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Lazarev S, Uzhviyuk S, Rayev M, Timganova V, Bochkova M, Khaziakhmatova O, Malashchenko V, Litvinova L, Zamorina S. Interaction of Graphene Oxide Nanoparticles with Human Mesenchymal Stem Cells Visualized in the Cell-IQ System. Molecules 2023; 28:molecules28104148. [PMID: 37241889 DOI: 10.3390/molecules28104148] [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: 04/25/2023] [Revised: 05/11/2023] [Accepted: 05/15/2023] [Indexed: 05/28/2023] Open
Abstract
Graphene oxide is a promising nanomaterial with many potential applications. However, before it can be widely used in areas such as drug delivery and medical diagnostics, its influence on various cell populations in the human body must be studied to ensure its safety. We investigated the interaction of graphene oxide (GO) nanoparticles with human mesenchymal stem cells (hMSCs) in the Cell-IQ system, evaluating cell viability, mobility, and growth rate. GO nanoparticles of different sizes coated with linear or branched polyethylene glycol (P or bP, respectively) were used at concentrations of 5 and 25 μg/mL. Designations were the following: P-GOs (Ø 184 ± 73 nm), bP-GOs (Ø 287 ± 52 nm), P-GOb (Ø 569 ± 14 nm), and bP-GOb (Ø 1376 ± 48 nm). After incubating the cells with all types of nanoparticles for 24 h, the internalization of the nanoparticles by the cells was observed. We found that all GO nanoparticles used in this study exerted a cytotoxic effect on hMSCs when used at a high concentration (25 μg/mL), whereas at a low concentration (5 μg/mL) a cytotoxic effect was observed only for bP-GOb particles. We also found that P-GOs particles decreased cell mobility at a concentration of 25 μg/mL, whereas bP-GOb particles increased it. Larger particles (P-GOb and bP-GOb) increased the rate of movement of hMSCs regardless of concentration. There were no statistically significant differences in the growth rate of cells compared with the control group.
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Affiliation(s)
- Sergey Lazarev
- Institute of Ecology and Genetics of Microorganisms, Ural Branch of the Russian Academy of Sciences-Branch of Perm Federal Research Center, 614081 Perm, Russia
- Department of Microbiology and Immunology, Faculty of Biology, Perm State University, 614990 Perm, Russia
| | - Sofya Uzhviyuk
- Institute of Ecology and Genetics of Microorganisms, Ural Branch of the Russian Academy of Sciences-Branch of Perm Federal Research Center, 614081 Perm, Russia
| | - Mikhail Rayev
- Institute of Ecology and Genetics of Microorganisms, Ural Branch of the Russian Academy of Sciences-Branch of Perm Federal Research Center, 614081 Perm, Russia
- Department of Microbiology and Immunology, Faculty of Biology, Perm State University, 614990 Perm, Russia
| | - Valeria Timganova
- Institute of Ecology and Genetics of Microorganisms, Ural Branch of the Russian Academy of Sciences-Branch of Perm Federal Research Center, 614081 Perm, Russia
| | - Maria Bochkova
- Institute of Ecology and Genetics of Microorganisms, Ural Branch of the Russian Academy of Sciences-Branch of Perm Federal Research Center, 614081 Perm, Russia
- Department of Microbiology and Immunology, Faculty of Biology, Perm State University, 614990 Perm, Russia
| | - Olga Khaziakhmatova
- Department of Microbiology and Immunology, Faculty of Biology, Immanuel Kant Baltic Federal University, 236041 Kaliningrad, Russia
| | - Vladimir Malashchenko
- Department of Microbiology and Immunology, Faculty of Biology, Immanuel Kant Baltic Federal University, 236041 Kaliningrad, Russia
| | - Larisa Litvinova
- Department of Microbiology and Immunology, Faculty of Biology, Immanuel Kant Baltic Federal University, 236041 Kaliningrad, Russia
| | - Svetlana Zamorina
- Institute of Ecology and Genetics of Microorganisms, Ural Branch of the Russian Academy of Sciences-Branch of Perm Federal Research Center, 614081 Perm, Russia
- Department of Microbiology and Immunology, Faculty of Biology, Perm State University, 614990 Perm, Russia
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Perikala M, Valoor R, Bhaskar N, Bhardwaj A, Basu B. One-Step Colloidal Synthesis of Non-Toxic Electroactive Carbon Dots with a Better Threshold Cytotoxicity and Cytocompatibility. ACS APPLIED MATERIALS & INTERFACES 2023; 15:281-291. [PMID: 36576301 DOI: 10.1021/acsami.2c16046] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
Carbon dots (CDs), because of their characteristic size (<10 nm) and highly fluorescent nature, can be internalized in biological cells or can be tagged to the key components of a living system. While these attributes can be potentially exploited for biomedical applications, the toxicity of CDs remains an important issue to be addressed. Both the synthesis approach and morphological attributes critically determine the dose-dependent toxicity and cytocompatibility of CDs. Against this perspective, we report herein a one-step colloidal synthesis of CDs using different reaction solvents that lead to the formation of three types of CDs (type I, type II, and type III CDs). The cytocompatibility and cellular uptake of CDs in human mesenchymal stem cells (hMSCs) are dependent on the nature of functionalization and concomitantly on the type of precursors. In particular, type I CDs are synthesized using citric acid, hexadecylamine, and octadecene that are immiscible in culture media. The type II CDs synthesized using citric acid and octadecene emit green fluorescence at a 488 nm excitation and were found to be agglomerated when internalized in hMSCs, whereas the type III CDs, synthesized using citric acid and deionized water, exhibit an agglomeration-free behavior. Further, type III CDs show a wide particle distribution, wide emission bandwidth range of 280-700 nm, threshold toxicity of 1 mg/mL, and good cytocompatibility with hMSCs, much better than those in the published reports. When benchmarked against commercial graphene quantum dots, the as-synthesized type III CDs have better electrical conductivity and cytocompatibility at a given dosage. Thus, the electroactive nature of synthesized type III CDs along with their inherent fluorescent property and less cytotoxicity would enable their potential applications in bio-imaging, directional lineage commitment, and cell-based therapy.
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Affiliation(s)
- Manasa Perikala
- Instrumentation and Applied Physics, Indian Institute of Science, Bangalore560012, India
| | - Remya Valoor
- Laboratory for Biomaterials, Material Research Centre, Indian Institute of Science, Bangalore560012, India
| | - Nitu Bhaskar
- Laboratory for Biomaterials, Material Research Centre, Indian Institute of Science, Bangalore560012, India
| | - Asha Bhardwaj
- Instrumentation and Applied Physics, Indian Institute of Science, Bangalore560012, India
| | - B Basu
- Laboratory for Biomaterials, Material Research Centre, Indian Institute of Science, Bangalore560012, India
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Cruz LJ, Rezaei S, Grosveld F, Philipsen S, Eich C. Nanoparticles targeting hematopoietic stem and progenitor cells: Multimodal carriers for the treatment of hematological diseases. Front Genome Ed 2022; 4:1030285. [PMID: 36407494 PMCID: PMC9666682 DOI: 10.3389/fgeed.2022.1030285] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2022] [Accepted: 10/10/2022] [Indexed: 10/03/2023] Open
Abstract
Modern-day hematopoietic stem cell (HSC) therapies, such as gene therapy, modify autologous HSCs prior to re-infusion into myelo-conditioned patients and hold great promise for treatment of hematological disorders. While this approach has been successful in numerous clinical trials, it relies on transplantation of ex vivo modified patient HSCs, which presents several limitations. It is a costly and time-consuming procedure, which includes only few patients so far, and ex vivo culturing negatively impacts on the viability and stem cell-properties of HSCs. If viral vectors are used, this carries the additional risk of insertional mutagenesis. A therapy delivered to HSCs in vivo, with minimal disturbance of the HSC niche, could offer great opportunities for novel treatments that aim to reverse disease symptoms for hematopoietic disorders and could bring safe, effective and affordable genetic therapies to all parts of the world. However, substantial unmet needs exist with respect to the in vivo delivery of therapeutics to HSCs. In the last decade, in particular with the development of gene editing technologies such as CRISPR/Cas9, nanoparticles (NPs) have become an emerging platform to facilitate the manipulation of cells and organs. By employing surface modification strategies, different types of NPs can be designed to target specific tissues and cell types in vivo. HSCs are particularly difficult to target due to the lack of unique cell surface markers that can be utilized for cell-specific delivery of therapeutics, and their shielded localization in the bone marrow (BM). Recent advances in NP technology and genetic engineering have resulted in the development of advanced nanocarriers that can deliver therapeutics and imaging agents to hematopoietic stem- and progenitor cells (HSPCs) in the BM niche. In this review we provide a comprehensive overview of NP-based approaches targeting HSPCs to control and monitor HSPC activity in vitro and in vivo, and we discuss the potential of NPs for the treatment of malignant and non-malignant hematological disorders, with a specific focus on the delivery of gene editing tools.
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Affiliation(s)
- Luis J. Cruz
- Translational Nanobiomaterials and Imaging, Department of Radiology, Leiden University Medical Center, Leiden, Netherlands
| | - Somayeh Rezaei
- Translational Nanobiomaterials and Imaging, Department of Radiology, Leiden University Medical Center, Leiden, Netherlands
| | - Frank Grosveld
- Erasmus University Medical Center, Department of Cell Biology, Rotterdam, Netherlands
| | - Sjaak Philipsen
- Erasmus University Medical Center, Department of Cell Biology, Rotterdam, Netherlands
| | - Christina Eich
- Translational Nanobiomaterials and Imaging, Department of Radiology, Leiden University Medical Center, Leiden, Netherlands
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Chen X, Chen J, Huang N. The structure, formation, and effect of plasma protein layer on the blood contact materials: A review. BIOSURFACE AND BIOTRIBOLOGY 2021. [DOI: 10.1049/bsb2.12029] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Affiliation(s)
- Xiao Chen
- Institute of Biomaterials and Surface Engineering Key Lab. for Advanced Technologies of Materials Ministry of Education Southwest Jiaotong University Chengdu China
| | - Jiang Chen
- Institute of Biomaterials and Surface Engineering Key Lab. for Advanced Technologies of Materials Ministry of Education Southwest Jiaotong University Chengdu China
| | - Nan Huang
- Institute of Biomaterials and Surface Engineering Key Lab. for Advanced Technologies of Materials Ministry of Education Southwest Jiaotong University Chengdu China
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Krenzlin H, Foelger A, Mailänder V, Blase C, Brockmann M, Düber C, Ringel F, Keric N. Novel Biodegradable Composite of Calcium Phosphate Cement and the Collagen I Mimetic P-15 for Pedicle Screw Augmentation in Osteoporotic Bone. Biomedicines 2021; 9:biomedicines9101392. [PMID: 34680509 PMCID: PMC8533375 DOI: 10.3390/biomedicines9101392] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 09/27/2021] [Accepted: 09/28/2021] [Indexed: 11/26/2022] Open
Abstract
Osteoporotic vertebral fractures often necessitate fusion surgery, with high rates of implant failure. We present a novel bioactive composite of calcium phosphate cement (CPC) and the collagen I mimetic P-15 for pedicle screw augmentation in osteoporotic bone. Methods involved expression analysis of osteogenesis-related genes during osteoblastic differentiation by RT-PCR and immunostaining of osteopontin and Ca2+ deposits. Untreated and decalcified sheep vertebrae were utilized for linear pullout testing of pedicle screws. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DEXA). Expression of ALPI II (p < 0.0001), osteopontin (p < 0.0001), RUNX2 (p < 0.0001), and osteocalcin (p < 0.0001) was upregulated after co-culture of MSC with CPC-P-15. BMD was decreased by 28.75% ± 2.6%. Pullout loads in untreated vertebrae were 1405 ± 6 N (p < 0.001) without augmentation, 2010 ± 168 N (p < 0.0001) after augmentation with CPC-P-15, and 2112 ± 98 N (p < 0.0001) with PMMA. In decalcified vertebrae, pullout loads were 828 ± 66 N (p < 0.0001) without augmentation, 1324 ± 712 N (p = 0.04) with PMMA, and 1252 ± 131 N (p < 0.0078) with CPC-P-15. CPC-P-15 induces osteoblastic differentiation of human MES and improves pullout resistance of pedicle screws in osteoporotic and non-osteoporotic bone.
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Affiliation(s)
- Harald Krenzlin
- Department of Neurosurgery, University Medical Center Mainz, 55131 Mainz, Germany; (A.F.); (F.R.); (N.K.)
- Correspondence:
| | - Andrea Foelger
- Department of Neurosurgery, University Medical Center Mainz, 55131 Mainz, Germany; (A.F.); (F.R.); (N.K.)
| | - Volker Mailänder
- Max Planck Institute for Polymer Research, 55128 Mainz, Germany;
- Center for Translational Nanomedicine, University Medical Center Mainz, 55131 Maniz, Germany
| | - Christopher Blase
- Personalized Biomedical Engineering Lab, Frankfurt University of Applied Sciences, 60318 Frankfurt am Main, Germany;
| | - Marc Brockmann
- Department of Neuroradiology, University Medical Center Mainz, 55131 Mainz, Germany;
| | - Christoph Düber
- Department of Radiology, University Medical Center Mainz, 55131 Mainz, Germany;
| | - Florian Ringel
- Department of Neurosurgery, University Medical Center Mainz, 55131 Mainz, Germany; (A.F.); (F.R.); (N.K.)
| | - Naureen Keric
- Department of Neurosurgery, University Medical Center Mainz, 55131 Mainz, Germany; (A.F.); (F.R.); (N.K.)
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De Simone U, Spinillo A, Caloni F, Avanzini MA, Coccini T. In vitro evaluation of magnetite nanoparticles in human mesenchymal stem cells: comparison of different cytotoxicity assays. Toxicol Mech Methods 2019; 30:48-59. [PMID: 31364912 DOI: 10.1080/15376516.2019.1650151] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
This work was aimed at defining the suitable test for evaluating Fe3O4 NPs cytotoxicity after short-term exposure in human mesenchymal stem cells (hMSCs) using different viability tests, namely NRU, MTT and TB assays, paralleled by cell morphology analyses for cross checking. MTT and NRU data (culture medium with/without hMSCs plus Fe3O4NPs) indicated artificial/false increments in cell viability after Fe3O4NPs. These observations did not fit with the morphological analyses showing reduced cell density, loss of monolayer features, and morphological alterations at Fe3O4NPs ≥50 μg/ml. Fe3O4NPs alone induced a substantial increased absorbance at the wavelength required for MTT and NRU. A significant death (25%) of hMSC at Fe3O4NPs ≥10 μg/ml, with a maximum effect (45%) at 300 μg/ml after 24 h, exacerbated after 48 h, was observed when applying TB test. These results paralleled the effects on cell morphology. The optical properties and stability of Fe3O4NP suspension (tendency to agglomerate in a specific culture medium) represent factors that limit in vitro result interpretation. These findings suggest the non applicability of the spectrophotometric assays for hMSC culture conditions, while TB is an accurate method for determining cell viability after Fe3O4NP exposure in this model. In relation to NPs safety assessment: cell-based assays must be considered on case-by-case basis; selection of relevant cell models is also important for predictive toxicological studies; application of a testing strategy is fundamental for understanding the toxicity pathways driving cellular responses.
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Affiliation(s)
- Uliana De Simone
- Laboratory of Clinical and Experimental Toxicology, Toxicology Unit, ICS Maugeri SpA-SB, IRCCS, Pavia, Italy
| | - Arsenio Spinillo
- Department of Obstetrics and Gynecology, Fondazione IRCCS Policlinico San Matteo and University of Pavia, Pavia, Italy
| | - Francesca Caloni
- Department of Veterinary Medicine (DIMEVET), Università degli Studi di Milano, Milano, Italy
| | - Maria Antonietta Avanzini
- Laboratory of Transplant Immunology/Cell Factory, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Teresa Coccini
- Laboratory of Clinical and Experimental Toxicology, Toxicology Unit, ICS Maugeri SpA-SB, IRCCS, Pavia, Italy
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Coccini T, De Simone U, Roccio M, Croce S, Lenta E, Zecca M, Spinillo A, Avanzini MA. In vitro toxicity screening of magnetite nanoparticles by applying mesenchymal stem cells derived from human umbilical cord lining. J Appl Toxicol 2019; 39:1320-1336. [PMID: 31211441 DOI: 10.1002/jat.3819] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2019] [Revised: 04/18/2019] [Accepted: 04/18/2019] [Indexed: 01/05/2023]
Abstract
Despite the growing interest in nanoparticles (NPs), their toxicity has not yet been defined and the development of new strategies and predictive models are required. Human stem cells (SCs) offer a promising and innovative cell-based model. Among SCs, mesenchymal SCs (MSCs) derived from cord lining membrane (CL) may represent a new species-specific tool for establishing efficient platforms for primary screening and toxicity/safety testing of NPs. Superparamagnetic iron oxide NPs, including magnetite (Fe3 O4 NPs), have aroused great public health and scientific concerns despite their extensive uses. In this study, CL-MSCs were characterized and applied for in vitro toxicity screening of Fe3 O4 NPs. Cytotoxicity, internalization/uptake, differentiation and proliferative capacity were evaluated after exposure to different Fe3 O4 NP concentrations. Data were compared with those obtained from bone marrow (BM)-MSCs. We observed, at early passages (P3), that: (1) cytotoxicity occurred at 10 μg/mL in CL-MSCs and 100 μg/mL in BM-MSCs (no differences in toxicity, between CL- and BM-MSCs, were observed at higher dosage, 100-300 μg/mL); (2) cell density decrease and monolayer features loss were affected at ≥50 μg/mL in CL-MSCs only; and (3) NP uptake was concentration-dependent in both MSCs. After 100 μg/mL Fe3 O4 NP exposures, the capacity of proliferation was decreased (P5-P9) in CL-MSCs without morphology alteration. Moreover, a progressive decrease of intracellular Fe3 O4 NPs was observed over culture time. Antigen surface expression and multilineage differentiation were not influenced. These findings suggest that CL-MSCs could be used as a reliable cell-based model for Fe3 O4 NP toxicity screening evaluation and support the use of this approach for improving the confidence degree on the safety of NPs to predict health outcomes.
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Affiliation(s)
- Teresa Coccini
- Laboratory of Clinical and Experimental Toxicology, Toxicology Unit, ICS Maugeri SpA-SB, IRCCS, Pavia, Italy
| | - Uliana De Simone
- Laboratory of Clinical and Experimental Toxicology, Toxicology Unit, ICS Maugeri SpA-SB, IRCCS, Pavia, Italy
| | - Marianna Roccio
- Department of Obstetrics and Gynecology, Fondazione IRCCS Policlinico San Matteo and University of Pavia, Pavia, Italy
| | - Stefania Croce
- Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy
| | - Elisa Lenta
- Laboratory of Transplant Immunology/Cell Factory, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Marco Zecca
- Paediatric Haematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Arsenio Spinillo
- Department of Obstetrics and Gynecology, Fondazione IRCCS Policlinico San Matteo and University of Pavia, Pavia, Italy
| | - Maria Antonietta Avanzini
- Laboratory of Transplant Immunology/Cell Factory, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
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Wathiong B, Deville S, Jacobs A, Smisdom N, Gervois P, Lambrichts I, Ameloot M, Hooyberghs J, Nelissen I. Role of nanoparticle size and sialic acids in the distinct time-evolution profiles of nanoparticle uptake in hematopoietic progenitor cells and monocytes. J Nanobiotechnology 2019; 17:62. [PMID: 31084605 PMCID: PMC6513515 DOI: 10.1186/s12951-019-0495-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2018] [Accepted: 05/04/2019] [Indexed: 12/30/2022] Open
Abstract
Background Human hematopoietic progenitor cells (HPCs) are important for cell therapy in cancer and tissue regeneration. In vitro studies have shown a transient association of 40 nm polystyrene nanoparticles (PS NPs) with these cells, which is of interest for intelligent design and application of NPs in HPC-based regenerative protocols. In this study, we aimed to investigate the involvement of nanoparticles’ size and membrane-attached glycan molecules in the interaction of HPCs with PS NPs, and compared it with monocytes. Human cord blood-derived HPCs and THP-1 cells were exposed to fluorescently labelled, carboxylated PS NPs of 40, 100 and 200 nm. Time-dependent nanoparticle membrane association and/or uptake was observed by measuring fluorescence intensity of exposed cells at short time intervals using flow cytometry. By pretreating the cells with neuraminidase, we studied the possible effect of membrane-associated sialic acids in the interaction with NPs. Confocal microscopy was used to visualize the cell-specific character of the NP association. Results Confocal images revealed that the majority of PS NPs was initially observed to be retained at the outer membrane of HPCs, while the same NPs showed immediate internalization by THP-1 monocytic cells. After prolonged exposure up to 4 h, PS NPs were also observed to enter the HPCs’ intracellular compartment. Cell-specific time courses of NP association with HPCs and THP-1 cells remained persistent after cells were enzymatically treated with neuraminidase, but significantly increased levels of NP association could be observed, suggesting a role for membrane-associated sialic acids in this process. Conclusions We conclude that the terminal membrane-associated sialic acids contribute to the NP retention at the outer cell membrane of HPCs. This retention behavior is a unique characteristic of the HPCs and is independent of NP size. Electronic supplementary material The online version of this article (10.1186/s12951-019-0495-x) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Bart Wathiong
- Health Department, Flemish Institute For Technological Research (VITO), Boeretang 200, 2400, Mol, Belgium
| | - Sarah Deville
- Health Department, Flemish Institute For Technological Research (VITO), Boeretang 200, 2400, Mol, Belgium
| | - An Jacobs
- Health Department, Flemish Institute For Technological Research (VITO), Boeretang 200, 2400, Mol, Belgium
| | - Nick Smisdom
- Biomedical Research Institute (BIOMED), Hasselt University, Agoralaan Building C, 3590, Diepenbeek, Belgium
| | - Pascal Gervois
- Biomedical Research Institute (BIOMED), Hasselt University, Agoralaan Building C, 3590, Diepenbeek, Belgium
| | - Ivo Lambrichts
- Biomedical Research Institute (BIOMED), Hasselt University, Agoralaan Building C, 3590, Diepenbeek, Belgium
| | - Marcel Ameloot
- Biomedical Research Institute (BIOMED), Hasselt University, Agoralaan Building C, 3590, Diepenbeek, Belgium
| | - Jef Hooyberghs
- Health Department, Flemish Institute For Technological Research (VITO), Boeretang 200, 2400, Mol, Belgium.,Theoretical Physics, Hasselt University, Agoralaan Building D, 3590, Diepenbeek, Belgium
| | - Inge Nelissen
- Health Department, Flemish Institute For Technological Research (VITO), Boeretang 200, 2400, Mol, Belgium.
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Labusca L, Herea DD, Mashayekhi K. Stem cells as delivery vehicles for regenerative medicine-challenges and perspectives. World J Stem Cells 2018. [PMID: 29849930 DOI: : 10.4252/wjsc.v10.i5.43] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The use of stem cells as carriers for therapeutic agents is an appealing modality for targeting tissues or organs of interest. Combined delivery of cells together with various information molecules as therapeutic agents has the potential to enhance, modulate or even initiate local or systemic repair processes, increasing stem cell efficiency for regenerative medicine applications. Stem-cell-mediated delivery of genes, proteins or small molecules takes advantage of the innate capability of stem cells to migrate and home to injury sites. As the native migratory properties are affected by in vitro expansion, the existent methods for enhancing stem cell targeting capabilities (modified culture methods, genetic modification, cell surface engineering) are described. The role of various nanoparticles in equipping stem cells with therapeutic small molecules is revised together with their class-specific advantages and shortcomings. Modalities to circumvent common challenges when designing a stem-cell-mediated targeted delivery system are described as well as future prospects in using this approach for regenerative medicine applications.
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Affiliation(s)
- Luminita Labusca
- Orthopedics and Traumatology Clinic, Emergency County Hospital Saint Spiridon Iasi Romania, Iasi 700000, Romania
| | - Dumitru Daniel Herea
- Stem Cell Laboratory, National Institute of Research and Development for Technical Physics (NIRDTP), Iasi 700349, Romania
| | - Kaveh Mashayekhi
- Systems Bioinformatics and Modelling SBIM, Frankfurt 45367, Germany
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Labusca L, Herea DD, Mashayekhi K. Stem cells as delivery vehicles for regenerative medicine-challenges and perspectives. World J Stem Cells 2018; 10:43-56. [PMID: 29849930 PMCID: PMC5973910 DOI: 10.4252/wjsc.v10.i5.43] [Citation(s) in RCA: 69] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Revised: 04/26/2018] [Accepted: 05/09/2018] [Indexed: 02/06/2023] Open
Abstract
The use of stem cells as carriers for therapeutic agents is an appealing modality for targeting tissues or organs of interest. Combined delivery of cells together with various information molecules as therapeutic agents has the potential to enhance, modulate or even initiate local or systemic repair processes, increasing stem cell efficiency for regenerative medicine applications. Stem-cell-mediated delivery of genes, proteins or small molecules takes advantage of the innate capability of stem cells to migrate and home to injury sites. As the native migratory properties are affected by in vitro expansion, the existent methods for enhancing stem cell targeting capabilities (modified culture methods, genetic modification, cell surface engineering) are described. The role of various nanoparticles in equipping stem cells with therapeutic small molecules is revised together with their class-specific advantages and shortcomings. Modalities to circumvent common challenges when designing a stem-cell-mediated targeted delivery system are described as well as future prospects in using this approach for regenerative medicine applications.
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Affiliation(s)
- Luminita Labusca
- Orthopedics and Traumatology Clinic, Emergency County Hospital Saint Spiridon Iasi Romania, Iasi 700000, Romania
| | - Dumitru Daniel Herea
- Stem Cell Laboratory, National Institute of Research and Development for Technical Physics (NIRDTP), Iasi 700349, Romania
| | - Kaveh Mashayekhi
- Systems Bioinformatics and Modelling SBIM, Frankfurt 45367, Germany
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Huang WC, Lu IL, Chiang WH, Lin YW, Tsai YC, Chen HH, Chang CW, Chiang CS, Chiu HC. Tumortropic adipose-derived stem cells carrying smart nanotherapeutics for targeted delivery and dual-modality therapy of orthotopic glioblastoma. J Control Release 2017; 254:119-130. [DOI: 10.1016/j.jconrel.2017.03.035] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2016] [Revised: 12/30/2016] [Accepted: 03/19/2017] [Indexed: 01/07/2023]
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12
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Nold P, Hartmann R, Feliu N, Kantner K, Gamal M, Pelaz B, Hühn J, Sun X, Jungebluth P, Del Pino P, Hackstein H, Macchiarini P, Parak WJ, Brendel C. Optimizing conditions for labeling of mesenchymal stromal cells (MSCs) with gold nanoparticles: a prerequisite for in vivo tracking of MSCs. J Nanobiotechnology 2017; 15:24. [PMID: 28356160 PMCID: PMC5372278 DOI: 10.1186/s12951-017-0258-5] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2016] [Accepted: 03/20/2017] [Indexed: 12/23/2022] Open
Abstract
Background Mesenchymal stromal cells (MSCs) have an inherent migratory capacity towards tumor tissue in vivo. With the future objective to quantify the tumor homing efficacy of MSCs, as first step in this direction we investigated the use of inorganic nanoparticles (NPs), in particular ca. 4 nm-sized Au NPs, for MSC labeling. Time dependent uptake efficiencies of NPs at different exposure concentrations and times were determined via inductively coupled plasma mass spectrometry (ICP-MS). Results The labeling efficiency of the MSCs was determined in terms of the amount of exocytosed NPs versus the amount of initially endocytosed NPs, demonstrating that at high concentrations the internalized Au NPs were exocytosed over time, leading to continuous exhaustion. While exposure to NPs did not significantly impair cell viability or expression of surface markers, even at high dose levels, MSCs were significantly affected in their proliferation and migration potential. These results demonstrate that proliferation or migration assays are more suitable to evaluate whether labeling of MSCs with certain amounts of NPs exerts distress on cells. However, despite optimized conditions the labeling efficiency varied considerably in MSC lots from different donors, indicating cell specific loading capacities for NPs. Finally, we determined the detection limits of Au NP-labeled MSCs within murine tissue employing ICP-MS and demonstrate the distribution and homing of NP labeled MSCs in vivo. Conclusion Although large amounts of NPs improve contrast for imaging, duration and extend of labeling needs to be adjusted carefully to avoid functional deficits in MSCs. We established an optimized labeling strategy for human MSCs with Au NPs that preserves their migratory capacity in vivo. Electronic supplementary material The online version of this article (doi:10.1186/s12951-017-0258-5) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Philipp Nold
- Department of Hematology, Oncology and Immunology, Philipps University Marburg, Marburg, Germany
| | - Raimo Hartmann
- Department of Physics, Philipps-University of Marburg, Marburg, Germany
| | - Neus Feliu
- Department of Physics, Philipps-University of Marburg, Marburg, Germany
| | - Karsten Kantner
- Department of Physics, Philipps-University of Marburg, Marburg, Germany
| | - Mahmoud Gamal
- Department of Physics, Philipps-University of Marburg, Marburg, Germany
| | - Beatriz Pelaz
- Department of Physics, Philipps-University of Marburg, Marburg, Germany
| | - Jonas Hühn
- Department of Physics, Philipps-University of Marburg, Marburg, Germany
| | - Xing Sun
- Department of Physics, Philipps-University of Marburg, Marburg, Germany
| | | | - Pablo Del Pino
- Department of Physics, Philipps-University of Marburg, Marburg, Germany
| | - Holger Hackstein
- Institute for Clinical Immunology and Transfusion Medicine, Justus-Liebig University Giessen, Giessen, Germany
| | - Paolo Macchiarini
- Laboratory of Bioengineering & Regenerative Medicine (BioReM), Kazan Federal University, Kazan, Russia
| | - Wolfgang J Parak
- Department of Physics, Philipps-University of Marburg, Marburg, Germany. .,CIC Biomagune, San Sebastián, Spain.
| | - Cornelia Brendel
- Department of Hematology, Oncology and Immunology, Philipps University Marburg, Marburg, Germany.
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13
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Deville S, Hadiwikarta WW, Smisdom N, Wathiong B, Ameloot M, Nelissen I, Hooyberghs J. Transient loading of CD34 + hematopoietic progenitor cells with polystyrene nanoparticles. Int J Nanomedicine 2017; 12:459-472. [PMID: 28138242 PMCID: PMC5238761 DOI: 10.2147/ijn.s119407] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
CD34+ hematopoietic progenitor cells (HPCs) offer great opportunities to develop new treatments for numerous malignant and non-malignant diseases. Nanoparticle (NP)-based strategies can further enhance this potential, and therefore a thorough understanding of the loading behavior of HPCs towards NPs is essential for a successful application. The present study focusses on the interaction kinetics of 40 nm sized carboxylated polystyrene (PS) NPs with HPCs. Interestingly, a transient association of the NPs with HPCs is observed, reaching a maximum within 1 hour and declining afterwards. This behavior is not seen in dendritic cells (CD34-DCs) differentiated from HPCs, which display a monotonic increase in NP load. We demonstrate that this transient interaction requires an energy-dependent cellular process, suggesting active loading and release of NPs by HPCs. This novel observation offers a unique approach to transiently equip HPCs. A simple theoretical approach modeling the kinetics of NP loading and release is presented, contributing to a framework of describing this phenomenon.
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Affiliation(s)
- Sarah Deville
- VITO, Flemish Institute for Technological Research, Mol, Belgium; Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium
| | | | - Nick Smisdom
- VITO, Flemish Institute for Technological Research, Mol, Belgium; Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium
| | - Bart Wathiong
- VITO, Flemish Institute for Technological Research, Mol, Belgium; Theoretical Physics, Hasselt University, Diepenbeek, Belgium
| | - Marcel Ameloot
- Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium
| | - Inge Nelissen
- VITO, Flemish Institute for Technological Research, Mol, Belgium
| | - Jef Hooyberghs
- VITO, Flemish Institute for Technological Research, Mol, Belgium; Theoretical Physics, Hasselt University, Diepenbeek, Belgium
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14
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Yi DK, Nanda SS, Kim K, Tamil Selvan S. Recent progress in nanotechnology for stem cell differentiation, labeling, tracking and therapy. J Mater Chem B 2017; 5:9429-9451. [DOI: 10.1039/c7tb02532g] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Nanotechnology advancements for stem cell differentiation, labeling, tracking and therapeutic applications in cardiac repair, bone, and liver regeneration are delineated.
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Affiliation(s)
- Dong Kee Yi
- Department of Chemistry
- Myongji University
- Yongin 449-728
- South Korea
| | | | - Kwangmeyung Kim
- Center for Theragnosis
- Biomedical Research Institute
- Korea Institute of Science and Technology (KIST)
- Seoul
- South Korea
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15
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Schöttler S, Landfester K, Mailänder V. Die Steuerung des Stealth-Effekts von Nanoträgern durch das Verständnis der Proteinkorona. Angew Chem Int Ed Engl 2016. [DOI: 10.1002/ange.201602233] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Affiliation(s)
- Susanne Schöttler
- Max-Planck-Institut für Polymerforschung; Ackermannweg 10 55128 Mainz Deutschland
- Hautklinik; Universitätsmedizin der Johannes Gutenberg-Universität; Langenbeckstraße 1 55131 Mainz Deutschland
| | - Katharina Landfester
- Max-Planck-Institut für Polymerforschung; Ackermannweg 10 55128 Mainz Deutschland
| | - Volker Mailänder
- Max-Planck-Institut für Polymerforschung; Ackermannweg 10 55128 Mainz Deutschland
- Hautklinik; Universitätsmedizin der Johannes Gutenberg-Universität; Langenbeckstraße 1 55131 Mainz Deutschland
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16
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Schöttler S, Landfester K, Mailänder V. Controlling the Stealth Effect of Nanocarriers through Understanding the Protein Corona. Angew Chem Int Ed Engl 2016; 55:8806-15. [PMID: 27303916 DOI: 10.1002/anie.201602233] [Citation(s) in RCA: 201] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2016] [Revised: 04/21/2016] [Indexed: 12/13/2022]
Abstract
The past decade has seen a significant increase in interest in the use of polymeric nanocarriers in medical applications. In particular, when used as drug vectors in targeted delivery, nanocarriers could overcome many obstacles for drug therapy. Nevertheless, their application is still impeded by the complex composition of the blood proteins covering the particle surface, termed the protein corona. The protein corona complicates any prediction of cell interactions, biodistribution, and toxicity. In particular, the unspecific uptake of nanocarriers is a major obstacle in clinical studies. This Minireview provides an overview of what we currently know about the characteristics of the protein corona of nanocarriers, with a focus on surface functionalization that reduces unspecific uptake (the stealth effect). The ongoing improvement of nanocarriers to allow them to meet all the requirements necessary for successful application, including targeted delivery and stealth, are further discussed.
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Affiliation(s)
- Susanne Schöttler
- Max Planck Institute for Polymer Research, Ackermannweg 10, 55128, Mainz, Germany.,Dermatology Clinic, University Medical Center of the Johannes Gutenberg-University, Langenbeckstr. 1, 55131, Mainz, Germany
| | - Katharina Landfester
- Max Planck Institute for Polymer Research, Ackermannweg 10, 55128, Mainz, Germany.
| | - Volker Mailänder
- Max Planck Institute for Polymer Research, Ackermannweg 10, 55128, Mainz, Germany.,Dermatology Clinic, University Medical Center of the Johannes Gutenberg-University, Langenbeckstr. 1, 55131, Mainz, Germany
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17
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Lineage-related and particle size-dependent cytotoxicity of chitosan nanoparticles on mouse bone marrow-derived hematopoietic stem and progenitor cells. Food Chem Toxicol 2015; 85:31-44. [PMID: 26051352 DOI: 10.1016/j.fct.2015.05.017] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2015] [Revised: 05/19/2015] [Accepted: 05/27/2015] [Indexed: 12/12/2022]
Abstract
Chitosan nanoparticles (CSNPs) have potential applications in stem cell research. In this study, ex vivo cytotoxicity of CSNPs on mouse bone marrow-derived (MBMCs) hematopoietic stem and progenitor cells (HSPCs) was determined. MBMCs were exposed to CSNPs of different particle sizes at various concentrations for up to 72 h. Cytotoxicity effect of CSNPs on MBMCs was determined using MTT, Live/Dead Viability/Cytotoxicity assays and flow cytometry analysis of surface antigens on HSCs (Sca-1(+)), myeloid-committed progenitors (CD11b(+), Gr-1(+)), and lymphoid-committed progenitors (CD45(+), CD3e(+)). At 24 h incubation, MBMCs' viability was not affected by CSNPs. At 48 and 72 h, significant reduction was detected at higher CSNPs concentrations. Small CSNPs (200 nm) significantly reduced MBMCs' viability while medium-sized particle (∼400 nm) selectively promoted MBMCs growth. Surface antigen assessment demonstrated lineage-dependent effect. Significant decrease in Sca-1(+) cells percentage was observed for medium-sized particle at the lowest CSNPs concentration. Meanwhile, reduction of CD11b(+) and Gr-1(+) cells percentage was detected at high and intermediate concentrations of medium-sized and large CSNPs. Percentage of CD45(+) and CD3e(+) cells along with ROS levels were not significantly affected by CSNPs. In conclusion, medium-sized and large CSNPs were relatively non-toxic at lower concentrations. However, further investigations are necessary for therapeutic applications.
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