hospital, School of MedicineFudan UniversityShanghaiChina
| | - Heng Wang
- Department of Plastic Surgery, Huadong Hospital, School of MedicineFudan UniversityShanghaiChina
| | - Dong Dong
- Department of Plastic Surgery, Huadong Hospital, School of MedicineFudan UniversityShanghaiChina
| | - Jingjing Zhu
- Department of Plastic Surgery, Huadong Hospital, School of MedicineFudan UniversityShanghaiChina
| | - Yu Guo
- Department of Plastic Surgery, Huadong Hospital, School of MedicineFudan UniversityShanghaiChina
| | - Yiqun Zhou
- Department of Plastic Surgery, Huadong Hospital, School of MedicineFudan UniversityShanghaiChina
| | - Tianyi Liu
- Shanghai Key Laboratory of Clinical Geriatric MedicineHuadong HospitalShanghaiChina
- Department of Plastic Surgery, Huadong Hospital, School of MedicineFudan UniversityShanghaiChina
| | - Wei Fu
- Institute of Pediatric Translational Medicine, Shanghai Institute of Pediatric Congenital Heart Disease, Shanghai Children's Medical Center, School of MedicineShanghai Jiao Tong UniversityShanghaiChina
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6
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Jain S, Bhatt J, Gupta S, Bhatia DD. Nanotechnology at the crossroads of stem cell medicine. Biomater Sci 2024; 13:161-178. [PMID: 39584588 DOI: 10.1039/d4bm01257g] [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: 11/26/2024]
Abstract
Nanotechnology in stem cell medicine is an interdisciplinary field which has gained a lot of interest recently. This domain addresses key challenges associated with stem cell medicine such as cell isolation, targeted delivery, and tracking. Nanotechnology-based approaches, including magnetic cell sorting, fluorescent tagging, and drug or biomolecule conjugation for delivery, have enhanced precision in stem cell isolation and guided cell migration, increasing the therapeutic potential. Recent studies have focused on using nanomaterials and scaffolds to drive stem cell differentiation by activating specific molecular pathways, achieved through embedding biomolecules within the scaffold or through the scaffold's material composition and structure alone. These innovations hold promise in therapeutic applications across various diseases, including cancer stem cell targeting, neurodegenerative disorders, pre-eclampsia, cardiovascular conditions, and organoid development. This review examines recent advancements in the field, explores potential applications like biosensors and nanochips, and highlights the challenges and research gaps.
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Affiliation(s)
- Sweny Jain
- Department of Biological Sciences and Engineering, Indian Institute of Technology, Gandhinagar, Palaj, Gujarat, 382355, India.
| | - Jay Bhatt
- Department of Biological Sciences and Engineering, Indian Institute of Technology, Gandhinagar, Palaj, Gujarat, 382355, India.
| | - Sharad Gupta
- Department of Biological Sciences and Engineering, Indian Institute of Technology, Gandhinagar, Palaj, Gujarat, 382355, India.
| | - Dhiraj Devidas Bhatia
- Department of Biological Sciences and Engineering, Indian Institute of Technology, Gandhinagar, Palaj, Gujarat, 382355, India.
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Sher EK, Kalić A, Džidić-Krivić A, Zećo MB, Pinjić E, Sher F. Cellular therapeutic potential of genetically engineered stem cells in cancer treatment. Biotechnol Genet Eng Rev 2024; 40:4062-4097. [PMID: 37132363 DOI: 10.1080/02648725.2023.2204720] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Accepted: 04/13/2023] [Indexed: 05/04/2023]
Abstract
Traditional therapeutic approaches in the treatment of cancer have many side effects and are often ineffective and non-specific, leading to the development of therapy-resistant tumour cells. Recently, numerous discoveries about stem cells have given a new outlook on their application in oncology. Stem cells are unique because of their biological attributes, including self-renewal, differentiation in different types of specialized cells and synthesis of molecules that interplay with tumour niche. They are already used as an effective therapeutic option for haematological malignancies, such as multiple myeloma and leukaemia. The main goal of this study is to investigate the possible applications of different types of stem cells in cancer treatment and to summarize novel advances, as well as the limitations of their application in cancer treatment. Research and clinical trials that are underway revealed and confirmed the enormous potential of regenerative medicine in the treatment of cancer, especially when combined with different nanomaterials. Nanoengineering of stem cells has been the focus of novel studies in the area of regenerative medicine, such as the production of nanoshells and nanocarriers that enhance the transport and uptake of stem cells in their targeted tumour niche and enable the effective monitoring of stem cell effects on tumour cells. Although nanotechnology has a lot of limitations, it provides new opportunities for the development of effective and innovative stem cell therapies.
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Affiliation(s)
- Emina Karahmet Sher
- Department of Biosciences, School of Science and Technology, Nottingham Trent University, Nottingham, UK
| | - Azra Kalić
- Faculty of pharmacy, University of modern sciences - CKM, Mostar, Bosnia and Herzegovina
| | - Amina Džidić-Krivić
- International Society of Engineering Science and Technology, Nottingham, UK
- Department of Neurology, Cantonal Hospital Zenica, Zenica, Bosnia and Herzegovina
| | - Merima Beća- Zećo
- Faculty of pharmacy, University of modern sciences - CKM, Mostar, Bosnia and Herzegovina
- International Society of Engineering Science and Technology, Nottingham, UK
| | - Emma Pinjić
- Department of Radiology, Beth Israel Deaconess Medical Center (BIDMC), Boston, MA, USA
| | - Farooq Sher
- Department of Engineering, School of Science and Technology, Nottingham Trent University, Nottingham, UK
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Farasatkia A, Maeso L, Gharibi H, Dolatshahi-Pirouz A, Stojanovic GM, Edmundo Antezana P, Jeong JH, Federico Desimone M, Orive G, Kharaziha M. Design of nanosystems for melanoma treatment. Int J Pharm 2024; 665:124701. [PMID: 39278291 DOI: 10.1016/j.ijpharm.2024.124701] [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: 06/25/2024] [Revised: 08/24/2024] [Accepted: 09/10/2024] [Indexed: 09/18/2024]
Abstract
Melanoma is a prevalent and concerning form of skin cancer affecting millions of individuals worldwide. Unfortunately, traditional treatments can be invasive and painful, prompting the need for alternative therapies with improved efficacy and patient outcomes. Nanosystems offer a promising solution to these obstacles through the rational design of nanoparticles (NPs) which are structured into nanocomposite forms, offering efficient approaches to cancer treatment procedures. A range of NPs consisting of polymeric, metallic and metal oxide, carbon-based, and virus-like NPs have been studied for their potential in treating skin cancer. This review summarizes the latest developments in functional nanosystems aimed at enhancing melanoma treatment. The fundamentals of these nanosystems, including NPs and the creation of various functional nanosystem types, facilitating melanoma treatment are introduced. Then, the advances in the applications of functional nanosystems for melanoma treatment are summarized, outlining both their benefits and the challenges encountered in implementing nanosystem therapies.
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Affiliation(s)
- Asal Farasatkia
- Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111, Iran
| | - Lidia Maeso
- NanoBioCel Research Group, School of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain
| | - Hamidreza Gharibi
- Department of Health Technology, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark
| | | | - Goran M Stojanovic
- Department of Electronics, Faculty of Technical Sciences, University of Novi Sad, 21000, Novi Sad, Serbia
| | - Pablo Edmundo Antezana
- Universidad de Buenos Aires, Instituto de Química y Metabolismo del Fármaco (IQUIMEFA, CONICET), Facultad de Farmacia y Bioquímica, Buenos Aires, Argentina
| | - Jee-Heon Jeong
- Laboratory of Drug Delivery and Cell Therapy (LDDCT). Department of Precision Medicine. School of Medicine, Sungkyunkwan University. South Korea
| | - Martin Federico Desimone
- Universidad de Buenos Aires, Instituto de Química y Metabolismo del Fármaco (IQUIMEFA, CONICET), Facultad de Farmacia y Bioquímica, Buenos Aires, Argentina; Instituto de Ciências Biológicas (ICB), Universidade Federal do Rio Grande - FURG, Rio Grande, RS, Brazil
| | - Gorka Orive
- NanoBioCel Research Group, School of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain; Bioaraba, NanoBioCel Research Group, Vitoria-Gasteiz, Spain; Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz, Spain; University Institute for Regenerative Medicine and Oral Implantology - UIRMI (UPV/EHU-Fundación Eduardo Anitua), Vitoria 01007, Spain.
| | - Mahshid Kharaziha
- Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111, Iran.
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Mansor NI, Balqis TN, Lani MN, Lye KL, Nor Muhammad NA, Ismail WIW, Abidin SZ. Nature's Secret Neuro-Regeneration Pathway in Axolotls, Polychaetes and Planarians for Human Therapeutic Target Pathways. Int J Mol Sci 2024; 25:11904. [PMID: 39595973 PMCID: PMC11593954 DOI: 10.3390/ijms252211904] [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: 10/03/2024] [Revised: 11/03/2024] [Accepted: 11/04/2024] [Indexed: 11/28/2024] Open
Abstract
Despite significant improvements in the comprehension of neuro-regeneration, restoring nerve injury in humans continues to pose a substantial therapeutic difficulty. In the peripheral nervous system (PNS), the nerve regeneration process after injury relies on Schwann cells. These cells play a crucial role in regulating and releasing different extracellular matrix proteins, including laminin and fibronectin, which are essential for facilitating nerve regeneration. However, during regeneration, the nerve is required to regenerate for a long distance and, subsequently, loses its capacity to facilitate regeneration during this progression. Meanwhile, it has been noted that nerve regeneration has limited capabilities in the central nervous system (CNS) compared to in the PNS. The CNS contains factors that impede the regeneration of axons following injury to the axons. The presence of glial scar formation results from this unfavourable condition, where glial cells accumulate at the injury site, generating a physical and chemical barrier that hinders the regeneration of neurons. In contrast to humans, several species, such as axolotls, polychaetes, and planarians, possess the ability to regenerate their neural systems following amputation. This ability is based on the vast amount of pluripotent stem cells that have the remarkable capacity to differentiate and develop into any cell within their body. Although humans also possess these cells, their numbers are extremely limited. Examining the molecular pathways exhibited by these organisms has the potential to offer a foundational understanding of the human regeneration process. This review provides a concise overview of the molecular pathways involved in axolotl, polychaete, and planarian neuro-regeneration. It has the potential to offer a new perspective on therapeutic approaches for neuro-regeneration in humans.
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Affiliation(s)
- Nur Izzati Mansor
- Department of Nursing, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras 56000, Kuala Lumpur, Malaysia;
| | - Tengku Nabilatul Balqis
- Faculty of Science and Marine Environment, Universiti Malaysia Terengganu, Kuala Nerus 21030, Terengganu, Malaysia; (T.N.B.); (W.I.W.I.)
| | - Mohd Nizam Lani
- Faculty of Fisheries and Food Science, Universiti Malaysia Terengganu, Kuala Nerus 21030, Terengganu, Malaysia;
| | - Kwan Liang Lye
- ME Scientifique Sdn Bhd, Taman Universiti Indah, Seri Kembangan 43300, Selangor, Malaysia;
| | - Nor Azlan Nor Muhammad
- Institute of Systems Biology (INBIOSIS), Universiti Kebangsaan Malaysia, Bangi 43600, Selangor, Malaysia;
| | - Wan Iryani Wan Ismail
- Faculty of Science and Marine Environment, Universiti Malaysia Terengganu, Kuala Nerus 21030, Terengganu, Malaysia; (T.N.B.); (W.I.W.I.)
- Research Interest Group Biological Security and Sustainability (BIOSES), Faculty of Science and Marine Environment, Universiti Malaysia Terengganu, Kuala Nerus 21030, Terengganu, Malaysia
| | - Shahidee Zainal Abidin
- Faculty of Science and Marine Environment, Universiti Malaysia Terengganu, Kuala Nerus 21030, Terengganu, Malaysia; (T.N.B.); (W.I.W.I.)
- Research Interest Group Biological Security and Sustainability (BIOSES), Faculty of Science and Marine Environment, Universiti Malaysia Terengganu, Kuala Nerus 21030, Terengganu, Malaysia
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10
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Ruan WJ, Xu SS, Xu DH, Li ZP. Orthopedic revolution: The emerging role of nanotechnology. World J Orthop 2024; 15:932-938. [PMID: 39473517 PMCID: PMC11514548 DOI: 10.5312/wjo.v15.i10.932] [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: 02/21/2024] [Revised: 08/24/2024] [Accepted: 09/11/2024] [Indexed: 10/11/2024] Open
Abstract
This review summarizes the latest progress in orthopedic nanotechnology, explores innovative applications of nanofibers in tendon repair, and evaluates the potential of selenium and cerium oxide nanoparticles in osteoarthritis and osteoblast differentiation. This review also describes the emerging applications of injectable hydrogels in cartilage engineering, emphasizing the critical role of interdisciplinary research and highlighting the challenges and future prospects of integrating nanotechnology into orthopedic clinical practice. This comprehensive approach provides a holistic perspective on the transformative impact of nanotechnology in orthopedics, offering valuable insights for future research and clinical applications.
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Affiliation(s)
- Wen-Jie Ruan
- Department of Sports Medicine, Zhejiang Provincial People's Hospital (The Affiliated People's Hospital), Hangzhou 310000, Zhejiang Province, China
| | - Si-Si Xu
- School of Medicine, Taizhou University, Taizhou 318000, Zhejiang Province, China
| | - Dong-Hui Xu
- School of Medicine, Taizhou University, Taizhou 318000, Zhejiang Province, China
| | - Zhi-Peng Li
- The Second Department of Orthopedics, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450015, Henan Province, China
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11
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Hilal-Alnaqbi A, Dagher S, Alkhatib R, Karam S. Effect of Gold Nanoparticles on Growth Characteristics of Mouse Gastric Stem Cells in Vitro. MEASUREMENT: INTERDISCIPLINARY RESEARCH AND PERSPECTIVES 2024:1-10. [DOI: 10.1080/15366367.2024.2386629] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/02/2024]
Affiliation(s)
| | - Sawsan Dagher
- Electromechanical Engineering, Abu Dhabi Polytechnic
| | | | - Sherif Karam
- Anatomy, College of Medicine and Health Sciences, United Arab Emirates University
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12
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Borase HP, Singhal RS, Patil SV. Copper oxide nanoparticles exhibit variable response against enzymatic toxicity biomarkers of Moina macrocopa. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2024; 31:54325-54337. [PMID: 37821732 DOI: 10.1007/s11356-023-30145-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Accepted: 09/25/2023] [Indexed: 10/13/2023]
Abstract
Growing toxicity of nanomaterials to aquatic organisms is a major area of concern as it is destroying the carefully evolved aquatic ecosystem and food web. Copper oxide nanoparticles (CuONPs) are among the top industrially manufactured nanomaterials having multifaceted applications in medicine, agriculture, energy, water technology, and other areas. However, reports on detailed scientific understanding behind toxic effects of CuONPs on aquatic organisms are scant. The present work reports on the interaction of CuONPs of 10 ± 05 nm with an ecologically significant aquatic species, Moina macrocopa, at morphological and enzymatic levels. CuONPs were found to be severely toxic just within 48 h of exposure as seen from the lethal value (48 h LC50) of 0.137 ± 0.002 ppm. Profiling of enzymatic toxicity biomarkers indicated variable response of CuONPs on selected enzymes of M. macrocopa at two sub-lethal concentrations (0.013 to 0.039 ppm). While the activities of acetyl cholinesterase and digestive enzymes (trypsin, amylase) were found to be significantly (p < 0.001) lowered after exposure to CuONPs, the β-galactosidase activity was completely inhibited. Among the antioxidant enzymes that were assayed, superoxide dismutase and glutathione-S-transferase activity was found to increase (p > 0.001), while that of catalase decreased (p > 0.001, < 0.05) with increase in exposure to CuONPs. An upsurge of several folds was seen in the activity of alkaline phosphatase after exposure to CuONPs as compared to the control group. CuONPs accumulated in the gut region of M. macrocopa which provided an ideal environment for CuONP to interact and alter the enzymes in M. macrocopa. This report highlights the use of enzymes as sensitive biomarker to detect toxicity of trace amount of CuONPs in a very sensitive non-target crustacean species found in water bodies.
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Affiliation(s)
- Hemant Pandit Borase
- Food Engineering and Technology Department, Institute of Chemical Technology, Mumbai, 400019, Maharashtra, India
| | - Rekha S Singhal
- Food Engineering and Technology Department, Institute of Chemical Technology, Mumbai, 400019, Maharashtra, India
| | - Satish Vitthal Patil
- School of Life Sciences, Kavayitri Bahinabai Chaudhari, North Maharashtra University, Jalgaon, 425001, Maharashtra, India.
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13
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Krsek A, Jagodic A, Baticic L. Nanomedicine in Neuroprotection, Neuroregeneration, and Blood-Brain Barrier Modulation: A Narrative Review. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1384. [PMID: 39336425 PMCID: PMC11433843 DOI: 10.3390/medicina60091384] [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: 08/01/2024] [Revised: 08/19/2024] [Accepted: 08/22/2024] [Indexed: 09/30/2024]
Abstract
Nanomedicine is a newer, promising approach to promote neuroprotection, neuroregeneration, and modulation of the blood-brain barrier. This review includes the integration of various nanomaterials in neurological disorders. In addition, gelatin-based hydrogels, which have huge potential due to biocompatibility, maintenance of porosity, and enhanced neural process outgrowth, are reviewed. Chemical modification of these hydrogels, especially with guanidine moieties, has shown improved neuron viability and underscores tailored biomaterial design in neural applications. This review further discusses strategies to modulate the blood-brain barrier-a factor critically associated with the effective delivery of drugs to the central nervous system. These advances bring supportive solutions to the solving of neurological conditions and innovative therapies for their treatment. Nanomedicine, as applied to neuroscience, presents a significant leap forward in new therapeutic strategies that might help raise the treatment and management of neurological disorders to much better levels. Our aim was to summarize the current state-of-knowledge in this field.
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Affiliation(s)
- Antea Krsek
- Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia;
| | - Ana Jagodic
- Department of Family Medicine, Community Health Center Krapina, 49000 Krapina, Croatia;
| | - Lara Baticic
- Department of Medical Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia
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14
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Xue Y, Zhang Y, Zhong Y, Du S, Hou X, Li W, Li H, Wang S, Wang C, Yan J, Kang DD, Deng B, McComb DW, Irvine DJ, Weiss R, Dong Y. LNP-RNA-engineered adipose stem cells for accelerated diabetic wound healing. Nat Commun 2024; 15:739. [PMID: 38272900 PMCID: PMC10811230 DOI: 10.1038/s41467-024-45094-5] [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: 05/07/2023] [Accepted: 01/15/2024] [Indexed: 01/27/2024] Open
Abstract
Adipose stem cells (ASCs) have attracted considerable attention as potential therapeutic agents due to their ability to promote tissue regeneration. However, their limited tissue repair capability has posed a challenge in achieving optimal therapeutic outcomes. Herein, we conceive a series of lipid nanoparticles to reprogram ASCs with durable protein secretion capacity for enhanced tissue engineering and regeneration. In vitro studies identify that the isomannide-derived lipid nanoparticles (DIM1T LNP) efficiently deliver RNAs to ASCs. Co-delivery of self-amplifying RNA (saRNA) and E3 mRNA complex (the combination of saRNA and E3 mRNA is named SEC) using DIM1T LNP modulates host immune responses against saRNAs and facilitates the durable production of proteins of interest in ASCs. The DIM1T LNP-SEC engineered ASCs (DS-ASCs) prolong expression of hepatocyte growth factor (HGF) and C-X-C motif chemokine ligand 12 (CXCL12), which show superior wound healing efficacy over their wild-type and DIM1T LNP-mRNA counterparts in the diabetic cutaneous wound model. Overall, this work suggests LNPs as an effective platform to engineer ASCs with enhanced protein generation ability, expediting the development of ASCs-based cell therapies.
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Affiliation(s)
- Yonger Xue
- Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA
- Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Yuebao Zhang
- Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA
| | - Yichen Zhong
- Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA
- Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Shi Du
- Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA
| | - Xucheng Hou
- Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Wenqing Li
- Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA
| | - Haoyuan Li
- Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Siyu Wang
- Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Chang Wang
- Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Jingyue Yan
- Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA
| | - Diana D Kang
- Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA
| | - Binbin Deng
- Center for Electron Microscopy and Analysis, The Ohio State University, Columbus, OH, USA
| | - David W McComb
- Center for Electron Microscopy and Analysis, The Ohio State University, Columbus, OH, USA
- Department of Materials Science and Engineering, The Ohio State University, Columbus, OH, USA
| | - Darrell J Irvine
- Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
- Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA
- Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
- Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA
- Howard Hughes Medical Institute, Chevy Chase, MD, USA
| | - Ron Weiss
- Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
- Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA
- Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA
| | - Yizhou Dong
- Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
- Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
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15
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Bharti S, Kumar A. Synergies in stem cell research: Integrating technologies, strategies, and bionanomaterial innovations. Acta Histochem 2024; 126:152119. [PMID: 38041895 DOI: 10.1016/j.acthis.2023.152119] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 11/19/2023] [Accepted: 11/19/2023] [Indexed: 12/04/2023]
Abstract
Since the 1960 s, there has been a substantial amount of research directed towards investigating the biology of several types of stem cells, including embryonic stem cells, brain cells, and mesenchymal stem cells. In contemporary times, a wide array of stem cells has been utilized to treat several disorders, including bone marrow transplantation. In recent years, stem cell treatment has developed as a very promising and advanced field of scientific research. The progress of therapeutic methodologies has resulted in significant amounts of anticipation and expectation. Recently, there has been a notable proliferation of experimental methodologies aimed at isolating and developing stem cells, which have emerged concurrently. Stem cells possess significant vitality and exhibit vigorous proliferation, making them suitable candidates for in vitro modification. This article examines the progress made in stem cell isolation and explores several methodologies employed to promote the differentiation of stem cells. This study also explores the method of isolating bio-nanomaterials and discusses their viewpoint in the context of stem cell research. It also covers the potential for investigating stem cell applications in bioprinting and the usage of bionanomaterial in stem cell-related technologies and research. In conclusion, the review article concludes by highlighting the importance of incorporating state-of-the-art methods and technological breakthroughs into the future of stem cell research. Putting such an emphasis on constant innovation highlights the ever-changing character of science and the never-ending drive toward unlocking the maximum therapeutic potential of stem cells. This review would be a useful resource for researchers, clinicians, and policymakers in the stem cell research area, guiding the next steps in this fast-developing scientific concern.
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Affiliation(s)
- Sharda Bharti
- Department of Biotechnology, National Institute of Technology, Raipur, CG, India
| | - Awanish Kumar
- Department of Biotechnology, National Institute of Technology, Raipur, CG, India.
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16
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Ghosh S, Bhatti GK, Sharma PK, Kandimalla R, Mastana SS, Bhatti JS. Potential of Nano-Engineered Stem Cells in the Treatment of Multiple Sclerosis: A Comprehensive Review. Cell Mol Neurobiol 2023; 44:6. [PMID: 38104307 PMCID: PMC11397842 DOI: 10.1007/s10571-023-01434-5] [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: 06/12/2023] [Accepted: 11/06/2023] [Indexed: 12/19/2023]
Abstract
Multiple sclerosis (MS) is a chronic and degrading autoimmune disorder mainly targeting the central nervous system, leading to progressive neurodegeneration, demyelination, and axonal damage. Current treatment options for MS are limited in efficacy, generally linked to adverse side effects, and do not offer a cure. Stem cell therapies have emerged as a promising therapeutic strategy for MS, potentially promoting remyelination, exerting immunomodulatory effects and protecting against neurodegeneration. Therefore, this review article focussed on the potential of nano-engineering in stem cells as a therapeutic approach for MS, focusing on the synergistic effects of combining stem cell biology with nanotechnology to stimulate the proliferation of oligodendrocytes (OLs) from neural stem cells and OL precursor cells, by manipulating neural signalling pathways-PDGF, BMP, Wnt, Notch and their essential genes such as Sox, bHLH, Nkx. Here we discuss the pathophysiology of MS, the use of various types of stem cells in MS treatment and their mechanisms of action. In the context of nanotechnology, we present an overview of its applications in the medical and research field and discuss different methods and materials used to nano-engineer stem cells, including surface modification, biomaterials and scaffolds, and nanoparticle-based delivery systems. We further elaborate on nano-engineered stem cell techniques, such as nano script, nano-exosome hybrid, nano-topography and their potentials in MS. The article also highlights enhanced homing, engraftment, and survival of nano-engineered stem cells, targeted and controlled release of therapeutic agents, and immunomodulatory and tissue repair effects with their challenges and limitations. This visual illustration depicts the process of utilizing nano-engineering in stem cells and exosomes for the purpose of delivering more accurate and improved treatments for Multiple Sclerosis (MS). This approach targets specifically the creation of oligodendrocytes, the breakdown of which is the primary pathological factor in MS.
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Affiliation(s)
- Sushruta Ghosh
- Laboratory of Translational Medicine and Nanotherapeutics, Department of Human Genetics and Molecular Medicine, School of Health Sciences Central, University of Punjab, Bathinda, India
| | - Gurjit Kaur Bhatti
- Department of Medical Lab Technology, University Institute of Applied Health Sciences, Chandigarh University, Mohali, India
| | - Pushpender Kumar Sharma
- Amity Institute of Biotechnology, Amity University, Rajasthan, India
- Amity Centre for Nanobiotechnology and Nanomedicine, Amity University, Rajasthan, India
| | - Ramesh Kandimalla
- Department of Biochemistry, Kakatiya Medical College, Warangal, Telangana, India
- Department of Applied Biology, CSIR-Indian Institute of Technology, Hyderabad, India
| | - Sarabjit Singh Mastana
- School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, UK
| | - Jasvinder Singh Bhatti
- Laboratory of Translational Medicine and Nanotherapeutics, Department of Human Genetics and Molecular Medicine, School of Health Sciences Central, University of Punjab, Bathinda, India.
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17
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Oz T, Kaushik A, Kujawska M. Neural stem cells for Parkinson's disease management: Challenges, nanobased support, and prospects. World J Stem Cells 2023; 15:687-700. [PMID: 37545757 PMCID: PMC10401423 DOI: 10.4252/wjsc.v15.i7.687] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 04/27/2023] [Accepted: 05/16/2023] [Indexed: 07/25/2023] Open
Abstract
Parkinson's disease (PD), characterized by loss of nigrostriatal dopaminergic neurons, is one of the most predominant neurodegenerative diseases affecting the elderly population worldwide. The concept of stem cell therapy in managing neurodegenerative diseases has evolved over the years and has recently rapidly progressed. Neural stem cells (NSCs) have a few key features, including self-renewal, proliferation, and multipotency, which make them a promising agent targeting neurodegeneration. It is generally agreed that challenges for NSC-based therapy are present at every stage of the transplantation process, including preoperative cell preparation and quality control, perioperative procedures, and postoperative graft preservation, adherence, and overall therapy success. In this review, we provided a comprehensive, careful, and critical discussion of experimental and clinical data alongside the pros and cons of NSC-based therapy in PD. Given the state-of-the-art accomplishments of stem cell therapy, gene therapy, and nanotechnology, we shed light on the perspective of complementing the advantages of each process by developing nano-stem cell therapy, which is currently a research hotspot. Although various obstacles and challenges remain, nano-stem cell therapy holds promise to cure PD, however, continuous improvement and development from the stage of laboratory experiments to the clinical application are necessary.
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Affiliation(s)
- Tuba Oz
- Department of Toxicology, Poznan University of Medical Sciences, Poznan 60-631, Poland
| | - Ajeet Kaushik
- NanoBioTech Laboratory, Health System Engineering, Department of Environmental Engineering, Florida Polytechnic University, Lakeland, FL 33805, United States
- School of Engineering, University of Petroleum and Energy Studies, Dehradun 248007, India
| | - Małgorzata Kujawska
- Department of Toxicology, Poznan University of Medical Sciences, Poznan 60-631, Poland.
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18
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Shibu MA, Huang CY, Ding DC. Comparison of two hepatocyte differentiation protocols in human umbilical cord mesenchymal stem cells: In vitro study. Tissue Cell 2023; 83:102153. [PMID: 37413859 DOI: 10.1016/j.tice.2023.102153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2023] [Revised: 06/28/2023] [Accepted: 06/29/2023] [Indexed: 07/08/2023]
Abstract
Human umbilical cord mesenchymal stromal cells (HUCMSCs) are an emerging source of cell therapy due to their self-renew and differentiation ability. They can differentiate into three germ layers, including the potential to generate hepatocytes. This study determined the transplantation efficiency and suitability of HUCMSCs-derived hepatocyte-like cells (HLCs) for their therapeutic application for liver diseases. This study aims to formulate ideal conditions to induce HUCMSCs into the hepatic lineage and investigate the efficiency of the differentiated HLCs based on their expression characteristics and capacity to integrate into the damaged liver of CCl4-challenged mice. Hepatocyte growth factor (HGF) and Activin A, Wnt3a were found to optimally promote the endodermal expansion of HUCMSCs, which showed phenomenal expression of hepatic markers upon differentiation in the presence of oncostatin M and dexamethasone. HUCMSCs expressed MSC-related surface markers and could undergo tri-lineage differentiations. Two hepatogenic differentiation protocols (differentiated hepatocyte protocol 1 [DHC1]: 32 days and DHC2: 15 days) were experimented with. The proliferation rate was faster in DHC2 than in DHC1 on day 7 of differentiation. The migration capability was the same in both DHC1 and DHC2. Hepatic markers like CK18, CK19, ALB, and AFP were upregulated. The mRNA levels of albumin, α1AT, αFP, CK18, TDO2, CYP3A4, CYP7A1, HNF4A, CEBPA, PPARA, and PAH were even higher in the HUCMSCs-derived HCLs than in the primary hepatocytes. Western blot confirmed HNF3B and CK18 protein expression in a step-wise manner differentiated from HUCMSCs. The metabolic function of differentiated hepatocytes was evident by increasing PAS staining and urea production. Pre-treating HUCMSCs with a hepatic differentiation medium containing HGF can drive their differentiation towards endodermal and hepatic lineages, enabling efficient integration into the damaged liver. This approach represents a potential alternative protocol for cell-based therapy that could enhance the integration potential of HUCMSC-derived HLCs.
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Affiliation(s)
| | - Chih-Yang Huang
- Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan; Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan; Department of Biological Science and Technology, Asia University, Taichung 413, Taiwan; Center of General Education, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien 970, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University Hospital, Taichung 404, Taiwan
| | - Dah-Ching Ding
- Department of Obstetrics and Gynecology, Buddhist Tzu Chi General Hospital, Tzu Chi University, Hualien 970, Taiwan; Graduate Institute of Medical Science, Tzu Chi University, Hualien 970, Taiwan.
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19
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Salem SS. A mini review on green nanotechnology and its development in biological effects. Arch Microbiol 2023; 205:128. [PMID: 36944830 PMCID: PMC10030434 DOI: 10.1007/s00203-023-03467-2] [Citation(s) in RCA: 57] [Impact Index Per Article: 28.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2023] [Revised: 02/28/2023] [Accepted: 03/04/2023] [Indexed: 03/23/2023]
Abstract
The utilization of living organisms for the creation of inorganic nanoscale particles is a potential new development in the realm of biotechnology. An essential milestone in the realm of nanotechnology is the process of creating dependable and environmentally acceptable metallic nanoparticles. Due to its increasing popularity and ease, use of ambient biological resources is quickly becoming more significant in this field of study. The phrase "green nanotechnology" has gained a lot of attention and refers to a variety of procedures that eliminate or do away with hazardous compounds to repair the environment. Green nanomaterials can be used in a variety of biotechnological sectors such as medicine and biology, as well as in the food and textile industries, wastewater treatment and agriculture field. The construction of an updated level of knowledge with utilization and a study of the ambient biological systems that might support and revolutionize the creation of nanoparticles (NPs) are presented in this article.
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Affiliation(s)
- Salem S Salem
- Botany and Microbiology Department, Faculty of Science, AL-Azhar University, Nasr City, Cairo, 11884, Egypt.
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Li S, Tang H, Li C, Ma J, Ali M, Dong Q, Wu J, Hui Y, Sun C. Synthetic Biology Technologies And Genetically Engineering Strategies For Enhanced Cell Therapeutics. Stem Cell Rev Rep 2023; 19:309-321. [PMID: 36166137 PMCID: PMC9514184 DOI: 10.1007/s12015-022-10454-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/13/2022] [Indexed: 02/07/2023]
Abstract
Stem cell therapy mainly uses natural stem cells for transplantation, and the use of genetic engineering to optimize stem cell products is a very important process. This article reviews successful gene modification methods in the field of immune cell therapy and summarizes some attempts at stem cell gene editing in current research. Cell bridging is an innovative cutting-edge strategy that includes the specific recognition and signal transduction of artificial receptors. The "off-the-shelf" cell strategies mainly introduce the advantages of allogeneic cell therapy and how to overcome issues such as immunogenicity. Gene regulatory systems allow us to manipulate cells with small molecules to control cellular phenotypes. In addition, we also summarize some important genes that can provide a reference for cell genetic engineering. In conclusion, we summarize a variety of technical strategies for gene editing cells to provide useful ideas and experiences for future stem cell therapy research.
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Affiliation(s)
- Siyu Li
- Department of Biochemistry and Molecular Biology, Harbin Medical University, 157 BaoJian Road Nangang Dist, Harbin, 150086, People's Republic of China
| | - Hao Tang
- Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China
| | - Cheng Li
- Department of Biochemistry and Molecular Biology, Harbin Medical University, 157 BaoJian Road Nangang Dist, Harbin, 150086, People's Republic of China
| | - Jiajia Ma
- Department of Biochemistry and Molecular Biology, Harbin Medical University, 157 BaoJian Road Nangang Dist, Harbin, 150086, People's Republic of China
| | - Maqsood Ali
- Department of Biochemistry and Molecular Biology, Harbin Medical University, 157 BaoJian Road Nangang Dist, Harbin, 150086, People's Republic of China
| | - Qi Dong
- Department of Biochemistry and Molecular Biology, Harbin Medical University, 157 BaoJian Road Nangang Dist, Harbin, 150086, People's Republic of China
| | - Jiajia Wu
- Department of Biochemistry and Molecular Biology, Harbin Medical University, 157 BaoJian Road Nangang Dist, Harbin, 150086, People's Republic of China
| | - Yang Hui
- Department of Biochemistry and Molecular Biology, Harbin Medical University, 157 BaoJian Road Nangang Dist, Harbin, 150086, People's Republic of China.
- Basic Medical Institute of Heilongjiang Medical Science Academy, Harbin, China.
| | - Chongran Sun
- Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou City, Xihu District, 310058, People's Republic of China.
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21
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Xue J, Qin C, Wu C. 3D printing of cell-delivery scaffolds for tissue regeneration. Regen Biomater 2023; 10:rbad032. [PMID: 37081861 PMCID: PMC10112960 DOI: 10.1093/rb/rbad032] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 02/27/2023] [Accepted: 03/25/2023] [Indexed: 04/22/2023] Open
Abstract
Tissue engineering strategy that combine biomaterials with living cells has shown special advantages in tissue regeneration and promoted the development of regenerative medicine. In particular, the rising of 3D printing technology further enriched the structural design and composition of tissue engineering scaffolds, which also provided convenience for cell loading and cell delivery of living cells. In this review, two types of cell-delivery scaffolds for tissue regeneration, including 3D printed scaffolds with subsequent cell-seeding and 3D cells bioprinted scaffolds, are mainly reviewed. We devote a major part to present and discuss the recent advances of two 3D printed cell-delivery scaffolds in regeneration of various tissues, involving bone, cartilage, skin tissues etc. Although two types of 3D printed cell-delivery scaffolds have some shortcomings, they do have generally facilitated the exploration of tissue engineering scaffolds in multiple tissue regeneration. It is expected that 3D printed cell-delivery scaffolds will be further explored in function mechanism of seeding cells in vivo, precise mimicking of complex tissues and even organ reconstruction under the cooperation of multiple fields in future.
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Affiliation(s)
| | | | - Chengtie Wu
- Correspondence address. Tel: +86 21 52412249, E-mail:
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22
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Suner SS, Kurt SB, Demirci S, Sahiner N. The advances in functionalized carbon nanomaterials for drug delivery. FUNCTIONALIZED CARBON NANOMATERIALS FOR THERANOSTIC APPLICATIONS 2023:197-241. [DOI: 10.1016/b978-0-12-824366-4.00011-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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23
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Ojha A, Jaiswal S, Bharti P, Mishra SK. Nanoparticles and Nanomaterials-Based Recent Approaches in Upgraded Targeting and Management of Cancer: A Review. Cancers (Basel) 2022; 15:cancers15010162. [PMID: 36612158 PMCID: PMC9817889 DOI: 10.3390/cancers15010162] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Revised: 12/08/2022] [Accepted: 12/15/2022] [Indexed: 12/29/2022] Open
Abstract
Along with the extensive improvement in tumor biology research and different therapeutic developments, cancer remains a dominant and deadly disease. Tumor heterogeneity, systemic toxicities, and drug resistance are major hurdles in cancer therapy. Chemotherapy, radiotherapy, phototherapy, and surgical therapy are some prominent areas of cancer treatment. During chemotherapy for cancer, chemotherapeutic agents are distributed all over the body and also damage normal cells. With advancements in nanotechnology, nanoparticles utilized in all major areas of cancer therapy offer the probability to advance drug solubility, and stability, extend drug half-lives in plasma, reduce off-target effects, and quintessence drugs at a target site. The present review compiles the use of different types of nanoparticles in frequently and recently applied therapeutics of cancer therapy. A recent area of cancer treatment includes cancer stem cell therapy, DNA/RNA-based immunomodulation therapy, alteration of the microenvironment, and cell membrane-mediated biomimetic approach. Biocompatibility and bioaccumulation of nanoparticles is the major impediment in nano-based therapy. More research is required to develop the next generation of nanotherapeutics with the incorporation of new molecular entities, such as kinase inhibitors, siRNA, mRNA, and gene editing. We assume that nanotherapeutics will dramatically improve patient survival, move the model of cancer treatment, and develop certainty in the foreseeable future.
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Affiliation(s)
- Anupama Ojha
- Department of Allied Health Science, Mahayogi Gorakhnath University, Gorakhpur 273007, India
| | - Sonali Jaiswal
- Department of Biotechnology, DDU Gorakhpur University, Gorakhpur 273009, India
| | - Priyanka Bharti
- Department of Biotechnology, DDU Gorakhpur University, Gorakhpur 273009, India
| | - Sarad Kumar Mishra
- Department of Biotechnology, DDU Gorakhpur University, Gorakhpur 273009, India
- Correspondence:
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24
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Damavandi AR, Mirmosayyeb O, Ebrahimi N, Zalpoor H, khalilian P, Yahiazadeh S, Eskandari N, Rahdar A, Kumar PS, Pandey S. Advances in nanotechnology versus stem cell therapy for the theranostics of multiple sclerosis disease. APPLIED NANOSCIENCE 2022. [DOI: 10.1007/s13204-022-02698-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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25
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Lawand PV, Desai S. Nanobiotechnology-Modified Cellular and Molecular Therapy as a Novel Approach for Autoimmune Diabetes Management. Pharm Nanotechnol 2022; 10:279-288. [PMID: 35927916 DOI: 10.2174/2211738510666220802111315] [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: 02/01/2022] [Revised: 04/26/2022] [Accepted: 05/09/2022] [Indexed: 06/15/2023]
Abstract
Several cellular and molecular therapies such as stem cell therapy, cell replacement therapy, gene modification therapy, and tolerance induction therapy have been researched to procure a permanent cure for Type 1 Diabetes. However, due to the induction of undesirable side effects, their clinical utility is questionable. These anti-diabetic therapies can be modified with nanotechnological tools for reducing adverse effects by selectively targeting genes and/or receptors involved directly or indirectly in diabetes pathogenesis, such as the glucagon-like peptide 1 receptor, epidermal growth factor receptor, human leukocyte antigen (HLA) gene, miRNA gene and hepatocyte growth factor (HGF) gene. This paper will review the utilities of nanotechnology in stem cell therapy, cell replacement therapy, beta-cell proliferation strategies, immune tolerance induction strategies, and gene therapy for type 1 diabetes management.
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Affiliation(s)
- Priyanka Vasant Lawand
- Department of Pharmacology, Dr. D.Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, India
| | - Shivani Desai
- Department of Pharmacy Practice, Dr. D.Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, India
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26
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Sawah D, Sahloul M, Ciftci F. Nano-material utilization in stem cells for regenerative medicine. BIOMED ENG-BIOMED TE 2022; 67:429-442. [DOI: 10.1515/bmt-2022-0123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 08/25/2022] [Indexed: 11/15/2022]
Abstract
Abstract
The utilization of nanotechnology in regenerative medicine has been globally proven to be the main solution to many issues faced with tissue engineering today, and the theoretical and empirical investigations of the association of nanomaterials with stem cells have made significant progress as well. For their ability to self-renew and differentiate into a variety of cell types, stem cells have become popular candidates for cell treatment in recent years, particularly in cartilage and Ocular regeneration. However, there are still several challenges to overcome before it may be used in a wide range of therapeutic contexts. This review paper provides a review of the various implications of nanomaterials in tissue and cell regeneration, the stem cell and scaffold application in novel treatments, and the basic developments in stem cell-based therapies, as well as the hurdles that must be solved for nanotechnology to be used in its full potential. Due to the increased interest in the continuously developing field of nanotechnology, demonstrating, and pinpointing the most recognized and used applications of nanotechnology in regenerative medicine became imperative to provide students, researchers, etc. who are interested.
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Affiliation(s)
- Darin Sawah
- Department of Biomedical Engineering , Fatih Sultan Mehmet Vakif University , Istanbul , Turkey
| | - Maha Sahloul
- Department of Biomedical Engineering , Fatih Sultan Mehmet Vakif University , Istanbul , Turkey
| | - Fatih Ciftci
- Department of Biomedical Engineering , Fatih Sultan Mehmet Vakif University , Istanbul , Turkey
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27
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Diez‐Pascual AM, Rahdar A. Functional Nanomaterials in Biomedicine: Current Uses and Potential Applications. ChemMedChem 2022; 17:e202200142. [PMID: 35729066 PMCID: PMC9544115 DOI: 10.1002/cmdc.202200142] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Revised: 06/19/2022] [Indexed: 11/07/2022]
Abstract
Nanomaterials, that is, materials made up of individual units between 1 and 100 nanometers, have lately involved a lot of attention since they offer a lot of potential in many fields, including pharmacy and biomedicine, owed to their exceptional physicochemical properties arising from their high surface area and nanoscale size. Smart engineering of nanostructures through appropriate surface or bulk functionalization endows them with multifunctional capabilities, opening up new possibilities in the biomedical field such as biosensing, drug delivery, imaging, medical implants, cancer treatment and tissue engineering. This article highlights up-to-date research in nanomaterials functionalization for biomedical applications. A summary of the different types of nanomaterials and the surface functionalization strategies is provided. Besides, the use of nanomaterials in diagnostic imaging, drug/gene delivery, regenerative medicine, cancer treatment and medical implants is reviewed. Finally, conclusions and future perspectives are provided.
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Affiliation(s)
- Ana María Diez‐Pascual
- Universidad de AlcaláDepartamento de Química Analítica Química Física e Ingeniería QuímicaCarretera Madrid-Barcelona Km. 33.628871Alcalá de Henares, MadridSpain
| | - Abbas Rahdar
- Department of PhysicsUniversity of ZabolZabol98613-35856Iran
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Dechsupa N, Kosintarajit P, Kamkan K, Khanjina T, Sirikul C, Innuan P, Suwan A, Anukul N, Kantapan J. Iron(III)-Quercetin Complexes' Safety for MRI Cell Tracking in Cell Therapy Applications: Cytotoxic and Genotoxic Assessment. NANOMATERIALS (BASEL, SWITZERLAND) 2022; 12:2776. [PMID: 36014641 PMCID: PMC9414527 DOI: 10.3390/nano12162776] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Revised: 08/05/2022] [Accepted: 08/10/2022] [Indexed: 06/15/2023]
Abstract
The theranostic agent iron-quercetin complex (IronQ) provides a T1-positive magnetic resonance imaging (MRI) contrast agent. The magnetically IronQ-labeled cells can be used for cell tracking and have active biological applications in promoting cell and tissue regeneration. However, a detailed investigation of IronQ's cytotoxicity and genotoxicity is necessary. Thus, this study aimed to evaluate the possibility of IronQ inducing cytotoxicity and genotoxicity in peripheral blood mononuclear cells (PBMCs). We evaluated the vitality of cells, the production of reactive oxygen species (ROS), the level of antioxidant enzymes, and the stability of the genetic material in PBMCs treated with IronQ. The results show that IronQ had a negligible impact on toxicological parameters such as ROS production and lipid peroxidation, indicating that it is not harmful. IronQ-labeled PMBCs experienced an insignificant depletion of antioxidant enzyme levels at the highest concentration of IronQ. There is no evident genotoxicity in the magnetically IronQ-labeled PBMCs. The results show that IronQ does not potentiate the cytotoxicity and genotoxicity effects of the labeled PMBCs and might be safe for therapeutic and cell tracking purposes. These results could provide a reference guideline for the toxicological analysis of IronQ in in vivo studies.
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Affiliation(s)
- Nathupakorn Dechsupa
- Molecular Imaging and Therapy Research Unit, Faculty of Associated Medical Sciences, Department of Radiologic Technology, Chiang Mai University, Chiang Mai 50200, Thailand
- Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
- Center of Radiation Research and Medical Imaging, Faculty of Associated Medical Sciences, Department of Radiologic Technology, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Panida Kosintarajit
- Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Kanyapak Kamkan
- Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Thanyalak Khanjina
- Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Chonticha Sirikul
- Division of Transfusion Science, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Phattarawadee Innuan
- Molecular Imaging and Therapy Research Unit, Faculty of Associated Medical Sciences, Department of Radiologic Technology, Chiang Mai University, Chiang Mai 50200, Thailand
- Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Authaphinya Suwan
- Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Nampeung Anukul
- Division of Transfusion Science, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Jiraporn Kantapan
- Molecular Imaging and Therapy Research Unit, Faculty of Associated Medical Sciences, Department of Radiologic Technology, Chiang Mai University, Chiang Mai 50200, Thailand
- Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
- Center of Radiation Research and Medical Imaging, Faculty of Associated Medical Sciences, Department of Radiologic Technology, Chiang Mai University, Chiang Mai 50200, Thailand
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29
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Westermayr J, Chaudhuri S, Jeindl A, Hofmann OT, Maurer RJ. Long-range dispersion-inclusive machine learning potentials for structure search and optimization of hybrid organic-inorganic interfaces. DIGITAL DISCOVERY 2022; 1:463-475. [PMID: 36091414 PMCID: PMC9358753 DOI: 10.1039/d2dd00016d] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Accepted: 06/03/2022] [Indexed: 12/16/2022]
Abstract
The computational prediction of the structure and stability of hybrid organic-inorganic interfaces provides important insights into the measurable properties of electronic thin film devices, coatings, and catalyst surfaces and plays an important role in their rational design. However, the rich diversity of molecular configurations and the important role of long-range interactions in such systems make it difficult to use machine learning (ML) potentials to facilitate structure exploration that otherwise requires computationally expensive electronic structure calculations. We present an ML approach that enables fast, yet accurate, structure optimizations by combining two different types of deep neural networks trained on high-level electronic structure data. The first model is a short-ranged interatomic ML potential trained on local energies and forces, while the second is an ML model of effective atomic volumes derived from atoms-in-molecules partitioning. The latter can be used to connect short-range potentials to well-established density-dependent long-range dispersion correction methods. For two systems, specifically gold nanoclusters on diamond (110) surfaces and organic π-conjugated molecules on silver (111) surfaces, we train models on sparse structure relaxation data from density functional theory and show the ability of the models to deliver highly efficient structure optimizations and semi-quantitative energy predictions of adsorption structures.
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Affiliation(s)
- Julia Westermayr
- Department of Chemistry, University of Warwick Coventry CV4 7AL UK
| | - Shayantan Chaudhuri
- Department of Chemistry, University of Warwick Coventry CV4 7AL UK
- Centre for Doctoral Training in Diamond Science and Technology, University of Warwick Coventry CV4 7AL UK
| | - Andreas Jeindl
- Institute of Solid State Physics, Graz University of Technology 8010 Graz Austria
| | - Oliver T Hofmann
- Institute of Solid State Physics, Graz University of Technology 8010 Graz Austria
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Zarepour A, Bal Öztürk A, Koyuncu Irmak D, Yaşayan G, Gökmen A, Karaöz E, Zarepour A, Zarrabi A, Mostafavi E. Combination Therapy Using Nanomaterials and Stem Cells to Treat Spinal Cord Injuries. Eur J Pharm Biopharm 2022; 177:224-240. [PMID: 35850168 DOI: 10.1016/j.ejpb.2022.07.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Revised: 06/29/2022] [Accepted: 07/08/2022] [Indexed: 02/07/2023]
Abstract
As a part of the central nervous system, the spinal cord (SC) provides most of the communications between the brain and other parts of the body. Any damage to SC interrupts this communication, leading to serious problems, which may remain for the rest of their life. Due to its significant impact on patients' quality of life and its exorbitant medical costs, SC injury (SCI) is known as one of the most challengeable diseases in the world. Thus, it is critical to introduce highly translatable therapeutic platforms for SCI treatment. So far, different strategies have been introduced, among which utilizing various types of stem cells is one of the most interesting ones. The capability of stem cells to differentiate into several types of cell lines makes them promising candidates for the regeneration of injured tissues. One of the other interesting and novel strategies for SCI treatment is the application of nanomaterials, which could appear as a carrier for therapeutic agents or as a platform for culturing the cells. Combining these two approaches, stem cells and nanomaterials, could provide promising therapeutic strategies for SCI management. Accordingly, in this review we have summarized some of the recent advancements in which the applications of different types of stem cells and nanomaterials, alone and in combination forms, were evaluated for SCI treatment.
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Affiliation(s)
- Arezou Zarepour
- Radiology Department, Kashan University of Medical Sciences, Kashan, Isfahan, Iran
| | - Ayça Bal Öztürk
- Department of Stem Cell and Tissue Engineering, Institute of Health Sciences, Istinye University, Istanbul, Turkey; Department of Analytical Chemistry, Faculty of Pharmacy, Istinye University, Zeytinburnu, Turkey
| | | | - Gökçen Yaşayan
- Department of Pharmaceutical Technology, Faculty of Pharmacy, Yeditepe University, Istanbul, Turkey
| | - Aylin Gökmen
- Molecular Biology and Genetics Department, Faculty of Engineering and Natural Sciences, Bahcesehir University, Besiktas, Istanbul, Turkey
| | - Erdal Karaöz
- Liv Hospital, Center for Regenerative Medicine and Stem Cell Manufacturing (LivMedCell), İstanbul, Turkey
| | - Atefeh Zarepour
- Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Istinye University, Sariyer, Istanbul 34396, Turkey
| | - Ali Zarrabi
- Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Istinye University, Sariyer, Istanbul 34396, Turkey.
| | - Ebrahim Mostafavi
- Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
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31
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Hong IS. Enhancing Stem Cell-Based Therapeutic Potential by Combining Various Bioengineering Technologies. Front Cell Dev Biol 2022; 10:901661. [PMID: 35865629 PMCID: PMC9294278 DOI: 10.3389/fcell.2022.901661] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Accepted: 06/17/2022] [Indexed: 12/05/2022] Open
Abstract
Stem cell-based therapeutics have gained tremendous attention in recent years due to their wide range of applications in various degenerative diseases, injuries, and other health-related conditions. Therapeutically effective bone marrow stem cells, cord blood- or adipose tissue-derived mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and more recently, induced pluripotent stem cells (iPSCs) have been widely reported in many preclinical and clinical studies with some promising results. However, these stem cell-only transplantation strategies are hindered by the harsh microenvironment, limited cell viability, and poor retention of transplanted cells at the sites of injury. In fact, a number of studies have reported that less than 5% of the transplanted cells are retained at the site of injury on the first day after transplantation, suggesting extremely low (<1%) viability of transplanted cells. In this context, 3D porous or fibrous national polymers (collagen, fibrin, hyaluronic acid, and chitosan)-based scaffold with appropriate mechanical features and biocompatibility can be used to overcome various limitations of stem cell-only transplantation by supporting their adhesion, survival, proliferation, and differentiation as well as providing elegant 3-dimensional (3D) tissue microenvironment. Therefore, stem cell-based tissue engineering using natural or synthetic biomimetics provides novel clinical and therapeutic opportunities for a number of degenerative diseases or tissue injury. Here, we summarized recent studies involving various types of stem cell-based tissue-engineering strategies for different degenerative diseases. We also reviewed recent studies for preclinical and clinical use of stem cell-based scaffolds and various optimization strategies.
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Affiliation(s)
- In-Sun Hong
- Department of Health Sciences and Technology, GAIHST, Gachon University, Seongnam, South Korea
- Department of Molecular Medicine, School of Medicine, Gachon University, Seongnam, South Korea
- *Correspondence: In-Sun Hong,
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32
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Díez-Pascual AM. Surface Engineering of Nanomaterials with Polymers, Biomolecules, and Small Ligands for Nanomedicine. MATERIALS (BASEL, SWITZERLAND) 2022; 15:3251. [PMID: 35591584 PMCID: PMC9104878 DOI: 10.3390/ma15093251] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Revised: 04/26/2022] [Accepted: 04/28/2022] [Indexed: 11/18/2022]
Abstract
Nanomedicine is a speedily growing area of medical research that is focused on developing nanomaterials for the prevention, diagnosis, and treatment of diseases. Nanomaterials with unique physicochemical properties have recently attracted a lot of attention since they offer a lot of potential in biomedical research. Novel generations of engineered nanostructures, also known as designed and functionalized nanomaterials, have opened up new possibilities in the applications of biomedical approaches such as biological imaging, biomolecular sensing, medical devices, drug delivery, and therapy. Polymers, natural biomolecules, or synthetic ligands can interact physically or chemically with nanomaterials to functionalize them for targeted uses. This paper reviews current research in nanotechnology, with a focus on nanomaterial functionalization for medical applications. Firstly, a brief overview of the different types of nanomaterials and the strategies for their surface functionalization is offered. Secondly, different types of functionalized nanomaterials are reviewed. Then, their potential cytotoxicity and cost-effectiveness are discussed. Finally, their use in diverse fields is examined in detail, including cancer treatment, tissue engineering, drug/gene delivery, and medical implants.
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Affiliation(s)
- Ana M Díez-Pascual
- Universidad de Alcalá, Facultad de Ciencias, Departamento de Química Analítica, Química Física e Ingeniería Química, Ctra. Madrid-Barcelona, Km. 33.6, 28805 Alcalá de Henares, Madrid, Spain
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33
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Younis MA, Tawfeek HM, Abdellatif AAH, Abdel-Aleem JA, Harashima H. Clinical translation of nanomedicines: Challenges, opportunities, and keys. Adv Drug Deliv Rev 2022; 181:114083. [PMID: 34929251 DOI: 10.1016/j.addr.2021.114083] [Citation(s) in RCA: 157] [Impact Index Per Article: 52.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 12/12/2021] [Accepted: 12/13/2021] [Indexed: 02/07/2023]
Abstract
Despite the massive interest and recent developments in the field of nanomedicine, only a limited number of formulations have found their way to the clinics. This shortcoming reveals the challenges facing the clinical translation of this technology. In the current article, we summarize and evaluate the status, market situation, and clinical profiles of the reported nanomedicines, the shortcomings limiting their clinical translation, as well as some approaches designed to break through this barrier. Moreover, some emerging technologies that have the potential to compete with nanomedicines are highlighted. Lastly, we identify the key factors that should be considered in nanomedicine-related research to be clinically-translatable. These can be classified into five areas: rational design during the research and development stage, the recruitment of representative preclinical models, careful design of clinical trials, development of specific and uniform regulatory protocols, and calls for non-classic sponsorship. This new field of endeavor was firmly established during the last two decades and more in-depth progress is expected in the coming years.
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Affiliation(s)
- Mahmoud A Younis
- Laboratory of Innovative Nanomedicine, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan; Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.
| | - Hesham M Tawfeek
- Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.
| | - Ahmed A H Abdellatif
- Department of Pharmaceutics, College of Pharmacy, Qassim University, Buraidah 51452, Saudi Arabia; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt
| | - Jelan A Abdel-Aleem
- Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt
| | - Hideyoshi Harashima
- Laboratory of Innovative Nanomedicine, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
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Al-Ghadban S, Artiles M, Bunnell BA. Adipose Stem Cells in Regenerative Medicine: Looking Forward. Front Bioeng Biotechnol 2022; 9:837464. [PMID: 35096804 PMCID: PMC8792599 DOI: 10.3389/fbioe.2021.837464] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 12/27/2021] [Indexed: 12/16/2022] Open
Abstract
Over the last decade, stem cell-based regenerative medicine has progressed to clinical testing and therapeutic applications. The applications range from infusions of autologous and allogeneic stem cells to stem cell-derived products. Adult stem cells from adipose tissue (ASCs) show significant promise in treating autoimmune and neurodegenerative diseases, vascular and metabolic diseases, bone and cartilage regeneration and wound defects. The regenerative capabilities of ASCs in vivo are primarily orchestrated by their secretome of paracrine factors and cell-matrix interactions. More recent developments are focused on creating more complex structures such as 3D organoids, tissue elements and eventually fully functional tissues and organs to replace or repair diseased or damaged tissues. The current and future applications for ASCs in regenerative medicine are discussed here.
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Affiliation(s)
| | | | - Bruce A. Bunnell
- Department of Microbiology Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX, United States
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35
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Xue Y, Baig R, Dong Y. Recent advances of biomaterials in stem cell therapies. NANOTECHNOLOGY 2022; 33:10.1088/1361-6528/ac4520. [PMID: 34933291 PMCID: PMC10068913 DOI: 10.1088/1361-6528/ac4520] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Accepted: 12/21/2021] [Indexed: 06/14/2023]
Abstract
Stem cells have been utilized as 'living drugs' in clinics for decades. Their self-renewal, differentiation, and immunomodulating properties provide potential solutions for a variety of malignant diseases and disorders. However, the pathological environment may diminish the therapeutic functions and survival of the transplanted stem cells, causing failure in clinical translation. To overcome these challenges, researchers have developed biomaterial-based strategies that facilitatein vivotracking, functional engineering, and protective delivery of stem cells, paving the way for next-generation stem cell therapies. In this perspective, we briefly overview different types of stem cells and the major clinical challenges and summarize recent progress of biomaterials applied to boost stem cell therapies.
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Affiliation(s)
- Yonger Xue
- Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH 43210, United States of America
| | - Rafia Baig
- Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH 43210, United States of America
| | - Yizhou Dong
- Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH 43210, United States of America
- Department of Biomedical Engineering, The Ohio State University, Columbus, OH 43210, United States of America
- The Center for Clinical and Translational Science, The Ohio State University, Columbus, OH 43210, United States of America
- The Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, United States of America
- Dorothy M. Davis Heart & Lung Research Institute, The Ohio State University, Columbus, OH 43210, United States of America
- Department of Radiation Oncology, The Ohio State University, Columbus, OH 43210, United States of America
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36
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Liu G, ZHOU YUAN, Zhang X, Guo S. Advances in Hydrogels for Stem Cell Therapy: Regulation Mechanisms and Tissue Engineering Applications. J Mater Chem B 2022; 10:5520-5536. [DOI: 10.1039/d2tb01044e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Stem cell therapy has shown unparalleled potential in tissue engineering, but it still faces challenges in the regulation of stem cell fate. Inspired by the native stem cell niche, a...
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37
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Barlian A, Vanya K. Nanotopography in directing osteogenic differentiation of mesenchymal stem cells: potency and future perspective. Future Sci OA 2022; 8:FSO765. [PMID: 34900339 PMCID: PMC8656311 DOI: 10.2144/fsoa-2021-0097] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 10/14/2021] [Indexed: 12/11/2022] Open
Abstract
Severe bone injuries can result in disabilities and thus affect a person's quality of life. Mesenchymal stem cells (MSCs) can be an alternative for bone healing by growing them on nanopatterned substrates that provide mechanical signals for differentiation. This review aims to highlight the role of nanopatterns in directing or inducing MSC osteogenic differentiation, especially in bone tissue engineering. Nanopatterns can upregulate the expression of osteogenic markers, which indicates a faster differentiation process. Combined with growth factors, nanopatterns can further upregulate osteogenic markers, but with fewer growth factors needed, thereby reducing the risks and costs involved. Nanopatterns can be applied in scaffolds for tissue engineering for their lasting effects, even in vivo, thus having great potential for future bone treatment.
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Affiliation(s)
- Anggraini Barlian
- School of Life Science & Technology, Institute of Technology Bandung, Bandung, West Java, 40132, Indonesia
- Research Center for Nanosciences & Nanotechnology, Institute of Technology Bandung, Bandung, West Java, 40132, Indonesia
| | - Katherine Vanya
- School of Life Science & Technology, Institute of Technology Bandung, Bandung, West Java, 40132, Indonesia
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38
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Liu B, Tao C, Wu Z, Yao H, Wang DA. Engineering strategies to achieve efficient in vitro expansion of haematopoietic stem cells: development and improvement. J Mater Chem B 2022; 10:1734-1753. [DOI: 10.1039/d1tb02706a] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Haematopoietic stem cells are the basis for building and maintaining lifelong haematopoietic mechanisms and important resources for the treatment of blood disorders. Haematopoietic niches are microenvironment in the body where...
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39
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Khan SS, Ullah I, Ullah S, An R, Xu H, Nie K, Liu C, Liu L. Recent Advances in the Surface Functionalization of Nanomaterials for Antimicrobial Applications. MATERIALS (BASEL, SWITZERLAND) 2021; 14:6932. [PMID: 34832332 PMCID: PMC8623114 DOI: 10.3390/ma14226932] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 11/05/2021] [Accepted: 11/10/2021] [Indexed: 12/16/2022]
Abstract
Innovations in nanotechnology have had an immense impact on medicine, such as in drug delivery, tissue engineering, and medical devices that combat different pathogens. The pathogens that may cause biofilm-associated nosocomial diseases are multidrug-resistant (MDR) bacteria, such as Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa), Staphylococcus aureus (S. aureus), including both Gram-positive and Gram-negative bacterial species. About 65-80% of infections are caused by biofilm-associated pathogens creating a move in the international community toward developing antimicrobial therapies to eliminate such pathogenic infections. Several nanomaterials (NMs) have been discovered and significantly employed in various antipathogenic therapies. These NMs have unique properties of singlet oxygen production, high absorption of near-infrared irradiation, and reasonable conversion of light to heat. In this review, functionalized NPs that combat different pathogenic infections are introduced. This review highlights NMs that combat infections caused by multidrug-resistant (MDR) and other pathogenic microorganisms. It also highlights the biomedical application of NPs with regard to antipathogenic activities.
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Affiliation(s)
| | | | | | | | | | | | | | - Luo Liu
- College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China; (S.S.K.); (I.U.); (S.U.); (R.A.); (H.X.); (K.N.); (C.L.)
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Attia N, Mashal M, Puras G, Pedraz JL. Mesenchymal Stem Cells as a Gene Delivery Tool: Promise, Problems, and Prospects. Pharmaceutics 2021; 13:843. [PMID: 34200425 PMCID: PMC8229096 DOI: 10.3390/pharmaceutics13060843] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 05/24/2021] [Accepted: 05/31/2021] [Indexed: 12/13/2022] Open
Abstract
The cell-based approach in gene therapy arises as a promising strategy to provide safe, targeted, and efficient gene delivery. Owing to their unique features, as homing and tumor-tropism, mesenchymal stem cells (MSCs) have recently been introduced as an encouraging vehicle in gene therapy. Nevertheless, non-viral transfer of nucleic acids into MSCs remains limited due to various factors related to the main stakeholders of the process (e.g., nucleic acids, carriers, or cells). In this review, we have summarized the main types of nucleic acids used to transfect MSCs, the pros and cons, and applications of each. Then, we have emphasized on the most efficient lipid-based carriers for nucleic acids to MSCs, their main features, and some of their applications. While a myriad of studies have demonstrated the therapeutic potential for engineered MSCs therapy in various illnesses, optimization for clinical use is an ongoing challenge. On the way of improvement, genetically modified MSCs have been combined with various novel techniques and tools (e.g., exosomes, spheroids, 3D-Bioprinting, etc.,) aiming for more efficient and safe applications in biomedicine.
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Affiliation(s)
- Noha Attia
- Laboratory of Pharmaceutics, NanoBioCel Research Group, School of Pharmacy, University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain; (N.A.); (M.M.)
- Department of Basic Sciences, The American University of Antigua-College of Medicine, Coolidge 1451, Antigua and Barbuda
- The Center of Research and Evaluation, The American University of Antigua-College of Medicine, Coolidge 1451, Antigua and Barbuda
- Histology and Cell Biology Department, Faculty of Medicine, University of Alexandria, Alexandria 21561, Egypt
| | - Mohamed Mashal
- Laboratory of Pharmaceutics, NanoBioCel Research Group, School of Pharmacy, University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain; (N.A.); (M.M.)
- The Center of Research and Evaluation, The American University of Antigua-College of Medicine, Coolidge 1451, Antigua and Barbuda
| | - Gustavo Puras
- Laboratory of Pharmaceutics, NanoBioCel Research Group, School of Pharmacy, University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain; (N.A.); (M.M.)
- Networking Research Centre of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Institute of Health Carlos III, 28029 Madrid, Spain
- Bioaraba, NanoBioCel Research Group, 01006 Vitoria-Gasteiz, Spain
- Laboratory of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain
| | - Jose Luis Pedraz
- Laboratory of Pharmaceutics, NanoBioCel Research Group, School of Pharmacy, University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain; (N.A.); (M.M.)
- Networking Research Centre of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Institute of Health Carlos III, 28029 Madrid, Spain
- Bioaraba, NanoBioCel Research Group, 01006 Vitoria-Gasteiz, Spain
- Laboratory of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain
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Jing G, Li K, Sun F, Niu J, Zhu R, Qian Y, Wang S. Layer-Number-Dependent Effects of Graphene Oxide on the Pluripotency of Mouse Embryonic Stem Cells Through the Regulation of the Interaction Between the Extracellular Matrix and Integrins. Int J Nanomedicine 2021; 16:3819-3832. [PMID: 34121840 PMCID: PMC8189697 DOI: 10.2147/ijn.s301892] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Accepted: 05/11/2021] [Indexed: 01/07/2023] Open
Abstract
Introduction Embryonic stem cells (ESCs) possess great application prospects in biological research and regenerative medicine, so it is important to obtain ESCs with excellent and stable cellular states during in vitro expansion. The feeder layer culture system with the addition of leukemia inhibitory factor (LIF) is currently applied in ESC cultures, but it has a series of disadvantages that could influence the culture efficiency and quality of the ESCs. With the development of nanotechnology, many studies have applied nanomaterials to optimize the stem cell culture system and regulate the fate of stem cells. In this study, we investigated the layer-number-dependent biofunction of graphene oxide (GO) on the pluripotency of ESCs from mice (mESCs). Methods Single-layer GO (SGO) and multi-layer GO (MGO) were characterized and their effects on the cytotoxicity and self-renewal of mESCs were detected in vitro. The differentiation potentials of mESCs were identified through the formation of embryoid bodies and teratomas. The regulatory mechanism of GO was verified by blocking the target receptors on the surface of mESCs using antibodies. Results Both SGO and MGO were biocompatible with mESCs, but only MGO effectively sustained their self-renewal and differentiation potential. In addition, GO influenced the cellular activities of mESCs by regulating the interactions between extracellular matrix proteins and integrins. Conclusion This work demonstrates the layer-number-dependent effects of GO on regulating the cell behavior of mESCs and reveals the extracellular regulatory mechanism of this process.
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Affiliation(s)
- Guoxin Jing
- Research Center for Translational Medicine at East Hospital, School of Life Science and Technology, Tongji University, Shanghai, People's Republic of China
| | - Kun Li
- Research Center for Translational Medicine at East Hospital, School of Life Science and Technology, Tongji University, Shanghai, People's Republic of China
| | - Feiyue Sun
- Research Center for Translational Medicine at East Hospital, School of Life Science and Technology, Tongji University, Shanghai, People's Republic of China
| | - Jintong Niu
- Research Center for Translational Medicine at East Hospital, School of Life Science and Technology, Tongji University, Shanghai, People's Republic of China
| | - Rongrong Zhu
- Research Center for Translational Medicine at East Hospital, School of Life Science and Technology, Tongji University, Shanghai, People's Republic of China
| | - Yechang Qian
- Department of Respiratory Disease, Baoshan District Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, People's Republic of China
| | - Shilong Wang
- Research Center for Translational Medicine at East Hospital, School of Life Science and Technology, Tongji University, Shanghai, People's Republic of China
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Azimifar MA, Salmasi Z, Doosti A, Babaei N, Hashemi M. Evaluation of the efficiency of modified PAMAM dendrimer with low molecular weight protamine peptide to deliver IL-12 plasmid into stem cells as cancer therapy vehicles. Biotechnol Prog 2021; 37:e3175. [PMID: 34013634 DOI: 10.1002/btpr.3175] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 05/12/2021] [Accepted: 05/18/2021] [Indexed: 12/23/2022]
Abstract
Interleukin 12 (IL-12) is considered as an important molecule for cancer immunotherapy with significant roles in hindering tumor activity, mostly mediated by tumor-associated macrophages and anti-angiogenic factors. Mesenchymal stem cells (MSCs) have been come out as promising carriers to increase the accumulation of drug/gene in tumor sites. As a vehicle, MSCs have various advantages, including tumor-specific propensity and migratory ability; however, they have limited transfection efficiency, compared to other cells. In this study, we introduced a novel delivery system based on poly-(amidoamine) (PAMAM) (G5) to deliver a plasmid encoding IL-12 to MSCs. Initially, 30% of the amine surface of PAMAM was substituted by 10-bromodecanoic acid. Then, the low molecular weight of protamine peptide was conjugated to PAMAM and PAMAM-alkyl with N-succinimidyl 3-(2-pyridyldithio) propionate as a linker. Physicochemical properties of this modified PAMAM were evaluated, including size and surface charge, toxicity, transfection efficiency to deliver reporter and IL-12 genes into MSCs and finally the migration potential of the engineered stem cells into cancer and normal cell lines (HepG2 and NIH/3 T3). The results showed that alkyl-peptide modified PAMAM with low toxicity had a higher potential to deliver green fluorescent protein and IL-12 genes to stem cells, than PMAMAM, PAMAM-alkyl and PAMAM-peptide. These engineered stem cells had a greater ability to migrate to cancer cells than normal cells. It can be concluded that engineered stem cells containing the IL-12 gene can be considered as an efficient cell carrier for cancer immunotherapy. Further clinical studies are needed to confirm these results.
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Affiliation(s)
- Mohammad Amin Azimifar
- Department of Cell Molecular Biology, Bushehr Branch, Islamic Azad University, Bushehr, Iran
| | - Zahra Salmasi
- Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Abbas Doosti
- Biotechnology Research Center, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
| | - Nahid Babaei
- Department of Cell Molecular Biology, Bushehr Branch, Islamic Azad University, Bushehr, Iran
| | - Maryam Hashemi
- Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
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El-Jawhari JJ, Ganguly P, Jones E, Giannoudis PV. Bone Marrow Multipotent Mesenchymal Stromal Cells as Autologous Therapy for Osteonecrosis: Effects of Age and Underlying Causes. Bioengineering (Basel) 2021; 8:69. [PMID: 34067727 PMCID: PMC8156020 DOI: 10.3390/bioengineering8050069] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2021] [Revised: 04/29/2021] [Accepted: 05/13/2021] [Indexed: 12/21/2022] Open
Abstract
Bone marrow (BM) is a reliable source of multipotent mesenchymal stromal cells (MSCs), which have been successfully used for treating osteonecrosis. Considering the functional advantages of BM-MSCs as bone and cartilage reparatory cells and supporting angiogenesis, several donor-related factors are also essential to consider when autologous BM-MSCs are used for such regenerative therapies. Aging is one of several factors contributing to the donor-related variability and found to be associated with a reduction of BM-MSC numbers. However, even within the same age group, other factors affecting MSC quantity and function remain incompletely understood. For patients with osteonecrosis, several underlying factors have been linked to the decrease of the proliferation of BM-MSCs as well as the impairment of their differentiation, migration, angiogenesis-support and immunoregulatory functions. This review discusses the quality and quantity of BM-MSCs in relation to the etiological conditions of osteonecrosis such as sickle cell disease, Gaucher disease, alcohol, corticosteroids, Systemic Lupus Erythematosus, diabetes, chronic renal disease and chemotherapy. A clear understanding of the regenerative potential of BM-MSCs is essential to optimize the cellular therapy of osteonecrosis and other bone damage conditions.
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Affiliation(s)
- Jehan J El-Jawhari
- Department of Biosciences, School of Science and Technology, Nottingham Trent University, Nottingham NG11 8NS, UK
- Clinical Pathology Department, Mansoura University, Mansoura 35516, Egypt
| | - Payal Ganguly
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, School of Medicine, University of Leeds, Leeds LS2 9JT, UK; (P.G.); (E.J.); (P.V.G.)
| | - Elena Jones
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, School of Medicine, University of Leeds, Leeds LS2 9JT, UK; (P.G.); (E.J.); (P.V.G.)
| | - Peter V Giannoudis
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, School of Medicine, University of Leeds, Leeds LS2 9JT, UK; (P.G.); (E.J.); (P.V.G.)
- Academic Department of Trauma and Orthopedic, School of Medicine, University of Leeds, Leeds LS2 9JT, UK
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