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Luo X, McAndrews KM, Kalluri R. Natural and Bioengineered Extracellular Vesicles in Diagnosis, Monitoring and Treatment of Cancer. ACS NANO 2025; 19:5871-5896. [PMID: 39869032 PMCID: PMC12002402 DOI: 10.1021/acsnano.4c11630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/28/2025]
Abstract
Extracellular vesicles (EVs) are cell derived nanovesicles which are implicated in both physiological and pathological intercellular communication, including the initiation, progression, and metastasis of cancer. The exchange of biomolecules between stromal cells and cancer cells via EVs can provide a window to monitor cancer development in real time for better diagnostic and interventional strategies. In addition, the process of secretion and internalization of EVs by stromal and cancer cells in the tumor microenvironment (TME) can be exploited for delivering therapeutics. EVs have the potential to provide a targeted, biocompatible, and efficient delivery platform for the treatment of cancer and other diseases. Natural as well as engineered EVs as nanomedicine have immense potential for disease intervention. Here, we provide an overview of current knowledge of EVs' function in cancer progression, diagnostic and therapeutic applications for EVs in the cancer setting, as well as current EV engineering strategies.
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Affiliation(s)
- Xin Luo
- Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77054, United States
- Department of Bioengineering, Rice University, Houston, Texas 77005, United States
| | - Kathleen M. McAndrews
- Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77054, United States
| | - Raghu Kalluri
- Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77054, United States
- Department of Bioengineering, Rice University, Houston, Texas 77005, United States
- Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, United States
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Yang X, Kubican SE, Yi Z, Tong S. Advances in magnetic nanoparticles for molecular medicine. Chem Commun (Camb) 2025; 61:3093-3108. [PMID: 39846549 PMCID: PMC11756346 DOI: 10.1039/d4cc05167j] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Accepted: 01/20/2025] [Indexed: 01/24/2025]
Abstract
Magnetic nanoparticles (MNPs) are highly versatile nanomaterials in nanomedicine, owing to their diverse magnetic properties, which can be tailored through variations in size, shape, composition, and exposure to inductive magnetic fields. Over four decades of research have led to the clinical approval or ongoing trials of several MNP formulations, fueling continued innovation. Beyond traditional applications in drug delivery, imaging, and cancer hyperthermia, MNPs have increasingly advanced into molecular medicine. Under external magnetic fields, MNPs can generate mechano- or thermal stimuli to modulate individual molecules or cells deep within tissue, offering precise, remote control of biological processes at cellular and molecular levels. These unique capabilities have opened new avenues in emerging fields such as genome editing, cell therapies, and neuroscience, underpinned by a growing understanding of nanomagnetism and the molecular mechanisms responding to mechanical and thermal cues. Research on MNPs as a versatile synthetic material capable of engineering control at the cellular and molecular levels holds great promise for advancing the frontiers of molecular medicine, including areas such as genome editing and synthetic biology. This review summarizes recent clinical studies showcasing the classical applications of MNPs and explores their integration into molecular medicine, with the goal of inspiring the development of next-generation MNP-based platforms for disease treatment.
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Affiliation(s)
- Xiaoyue Yang
- F. Joseph Halcomb III, M. D. Department of Biomedical Engineering, University of Kentucky, Lexington, Kentucky 40536, USA.
| | - Sarah E Kubican
- F. Joseph Halcomb III, M. D. Department of Biomedical Engineering, University of Kentucky, Lexington, Kentucky 40536, USA.
| | - Zhongchao Yi
- F. Joseph Halcomb III, M. D. Department of Biomedical Engineering, University of Kentucky, Lexington, Kentucky 40536, USA.
| | - Sheng Tong
- F. Joseph Halcomb III, M. D. Department of Biomedical Engineering, University of Kentucky, Lexington, Kentucky 40536, USA.
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Liang QL, Liu H, Wang T, Lau CH, Wang J, Mo ZY, Zhou ZM, Zhou ZY, Zhu H, Chen G, Tong S. UV radiation enhanced encapsulation of superparamagnetic iron oxide nanoparticles (MNPs) in microparticles derived from tumor repopulating cells. Biochem Biophys Res Commun 2024; 741:151050. [PMID: 39586131 DOI: 10.1016/j.bbrc.2024.151050] [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: 09/18/2024] [Revised: 11/06/2024] [Accepted: 11/21/2024] [Indexed: 11/27/2024]
Abstract
Extracellular vesicles (EVs) such as microparticles secreted by the cells can be manipulated and used for delivering therapeutic drugs to target and eradicate cancer cells. However, high encapsulation efficiency and mass production of the microparticles remain difficult to achieve. Efficient and targeted delivery to cancer cells is another hurdle to be addressed. To overcome these issues, we integrated superparamagnetic iron oxide nanoparticles (MNPs) with microparticles. First of all, exposure of highly aggressive tumor-repopulating cells (TRC) to UV radiation dramatically improved microparticle production. These TRC cells were selected from diverse cancer cell lines that are 3D culturing in soft fibrin gel. These microparticles derived from 3D-cultured TRCs have lower membrane stiffness than 2D-cultured cells. Ferrozine assay showed that endocytosis and encapsulation of MNPs during microparticle production were higher in 3D-cultured TRC cells than in 2D cultured cells. Packaging of MNPs into microparticles also enhanced cellular uptake of MNPs without inducing cytotoxicity to treated cells. Compared to the naked MNPs, ex vivo fluorescence imaging shows that mice tail-vein injected with microparticle-encapsulated MNPs displayed continuous increments of intratumoral accumulation of MNPs. Furthermore, MRI images revealed a higher T2 contrast and an uneven distribution of the T2 contrast in the tumor of mice tail-vein injected with microparticle-encapsulated MNPs than naked MNPs. This study provides a new platform for cancer imaging by integrating MNPs and microparticles derived from tumor-repopulating cells.
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Affiliation(s)
- Qing-Le Liang
- Department of Clinical Laboratory Medicine, Chongqing University Jiangjin Hospital, Chongqing, China
| | - He Liu
- Department of Radiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Tao Wang
- Department of Biology, College of Science, Shantou University, Shantou, Guangdong, China
| | - Cia-Hin Lau
- Department of Biology, College of Science, Shantou University, Shantou, Guangdong, China
| | - Jianchao Wang
- Department of Pathology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, China
| | - Zheng-Ying Mo
- Department of Oncology, Tai-He Hospital, Hubei University of Medicine, Shiyan, Hubei, China
| | - Zhang-Ming Zhou
- Department of Neurosurgery, Dujiangyan Medical Center, Chengdu, China
| | - Zhe-Yu Zhou
- Department of Radiology, Tai-He Hospital, Hubei University of Medicine, Shiyan, Hubei, China
| | - Haibao Zhu
- Department of Biology, College of Science, Shantou University, Shantou, Guangdong, China; Guangdong Provincial Key Laboratory of Marine Biotechnology, Shantou University, Shantou, Guangdong, China; Shantou Key Laboratory of Marine Microbial Resources and Interactions with Environment, Shantou University, Shantou, Guangdong, China.
| | - Gang Chen
- Department of Pathology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, China.
| | - Sheng Tong
- Department of Biomedical Engineering, University of Kentucky, USA.
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Yang X, Yi Z, Liang Y, Tong S. Magnetic Iron Oxide Nanoparticles Enhance Exosome Production by Upregulating Exosome Transport and Secretion Pathways. ACS APPLIED MATERIALS & INTERFACES 2024; 16:67235-67245. [PMID: 39582356 PMCID: PMC11807419 DOI: 10.1021/acsami.4c13821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/26/2024]
Abstract
Exosomes are cell-released nanovesicles that regulate intercellular communication by transporting a variety of bioactive molecules. They play a crucial role in various physiological and pathological processes, such as the immune response, tissue regeneration, aging, and tumor progression. There has been growing interest in controlling exosome production, which could offer valuable tools for unraveling complex cell communication networks and enabling novel therapeutic applications. Magnetic iron oxide nanoparticles (MNPs), one of the few nanomaterials approved for clinical use, have been shown to remotely modulate cellular activities such as cytoskeleton reorganization, ion channel activation, and cell polarization. In this study, we systematically investigate the effects of MNPs, acting as nanoscale force transducers, on exosome production in two distinct cell types with different responses to mechanical stimuli. Our findings reveal that magnetic force applied to intracellular MNPs induces vesicle relocation and promotes the formation of actin stress fibers. Gene expression analysis further shows that intracellular magnetic force upregulates genes related to exosome transport and secretion as well as other pathways linked to exosome biogenesis. Notably, these forces substantially enhance exosome production, particularly MNP-containing exosomes, which are accompanied by increased intercellular exchange of MNPs. In summary, our study offers valuable insights into MNP-driven exosome production and presents potential strategies for enhancing cell communication and modulating nanoparticle distribution in nanomedicine.
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Affiliation(s)
- Xiaoyue Yang
- F. Joseph Halcomb III, M.D. Department of Biomedical Engineering, University of Kentucky, Lexington, Kentucky 40536, USA
| | - Zhongchao Yi
- F. Joseph Halcomb III, M.D. Department of Biomedical Engineering, University of Kentucky, Lexington, Kentucky 40536, USA
| | - Ying Liang
- New York Blood Center, New York, New York 10065, USA
| | - Sheng Tong
- F. Joseph Halcomb III, M.D. Department of Biomedical Engineering, University of Kentucky, Lexington, Kentucky 40536, USA
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Yi Z, Yang X, Liang Y, Tong S. Iron oxide nanozymes enhanced by ascorbic acid for macrophage-based cancer therapy. NANOSCALE 2024; 16:14330-14338. [PMID: 39015956 PMCID: PMC11305150 DOI: 10.1039/d4nr01208a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Accepted: 07/11/2024] [Indexed: 07/18/2024]
Abstract
In recent years, using pharmacological ascorbic acid has emerged as a promising therapeutic approach in cancer treatment, owing to its capacity to induce extracellular hydrogen peroxide (H2O2) production in solid tumors. The H2O2 is then converted into cytotoxic hydroxyl free radicals (HO˙) by redox-active Fe2+ inside cells. However, the high dosage of ascorbic acid required for efficacy is hampered by adverse effects such as kidney stone formation. In a recent study, we demonstrated the efficient catalytic conversion of H2O2 to HO˙ by wüstite (Fe1-xO) nanoparticles (WNPs) through a heterogenous Fenton reaction. Here, we explore whether WNPs can enhance the therapeutic potential of ascorbic acid, thus mitigating its dose-related limitations. Our findings reveal distinct pH dependencies for WNPs and ascorbic acid in the Fenton reaction and H2O2 generation, respectively. Importantly, WNPs exhibit the capability to either impede or enhance the cytotoxic effect of ascorbic acid, depending on the spatial segregation of the two reagents by cellular compartments. Furthermore, our study demonstrates that treatment with ascorbic acid promotes the polarization of WNP-loaded macrophages toward a pro-inflammatory M1 phenotype, significantly suppressing the growth of 4T1 breast cancer cells. This study highlights the importance of orchestrating the interplay between ascorbic acid and nanozymes in cancer therapy and presents a novel macrophage-based cell therapy approach.
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Affiliation(s)
- Zhongchao Yi
- Department of Biomedical Engineering, University of Kentucky, Lexington, Kentucky 40536, USA.
| | - Xiaoyue Yang
- Department of Biomedical Engineering, University of Kentucky, Lexington, Kentucky 40536, USA.
| | - Ying Liang
- New York Blood Center, New York, New York 10065, USA
| | - Sheng Tong
- Department of Biomedical Engineering, University of Kentucky, Lexington, Kentucky 40536, USA.
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Ghimire U, Jang SR, Adhikari JR, Kandel R, Song JH, Park CH. Conducting biointerface of spider-net-like chitosan-adorned polyurethane/SPIONs@SrO 2-fMWCNTs for bone tissue engineering and antibacterial efficacy. Int J Biol Macromol 2024; 264:130602. [PMID: 38447824 DOI: 10.1016/j.ijbiomac.2024.130602] [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: 10/30/2023] [Revised: 02/24/2024] [Accepted: 02/26/2024] [Indexed: 03/08/2024]
Abstract
In pursuit of enhancing bone cell proliferation, this study delves into the fabrication of porous scaffolds through the integration of nanomaterials. Specifically, we present the development of highly conductive chitosan (CS) nanonets on fibro-porous polyurethane (PU) bio-membranes. These nanofibers comprise functionalized multiwall carbon nanotubes (fMWCNTs), well-dispersed superparamagnetic iron oxide (SPIONs), and strontium oxide (SrO2) nanoparticles. The resulting porous scaffold exhibits remarkable interfacial biocompatibility, antibacterial properties, and load-bearing capability. Through meticulous in vitro investigations, the CS-PU/SPIONs/SrO2-fMWCNTs nanofibrous scaffolds have demonstrated a propensity to promote bone cell regeneration. Notably, the integration of these nanomaterials has been found to upregulate crucial bone-related markers, including ALP, ARS, COL-I, RUNX2, and SPP-I. The evaluation of these markers, conducted through quantitative real-time polymerase chain reaction (qRT-PCR) and immunocytochemistry, substantiates the improved cell survival and enhanced osteogenic differentiation facilitated by the integrated nanomaterials. This comprehensive analysis underscores the efficacy of CS-PU/SPIONs/SrO2-fMWCNTs bioscaffolds in promoting MC3T3-E1 cell regeneration within, thereby holding promise for advancements in bone tissue engineering and regenerative medicine.
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Affiliation(s)
- Upasana Ghimire
- Department of Bionanotechnology and Bioconvergence Engineering, Graduate School, Jeonbuk National University, Jeonju 561-756, Republic of Korea
| | - Se Rim Jang
- Division of Mechanical Design Engineering, Jeonbuk National University, Jeonju 561-756, Republic of Korea
| | - Jhalak Raj Adhikari
- Department of Mechanical Design Engineering, Jeonbuk National University, Jeonju 561-756, Republic of Korea
| | - Rupesh Kandel
- Department of Bionanotechnology and Bioconvergence Engineering, Graduate School, Jeonbuk National University, Jeonju 561-756, Republic of Korea; Department of IT Convergence Mechatronics Engineering, Jeonbuk National University, 567 Baekje-daero, Deokjin-gu, Jeonju-si 54896, Jeollabuk-do, Republic of Korea.
| | - Jun Hee Song
- Department of IT Convergence Mechatronics Engineering, Jeonbuk National University, 567 Baekje-daero, Deokjin-gu, Jeonju-si 54896, Jeollabuk-do, Republic of Korea.
| | - Chan Hee Park
- Department of Bionanotechnology and Bioconvergence Engineering, Graduate School, Jeonbuk National University, Jeonju 561-756, Republic of Korea; Division of Mechanical Design Engineering, Jeonbuk National University, Jeonju 561-756, Republic of Korea.
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El-Latif NA, El Zehary RR, Ibrahim FM, Denewar M. Bone marrow stem cells with or without superparamagnetic iron oxide nanoparticles as a magnetic targeting tool: Which is better in regeneration of neurolysed facial nerve? An experimental study. Heliyon 2024; 10:e26675. [PMID: 38434051 PMCID: PMC10906296 DOI: 10.1016/j.heliyon.2024.e26675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2023] [Revised: 01/29/2024] [Accepted: 02/16/2024] [Indexed: 03/05/2024] Open
Abstract
Aim This study was performed to evaluate neural regenerative capacities of bone marrow stem cells (BMSCs) with or without superparamagnetic iron oxide nanoparticles (SPIONs) as a magnetic targeting tool after neurolysis of the facial nerve (FN) in albino rats. Methods Thirty-eight male albino rats were selected. Two of them were euthanized for normal FN histology assessment. Thirty-six rats were injected with ethanol in the FN nerve for neurolysis induction and assessed one week post-operatively by eye blinking test. Animals were divided into three groups, each containing twelve rats: Group I (positive control) was injected with Dulbecco Modified Eagle's medium (DMEM-F12), group II was injected with BMSCs in DMEM-F12, and group III was injected with BMSCs in DMEM-F12 with poly l-lysine coated SPIONs (0.5 mmol/mL). Monitoring of SPIONs in the rat's body was carried out by MRI. A circular neodymium magnet N52 (0.57 T, 2 × 5 mm) was placed on each rat in group III just below the right ear at the site of surgery to attract SPIONs labeled BMSCs, left in place for 24 h, and then removed. From each group, six rats were euthanized at the end of the 4th and 8th week of treatment, respectively. The right FN trunks were extracted for routine histological examination using H&E stain. Immunohistochemical examination by anti-S100B was performed to characterize the thickness of the myelin sheath formed by the Schwann cells. Ultra-structural examination was performed to study changes in axons, myelin sheaths, and Schwann cells. Results Regeneration of nerve fibers, Schwan cells, and myelin sheaths was better in group II than in groups I and III histologically, immunohistochemically, and ultra-structurally. Conclusion BMSCs alone could ameliorate FN regeneration better than magnetic targeting treatment using BMSCs labeled with SPIONs.
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Affiliation(s)
| | | | | | - Mona Denewar
- Oral Biology, Faculty of Dentistry, Mansoura University, Egypt
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Ma C, Izumiya M, Nobuoka H, Ueno R, Mimura M, Ueda K, Ishida H, Tomotsune D, Johkura K, Yue F, Saito N, Haniu H. Three-Dimensional Modeling with Osteoblast-like Cells under External Magnetic Field Conditions Using Magnetic Nano-Ferrite Particles for the Development of Cell-Derived Artificial Bone. NANOMATERIALS (BASEL, SWITZERLAND) 2024; 14:251. [PMID: 38334522 PMCID: PMC10857141 DOI: 10.3390/nano14030251] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Revised: 01/21/2024] [Accepted: 01/22/2024] [Indexed: 02/10/2024]
Abstract
The progress in artificial bone research is crucial for addressing fractures and bone defects in the aging population. However, challenges persist in terms of biocompatibility and structural complexity. Nanotechnology provides a promising avenue by which to overcome these challenges, with nano-ferrite particles (NFPs) exhibiting superparamagnetic properties. The ability to control cell positioning using a magnetic field opens up new possibilities for customizing artificial bones with specific shapes. This study explores the biological effects of NFPs on osteoblast-like cell lines (MC3T3-E1), including key analyses, such as cell viability, cellular uptake of NFPs, calcification processes, cell migration under external magnetic field conditions, and three-dimensional modeling. The results indicate that the impact of NFPs on cell proliferation is negligible. Fluorescence and transmission electron microscopy validated the cellular uptake of NFPs, demonstrating the potential for precise cell positioning through an external magnetic field. Under calcification-inducing conditions, the cells exhibited sustained calcification ability even in the presence of NFPs. The cell movement analysis observed the controlled movement of NFP-absorbing cells under an external magnetic field. Applying a magnetic field along the z-axis induced the three-dimensional shaping of cells incorporating NFPs, resulting in well-arranged z-axis directional patterns. In this study, NFPs demonstrated excellent biocompatibility and controllability under an external magnetic field, laying the foundation for innovative treatment strategies for customizing artificial bones.
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Affiliation(s)
- Chuang Ma
- Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan; (C.M.); (M.I.); (H.N.); (R.U.); (M.M.); (K.U.); (H.I.); (D.T.); (F.Y.); (N.S.)
- Biomedical Engineering Division, Graduate School of Medicine, Science and Technology, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan
| | - Makoto Izumiya
- Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan; (C.M.); (M.I.); (H.N.); (R.U.); (M.M.); (K.U.); (H.I.); (D.T.); (F.Y.); (N.S.)
- Biomedical Engineering Division, Graduate School of Medicine, Science and Technology, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan
| | - Hidehiko Nobuoka
- Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan; (C.M.); (M.I.); (H.N.); (R.U.); (M.M.); (K.U.); (H.I.); (D.T.); (F.Y.); (N.S.)
- Biomedical Engineering Division, Graduate School of Science and Technology, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan
| | - Rintaro Ueno
- Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan; (C.M.); (M.I.); (H.N.); (R.U.); (M.M.); (K.U.); (H.I.); (D.T.); (F.Y.); (N.S.)
- Biomedical Engineering Division, Graduate School of Science and Technology, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan
| | - Masaki Mimura
- Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan; (C.M.); (M.I.); (H.N.); (R.U.); (M.M.); (K.U.); (H.I.); (D.T.); (F.Y.); (N.S.)
- Biomedical Engineering Division, Graduate School of Science and Technology, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan
| | - Katsuya Ueda
- Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan; (C.M.); (M.I.); (H.N.); (R.U.); (M.M.); (K.U.); (H.I.); (D.T.); (F.Y.); (N.S.)
- Biomedical Engineering Division, Graduate School of Medicine, Science and Technology, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan
| | - Haruka Ishida
- Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan; (C.M.); (M.I.); (H.N.); (R.U.); (M.M.); (K.U.); (H.I.); (D.T.); (F.Y.); (N.S.)
- Biomedical Engineering Division, Graduate School of Medicine, Science and Technology, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan
| | - Daihachiro Tomotsune
- Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan; (C.M.); (M.I.); (H.N.); (R.U.); (M.M.); (K.U.); (H.I.); (D.T.); (F.Y.); (N.S.)
- Department of Histology and Embryology, School of Medicine, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan;
| | - Kohei Johkura
- Department of Histology and Embryology, School of Medicine, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan;
| | - Fengming Yue
- Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan; (C.M.); (M.I.); (H.N.); (R.U.); (M.M.); (K.U.); (H.I.); (D.T.); (F.Y.); (N.S.)
- Department of Histology and Embryology, School of Medicine, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan;
| | - Naoto Saito
- Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan; (C.M.); (M.I.); (H.N.); (R.U.); (M.M.); (K.U.); (H.I.); (D.T.); (F.Y.); (N.S.)
| | - Hisao Haniu
- Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan; (C.M.); (M.I.); (H.N.); (R.U.); (M.M.); (K.U.); (H.I.); (D.T.); (F.Y.); (N.S.)
- Biomedical Engineering Division, Graduate School of Medicine, Science and Technology, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan
- Biomedical Engineering Division, Graduate School of Science and Technology, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan
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Barreto da Silva T, Dias EA, Cardoso LMDF, Gama JFG, Alves LA, Henriques-Pons A. Magnetic Nanostructures and Stem Cells for Regenerative Medicine, Application in Liver Diseases. Int J Mol Sci 2023; 24:ijms24119293. [PMID: 37298243 DOI: 10.3390/ijms24119293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 05/08/2023] [Accepted: 05/19/2023] [Indexed: 06/12/2023] Open
Abstract
The term "liver disease" refers to any hepatic condition that leads to tissue damage or altered hepatic function and can be induced by virus infections, autoimmunity, inherited genetic mutations, high consumption of alcohol or drugs, fat accumulation, and cancer. Some types of liver diseases are becoming more frequent worldwide. This can be related to increasing rates of obesity in developed countries, diet changes, higher alcohol intake, and even the coronavirus disease 2019 (COVID-19) pandemic was associated with increased liver disease-related deaths. Although the liver can regenerate, in cases of chronic damage or extensive fibrosis, the recovery of tissue mass is impossible, and a liver transplant is indicated. Because of reduced organ availability, it is necessary to search for alternative bioengineered solutions aiming for a cure or increased life expectancy while a transplant is not possible. Therefore, several groups were studying the possibility of stem cells transplantation as a therapeutic alternative since it is a promising strategy in regenerative medicine for treating various diseases. At the same time, nanotechnological advances can contribute to specifically targeting transplanted cells to injured sites using magnetic nanoparticles. In this review, we summarize multiple magnetic nanostructure-based strategies that are promising for treating liver diseases.
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Affiliation(s)
- Tatiane Barreto da Silva
- Laboratory of Cellular Communication, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21045-900, Brazil
| | - Evellyn Araújo Dias
- Laboratory of Cellular Communication, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21045-900, Brazil
| | | | - Jaciara Fernanda Gomes Gama
- Laboratory of Cellular Communication, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21045-900, Brazil
| | - Luiz Anastácio Alves
- Laboratory of Cellular Communication, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21045-900, Brazil
| | - Andrea Henriques-Pons
- Laboratory of Innovations in Therapies, Education, and Bioproducts, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21041-361, Brazil
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Garg A, Khan S, Luu N, Nicholas DJ, Day V, King AL, Fear J, Lalor PF, Newsome PN. TGFβ 1 priming enhances CXCR3-mediated mesenchymal stromal cell engraftment to the liver and enhances anti-inflammatory efficacy. J Cell Mol Med 2023; 27:864-878. [PMID: 36824012 PMCID: PMC10002976 DOI: 10.1111/jcmm.17698] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 02/07/2023] [Accepted: 02/11/2023] [Indexed: 02/25/2023] Open
Abstract
The immunomodulatory characteristics of mesenchymal stromal cells (MSC) confers them with potential therapeutic value in the treatment of inflammatory/immune-mediated conditions. Previous studies have reported only modest beneficial effects in murine models of liver injury. In our study we explored the role of MSC priming to enhance their effectiveness. Herein we demonstrate that stimulation of human MSC with cytokine TGβ1 enhances their homing and engraftment to human and murine hepatic sinusoidal endothelium in vivo and in vitro, which was mediated by increased expression of CXCR3. Alongside improved hepatic homing there was also greater reduction in liver inflammation and necrosis, with no adverse effects, in the CCL4 murine model of liver injury treated with primed MSC. Priming of MSCs with TGFβ1 is a novel strategy to improve the anti-inflammatory efficacy of MSCs.
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Affiliation(s)
- Abhilok Garg
- National Institute for Health Research Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, UK.,Centre for Liver & Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - Sheeba Khan
- National Institute for Health Research Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, UK.,Centre for Liver & Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - N Luu
- National Institute for Health Research Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, UK.,Centre for Liver & Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - Davies J Nicholas
- National Institute for Health Research Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, UK.,Centre for Liver & Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - Victoria Day
- National Institute for Health Research Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, UK.,Centre for Liver & Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - Andrew L King
- National Institute for Health Research Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, UK.,Centre for Liver & Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - Janine Fear
- National Institute for Health Research Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, UK.,Centre for Liver & Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - Patricia F Lalor
- National Institute for Health Research Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, UK.,Centre for Liver & Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - Philip N Newsome
- National Institute for Health Research Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, UK.,Centre for Liver & Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.,Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
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11
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Peng Q, Guo X, Wang Y. Synergic Fabrication of Cabazitaxel-Loaded Dendritic Supramolecular Iron Nanomaterials for the Delivery of Tumor Regression and Magnetic Drug Targeting (MDT) in the Melanoma Tumor Model. J CLUST SCI 2022. [DOI: 10.1007/s10876-022-02391-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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12
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Optimization of Multimodal Nanoparticles Internalization Process in Mesenchymal Stem Cells for Cell Therapy Studies. Pharmaceutics 2022; 14:pharmaceutics14061249. [PMID: 35745821 PMCID: PMC9227698 DOI: 10.3390/pharmaceutics14061249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Revised: 06/06/2022] [Accepted: 06/09/2022] [Indexed: 11/17/2022] Open
Abstract
Considering there are several difficulties and limitations in labeling stem cells using multifunctional nanoparticles (MFNP), the purpose of this study was to determine the optimal conditions for labeling human bone marrow mesenchymal stem cells (hBM-MSC), aiming to monitor these cells in vivo. Thus, this study provides information on hBM-MSC direct labeling using multimodal nanoparticles in terms of concentration, magnetic field, and period of incubation while maintaining these cells’ viability and the homing ability for in vivo experiments. The cell labeling process was assessed using 10, 30, and 50 µg Fe/mL of MFNP, with periods of incubation ranging from 4 to 24 h, with or without a magnetic field, using optical microscopy, near-infrared fluorescence (NIRF), and inductively coupled plasma mass spectrometry (ICP-MS). After the determination of optimal labeling conditions, these cells were applied in vivo 24 h after stroke induction, intending to evaluate cell homing and improve NIRF signal detection. In the presence of a magnetic field and utilizing the maximal concentration of MFNP during cell labeling, the iron load assessed by NIRF and ICP-MS was four times higher than what was achieved before. In addition, considering cell viability higher than 98%, the recommended incubation time was 9 h, which corresponded to a 25.4 pg Fe/cell iron load (86% of the iron load internalized in 24 h). The optimization of cellular labeling for application in the in vivo study promoted an increase in the NIRF signal by 215% at 1 h and 201% at 7 h due to the use of a magnetized field during the cellular labeling process. In the case of BLI, the signal does not depend on cell labeling showing no significant differences between unlabeled or labeled cells (with or without a magnetic field). Therefore, the in vitro cellular optimized labeling process using magnetic fields resulted in a shorter period of incubation with efficient iron load internalization using higher MFNP concentration (50 μgFe/mL), leading to significant improvement in cell detection by NIRF technique without compromising cellular viability in the stroke model.
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13
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Garello F, Svenskaya Y, Parakhonskiy B, Filippi M. Micro/Nanosystems for Magnetic Targeted Delivery of Bioagents. Pharmaceutics 2022; 14:pharmaceutics14061132. [PMID: 35745705 PMCID: PMC9230665 DOI: 10.3390/pharmaceutics14061132] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Revised: 05/09/2022] [Accepted: 05/19/2022] [Indexed: 01/09/2023] Open
Abstract
Targeted delivery of pharmaceuticals is promising for efficient disease treatment and reduction in adverse effects. Nano or microstructured magnetic materials with strong magnetic momentum can be noninvasively controlled via magnetic forces within living beings. These magnetic carriers open perspectives in controlling the delivery of different types of bioagents in humans, including small molecules, nucleic acids, and cells. In the present review, we describe different types of magnetic carriers that can serve as drug delivery platforms, and we show different ways to apply them to magnetic targeted delivery of bioagents. We discuss the magnetic guidance of nano/microsystems or labeled cells upon injection into the systemic circulation or in the tissue; we then highlight emergent applications in tissue engineering, and finally, we show how magnetic targeting can integrate with imaging technologies that serve to assist drug delivery.
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Affiliation(s)
- Francesca Garello
- Molecular and Preclinical Imaging Centers, Department of Molecular Biotechnology and Health Sciences, University of Torino, Via Nizza 52, 10126 Torino, Italy;
| | - Yulia Svenskaya
- Science Medical Center, Saratov State University, 410012 Saratov, Russia;
| | - Bogdan Parakhonskiy
- Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium;
| | - Miriam Filippi
- Soft Robotics Laboratory, Department of Mechanical and Process Engineering, ETH Zurich, 8092 Zurich, Switzerland
- Correspondence:
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14
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Maric DM, Velikic G, Maric DL, Supic G, Vojvodic D, Petric V, Abazovic D. Stem Cell Homing in Intrathecal Applications and Inspirations for Improvement Paths. Int J Mol Sci 2022; 23:ijms23084290. [PMID: 35457107 PMCID: PMC9027729 DOI: 10.3390/ijms23084290] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 03/26/2022] [Accepted: 04/01/2022] [Indexed: 02/04/2023] Open
Abstract
A transplanted stem cell homing is a directed migration from the application site to the targeted tissue. Intrathecal application of stem cells is their direct delivery to cerebrospinal fluid, which defines the homing path from the point of injection to the brain. In the case of neurodegenerative diseases, this application method has the advantage of no blood–brain barrier restriction. However, the homing efficiency still needs improvement and homing mechanisms elucidation. Analysis of current research results on homing mechanisms in the light of intrathecal administration revealed a discrepancy between in vivo and in vitro results and a gap between preclinical and clinical research. Combining the existing research with novel insights from cutting-edge biochips, nano, and other technologies and computational models may bridge this gap faster.
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Affiliation(s)
- Dusan M. Maric
- Department for Research and Development, Clinic Orto MD-Parks Dr Dragi Hospital, 21000 Novi Sad, Serbia;
- Faculty of Dentistry Pancevo, University Business Academy, 26000 Pancevo, Serbia
- Vincula Biotech Group, 11000 Belgrade, Serbia;
| | - Gordana Velikic
- Department for Research and Development, Clinic Orto MD-Parks Dr Dragi Hospital, 21000 Novi Sad, Serbia;
- Vincula Biotech Group, 11000 Belgrade, Serbia;
- Correspondence: (G.V.); (D.L.M.)
| | - Dusica L. Maric
- Department of Anatomy, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia
- Correspondence: (G.V.); (D.L.M.)
| | - Gordana Supic
- Institute for Medical Research, Military Medical Academy, 11000 Belgrade, Serbia; (G.S.); (D.V.)
- Medical Faculty of Military Medical Academy, University of Defense, 11000 Belgrade, Serbia
| | - Danilo Vojvodic
- Institute for Medical Research, Military Medical Academy, 11000 Belgrade, Serbia; (G.S.); (D.V.)
- Medical Faculty of Military Medical Academy, University of Defense, 11000 Belgrade, Serbia
| | - Vedrana Petric
- Infectious Diseases Clinic, Clinical Center of Vojvodina, 21000 Novi Sad, Serbia;
- Department of Infectious Diseases, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia
| | - Dzihan Abazovic
- Vincula Biotech Group, 11000 Belgrade, Serbia;
- Department for Regenerative Medicine, Biocell Hospital, 11000 Belgrade, Serbia
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15
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Filippi M, Garello F, Yasa O, Kasamkattil J, Scherberich A, Katzschmann RK. Engineered Magnetic Nanocomposites to Modulate Cellular Function. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2022; 18:e2104079. [PMID: 34741417 DOI: 10.1002/smll.202104079] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 09/13/2021] [Indexed: 06/13/2023]
Abstract
Magnetic nanoparticles (MNPs) have various applications in biomedicine, including imaging, drug delivery and release, genetic modification, cell guidance, and patterning. By combining MNPs with polymers, magnetic nanocomposites (MNCs) with diverse morphologies (core-shell particles, matrix-dispersed particles, microspheres, etc.) can be generated. These MNCs retain the ability of MNPs to be controlled remotely using external magnetic fields. While the effects of these biomaterials on the cell biology are still poorly understood, such information can help the biophysical modulation of various cellular functions, including proliferation, adhesion, and differentiation. After recalling the basic properties of MNPs and polymers, and describing their coassembly into nanocomposites, this review focuses on how polymeric MNCs can be used in several ways to affect cell behavior. A special emphasis is given to 3D cell culture models and transplantable grafts, which are used for regenerative medicine, underlining the impact of MNCs in regulating stem cell differentiation and engineering living tissues. Recent advances in the use of MNCs for tissue regeneration are critically discussed, particularly with regard to their prospective involvement in human therapy and in the construction of advanced functional materials such as magnetically operated biomedical robots.
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Affiliation(s)
- Miriam Filippi
- Soft Robotics Laboratory, ETH Zurich, Tannenstrasse 3, Zurich, 8092, Switzerland
| | - Francesca Garello
- Department of Molecular Biotechnology and Health Sciences, University of Torino, Via Nizza 52, Torino, 10126, Italy
| | - Oncay Yasa
- Soft Robotics Laboratory, ETH Zurich, Tannenstrasse 3, Zurich, 8092, Switzerland
| | - Jesil Kasamkattil
- Department of Biomedicine, University Hospital Basel, Hebelstrasse 20, Basel, 4031, Switzerland
| | - Arnaud Scherberich
- Department of Biomedicine, University Hospital Basel, Hebelstrasse 20, Basel, 4031, Switzerland
- Department of Biomedical Engineering, University of Basel, Gewerbestrasse 14, Allschwil, 4123, Switzerland
| | - Robert K Katzschmann
- Soft Robotics Laboratory, ETH Zurich, Tannenstrasse 3, Zurich, 8092, Switzerland
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16
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Magnetic iron oxide nanoparticles for biomedical applications. CURRENT OPINION IN BIOMEDICAL ENGINEERING 2021; 20. [DOI: 10.1016/j.cobme.2021.100330] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
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17
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Zhuo Z, Wang J, Luo Y, Zeng R, Zhang C, Zhou W, Guo K, Wu H, Sha W, Chen H. Targeted extracellular vesicle delivery systems employing superparamagnetic iron oxide nanoparticles. Acta Biomater 2021; 134:13-31. [PMID: 34284151 DOI: 10.1016/j.actbio.2021.07.027] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Revised: 07/12/2021] [Accepted: 07/13/2021] [Indexed: 02/05/2023]
Abstract
In the past decade, the study of extracellular vesicles (EVs), especially exosomes (50-150 nm) have attracted growing interest in numerous areas of cancer and tissue regeneration due to their unique biological features. A low isolation yield and insufficient targeting abilities limit their therapeutic applicability. Recently, superparamagnetic iron oxide nanoparticles (SPIONs) with magnetic navigation have been exploited to enhance the targeting ability of EVs. To construct targeted EV delivery systems engineered by SPIONs, several groups have pioneered the use of different techniques, such as electroporation, natural incubation, and cell extrusion, to directly internalize SPIONs into EVs. Furthermore, some endogenous ligands, such as transferrins, antibodies, aptamers, and streptavidin, were shown to enable modification of SPIONs, which increases binding with EVs. In this review, we summarized recent advances in targeted EV delivery systems engineered by SPIONs and focused on the key methodological approaches and the current applications of magnetic EVs. This report aims to address the existing challenges and provide comprehensive insights into targeted EV delivery systems. STATEMENT OF SIGNIFICANCE: Targeted extracellular vesicle (EV) delivery systems engineered by superparamagnetic iron oxide nanoparticles (SPIONs) have attracted wide attention and research interest in recent years. Such strategies employ external magnet fields to manipulate SPION-functionalized EVs remotely, aiming to enhance their accumulation and penetration in vivo. Although iron oxide nanoparticle laden EVs are interesting, they are controversial at present, hampering the progress in their clinical application. A thorough integration of these studies is needed for an advanced insight and rational design of targeted EV delivery systems. In this review, we summarize the latest advances in the design strategies of targeted EV delivery systems engineered by SPIONs with a focus on their key methodological approaches, current applications, limitation and future perspectives, which may facilitate the development of natural theranostic nanoplatforms.
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Affiliation(s)
- Zewei Zhuo
- Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China; School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China
| | - Jinghua Wang
- Department of Hematology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
| | - Yujun Luo
- Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China; Shantou University Medical College, Shantou 515041, China
| | - Ruijie Zeng
- Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China; Shantou University Medical College, Shantou 515041, China
| | - Chen Zhang
- Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
| | - Weijie Zhou
- Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
| | - Kehang Guo
- Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
| | - Huihuan Wu
- Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
| | - Weihong Sha
- Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
| | - Hao Chen
- Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
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18
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Jeon S, Park SH, Kim E, Kim J, Kim SW, Choi H. A Magnetically Powered Stem Cell-Based Microrobot for Minimally Invasive Stem Cell Delivery via the Intranasal Pathway in a Mouse Brain. Adv Healthc Mater 2021; 10:e2100801. [PMID: 34160909 DOI: 10.1002/adhm.202100801] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Revised: 06/03/2021] [Indexed: 12/12/2022]
Abstract
Targeted stem cell delivery with microrobots has emerged as a potential alternative therapeutic strategy in regenerative medicine, and intranasal administration is an effective approach for minimally invasive delivery of therapeutic agents into the brain. In this study, a magnetically powered stem cell-based microrobot ("Cellbot") is used for minimally invasive targeted stem cell delivery to the brain through the intranasal passage. The Cellbot is developed by internalizing superparamagnetic iron oxide nanoparticles (SPIONs) into human nasal turbinate stem cells. The SPIONs have no influence on hNTSC characteristics, including morphology, cell viability, and neuronal differentiation. The Cellbots are capable of proliferation and differentiation into neurons, neural precursor cells, and neurogliocytes. The Cellbots in the microfluidic channel can be reliably manipulated by an external magnetic field for orientation and position control. Using an ex vivo model based on brain organoids, it is determined that the Cellbots can be transplanted into brain tissue. Using a murine model, it is demonstrated that the Cellbots can be intranasally administered and magnetically guided to the target tissue in vivo. This approach has the potential to effectively treat central nervous system disorders in a minimally invasive manner.
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Affiliation(s)
- Sungwoong Jeon
- Department of Robotics Engineering DGIST‐ETH Microrobotics Research Center Daegu Gyeongbuk Institute of Science and Technology (DGIST) Daegu 42988 Republic of Korea
| | - Sun Hwa Park
- Department of Otolaryngology‐Head and Neck Surgery Seoul St. Mary's Hospital The Catholic University Seoul 06591 Republic of Korea
| | - Eunhee Kim
- Department of Robotics Engineering DGIST‐ETH Microrobotics Research Center Daegu Gyeongbuk Institute of Science and Technology (DGIST) Daegu 42988 Republic of Korea
| | - Jin‐young Kim
- Department of Robotics Engineering DGIST‐ETH Microrobotics Research Center Daegu Gyeongbuk Institute of Science and Technology (DGIST) Daegu 42988 Republic of Korea
| | - Sung Won Kim
- Department of Otolaryngology‐Head and Neck Surgery Seoul St. Mary's Hospital The Catholic University Seoul 06591 Republic of Korea
| | - Hongsoo Choi
- Department of Robotics Engineering DGIST‐ETH Microrobotics Research Center Daegu Gyeongbuk Institute of Science and Technology (DGIST) Daegu 42988 Republic of Korea
- Robotics Research Center DGIST Daegu 42988 Republic of Korea
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19
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Arjona MI, González-Manchón C, Durán S, Duch M, Del Real RP, Kadambi A, Agusil JP, Redondo-Horcajo M, Pérez-García L, Gómez E, Suárez T, Plaza JA. Integrating magnetic capabilities to intracellular chips for cell trapping. Sci Rep 2021; 11:18495. [PMID: 34531498 PMCID: PMC8446022 DOI: 10.1038/s41598-021-98095-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 08/31/2021] [Indexed: 11/09/2022] Open
Abstract
Current microtechnologies have shown plenty of room inside a living cell for silicon chips. Microchips as barcodes, biochemical sensors, mechanical sensors and even electrical devices have been internalized into living cells without interfering their cell viability. However, these technologies lack from the ability to trap and preconcentrate cells in a specific region, which are prerequisites for cell separation, purification and posterior studies with enhanced sensitivity. Magnetic manipulation of microobjects, which allows a non-contacting method, has become an attractive and promising technique at small scales. Here, we show intracellular Ni-based chips with magnetic capabilities to allow cell enrichment. As a proof of concept of the potential to integrate multiple functionalities on a single device of this technique, we combine coding and magnetic manipulation capabilities in a single device. Devices were found to be internalized by HeLa cells without interfering in their viability. We demonstrated the tagging of a subpopulation of cells and their subsequent magnetic trapping with internalized barcodes subjected to a force up to 2.57 pN (for magnet-cells distance of 4.9 mm). The work opens the venue for future intracellular chips that integrate multiple functionalities with the magnetic manipulation of cells.
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Affiliation(s)
- María Isabel Arjona
- Instituto de Microelectrónica de Barcelona, IMB-CNM (CSIC), Esfera UAB, Campus UAB, 08193, Cerdanyola, Barcelona, Spain.
| | | | - Sara Durán
- Instituto de Microelectrónica de Barcelona, IMB-CNM (CSIC), Esfera UAB, Campus UAB, 08193, Cerdanyola, Barcelona, Spain
| | - Marta Duch
- Instituto de Microelectrónica de Barcelona, IMB-CNM (CSIC), Esfera UAB, Campus UAB, 08193, Cerdanyola, Barcelona, Spain
| | - Rafael P Del Real
- Instituto de Ciencia de Materiales de Madrid, ICMM (CSIC), Cantoblanco, 28049, Madrid, Spain
| | - Abhinav Kadambi
- Instituto de Microelectrónica de Barcelona, IMB-CNM (CSIC), Esfera UAB, Campus UAB, 08193, Cerdanyola, Barcelona, Spain
| | - Juan Pablo Agusil
- Instituto de Microelectrónica de Barcelona, IMB-CNM (CSIC), Esfera UAB, Campus UAB, 08193, Cerdanyola, Barcelona, Spain
| | | | - Lluïsa Pérez-García
- School of Pharmacy, University of Nottingham, University Park, Nottingham, UK
- Departament de Farmacologia, Toxicologia i Química Terapèutica, Universitat de Barcelona, 08028, Barcelona, Spain
- Institut de Nanociència i Nanotecnologia (IN2UB), Universitat de Barcelona, 08028, Barcelona, Spain
| | - Elvira Gómez
- Institut de Nanociència i Nanotecnologia (IN2UB), Universitat de Barcelona, 08028, Barcelona, Spain
- Departament de Ciència de Materials i Química Física, Universitat de Barcelona, 08028, Barcelona, Spain
| | - Teresa Suárez
- Centro de Investigaciones Biológicas Margarita Salas, CIB (CSIC), 28040, Madrid, Spain
| | - José Antonio Plaza
- Instituto de Microelectrónica de Barcelona, IMB-CNM (CSIC), Esfera UAB, Campus UAB, 08193, Cerdanyola, Barcelona, Spain
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20
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Simorgh S, Bagher Z, Farhadi M, Kamrava SK, Boroujeni ME, Namjoo Z, Hour FQ, Moradi S, Alizadeh R. Magnetic Targeting of Human Olfactory Mucosa Stem Cells Following Intranasal Administration: a Novel Approach to Parkinson's Disease Treatment. Mol Neurobiol 2021; 58:3835-3847. [PMID: 33860441 DOI: 10.1007/s12035-021-02392-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Accepted: 04/08/2021] [Indexed: 12/15/2022]
Abstract
Among the various therapeutic procedures used for improving PD, stem cell-based therapy has been shown to be a promising method. Olfactory ectomesenchymal stem cells (OE-MSCs) are a great source of stem cells for PD. Also, the intranasal administration (INA) of stem cells to the neural lesion has several advantages over the other approaches to cellular injections. However, improving the efficacy of INA to produce the highest number of cells at the lesion site has always been a controversial issue. For this purpose, this study was designed to apply the magnetically targeted cell delivery (MTCD) approach to OE-MSCs in the injured striatum area through the IN route in order to explore their outcomes in rat models of PD. Animals were randomly classified into four groups including control, PD model, treatment-NTC (treated with INA of non-target cells), and treatment-TC (treated with INA of target cells). The Alg-SPIONs-labeled OE-MSCs were stained successfully using the Prussian blue method with an intracellular iron concentration of 2.73 pg/cell. It was able to reduce signal intensity in the striatum region by increasing the number of these cells, as shown by the magnetic resonance imaging (MRI). Behavioral evaluation revealed that the administration of OE-MSCs with this novel advanced stem cell therapy alleviated Parkinson's motor dysfunction. Further, histological evaluations confirmed the functional enhancement of dopaminergic neuron cells by the expression of Nurr1, Dopamine transporter (DAT), and paired-like homeodomain transcription factor 3 (TH). Overall, this study showed that INA of OE-MSCs in the MTCD approach enhanced stem cells' therapeutic effects in PD models.
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Affiliation(s)
- Sara Simorgh
- Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Zohreh Bagher
- ENT and Head and Neck Research Center and Department, Hazrat Rasoul Akram Hospital, The Five Senses Health Institute, Iran University of Medical Sciences, Tehran, Iran
| | - Mohammad Farhadi
- ENT and Head and Neck Research Center and Department, Hazrat Rasoul Akram Hospital, The Five Senses Health Institute, Iran University of Medical Sciences, Tehran, Iran
| | - Seyed Kamran Kamrava
- ENT and Head and Neck Research Center and Department, Hazrat Rasoul Akram Hospital, The Five Senses Health Institute, Iran University of Medical Sciences, Tehran, Iran
| | - Mahdi Eskandarian Boroujeni
- Department of Human Molecular Genetics, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Poznan, Poland
| | - Zeinab Namjoo
- Department of Anatomical Science, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Farshid Qiyami Hour
- Department of Anatomical Sciences, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Salah Moradi
- Department of Life Science Engineering, Faculty of New Science and Technology, University of Tehran, Tehran, Iran
| | - Rafieh Alizadeh
- ENT and Head and Neck Research Center and Department, Hazrat Rasoul Akram Hospital, The Five Senses Health Institute, Iran University of Medical Sciences, Tehran, Iran.
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21
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Andrzejewska A, Dabrowska S, Lukomska B, Janowski M. Mesenchymal Stem Cells for Neurological Disorders. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2021; 8:2002944. [PMID: 33854883 PMCID: PMC8024997 DOI: 10.1002/advs.202002944] [Citation(s) in RCA: 187] [Impact Index Per Article: 46.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/02/2020] [Revised: 11/23/2020] [Indexed: 05/13/2023]
Abstract
Neurological disorders are becoming a growing burden as society ages, and there is a compelling need to address this spiraling problem. Stem cell-based regenerative medicine is becoming an increasingly attractive approach to designing therapies for such disorders. The unique characteristics of mesenchymal stem cells (MSCs) make them among the most sought after cell sources. Researchers have extensively studied the modulatory properties of MSCs and their engineering, labeling, and delivery methods to the brain. The first part of this review provides an overview of studies on the application of MSCs to various neurological diseases, including stroke, traumatic brain injury, spinal cord injury, multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease, Huntington's disease, Parkinson's disease, and other less frequently studied clinical entities. In the second part, stem cell delivery to the brain is focused. This fundamental but still understudied problem needs to be overcome to apply stem cells to brain diseases successfully. Here the value of cell engineering is also emphasized to facilitate MSC diapedesis, migration, and homing to brain areas affected by the disease to implement precision medicine paradigms into stem cell-based therapies.
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Affiliation(s)
- Anna Andrzejewska
- NeuroRepair DepartmentMossakowski Medical Research CentrePASWarsaw02‐106Poland
| | - Sylwia Dabrowska
- NeuroRepair DepartmentMossakowski Medical Research CentrePASWarsaw02‐106Poland
| | - Barbara Lukomska
- NeuroRepair DepartmentMossakowski Medical Research CentrePASWarsaw02‐106Poland
| | - Miroslaw Janowski
- NeuroRepair DepartmentMossakowski Medical Research CentrePASWarsaw02‐106Poland
- Center for Advanced Imaging ResearchDepartment of Diagnostic Radiology and Nuclear MedicineUniversity of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer CenterUniversity of MarylandBaltimoreMD21201‐1595USA
- Tumor Immunology and Immunotherapy ProgramUniversity of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer CenterUniversity of MarylandBaltimoreMD21201‐1595USA
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Intracellular detection and communication of a wireless chip in cell. Sci Rep 2021; 11:5967. [PMID: 33727598 PMCID: PMC7966781 DOI: 10.1038/s41598-021-85268-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Accepted: 02/22/2021] [Indexed: 12/16/2022] Open
Abstract
The rapid growth and development of technology has had significant implications for healthcare, personalized medicine, and our understanding of biology. In this work, we leverage the miniaturization of electronics to realize the first demonstration of wireless detection and communication of an electronic device inside a cell. This is a significant forward step towards a vision of non-invasive, intracellular wireless platforms for single-cell analyses. We demonstrate that a 25 \documentclass[12pt]{minimal}
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\begin{document}$$\upmu $$\end{document}μm wireless radio frequency identification (RFID) device can not only be taken up by a mammalian cell but can also be detected and specifically identified externally while located intracellularly. The S-parameters and power delivery efficiency of the electronic communication system is quantified before and after immersion in a biological environment; the results show distinct electrical responses for different RFID tags, allowing for classification of cells by examining the electrical output noninvasively. This versatile platform can be adapted for realization of a broad modality of sensors and actuators. This work precedes and facilitates the development of long-term intracellular real-time measurement systems for personalized medicine and furthering our understanding of intrinsic biological behaviors. It helps provide an advanced technique to better assess the long-term evolution of cellular physiology as a result of drug and disease stimuli in a way that is not feasible using current methods.
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Su Y, Zhang T, Huang T, Gao J. Current advances and challenges of mesenchymal stem cells-based drug delivery system and their improvements. Int J Pharm 2021; 600:120477. [PMID: 33737099 DOI: 10.1016/j.ijpharm.2021.120477] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2021] [Revised: 03/03/2021] [Accepted: 03/07/2021] [Indexed: 12/12/2022]
Abstract
Mesenchymal stem cells (MSCs) have recently emerged as a promising living carrier for targeted drug delivery. A wealth of literature has shown evidence for great advances in MSCs-based drug delivery system (MSCs-DDS) in the treatment of various diseases. Nevertheless, as this field of study rapidly advances, several challenges associated with this delivery strategy have arisen, mainly due to the inherent limitations of MSCs. To this end, several novel technologies are being developed in parallel to improve the efficiency or safety of this system. In this review, we introduce recent advances and summarize the present challenges of MSCs-DDS. We also highlight some potential technologies to improve MSCs-DDS, including nanotechnology, genome engineering technology, and biomimetic technology. Finally, prospects for application of artificially improved MSCs-DDS are addressed. The technologies summarized in this review provide a general guideline for the improvement of MSCs-DDS.
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Affiliation(s)
- Yuanqin Su
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Tianyuan Zhang
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou 310058, China
| | - Ting Huang
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Jianqing Gao
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou 310058, China; Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
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24
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Bao G. Magnetic Forces Enable Control of Biological Processes In Vivo. JOURNAL OF APPLIED MECHANICS 2021; 88:030801. [PMID: 34168385 PMCID: PMC8208485 DOI: 10.1115/1.4049331] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Revised: 11/20/2020] [Accepted: 11/21/2020] [Indexed: 05/23/2023]
Abstract
Similar to mechanical forces that can induce profound biological effects, magnetic fields can have a broad range of implications to biological systems, from magnetoreception that allows an organism to detect a magnetic field to perceive direction, altitude, or location, to the use of heating induced by magnetic field for altering neuron activity. This review focuses on the application of magnetic forces generated by magnetic iron oxide nanoparticles (MIONs), which can also provide imaging contrast and mechanical/thermal energy in response to an external magnetic field, a special feature that distinguishes MIONs from other nanomaterials. The magnetic properties of MIONs offer unique opportunities for enabling control of biological processes under different magnetic fields. Here, we describe the approaches of utilizing the forces generated by MIONs under an applied magnetic field to control biological processes and functions, including the targeting of drug molecules to a specific tissue, increasing the vessel permeability for improving drug delivery, and activating a particular viral vector for spatial control of genome editing in vivo. The opportunities of using nanomagnets for a broad range of biomedical applications are briefly discussed.
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Affiliation(s)
- Gang Bao
- Department of Bioengineering, Rice University, Houston, TX 77030
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25
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Ye D, Li M, Xie Y, Chen B, Han Y, Liu S, Wei QH, Gu N. Optical Imaging and High-Accuracy Quantification of Intracellular Iron Contents. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2021; 17:e2005474. [PMID: 33306269 DOI: 10.1002/smll.202005474] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 11/19/2020] [Indexed: 06/12/2023]
Abstract
Precise quantification of intracellular iron contents is important to biomedical applications of magnetic nanoparticles. Current approaches for iron quantification rely on specialized instruments while most only yield iron quantities averaged over plenty of cells. Here, a simple and robust approach, combining digital optical microscopy with the Beer-Lambert's law, that allows for imaging stainable iron distribution in individual cells and the quantification of stainable iron contents with an unprecedented accuracy of femtogram per pixel, is presented. It is further shown that this approach enables studying of the internalization and reduction dynamics of super-paramagnetic iron oxide nanoparticles (SPIONs) by stem cells in single cell level.
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Affiliation(s)
- Dewen Ye
- State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science & Medical Engineering, Southeast University, Nanjing, 210009, China
| | - Mingxi Li
- State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science & Medical Engineering, Southeast University, Nanjing, 210009, China
| | - Yuanyuan Xie
- Center for Clinic Stem Cell Research, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China
| | - Bo Chen
- Materials Science and Devices Institute, Suzhou University of Science and Technology, 1 Kerui Road, Suzhou, 215009, China
| | - Yuexia Han
- State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science & Medical Engineering, Southeast University, Nanjing, 210009, China
| | - Sijin Liu
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China
| | - Qi-Huo Wei
- Department of Mechanical and Energy Engineering, Southern University of Science and Technology, Shenzhen, 518055, China
- Department of Physics, Nanjing Medical University, Nanjing, 211166, China
| | - Ning Gu
- State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science & Medical Engineering, Southeast University, Nanjing, 210009, China
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Singh S, Chawla H, Chandra A, Garg S. Magnetic hybrid nanoparticles for drug delivery. MAGNETIC NANOPARTICLE-BASED HYBRID MATERIALS 2021:319-342. [DOI: 10.1016/b978-0-12-823688-8.00034-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Magnetic resonance imaging of umbilical cord stem cells labeled with superparamagnetic iron oxide nanoparticles: effects of labelling and transplantation parameters. Sci Rep 2020; 10:13684. [PMID: 32792506 PMCID: PMC7426806 DOI: 10.1038/s41598-020-70291-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Accepted: 07/28/2020] [Indexed: 12/18/2022] Open
Abstract
Cell tracking with magnetic resonance imaging (MRI) is important for evaluating the biodistribution of transplanted cells. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) have emerged as a promising therapeutic tool in regenerative medicine. We examined the UC-MSCs labeled with superparamagnetic (SPIO) and ultrasmall superparamagnetic iron oxide (USPIO) in terms of cell functioning and imaging efficiency in vitro and in vivo. The UC-MSCs were co-incubated with SPIO or USPIO at a concentration of 50 or 100 µg/mL of label. Viability and proliferation were assessed by Trypan blue dye exclusion and MTT assay, respectively. Differentiation (chondrogenesis, osteogenesis, and adipogenesis) was induced to examine the impact of labelling on stemness. For in vitro experiments, we used 7-T MRI to assess the T2 values of phantoms containing various concentrations of cell suspensions. For in vivo experiments, nine neonatal rats were divided into the control, SPIO, and USPIO groups. The UC-MSCs were injected directly into the rat brains. MRI images were obtained immediately and at 7 and 14 days post injection. The UC-MSCs were successfully labeled with SPIO and USPIO after 24 h of incubation. Cell viability was not changed by labelling. Nevertheless, labelling with 100 µg/mL USPIO led to a significant decrease in proliferation. The capacity for differentiation into cartilage was influenced by 100 µg/mL of SPIO. MRI showed that labeled cells exhibited clear hypointense signals, unlike unlabeled control cells. In the USPIO-labeled cells, a significant (P < 0.05) decrease in T2 values (= improved contrast) was observed when compared with the controls and between phantoms containing the fewest and the most cells (0.5 × 106 versus 2.0 × 106 cells/mL). In vivo, the labeled cells were discernible on T2-weighted images at days 0, 7, and 14. The presence of SPIO and USPIO particles at day 14 was confirmed by Prussian blue staining. Microscopy also suggested that the regions occupied by the particles were not as large as the corresponding hypointense areas observed on MRI. Both labels were readily taken up by the UC-MSCs and identified well on MRI. While SPIO and USPIO provide improved results in MRI studies, care must be taken while labelling cells with high concentrations of these agents.
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28
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Wang L, Xiu Y, Han B, Liu L, Niu X, Wang H. Magnetic mesoporous carbon material based electrochemical sensor for rapid detection of penicillin sodium in milk. J Food Sci 2020; 85:2435-2442. [PMID: 32645209 DOI: 10.1111/1750-3841.15328] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Revised: 05/11/2020] [Accepted: 05/20/2020] [Indexed: 11/28/2022]
Abstract
In recent years, to increase growth rate and prevent infectious diseases, an excessive use of antibiotics in livestock breeding processes has resulted in the presence of antibiotic residues in animal foods. In this experiment, a new kind of electrochemical sensor is prepared based on magnetic mesoporous hollow carbon microspheres (MHM) as a penicillinase (Pen X) adsorption carrier to rapidly detect penicillin sodium (Pen G), named Pen X/MHM/MGCE. The MHM-adsorbed penicillinase can be separated from the solution by magnetic attraction and fixed on a magnetic glassy carbon electrode by physical adsorption, which is easy to operate and avoids the interference of a crosslinking agent at the active site of the enzyme. A differential pulse voltammetry (DPV) method is used to immerse the working electrode in test samples containing different concentrations of penicillin sodium solution with 0.5 mg/mL oxidized hematoxylin. According to the quantitative relationship between the current value and the concentration of penicillin sodium, the concentration of penicillin sodium in the tested samples can be determined. The detection range of the sensor is 10-8 to 10-2 mg/mL, the linear relationship is good (R2 = 0.9983), and the detection limit (LOD) is 2.655 × 10-7 mg/mL (S/N = 3). The detection of penicillin sodium in milk using a standard addition method shows good recovery. Furthermore, the proposed method has the advantages of a wide detection range, good enzyme immobilization capacity, good precision and stability, convenient cleaning, and recycling of solid materials. Thus, it can successfully achieve rapid detection in milk samples. PRACTICAL APPLICATION: The sensor provides a low detection limit and high recovery rate of electrode material; therefore, the sensor can realize the rapid and quantitative detection of penicillin sodium in milk.
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Affiliation(s)
- Li Wang
- College of Food Science and Engineering, Jilin University, Changchun, 130062, P. R. China
| | - Yi Xiu
- College of Food Science and Engineering, Jilin University, Changchun, 130062, P. R. China
| | - Baoqing Han
- College of Food Science and Engineering, Jilin University, Changchun, 130062, P. R. China
| | - Lu Liu
- College of Food Science and Engineering, Jilin University, Changchun, 130062, P. R. China
| | - Xiaodi Niu
- College of Food Science and Engineering, Jilin University, Changchun, 130062, P. R. China
| | - Hongsu Wang
- College of Food Science and Engineering, Jilin University, Changchun, 130062, P. R. China
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Yasa IC, Ceylan H, Bozuyuk U, Wild AM, Sitti M. Elucidating the interaction dynamics between microswimmer body and immune system for medical microrobots. Sci Robot 2020; 5:5/43/eaaz3867. [DOI: 10.1126/scirobotics.aaz3867] [Citation(s) in RCA: 71] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Revised: 01/19/2020] [Accepted: 05/13/2020] [Indexed: 12/20/2022]
Abstract
The structural design parameters of a medical microrobot, such as the morphology and surface chemistry, should aim to minimize any physical interactions with the cells of the immune system. However, the same surface-borne design parameters are also critical for the locomotion performance of the microrobots. Understanding the interplay of such parameters targeting high locomotion performance and low immunogenicity at the same time is of paramount importance yet has so far been overlooked. Here, we investigated the interactions of magnetically steerable double-helical microswimmers with mouse macrophage cell lines and splenocytes, freshly harvested from mouse spleens, by systematically changing their helical morphology. We found that the macrophages and splenocytes can recognize and differentially elicit an immune response to helix turn numbers of the microswimmers that otherwise have the same size, bulk physical properties, and surface chemistries. Our findings suggest that the structural optimization of medical microrobots for the locomotion performance and interactions with the immune cells should be considered simultaneously because they are highly entangled and can demand a substantial design compromise from one another. Furthermore, we show that morphology-dependent interactions between macrophages and microswimmers can further present engineering opportunities for biohybrid microrobot designs. We demonstrate immunobots that can combine the steerable mobility of synthetic microswimmers and the immunoregulatory capability of macrophages for potential targeted immunotherapeutic applications.
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Affiliation(s)
- Immihan Ceren Yasa
- Physical Intelligence Department, Max Planck Institute for Intelligent Systems, 70569 Stuttgart, Germany
| | - Hakan Ceylan
- Physical Intelligence Department, Max Planck Institute for Intelligent Systems, 70569 Stuttgart, Germany
| | - Ugur Bozuyuk
- Physical Intelligence Department, Max Planck Institute for Intelligent Systems, 70569 Stuttgart, Germany
| | - Anna-Maria Wild
- Physical Intelligence Department, Max Planck Institute for Intelligent Systems, 70569 Stuttgart, Germany
| | - Metin Sitti
- Physical Intelligence Department, Max Planck Institute for Intelligent Systems, 70569 Stuttgart, Germany
- School of Medicine and School of Engineering, Koç University, 34450 Istanbul, Turkey
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Abstract
Magnetic targeting (MT) has been an emerging technology which is used to improve the delivery and retention of transplanted therapeutic cells in target site over the past 20 years. Meanwhile, stem cells have also been a research hotspot in cell therapy in recent years. Several researchers have combined the MT technology with Stem cell therapy in order to improve the efficacy. However, Different types of Magnetic Nano particles (MNPs) have presented different effects, and how to choose a proper MNPs became a question. This article aims to introduce the preparation method and application field of different types of magnetic Nanoparticles, discuss the pros and cons of different types of MNPs in stem cell therapy and make a prospect of MT technology in Stem cell therapy.
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Labusca L, Herea DD, Danceanu CM, Minuti AE, Stavila C, Grigoras M, Gherca D, Stoian G, Ababei G, Chiriac H, Lupu N. The effect of magnetic field exposure on differentiation of magnetite nanoparticle-loaded adipose-derived stem cells. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2020; 109:110652. [PMID: 32228923 DOI: 10.1016/j.msec.2020.110652] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Revised: 08/26/2019] [Accepted: 01/03/2020] [Indexed: 02/07/2023]
Abstract
Magnetic nanoparticles (MNPs) are versatile tools for various applications in biotechnology and nanomedicine. MNPs-mediated cell tracking, targeting and imaging are increasingly studied for regenerative medicine applications in cell therapy and tissue engineering. Mechanical stimulation influences mesenchymal stem cell differentiation. Here we show that MNPs-mediated magneto-mechanical stimulation of human primary adipose derived stem cells (ADSCs) exposed to variable magnetic field (MF) influences their adipogenic and osteogenic differentiation. ADSCs loaded with biocompatible magnetite nanoparticles of 6.6 nm, and with an average load of 21 picograms iron/cell were exposed to variable low intensity (0.5 mT - LMF) and higher intensity magnetic fields (14.7 and 21.6 mT - HMF). Type, duration, intensity and frequency of MF differently affect differentiation. Short time (2 days) intermittent exposure to LMF increases adipogenesis while longer (7 days) intermittent as well as continuous exposure favors osteogenesis. HMF (21.6 mT) short time intermittent exposure favors osteogenesis. Different exposure protocols can be used to increase differentiation dependently on expected results. Magnetic remotely-actuated MNPs up-taken by ADSCs promotes the shift towards osteoblastic lineage. ADSCs-MNPs under MF exposure could be used for enabling osteoblastic conversion during cell therapy for systemic osteoporosis. Current results enable further in vivo studies investigating the role of remotely-controlled magnetically actuated ADSCs-MNPs for the treatment of osteoporosis.
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Affiliation(s)
- Luminita Labusca
- National Institute of Research and Development for Technical Physics, 47 Mangeron Blvd., 700050, Iasi, Romania
| | - Dumitru-Daniel Herea
- National Institute of Research and Development for Technical Physics, 47 Mangeron Blvd., 700050, Iasi, Romania.
| | - Camelia-Mihaela Danceanu
- National Institute of Research and Development for Technical Physics, 47 Mangeron Blvd., 700050, Iasi, Romania; University "Al. I. Cuza", 11 Carol I Boulevard, 700506, Iasi, Romania
| | - Anca Emanuela Minuti
- National Institute of Research and Development for Technical Physics, 47 Mangeron Blvd., 700050, Iasi, Romania; University "Al. I. Cuza", 11 Carol I Boulevard, 700506, Iasi, Romania
| | - Cristina Stavila
- National Institute of Research and Development for Technical Physics, 47 Mangeron Blvd., 700050, Iasi, Romania; University "Al. I. Cuza", 11 Carol I Boulevard, 700506, Iasi, Romania
| | - Marian Grigoras
- National Institute of Research and Development for Technical Physics, 47 Mangeron Blvd., 700050, Iasi, Romania
| | - Daniel Gherca
- National Institute of Research and Development for Technical Physics, 47 Mangeron Blvd., 700050, Iasi, Romania
| | - George Stoian
- National Institute of Research and Development for Technical Physics, 47 Mangeron Blvd., 700050, Iasi, Romania
| | - Gabriel Ababei
- National Institute of Research and Development for Technical Physics, 47 Mangeron Blvd., 700050, Iasi, Romania
| | - Horia Chiriac
- National Institute of Research and Development for Technical Physics, 47 Mangeron Blvd., 700050, Iasi, Romania
| | - Nicoleta Lupu
- National Institute of Research and Development for Technical Physics, 47 Mangeron Blvd., 700050, Iasi, Romania
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Moayeri A, Darvishi M, Amraei M. Homing of Super Paramagnetic Iron Oxide Nanoparticles (SPIONs) Labeled Adipose-Derived Stem Cells by Magnetic Attraction in a Rat Model of Parkinson's Disease. Int J Nanomedicine 2020; 15:1297-1308. [PMID: 32161459 PMCID: PMC7049746 DOI: 10.2147/ijn.s238266] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Accepted: 02/07/2020] [Indexed: 12/11/2022] Open
Abstract
Introduction Stem cell therapies for neurodegenerative diseases such as Parkinson’s disease (PD) are intended to replace lost dopaminergic neurons. The basis of this treatment is to guide the migration of transplanted cells into the target tissue or injury site. The aim of this study is an evaluation of the homing of superparamagnetic iron oxide nanoparticles (SPIONs) labeled adipose-derived stem cells (ADSC) by an external magnetic field in a rat model of PD. Methods ADSCs were obtained from perinephric regions of male adult rats and cultured in a DMEM medium. ADSC markers were assessed by immunostaining with CD90, CD105, CD49d, and CD45. The SPION was coated using poly-L-lysine hydrobromide and transfection was determined in rat ADSC using the GFP reporter gene. For this in vivo study, rats with PD were divided into five groups: a positive control group, a control group with PD (lesion with 6-HD injection), and three treatment groups: the PD/ADSC group (PD transplant with ADSCs transfected by BrdU), PD/ADSC/SPION group (PD transplant with ADSCs labeled with SPION and transfected by GFP), and the PD/ADSC/SPION/EM group (PD transplant with ADSCs labeled with SPION and transfected by GFP induced with external magnet). Results ADSCs were immunoreactive to fat markers CD90 (90.73±1.7), CD105 (87.4±2.9) and CD49d (79.6±2.6), with negative immunostaining at the hematopoietic stem cell marker (CD45: 1.4±0.4). The efficiency of cells with SPION/PLL was about 96% of ADSC. The highest number of GFP-positive cells was in the ADSC/SPION/EM group (54.5±1.3), which was significantly different from that in ADSC/SPION group (30.83±3 and P<0.01). Conclusion Transfection of ADSC by SPION/PLL is an appropriate protocol for cell therapy. External magnets can be used for the delivery and homing of transplanted stem cells in the target tissue.
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Affiliation(s)
- Ardeshir Moayeri
- Department of Anatomy, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran
| | - Marzieh Darvishi
- Department of Anatomy, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran.,Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran
| | - Mansour Amraei
- Department of Physiology, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran
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Hour FQ, Moghadam AJ, Shakeri-Zadeh A, Bakhtiyari M, Shabani R, Mehdizadeh M. Magnetic targeted delivery of the SPIONs-labeled mesenchymal stem cells derived from human Wharton's jelly in Alzheimer's rat models. J Control Release 2020; 321:430-441. [PMID: 32097673 DOI: 10.1016/j.jconrel.2020.02.035] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Revised: 02/16/2020] [Accepted: 02/21/2020] [Indexed: 12/29/2022]
Abstract
Alzheimer's disease (AD) as a progressive neurodegenerative disorder is one of the leading causes of death globally. Among all treatment approaches, mesenchymal stem cells (MSCs)-based therapy is a promising modality for neurological disorders including the AD. This study aimed to magnetically deliver human Wharton's jelly-derived MSCs (WJ-MSCs) toward the hippocampal area within the AD rat's brain and determine the effects of them in cognitive improvement. Rats were randomly divided into five groups as follow: vehicle-treated control, AD model (injection of 8 μg/kg of amyloid β 1-42), IV-NTC (treated with IV-injected Non-Targeted Cells), IV-TC (treated with IV-injected Targeted Cells), and ICV-NTC (treated with Intracerebroventricular-injected Non-Targeted Cells). WJ-MSCs were labeled with dextran-coated superparamagnetic iron oxide nanoparticles (dex-SPIONs, 50 μg/ml), by bio-mimicry method. SPIONs-labeled MSCs were highly prussian blue positive with an intracellular iron concentration of 2.9 ± 0.08 pg/cell, which were successfully targeted into the hippocampus of AD rats by a halbach magnet array as magnetic targeted cell delivery (MTCD) technique. Presence of SPIONs-labeled cells in hippocampal area was proved by magnetic resonance imaging (MRI) in which signal intensity was reduced by increasing the number of these cells. Behavioral examinations showed that WJ-MSCs caused memory and cognitive improvement. Also, histological assessments showed functional improvement of hippocampal cells by expression of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE). Overall, this study indicates MTCD approach as an alternative in MSC-based regenerative medicine because it approximately has the same results as invasive directly ICV-injection method has.
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Affiliation(s)
- Farshid Qiyami Hour
- Department of Anatomical Sciences, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Amir Johari Moghadam
- Department of Anatomical Sciences, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Ali Shakeri-Zadeh
- Medical Physics Department, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mehrdad Bakhtiyari
- Department of Anatomical Sciences, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Ronak Shabani
- Department of Anatomical Sciences, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.
| | - Mehdi Mehdizadeh
- Department of Anatomical Sciences, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.
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Zhang B, Mo X, Yu F, Ma Y, Yan F. Ultrasound monitoring of magnet-guided delivery of mesenchymal stem cells labeled with magnetic lipid–polymer hybrid nanobubbles. Biomater Sci 2020; 8:3628-3639. [PMID: 32529995 DOI: 10.1039/d0bm00473a] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Mesenchymal stem cells labeled with positively charged magnetic lipid–polymer hybrid nanobubbles could be tracked for magnet-guided delivery onto the site of an injured artery using ultrasound.
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Affiliation(s)
- Bo Zhang
- Department of Ultrasound in Medicine
- Shanghai East Hospital
- Tongji University School of Medicine
- Shanghai
- China
| | - Xinhai Mo
- Department of Ultrasound in Medicine
- Shanghai East Hospital
- Tongji University School of Medicine
- Shanghai
- China
| | - Fei Yu
- Department of Ultrasound in Medicine
- Shanghai East Hospital
- Tongji University School of Medicine
- Shanghai
- China
| | - Yuqin Ma
- Department of Ultrasound
- Shenzhen Second People's Hospital
- The First Affiliated Hospital of Shenzhen University
- Shenzhen
- China
| | - Fei Yan
- CAS Key Laboratory of Quantitative Engineering Biology
- Shenzhen Institute of Synthetic Biology
- Shenzhen Institutes of Advanced Technology
- Chinese Academy of Sciences
- Shenzhen
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Bio-application of Inorganic Nanomaterials in Tissue Engineering. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020; 1249:115-130. [PMID: 32602094 DOI: 10.1007/978-981-15-3258-0_8] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Inorganic nanomaterials or nanoparticles (INPs) have drawn high attention for their usage in the biomedical field. In addition to the facile synthetic and modifiable property of INPs, INPs have various unique properties that originate from the components of the INPs, such as metal ions that are essential for the human body. Apart from their roles as components of the human body, inorganic materials have unique properties, such as magnetic, antibacterial, and piezoelectric, so that INPs have been widely used as either carriers or inducers. However, most of the bio-applicable INPs, especially those consisting of metal, can cause cytotoxicity. Therefore, INPs require modification to alleviate the harmful effect toward the cells by controlling the release of metal ions from INPs. Even though many attempts have been made to modify INPs, many things, including the side effects of INPs, still remain as obstacles in the bio-application, which need to be elucidated. In this chapter, we introduce novel INPs in terms of their synthetic method and bio-application in tissue engineering.
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Tong S, Zhu H, Bao G. Magnetic Iron Oxide Nanoparticles for Disease Detection and Therapy. MATERIALS TODAY (KIDLINGTON, ENGLAND) 2019; 31:86-99. [PMID: 32831620 PMCID: PMC7441585 DOI: 10.1016/j.mattod.2019.06.003] [Citation(s) in RCA: 101] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/20/2023]
Abstract
Magnetic iron oxide nanoparticles (MIONs) are among the first generation of nanomaterials that have advanced to clinic use. A broad range of biomedical techniques has been developed by combining the versatile nanomagnetism of MIONs with various forms of applied magnetic fields. MIONs can generate imaging contrast and provide mechanical/thermal energy in vivo in response to an external magnetic field, a special feature that distinguishes MIONs from other nanomaterials. These properties offer unique opportunities for nanomaterials engineering in biomedical research and clinical interventions. The past few decades have witnessed the evolution of the applications of MIONs from conventional drug delivery and hyperthermia to the regulation of molecular and cellular processes in the body. Here we review the most recent development in this field, including clinical studies of MIONs and the emerging techniques that may contribute to future innovation in medicine.
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Affiliation(s)
- Sheng Tong
- Department of Bioengineering, Rice University, Houston, Texas 77030, USA
| | - Haibao Zhu
- Department of Bioengineering, Rice University, Houston, Texas 77030, USA
| | - Gang Bao
- Department of Bioengineering, Rice University, Houston, Texas 77030, USA
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Sanz-Ortega L, Rojas JM, Portilla Y, Pérez-Yagüe S, Barber DF. Magnetic Nanoparticles Attached to the NK Cell Surface for Tumor Targeting in Adoptive Transfer Therapies Does Not Affect Cellular Effector Functions. Front Immunol 2019; 10:2073. [PMID: 31543880 PMCID: PMC6728794 DOI: 10.3389/fimmu.2019.02073] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2019] [Accepted: 08/16/2019] [Indexed: 02/05/2023] Open
Abstract
Adoptive cell transfer therapy is currently one of the most promising approaches for cancer treatment. This therapy has some limitations, however, such as the dispersion of in vivo-administered cells, causing only a small proportion to reach the tumor. Nanotechnological approaches could offer a solution for this drawback, as they can increase cell retention and accumulation in a region of interest. In particular, strategies employing magnetic nanoparticles (MNPs) to improve targeting of adoptively transferred T or NK cells have been explored in mice. In vivo magnetic retention is reported using the human NK cell line NK-92MI transfected with MNPs. Primary NK cells are nonetheless highly resistant to transfection, and thus we explore in here the possibility of attaching the MNPs to the NK cell surface to overcome this issue, and examine whether this association would affect NK effector functions. We assessed the attachment of MNPs coated with different polymers to the NK cell surface, and found that APS-MNP attached more efficiently to the NK-92MI cell surface. In association with MNPs, these cells preserved their main functions, exhibiting a continued capacity to degranulate, conjugate with and lyse target cells, produce IFN-γ, and respond to chemotactic signals. MNP-loaded NK-92MI cells were also retained in an in vitro capillary flow system by applying an EMF. A similar analysis was carried out in primary NK cells, isolated from mice, and expanded in vitro. These primary murine NK cells also maintained their functionality intact after MNP treatment and were successfully retained in vitro. This work therefore provides further support for using MNPs in combination with EMFs to favor specific retention of functional NK cells in a region of interest, which may prove beneficial to adoptive cell-therapy protocols.
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Affiliation(s)
- Laura Sanz-Ortega
- Department of Immunology and Oncology, and NanoBiomedicine Initiative, Centro Nacional de Biotecnología (CNB)-CSIC, Madrid, Spain
| | - José M Rojas
- Department of Immunology and Oncology, and NanoBiomedicine Initiative, Centro Nacional de Biotecnología (CNB)-CSIC, Madrid, Spain
| | - Yadileiny Portilla
- Department of Immunology and Oncology, and NanoBiomedicine Initiative, Centro Nacional de Biotecnología (CNB)-CSIC, Madrid, Spain
| | - Sonia Pérez-Yagüe
- Department of Immunology and Oncology, and NanoBiomedicine Initiative, Centro Nacional de Biotecnología (CNB)-CSIC, Madrid, Spain
| | - Domingo F Barber
- Department of Immunology and Oncology, and NanoBiomedicine Initiative, Centro Nacional de Biotecnología (CNB)-CSIC, Madrid, Spain
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Xia Y, Zhao Y, Zhang F, Chen B, Hu X, Weir MD, Schneider A, Jia L, Gu N, Xu HHK. Iron oxide nanoparticles in liquid or powder form enhanced osteogenesis via stem cells on injectable calcium phosphate scaffold. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 2019; 21:102069. [PMID: 31351236 DOI: 10.1016/j.nano.2019.102069] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/09/2019] [Revised: 07/09/2019] [Accepted: 07/15/2019] [Indexed: 01/14/2023]
Abstract
The objectives of this study were to incorporate iron oxide nanoparticles (IONPs) into calcium phosphate cement (CPC) to enhance bone engineering, and to investigate the effects of IONPs as a liquid or powder on stem cells using IONP-CPC scaffold for the first time. IONP-CPCs were prepared by adding 1% IONPs as liquid or powder. Human dental pulp stem cells (hDPSCs) were seeded. Subcutaneous implantation in mice was investigated. IONP-CPCs had better cell spreading, and greater ALP activity and bone mineral synthesis, than CPC control. Subcutaneous implantation for 6 weeks showed good biocompatibility for all groups. In conclusion, incorporating IONPs in liquid or powder form both substantially enhanced hDPSCs on IONP-CPC scaffold and exhibited excellent biocompatibility. IONP incorporation as a liquid was better than IONP powder in promoting osteogenic differentiation of hDPSCs. Incorporating IONPs and chitosan lactate together in CPC enhanced osteogenesis of hDPSCs more than using either alone.
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Affiliation(s)
- Yang Xia
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China; Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China; Department of Advanced Oral Sciences & Therapeutics, University of Maryland School of Dentistry, Baltimore, USA
| | - Yantao Zhao
- Beijing Engineering Research Center of Orthopaedic Implants, Fourth Medical Center of CPLA General Hospital, Beijing, 100048 China
| | - Feimin Zhang
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China; Collaborative Innovation Center of Suzhou Nano Science and Technology, Suzhou, China
| | - Bo Chen
- Materials Science and Devices Institute, Suzhou University of Science and Technology, Suzhou, China
| | - Xiantong Hu
- Beijing Engineering Research Center of Orthopaedic Implants, Fourth Medical Center of CPLA General Hospital, Beijing, 100048 China
| | - Michael D Weir
- Department of Advanced Oral Sciences & Therapeutics, University of Maryland School of Dentistry, Baltimore, USA
| | - Abraham Schneider
- Department of Oncology and Diagnostic Sciences, University of Maryland School of Dentistry, Baltimore, USA
| | - Lu Jia
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China
| | - Ning Gu
- Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China; Collaborative Innovation Center of Suzhou Nano Science and Technology, Suzhou, China.
| | - Hockin H K Xu
- Department of Advanced Oral Sciences & Therapeutics, University of Maryland School of Dentistry, Baltimore, USA; Center for Stem Cell Biology and Regenerative Medicine, University of Maryland School of Medicine, Baltimore, USA; University of Maryland Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, USA.
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Ahn YJ, Kong TH, Choi JS, Yun WS, Key J, Seo YJ. Strategies to enhance efficacy of SPION-labeled stem cell homing by magnetic attraction: a systemic review with meta-analysis. Int J Nanomedicine 2019; 14:4849-4866. [PMID: 31308662 PMCID: PMC6613362 DOI: 10.2147/ijn.s204910] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2019] [Accepted: 05/14/2019] [Indexed: 12/13/2022] Open
Abstract
Stem cells possess a promising potential in the clinical field. The application and effective delivery of stem cells to the desired target organ or site of injury plays an important role. This review describes strategies on understanding the effective delivery of stem cells labeled with superparamagnetic iron oxide nanoparticles (SPION) using an external magnet to enhance stem cell migration in vivo and in vitro. Fourteen total publications among 174 articles were selected. Stem cell type, SPION characteristics, labeling time, and magnetic force in vivo are considered important factors affecting the effective delivery of stem cells to the homing site. Most papers reported that the efficiency was increased when magnet is applied compared to those without. Ten studies analyzed the homing competency of SPION-labeled MSCs in vitro by observing the migration of the cell toward the external magnet. In cell-based experiments, the mechanism of magnetic attraction, the kind of nanoparticles, and various stem cells were studied well. Meta-analysis has shown the mean size of nanoparticles and degree of recovery or regeneration of damaged target organs upon in vivo studies. This strategy may provide a guideline for designing studies involving stem cell homing and further expand stem cell.
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Affiliation(s)
- Ye Ji Ahn
- Research Institute of Hearing Enhancement, Yonsei University Wonju College of Medicine, Wonju, South Korea.,Department of Otorhinolaryngology, Yonsei University Wonju College of Medicine, Wonju, South Korea
| | - Tae Hoon Kong
- Research Institute of Hearing Enhancement, Yonsei University Wonju College of Medicine, Wonju, South Korea.,Department of Otorhinolaryngology, Yonsei University Wonju College of Medicine, Wonju, South Korea
| | - Jin Sil Choi
- Research Institute of Hearing Enhancement, Yonsei University Wonju College of Medicine, Wonju, South Korea.,Department of Otorhinolaryngology, Yonsei University Wonju College of Medicine, Wonju, South Korea
| | - Wan Su Yun
- Department of Biomedical Engineering, Yonsei University, Wonju, South Korea
| | - Jaehong Key
- Department of Biomedical Engineering, Yonsei University, Wonju, South Korea
| | - Young Joon Seo
- Research Institute of Hearing Enhancement, Yonsei University Wonju College of Medicine, Wonju, South Korea.,Department of Otorhinolaryngology, Yonsei University Wonju College of Medicine, Wonju, South Korea
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Shin JE, Han J, Lim JH, Eun HS, Park KI. Human Neural Stem Cells: Translational Research for Neonatal Hypoxic-Ischemic Brain Injury. NEONATAL MEDICINE 2019. [DOI: 10.5385/nm.2019.26.1.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
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41
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Biosynthesis of magnetic nanoparticles from nano-degradation products revealed in human stem cells. Proc Natl Acad Sci U S A 2019; 116:4044-4053. [PMID: 30760598 DOI: 10.1073/pnas.1816792116] [Citation(s) in RCA: 73] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
While magnetic nanoparticles offer exciting possibilities for stem cell imaging or tissue bioengineering, their long-term intracellular fate remains to be fully documented. Besides, it appears that magnetic nanoparticles can occur naturally in human cells, but their origin and potentially endogenous synthesis still need further understanding. In an effort to explore the life cycle of magnetic nanoparticles, we investigated their transformations upon internalization in mesenchymal stem cells and as a function of the cells' differentiation status (undifferentiated, or undergoing adipogenesis, osteogenesis, and chondrogenesis). Using magnetism as a fingerprint of the transformation process, we evidenced an important degradation of the nanoparticles during chondrogenesis. For the other pathways, stem cells were remarkably "remagnetized" after degradation of nanoparticles. This remagnetization phenomenon is the direct demonstration of a possible neosynthesis of magnetic nanoparticles in cellulo and could lay some foundation to understand the presence of magnetic crystals in human cells. The neosynthesis was shown to take place within the endosomes and to involve the H-subunit of ferritin. Moreover, it appeared to be the key process to avoid long-term cytotoxicity (impact on differentiation) related to high doses of magnetic nanoparticles within stem cells.
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42
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Harrison RP, Chauhan VM, Onion D, Aylott JW, Sottile V. Intracellular processing of silica-coated superparamagnetic iron nanoparticles in human mesenchymal stem cells. RSC Adv 2019; 9:3176-3184. [PMID: 30774937 PMCID: PMC6350623 DOI: 10.1039/c8ra09089k] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2018] [Accepted: 12/21/2018] [Indexed: 01/28/2023] Open
Abstract
Silica-coated superparamagnetic iron nanoparticles (SiMAGs) are an exciting biomedical technology capable of targeted delivery of cell-based therapeutics and disease diagnosis. However, in order to realise their full clinical potential, their intracellular fate must be determined. The analytical techniques of super-resolution fluorescence microscopy, particle counting flow cytometry and pH-sensitive nanosensors were applied to elucidate mechanisms of intracellular SiMAG processing in human mesenchymal stem cell (hMSCs). Super-resolution microscopy showed SiMAG fluorescently-tagged nanoparticles are endocytosed and co-localised within lysosomes. When exposed to simulated lysosomal conditions SiMAGs were solubilised and exhibited diminishing fluorescence emission over 7 days. The in vitro intracellular metabolism of SiMAGs was monitored in hMSCs using flow cytometry and co-localised pH-sensitive nanosensors. A decrease in SiMAG fluorescence emission, which corresponded to a decrease in lysosomal pH was observed, mirroring ex vivo observations, suggesting SiMAG lysosomal exposure degrades fluorescent silica-coatings and iron cores. These findings indicate although there is a significant decrease in intracellular SiMAG loading, sufficient particles remain internalised (>50%) to render SiMAG treated cells amenable to long-term magnetic cell manipulation. Our analytical approach provides important insights into the understanding of the intracellular fate of SiMAG processing, which could be readily applied to other particle therapeutics, to advance their clinical translation.
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Affiliation(s)
- Richard P Harrison
- Wolfson Centre for Stem Cells, Tissue Engineering and Modelling (STEM), School of Medicine, Nottingham, NG7 2RD, UK. .,Centre for Biological Engineering, Loughborough University, Leicestershire LE11 3TU, UK
| | - Veeren M Chauhan
- School of Pharmacy, University of Nottingham, Boots Sciences Building, University Park, Nottingham, NG7 2RD, UK. ;
| | - David Onion
- University of Nottingham Flow Cytometry Facility, School of Life Sciences, University of Nottingham, NG7 2UH, UK
| | - Jonathan W Aylott
- School of Pharmacy, University of Nottingham, Boots Sciences Building, University Park, Nottingham, NG7 2RD, UK. ;
| | - Virginie Sottile
- Wolfson Centre for Stem Cells, Tissue Engineering and Modelling (STEM), School of Medicine, Nottingham, NG7 2RD, UK.
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43
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Sanz-Ortega L, Rojas JM, Marcos A, Portilla Y, Stein JV, Barber DF. T cells loaded with magnetic nanoparticles are retained in peripheral lymph nodes by the application of a magnetic field. J Nanobiotechnology 2019; 17:14. [PMID: 30670029 PMCID: PMC6341614 DOI: 10.1186/s12951-019-0440-z] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2018] [Accepted: 01/03/2019] [Indexed: 01/07/2023] Open
Abstract
Background T lymphocytes are highly dynamic elements of the immune system with a tightly regulated migration. T cell-based transfer therapies are promising therapeutic approaches which in vivo efficacy is often limited by the small proportion of administered cells that reaches the region of interest. Manipulating T cell localisation to improve specific targeting will increase the effectiveness of these therapies. Nanotechnology has been successfully used for localized release of drugs and biomolecules. In particular, magnetic nanoparticles (MNPs) loaded with biomolecules can be specifically targeted to a location by an external magnetic field (EMF). The present work studies whether MNP-loaded T cells could be targeted and retained in vitro and in vivo at a site of interest with an EMF. Results T cells were unable to internalize the different MNPs used in this study, which remained in close association with the cell membrane. T cells loaded with an appropriate MNP concentration were attracted to an EMF and retained in an in vitro capillary flow-system. MNP-loaded T cells were also magnetically retained in the lymph nodes after adoptive transfer in in vivo models. This enhanced in vivo retention was in part due to the EMF application and to a reduced circulating cell speed within the organ. This combined use of MNPs and EMFs did not alter T cell viability or function. Conclusions These studies reveal a promising approach to favour cell retention that could be implemented to improve cell-based therapy.![]() Electronic supplementary material The online version of this article (10.1186/s12951-019-0440-z) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Laura Sanz-Ortega
- Department of Immunology and Oncology, and NanoBiomedicine Initiative, Centro Nacional de Biotecnología (CNB)-CSIC, Darwin 3, Cantoblanco, 28049, Madrid, Spain
| | - José M Rojas
- Department of Immunology and Oncology, and NanoBiomedicine Initiative, Centro Nacional de Biotecnología (CNB)-CSIC, Darwin 3, Cantoblanco, 28049, Madrid, Spain.,Animal Health Research Centre (CISA)-INIA, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Valdeolmos, 28130, Madrid, Spain
| | - Ana Marcos
- Theodor Kocher Institute, University of Bern, 3012, Bern, Switzerland.,Section of Medicine, Department of Oncology, Microbiology and Immunology, University of Fribourg, 1700, Fribourg, Switzerland
| | - Yadileiny Portilla
- Department of Immunology and Oncology, and NanoBiomedicine Initiative, Centro Nacional de Biotecnología (CNB)-CSIC, Darwin 3, Cantoblanco, 28049, Madrid, Spain
| | - Jens V Stein
- Theodor Kocher Institute, University of Bern, 3012, Bern, Switzerland.,Section of Medicine, Department of Oncology, Microbiology and Immunology, University of Fribourg, 1700, Fribourg, Switzerland
| | - Domingo F Barber
- Department of Immunology and Oncology, and NanoBiomedicine Initiative, Centro Nacional de Biotecnología (CNB)-CSIC, Darwin 3, Cantoblanco, 28049, Madrid, Spain.
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Kouroupis D, Sanjurjo-Rodriguez C, Jones E, Correa D. Mesenchymal Stem Cell Functionalization for Enhanced Therapeutic Applications. TISSUE ENGINEERING PART B-REVIEWS 2018; 25:55-77. [PMID: 30165783 DOI: 10.1089/ten.teb.2018.0118] [Citation(s) in RCA: 68] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
IMPACT STATEMENT Culture expansion of MSCs has detrimental effects on various cell characteristics and attributes (e.g., phenotypic changes and senescence), which, in addition to inherent interdonor variability, negatively impact the standardization and reproducibility of their therapeutic potential. The identification of innate distinct functional MSC subpopulations, as well as the description of ex vivo protocols aimed at maintaining phenotypes and enhancing specific functions have the potential to overcome these limitations. The incorporation of those approaches into cell-based therapy would significantly impact the field, as more reproducible clinical outcomes may be achieved.
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Affiliation(s)
- Dimitrios Kouroupis
- 1 Department of Orthopedics, UHealth Sports Medicine Institute, University of Miami Miller School of Medicine, Miami, Florida.,2 Diabetes Research Institute & Cell Transplant Center, University of Miami Miller School of Medicine, Miami, Florida
| | - Clara Sanjurjo-Rodriguez
- 3 Leeds Institute of Rheumatic and Musculoskeletal Disease, Saint James University Hospital, University of Leeds, Leeds, United Kingdom.,4 Department of Biomedical Sciences, Medicine and Physiotherapy, University of A Coruña, CIBER-BBN-Institute of Biomedical Research of A Coruña (INIBIC), A Coruña, Spain
| | - Elena Jones
- 3 Leeds Institute of Rheumatic and Musculoskeletal Disease, Saint James University Hospital, University of Leeds, Leeds, United Kingdom
| | - Diego Correa
- 1 Department of Orthopedics, UHealth Sports Medicine Institute, University of Miami Miller School of Medicine, Miami, Florida.,2 Diabetes Research Institute & Cell Transplant Center, University of Miami Miller School of Medicine, Miami, Florida
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Harrison R, Lugo Leija HA, Strohbuecker S, Crutchley J, Marsh S, Denning C, El Haj A, Sottile V. Development and validation of broad-spectrum magnetic particle labelling processes for cell therapy manufacturing. Stem Cell Res Ther 2018; 9:248. [PMID: 30257709 PMCID: PMC6158868 DOI: 10.1186/s13287-018-0968-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Revised: 07/26/2018] [Accepted: 08/02/2018] [Indexed: 12/20/2022] Open
Abstract
Background Stem cells are increasingly seen as a solution for many health challenges for an ageing population. However, their potential benefits in the clinic are currently curtailed by technical challenges such as high cell dose requirements and point of care delivery, which pose sourcing and logistics challenges. Cell manufacturing solutions are currently in development to address the supply issue, and ancillary technologies such as nanoparticle-based labelling are being developed to improve stem cell delivery and enable post-treatment follow-up. Methods The application of magnetic particle (MP) labelling to potentially scalable cell manufacturing processes was investigated in a range of therapeutically relevant cells, including mesenchymal stromal cells (MSC), cardiomyocytes (CMC) and neural progenitor cells (ReN). The efficiency and the biological effect of particle labelling were analysed using fluorescent imaging and cellular assays. Results Flow cytometry and fluorescent microscopy confirmed efficient labelling of monolayer cultures. Viability was shown to be retained post labelling for all three cell types. MSC and CMC demonstrated higher tolerance to MP doses up to 100× the standard concentration. This approach was also successful for MP labelling of suspension cultures, demonstrating efficient MP uptake within 3 h, while cell viability was unaffected by this suspension labelling process. Furthermore, a procedure to enable the storing of MP-labelled cell populations to facilitate cold chain transport to the site of clinical use was investigated. When MP-labelled cells were stored in hypothermic conditions using HypoThermosol solution for 24 h, cell viability and differentiation potential were retained post storage for ReN, MSC and beating CMC. Conclusions Our results show that a generic MP labelling strategy was successfully developed for a range of clinically relevant cell populations, in both monolayer and suspension cultures. MP-labelled cell populations were able to undergo transient low-temperature storage whilst maintaining functional capacity in vitro. These results suggest that this MP labelling approach can be integrated into cell manufacturing and cold chain transport processes required for future cell therapy approaches. Electronic supplementary material The online version of this article (10.1186/s13287-018-0968-0) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Richard Harrison
- Wolfson Centre for Stem Cells, Tissue Engineering and Modelling (STEM), School of Medicine, The University of Nottingham, Nottingham, NG7 2RD, UK
| | - Hilda Anaid Lugo Leija
- Wolfson Centre for Stem Cells, Tissue Engineering and Modelling (STEM), School of Medicine, The University of Nottingham, Nottingham, NG7 2RD, UK
| | - Stephanie Strohbuecker
- Wolfson Centre for Stem Cells, Tissue Engineering and Modelling (STEM), School of Medicine, The University of Nottingham, Nottingham, NG7 2RD, UK
| | - James Crutchley
- Wolfson Centre for Stem Cells, Tissue Engineering and Modelling (STEM), School of Medicine, The University of Nottingham, Nottingham, NG7 2RD, UK
| | - Sarah Marsh
- Wolfson Centre for Stem Cells, Tissue Engineering and Modelling (STEM), School of Medicine, The University of Nottingham, Nottingham, NG7 2RD, UK
| | - Chris Denning
- Wolfson Centre for Stem Cells, Tissue Engineering and Modelling (STEM), School of Medicine, The University of Nottingham, Nottingham, NG7 2RD, UK
| | - Alicia El Haj
- Institute for Science and Technology in Medicine-Keele University, Stoke-on-Trent, ST4 7QB, UK
| | - Virginie Sottile
- Wolfson Centre for Stem Cells, Tissue Engineering and Modelling (STEM), School of Medicine, The University of Nottingham, Nottingham, NG7 2RD, UK.
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46
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Gonçalves AI, Miranda MS, Rodrigues MT, Reis RL, Gomes ME. Magnetic responsive cell-based strategies for diagnostics and therapeutics. Biomed Mater 2018; 13:054001. [DOI: 10.1088/1748-605x/aac78b] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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47
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Maniglio D, Benetti F, Minati L, Jovicich J, Valentini A, Speranza G, Migliaresi C. Theranostic gold-magnetite hybrid nanoparticles for MRI-guided radiosensitization. NANOTECHNOLOGY 2018; 29:315101. [PMID: 29762138 DOI: 10.1088/1361-6528/aac4ce] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
The main limitation of drug-enhanced radiotherapy concerns the difficulty to evaluate the effectiveness of cancer targeting after drug administration hindering the standardization of therapies based on current radiosensitizing compounds. The challenge regards the development of systems able to combine imaging and radiotherapy enhancement in order to perform highly reliable cancer theragnosis. For these reasons, gold-magnetite hybrid nanoparticles (H-NPs) are proposed as innovative theranostic nanotools for imaging-guided radiosensitization in cancer treatment. In this work we propose a novel method for the synthesis of hydrophilic and superparamagnetic Tween20-stabilized gold-magnetite H-NPs. Morphology and chemical composition of nanoparticles were assessed by transmission electron microscopy, x-ray diffraction analysis and ion-coupled plasma optical emission spectroscopy. Colloidal stability and magnetic properties of nanoparticles were determined by dynamic light scattering and magnetometry. The potentialities of H-NPs for magnetic resonance imaging were studied using a human 4T-MRI scanner. Nanoparticles were proven to induce concentration-dependent contrast enhancement in T2*-weighted MR-images. The cytotoxicity, the cellular uptake and the radiosensitization activity of H-NPs were investigated in human osteosarcoma MG63 cell cultures and murine 3T3 fibroblasts, using specific bioassays and laser scanning confocal microscopy. H-NPs did not exhibit significant toxicity and were demonstrated to be internalized by cells. A significant x-ray enhancement at specific H-NPs exposure concentrations was evidenced on MG63 cell line.
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Affiliation(s)
- D Maniglio
- Department of Industrial Engineering and BIOtech Research Center, Via delle Regole 101, University of Trento, I-38123 Trento, Italy
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Mohanty S, Jain KG, Nandy SB, Kakkar A, Kumar M, Dinda AK, Singh H, Ray A. Iron oxide labeling does not affect differentiation potential of human bone marrow mesenchymal stem cells exhibited by their differentiation into cardiac and neuronal cells. Mol Cell Biochem 2018; 448:17-26. [PMID: 29450799 DOI: 10.1007/s11010-018-3309-9] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2017] [Accepted: 01/25/2018] [Indexed: 01/22/2023]
Abstract
Mesenchymal stem cells (MSCs) have shown promising outcomes in cardiac and neuronal diseases. Efficient and noninvasive tracking of MSCs is essential to harness their therapeutic potential. Iron oxide nanoparticles (IONPs) have emerged as effective means to label stem cells and visualize them using magnetic resonance imaging (MRI). It is known that IONPs do not affect viability and cell proliferation of stem cells. However, very few studies have demonstrated differentiation potential of iron oxide-labeled MSCs and their differentiation into specific lineages that can contribute to cellular therapies. The differentiation of IONP-labeled human bone marrow mesenchymal stem cells (hBM-MSCs) into cardiac and neuronal lineages has never been studied. In this study, we have shown that IONP-labeled hBM-MSCs retain their differentiation potential to cardiac and neuronal cell lineages. We also confirmed that labeling hBM-MSCs with IONP does not affect their characteristic properties such as viability, cellular proliferation rate, surface marker profiling, and trilineage differentiation capacity. This study shows that IONP can be efficiently tracked, and its labeling does not alter stemness and differentiation potential of hBM-MSCs. Thus, the labeled hBM-MSCs can be used in clinical therapies and regenerative medicine.
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Affiliation(s)
- Sujata Mohanty
- Stem Cell Facility, Center of Excellence for Stem Cell Research, AIIMS, New Delhi, India.
| | - Krishan Gopal Jain
- Stem Cell Facility, Center of Excellence for Stem Cell Research, AIIMS, New Delhi, India
| | - Sushmita Bose Nandy
- Stem Cell Facility, Center of Excellence for Stem Cell Research, AIIMS, New Delhi, India.,Department of Biology, Chemistry and Environmental Sciences, Northern New Mexico College, Espanola, NM, USA
| | - Anupama Kakkar
- Stem Cell Facility, Center of Excellence for Stem Cell Research, AIIMS, New Delhi, India
| | - Manoj Kumar
- Center for Biomedical Engineering, IIT Delhi, New Delhi, India
| | | | - Harpal Singh
- Center for Biomedical Engineering, IIT Delhi, New Delhi, India
| | - Alok Ray
- Center for Biomedical Engineering, IIT Delhi, New Delhi, India
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Yun S, Shin TH, Lee JH, Cho MH, Kim IS, Kim JW, Jung K, Lee IS, Cheon J, Park KI. Design of Magnetically Labeled Cells (Mag-Cells) for in Vivo Control of Stem Cell Migration and Differentiation. NANO LETTERS 2018; 18:838-845. [PMID: 29393650 DOI: 10.1021/acs.nanolett.7b04089] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
Cell-based therapies are attractive for treating various degenerative disorders and cancer but delivering functional cells to the region of interest in vivo remains difficult. The problem is exacerbated in dense biological matrices such as solid tissues because these environments impose significant steric hindrances for cell movement. Here, we show that neural stem cells transfected with zinc-doped ferrite magnetic nanoparticles (ZnMNPs) can be pulled by an external magnet to migrate to the desired location in the brain. These magnetically labeled cells (Mag-Cells) can migrate because ZnMNPs generate sufficiently strong mechanical forces to overcome steric hindrances in the brain tissues. Once at the site of lesion, Mag-Cells show enhanced neuronal differentiation and greater secretion of neurotrophic factors than unlabeled control stem cells. Our study shows that ZnMNPs activate zinc-mediated Wnt signaling to facilitate neuronal differentiation. When implemented in a rodent brain stroke model, Mag-Cells led to significant recovery of locomotor performance in the impaired limbs of the animals. Our findings provide a simple magnetic method for controlling migration of stem cells with high therapeutic functions, offering a valuable tool for other cell-based therapies.
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Affiliation(s)
- Seokhwan Yun
- Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine , Seoul 03722, Korea
| | - Tae-Hyun Shin
- Center for NanoMedicine, Institute for Basic Science (IBS) , Seoul 03722, Korea
- Yonsei-IBS Institute, Yonsei University , Seoul 03722, Korea
- Department of Chemistry, Yonsei University , Seoul 03722, Korea
| | - Jae-Hyun Lee
- Center for NanoMedicine, Institute for Basic Science (IBS) , Seoul 03722, Korea
- Yonsei-IBS Institute, Yonsei University , Seoul 03722, Korea
- Department of Chemistry, Yonsei University , Seoul 03722, Korea
| | - Mi Hyeon Cho
- Center for NanoMedicine, Institute for Basic Science (IBS) , Seoul 03722, Korea
- Yonsei-IBS Institute, Yonsei University , Seoul 03722, Korea
- Department of Chemistry, Yonsei University , Seoul 03722, Korea
| | - Il-Sun Kim
- Department of Pediatrics, Severance Children's Hospital, Yonsei University College of Medicine , Seoul 03722, Korea
| | - Ji-Wook Kim
- Center for NanoMedicine, Institute for Basic Science (IBS) , Seoul 03722, Korea
- Yonsei-IBS Institute, Yonsei University , Seoul 03722, Korea
- Department of Chemistry, Yonsei University , Seoul 03722, Korea
| | - Kwangsoo Jung
- Department of Pediatrics, Severance Children's Hospital, Yonsei University College of Medicine , Seoul 03722, Korea
| | - Il-Shin Lee
- Department of Pediatrics, Severance Children's Hospital, Yonsei University College of Medicine , Seoul 03722, Korea
| | - Jinwoo Cheon
- Center for NanoMedicine, Institute for Basic Science (IBS) , Seoul 03722, Korea
- Yonsei-IBS Institute, Yonsei University , Seoul 03722, Korea
- Department of Chemistry, Yonsei University , Seoul 03722, Korea
| | - Kook In Park
- Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine , Seoul 03722, Korea
- Department of Pediatrics, Severance Children's Hospital, Yonsei University College of Medicine , Seoul 03722, Korea
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50
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Ma W, Xie Q, Zhang B, Chen H, Tang J, Lei Z, Wu M, Zhang D, Hu J. Neural Induction Potential and MRI of ADSCs Labeled Cationic Superparamagnetic Iron Oxide Nanoparticle In Vitro. CONTRAST MEDIA & MOLECULAR IMAGING 2018; 2018:6268437. [PMID: 29666564 PMCID: PMC5832102 DOI: 10.1155/2018/6268437] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/24/2017] [Revised: 12/21/2017] [Accepted: 12/31/2017] [Indexed: 01/28/2023]
Abstract
Magnetic resonance imaging (MRI) combined with contrast agents is believed to be useful for stem cell tracking in vivo, and the aim of this research was to investigate the biosafety and neural induction of SD rat-originated adipose derived stem cells (ADSCs) using cationic superparamagnetic iron oxide (SPIO) nanoparticle which was synthesized by the improved polyol method, in order to allow visualization using in vitro MRI. The scan protocols were performed with T2-mapping sequence; meanwhile, the ultrastructure of labeled cells was observed by transmission electron microscopy (TEM) while the iron content was measured by inductively coupled plasma-atomic emission spectrometry (ICP-AES). After neural induction, nestin and NSE (neural markers) were obviously expressed. In vitro MRI showed that the cationic PEG/PEI-modified SPIO nanoparticles could achieve great relaxation performance and favourable longevity. And the ICP-AES quantified the lowest iron content that could be detected by MRI as 1.56~1.8 pg/cell. This study showed that the cationic SPIO could be directly used to label ADSCs, which could then inductively differentiate into nerve and be imaged by in vitro MRI, which would exhibit important guiding significance for the further in vivo MRI towards animal models with neurodegenerative disorders.
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Affiliation(s)
- Weiqiong Ma
- Medical Imaging Department, Nan Sha Center Hospital, Guangzhou Municipal First People's Hospital, Guangzhou Medical University, The Second Affiliated Hospital of South China University of Technology, Guangzhou, Guangdong 511457, China
- Department of Radiology, Huizhou Municipal Central Hospital, Huizhou, Guangdong 516001, China
| | - Qi Xie
- Medical Imaging Department, Nan Sha Center Hospital, Guangzhou Municipal First People's Hospital, Guangzhou Medical University, The Second Affiliated Hospital of South China University of Technology, Guangzhou, Guangdong 511457, China
| | - Baolin Zhang
- School of Materials Science and Engineering, Guilin University of Technology, Guilin, Guangxi 541004, China
| | - Huixian Chen
- Medical Imaging Department, Nan Sha Center Hospital, Guangzhou Municipal First People's Hospital, Guangzhou Medical University, The Second Affiliated Hospital of South China University of Technology, Guangzhou, Guangdong 511457, China
| | - Jianyi Tang
- Medical Imaging Department, Nan Sha Center Hospital, Guangzhou Municipal First People's Hospital, Guangzhou Medical University, The Second Affiliated Hospital of South China University of Technology, Guangzhou, Guangdong 511457, China
| | - Zhengxian Lei
- Medical Imaging Department, Nan Sha Center Hospital, Guangzhou Municipal First People's Hospital, Guangzhou Medical University, The Second Affiliated Hospital of South China University of Technology, Guangzhou, Guangdong 511457, China
| | - Minyi Wu
- Medical Imaging Department, Nan Sha Center Hospital, Guangzhou Municipal First People's Hospital, Guangzhou Medical University, The Second Affiliated Hospital of South China University of Technology, Guangzhou, Guangdong 511457, China
| | - Dingxuan Zhang
- Medical Imaging Department, Nan Sha Center Hospital, Guangzhou Municipal First People's Hospital, Guangzhou Medical University, The Second Affiliated Hospital of South China University of Technology, Guangzhou, Guangdong 511457, China
| | - Jiani Hu
- Karmanos Cancer Institute, Wayne State University, 3990 John R. Street, Detroit, MI 48201, USA
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