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Sim KH, Mir M, Jelke S, Tarafder S, Kim J, Lee CH. Quantum dots-labeled polymeric scaffolds for in vivo tracking of degradation and tissue formation. Bioact Mater 2022; 16:285-292. [PMID: 35415285 PMCID: PMC8965775 DOI: 10.1016/j.bioactmat.2022.03.003] [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: 12/04/2021] [Revised: 02/10/2022] [Accepted: 03/03/2022] [Indexed: 12/04/2022] Open
Abstract
The inevitable gap between in vitro and in vivo degradation rate of biomaterials has been a challenging factor in the optimal designing of scaffold's degradation to be balanced with new tissue formation. To enable non-/minimum-invasive tracking of in vivo scaffold degradation, chemical modifications have been applied to label polymers with fluorescent dyes. However, the previous approaches may have limited expandability due to complicated synthesis processes. Here, we introduce a simple and efficient method to fluorescence labeling of polymeric scaffolds via blending with near-infrared (NIR) quantum dots (QDs), semiconductor nanocrystals with superior optical properties. QDs-labeled, 3D-printed PCL scaffolds showed promising efficiency and reliability in quantitative measurement of degradation using a custom-built fiber-optic imaging modality. Furthermore, QDs-PCL scaffolds showed neither cytotoxicity nor secondary labeling of adjacent cells. QDs-PCL scaffolds also supported the engineering of fibrous, cartilaginous, and osteogenic tissues from mesenchymal stem/progenitor cells (MSCs). In addition, QDs-PCL enabled a distinction between newly forming tissue and the remaining mass of scaffolds through multi-channel imaging. Thus, our findings suggest a simple and efficient QDs-labeling of PCL scaffolds and minimally invasive imaging modality that shows significant potential to enable in vivo tracking of scaffold degradation as well as new tissue formation.
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Affiliation(s)
- Kun Hee Sim
- Regenerative Engineering Laboratory, Center for Dental and Craniofacial Research, Columbia University Irving Medical Center, 630 West 168th Street, VC12-211, New York, NY, 10032, USA
| | - Mohammad Mir
- Department of Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ, 07030, USA
| | - Sophia Jelke
- Regenerative Engineering Laboratory, Center for Dental and Craniofacial Research, Columbia University Irving Medical Center, 630 West 168th Street, VC12-211, New York, NY, 10032, USA
| | - Solaiman Tarafder
- Regenerative Engineering Laboratory, Center for Dental and Craniofacial Research, Columbia University Irving Medical Center, 630 West 168th Street, VC12-211, New York, NY, 10032, USA
| | - Jinho Kim
- Department of Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ, 07030, USA
| | - Chang H. Lee
- Regenerative Engineering Laboratory, Center for Dental and Craniofacial Research, Columbia University Irving Medical Center, 630 West 168th Street, VC12-211, New York, NY, 10032, USA
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2
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Encapsulin Based Self-Assembling Iron-Containing Protein Nanoparticles for Stem Cells MRI Visualization. Int J Mol Sci 2021; 22:ijms222212275. [PMID: 34830156 PMCID: PMC8618560 DOI: 10.3390/ijms222212275] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 11/10/2021] [Accepted: 11/10/2021] [Indexed: 11/16/2022] Open
Abstract
Over the past decade, cell therapy has found many applications in the treatment of different diseases. Some of the cells already used in clinical practice include stem cells and CAR-T cells. Compared with traditional drugs, living cells are much more complicated systems that must be strictly controlled to avoid undesirable migration, differentiation, or proliferation. One of the approaches used to prevent such side effects involves monitoring cell distribution in the human body by any noninvasive technique, such as magnetic resonance imaging (MRI). Long-term tracking of stem cells with artificial magnetic labels, such as magnetic nanoparticles, is quite problematic because such labels can affect the metabolic process and cell viability. Additionally, the concentration of exogenous labels will decrease during cell division, leading to a corresponding decrease in signal intensity. In the current work, we present a new type of genetically encoded label based on encapsulin from Myxococcus xanthus bacteria, stably expressed in human mesenchymal stem cells (MSCs) and coexpressed with ferroxidase as a cargo protein for nanoparticles' synthesis inside encapsulin shells. mZip14 protein was expressed for the enhancement of iron transport into the cell. Together, these three proteins led to the synthesis of iron-containing nanoparticles in mesenchymal stem cells-without affecting cell viability-and increased contrast properties of MSCs in MRI.
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3
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Ehsani A, Jodaei A, Barzegar-Jalali M, Fathi E, Farahzadi R, Adibkia K. Nanomaterials and Stem Cell Differentiation Potential: An Overview of Biological Aspects and Biomedical Efficacy. Curr Med Chem 2021; 29:1804-1823. [PMID: 34254903 DOI: 10.2174/0929867328666210712193113] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 06/08/2021] [Accepted: 06/10/2021] [Indexed: 11/22/2022]
Abstract
Nanoparticles (NPs) due to their medical applications are widely used. Accordingly, the use of mesenchymal stem cells is one of the most important alternatives in tissue engineering field. NPs play effective roles in stem cells proliferation and differentiation. The combination of NPs and tissue regeneration by stem cells has created new therapeutic approach towards humanity. Of note, the physicochemical properties of NPs determine their biological function. Interestingly, various mechanisms such as modulation of signaling pathways and generation of reactive oxygen species, are involved in NPs-induced cellular proliferation and differentiation. This review summarized the types of nanomaterials effective on stem cell differentiation, the physicochemical features, biomedical application of these materials and relationship between nanomaterials and environment.
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Affiliation(s)
- Ali Ehsani
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Asma Jodaei
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Ezzatollah Fathi
- Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran
| | - Raheleh Farahzadi
- Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Khosro Adibkia
- Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran
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4
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Rajendran RL, Jogalekar MP, Gangadaran P, Ahn BC. Noninvasive in vivo cell tracking using molecular imaging: A useful tool for developing mesenchymal stem cell-based cancer treatment. World J Stem Cells 2020; 12:1492-1510. [PMID: 33505597 PMCID: PMC7789123 DOI: 10.4252/wjsc.v12.i12.1492] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Revised: 10/05/2020] [Accepted: 10/21/2020] [Indexed: 02/06/2023] Open
Abstract
Mounting evidence has emphasized the potential of cell therapies in treating various diseases by restoring damaged tissues or replacing defective cells in the body. Cell therapies have become a strong therapeutic modality by applying noninvasive in vivo molecular imaging for examining complex cellular processes, understanding pathophysiological mechanisms of diseases, and evaluating the kinetics/dynamics of cell therapies. In particular, mesenchymal stem cells (MSCs) have shown promise in recent years as drug carriers for cancer treatment. They can also be labeled with different probes and tracked in vivo to assess the in vivo effect of administered cells, and to optimize therapy. The exact role of MSCs in oncologic diseases is not clear as MSCs have been shown to be involved in tumor progression and inhibition, and the exact interactions between MSCs and specific cancer microenvironments are not clear. In this review, a multitude of labeling approaches, imaging modalities, and the merits/demerits of each strategy are outlined. In addition, specific examples of the use of MSCs and in vivo imaging in cancer therapy are provided. Finally, present limitations and future outlooks in terms of the translation of different imaging approaches in clinics are discussed.
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Affiliation(s)
| | | | - Prakash Gangadaran
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
- BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
| | - Byeong-Cheol Ahn
- BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu 41944, South Korea
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, South Korea.
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5
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Tosat-Bitrián C, Palomo V. CdSe quantum dots evaluation in primary cellular models or tissues derived from patients. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 2020; 30:102299. [PMID: 32931928 DOI: 10.1016/j.nano.2020.102299] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Revised: 08/29/2020] [Accepted: 09/01/2020] [Indexed: 12/18/2022]
Abstract
In recent years quantum dots (QDs) have risen as useful luminescent nanoparticles with multiple applications ranging from laser, image displays and biomedical applications. Here we review and discuss the studies of these nanoparticles in patient derived cellular samples or tissues, including cellular models from iPSCs from patients, biopsied and post-mortem tissue. QD-based multiplexed imaging has been proved to overcome most of the major drawbacks of conventional techniques, exhibiting higher sensitivity, reliability, accuracy and simultaneous labeling of key biomarkers. In this sense, QDs are very promising tools to be further used in clinical applications including diagnosis and therapy approaches. Analyzing the possibilities of these materials in these biological samples gives an overview of the future applications of the nanoparticles in models closer to patients and their specific disease.
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Affiliation(s)
| | - Valle Palomo
- Centro de Investigaciones Biológicas Margarita Salas CSIC, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto Carlos III, Madrid, Spain.
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6
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Sun Y, Lu Y, Yin L, Liu Z. The Roles of Nanoparticles in Stem Cell-Based Therapy for Cardiovascular Disease. Front Bioeng Biotechnol 2020; 8:947. [PMID: 32923434 PMCID: PMC7457042 DOI: 10.3389/fbioe.2020.00947] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2020] [Accepted: 07/22/2020] [Indexed: 12/15/2022] Open
Abstract
Cardiovascular disease (CVD) is currently one of the primary causes of mortality and morbidity worldwide. Nanoparticles (NPs) are playing increasingly important roles in regulating stem cell behavior because of their special features, including shape, size, aspect ratio, surface charge, and surface area. In terms of cardiac disease, NPs can facilitate gene delivery in stem cells, track the stem cells in vivo for long-term monitoring, and enhance retention after their transplantation. The advantages of applying NPs in peripheral vascular disease treatments include facilitating stem cell therapy, mimicking the extracellular matrix environment, and utilizing a safe non-viral gene delivery tool. However, the main limitation of NPs is toxicity, which is related to their size, shape, aspect ratio, and surface charge. Currently, there have been many animal models proving NPs’ potential in treating CVD, but no extensive applications of stem-cell therapy using NPs are available in clinical practice. In conclusion, NPs might have significant potential uses in clinical trials of CVD in the future, thereby meeting the changing needs of individual patients worldwide.
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Affiliation(s)
- Yuting Sun
- Department of Surgical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yuexin Lu
- Department of Surgical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Li Yin
- Department of Vascular Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Zhenjie Liu
- Department of Vascular Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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7
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Liu X, Yang Z, Sun J, Ma T, Hua F, Shen Z. A brief review of cytotoxicity of nanoparticles on mesenchymal stem cells in regenerative medicine. Int J Nanomedicine 2019; 14:3875-3892. [PMID: 31213807 PMCID: PMC6539172 DOI: 10.2147/ijn.s205574] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Accepted: 04/21/2019] [Indexed: 12/30/2022] Open
Abstract
Multipotent mesenchymal stem cells have shown great promise for application in regenerative medicine owing to their particular therapeutic effects, such as significant self-renewability, low immunogenicity, and ability to differentiate into a variety of specialized cells. However, there remain certain complicated and unavoidable problems that limit their further development and application. One of the challenges is to noninvasively monitor the delivery and biodistribution of transplanted stem cells during treatment without relying on behavioral endpoints or tissue histology, and it is important to explore the potential mechanisms to clarify how stem cells work in vivo. To solve these problems, various nanoparticles (NPs) and their corresponding imaging methods have been developed recently and have made great progress. In this review, we mainly discuss NPs used to label stem cells and their toxic effects on the latter, the imaging techniques to detect such NPs, and the current existing challenges in this field.
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Affiliation(s)
- Xuan Liu
- Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Soochow University, Suzhou, People's Republic of China
| | - Ziying Yang
- Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Soochow University, Suzhou, People's Republic of China
| | - Jiacheng Sun
- Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Soochow University, Suzhou, People's Republic of China
| | - Teng Ma
- Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Soochow University, Suzhou, People's Republic of China
| | - Fei Hua
- Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Soochow University, Suzhou, People's Republic of China
| | - Zhenya Shen
- Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Soochow University, Suzhou, People's Republic of China
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8
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Kundrotas G, Karabanovas V, Pleckaitis M, Juraleviciute M, Steponkiene S, Gudleviciene Z, Rotomskis R. Uptake and distribution of carboxylated quantum dots in human mesenchymal stem cells: cell growing density matters. J Nanobiotechnology 2019; 17:39. [PMID: 30866960 PMCID: PMC6417192 DOI: 10.1186/s12951-019-0470-6] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2018] [Accepted: 02/26/2019] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Human mesenchymal stem cells (MSCs) have drawn much attention in the field of regenerative medicine for their immunomodulatory and anti-inflammatory effects. MSCs possess specific tumor-oriented migration and incorporation highlighting the potential for MSCs to be used as an ideal carrier for anticancer agents. Bone marrow is the main source of MSCs for clinical applications. MSCs tracking in vivo is a critical component of the safety and efficacy evaluation of therapeutic cell products; therefore, cells must be labeled with contrast agents to enable visualization of the MSCs migration in vivo. Due to their unique properties, quantum dots (QDs) are emerging as optimal tools in long-term MSC optical imaging applications. The aim of this study was to investigate the uptake dynamics, cytotoxity, subcellular and extracellular distribution of non-targeted carboxylated quantum dots in human bone marrow MSCs at different cell growing densities. RESULTS QDs had no negative impact on MSC viability throughout the experiment and accumulated in all observed cells efficiently; however, in some MSCs QDs induced formation of lipid droplets. At low cell growing densities QDs distribute within MSCs cytoplasm already after 1 h of incubation reaching saturation after 6 h. After 24 h QDs localize mainly in the perinuclear region of the cells in endosomes. Interestingly, in more confluent culture QDs localize mostly outside MSCs. QDs abundantly mark MSC long filopodia-like structures attaching neighboring cells. At high cell density cultivation, we for the first time demonstrated that carboxylated QDs localize in human bone marrow MSC extracellular matrix. Moreover, we observed that average photoluminescence lifetime of QDs distributed in extracellular matrix are longer than lifetimes of QDs entrapped in endocytic vesicles; thus, for the first time showing the possibility to identify and distinguish localization of QDs in various extracellular and intracellular structures using fluorescence-lifetime imaging microscopy without additional staining assays. CONCLUSION Carboxylated QDs can be used as nonspecific and effective dye for staining of human bone marrow MSCs and their specific extracellular structures. These results are promising in fundamental stem cell biology as well as in cellular therapy, anticancer drug delivery and tissue engineering.
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Affiliation(s)
- Gabrielis Kundrotas
- Biobank, National Cancer Institute, Baublio Str. 3b, 08406, Vilnius, Lithuania
- Laboratory of Immunology, National Cancer Institute, Baublio Str. 3b, 08406, Vilnius, Lithuania
| | - Vitalijus Karabanovas
- Biomedical Physics Laboratory, National Cancer Institute, Baublio Str. 3b, 08406, Vilnius, Lithuania
- Department of Chemistry and Bioengineering, Vilnius Gediminas Technical University, Sauletekis Ave. 11, 10223, Vilnius, Lithuania
| | - Marijus Pleckaitis
- Biomedical Physics Laboratory, National Cancer Institute, Baublio Str. 3b, 08406, Vilnius, Lithuania
| | - Marina Juraleviciute
- Biomedical Physics Laboratory, National Cancer Institute, Baublio Str. 3b, 08406, Vilnius, Lithuania
| | - Simona Steponkiene
- Biomedical Physics Laboratory, National Cancer Institute, Baublio Str. 3b, 08406, Vilnius, Lithuania
| | - Zivile Gudleviciene
- Biobank, National Cancer Institute, Baublio Str. 3b, 08406, Vilnius, Lithuania
| | - Ricardas Rotomskis
- Biomedical Physics Laboratory, National Cancer Institute, Baublio Str. 3b, 08406, Vilnius, Lithuania.
- Biophotonics Group of Laser Research Center, Faculty of Physics, Vilnius University, Sauletekis Ave. 9, 10222, Vilnius, Lithuania.
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9
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Zhang C, Xie B, Zou Y, Zhu D, Lei L, Zhao D, Nie H. Zero-dimensional, one-dimensional, two-dimensional and three-dimensional biomaterials for cell fate regulation. Adv Drug Deliv Rev 2018; 132:33-56. [PMID: 29964080 DOI: 10.1016/j.addr.2018.06.020] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2018] [Revised: 05/01/2018] [Accepted: 06/25/2018] [Indexed: 02/06/2023]
Abstract
The interaction of biological cells with artificial biomaterials is one of the most important issues in tissue engineering and regenerative medicine. The interaction is strongly governed by physical and chemical properties of the materials and displayed with differentiated cellular behaviors, including cell self-renewal, differentiation, reprogramming, dedifferentiation, or transdifferentiation as a result. A number of engineered biomaterials with micro- or nano-structures have been developed to mimic structural components of cell niche and specific function of extra cellular matrix (ECM) over past two decades. In this review article, we briefly introduce the fabrication of biomaterials and their classification into zero-dimensional (0D), one-dimensional (1D), two-dimensional (2D) and three-dimensional (3D) ones. More importantly, the influence of different biomaterials on inducing cell self-renewal, differentiation, reprogramming, dedifferentiation, and transdifferentiation was discussed based on the progress at 0D, 1D, 2D and 3D levels, following which the current research limitations and research perspectives were provided.
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Affiliation(s)
- Can Zhang
- Department of Biomedical Engineering, College of Biology, Hunan University, Changsha 410082, China
| | - Bei Xie
- Department of Biomedical Engineering, College of Biology, Hunan University, Changsha 410082, China
| | - Yujian Zou
- Department of Biomedical Engineering, College of Biology, Hunan University, Changsha 410082, China
| | - Dan Zhu
- Department of Biomedical Engineering, College of Biology, Hunan University, Changsha 410082, China
| | - Lei Lei
- Department of Orthodontics, Xiangya Stomatological Hospital, Central South University, Changsha 410008, China.
| | - Dapeng Zhao
- Department of Biomedical Engineering, College of Biology, Hunan University, Changsha 410082, China.
| | - Hemin Nie
- Department of Biomedical Engineering, College of Biology, Hunan University, Changsha 410082, China; Shenzhen Research Institute of Hunan University, Nanshan Hi-new Technology and Industry Park, Shenzhen 518057, China.
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10
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Liu S, Tay LM, Anggara R, Chuah YJ, Kang Y. Long-Term Tracking Mesenchymal Stem Cell Differentiation with Photostable Fluorescent Nanoparticles. ACS APPLIED MATERIALS & INTERFACES 2016; 8:11925-33. [PMID: 27124820 DOI: 10.1021/acsami.5b12371] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/27/2023]
Abstract
Mesenchymal stem cells (MSCs) have proved to be a promising and abundant cell source for tissue and organ repair in regenerative medicine. However, the cell fate, distribution and migration of these transplanted cells are still unclear due to the limited tracking methods. It is desirable to develop a biocompatible and photostable probe to label the MSCs for long-term tracking without affecting the cell proliferation and potency. Herein we apply a recently developed nanoprobe system, in which di(thiophene-2-yl)-diketopyrrolopyrrole (DPP) is covalently linked in the middle of polycaprolactone (PCL) forming the PCL-DPP-PCL polymer complex. Although the PCL-DPP-PCL nanoparticles uptaken by the MSCs did not affect the cell viability, it was interesting that they exhibited different effects on the multilineage potency of the MSCs in the subsequent differentiation in vitro. Specifically, we found that the PCL-DPP-PCL labeling was unfavorable to the MSC osteogenic differentiation, whereas the labeled MSCs exhibited the same adipogenic and chondrogenic differentiations compared to the unlabeled controls as verified by gene expressions and histological staining. Furthermore, the PCL-DPP-PCL nanoparticles remained strong fluorescence intensity even after 4 weeks of differentiation. This study indicated that PCL-DPP-PCL nanoparticles could be used for long-term cell tracing in MSC differentiation into adipogenic and chondrogenic lineages.
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Affiliation(s)
- Shiying Liu
- School of Chemical and Biomedical Engineering, Nanyang Technological University , 62 Nanyang Drive, Singapore 637459, Singapore
| | - Li Min Tay
- School of Chemical and Biomedical Engineering, Nanyang Technological University , 62 Nanyang Drive, Singapore 637459, Singapore
- Nanyang Institute of Technology in Health & Medicine, Interdisciplinary Graduate School, Nanyang Technological University , Singapore
| | - Raditya Anggara
- School of Chemical and Biomedical Engineering, Nanyang Technological University , 62 Nanyang Drive, Singapore 637459, Singapore
| | - Yon Jin Chuah
- School of Chemical and Biomedical Engineering, Nanyang Technological University , 62 Nanyang Drive, Singapore 637459, Singapore
| | - Yuejun Kang
- Faculty of Materials and Energy, Institute for Clean Energy and Advanced Materials, Southwest University , 2 Tiansheng Road, Beibei, Chongqing 400715, China
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11
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Stem Cell Tracking with Nanoparticles for Regenerative Medicine Purposes: An Overview. Stem Cells Int 2015; 2016:7920358. [PMID: 26839568 PMCID: PMC4709786 DOI: 10.1155/2016/7920358] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2015] [Revised: 10/07/2015] [Accepted: 10/11/2015] [Indexed: 02/07/2023] Open
Abstract
Accurate and noninvasive stem cell tracking is one of the most important needs in regenerative medicine to determine both stem cell destinations and final differentiation fates, thus allowing a more detailed picture of the mechanisms involved in these therapies.
Given the great importance and advances in the field of nanotechnology for stem cell imaging, currently, several nanoparticles have become standardized products and have been undergoing fast commercialization. This review has been intended to summarize the current use of different engineered nanoparticles in stem cell tracking for regenerative medicine purposes, in particular by detailing their main features and exploring their biosafety aspects, the first step for clinical application. Moreover, this review has summarized the advantages and applications of stem cell tracking with nanoparticles in experimental and preclinical studies and investigated present limitations for their employment in the clinical setting.
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12
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Xing X, Zhang B, Wang X, Liu F, Shi D, Cheng Y. An "imaging-biopsy" strategy for colorectal tumor reconfirmation by multipurpose paramagnetic quantum dots. Biomaterials 2015; 48:16-25. [PMID: 25701028 DOI: 10.1016/j.biomaterials.2015.01.011] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2014] [Revised: 01/19/2015] [Accepted: 01/20/2015] [Indexed: 12/27/2022]
Abstract
Glucose transporter1 (Glut1) plays important roles in treatment of colorectal cancer (CRC) involving early-stage diagnosis, subtype, TNM stage, and therapeutic schedule. Currently, in situ marking and tracking of the tumor biomarkers via clinical imaging remains great challenges in early stage CRC diagnosis. In this study, we have developed a unique cell-targeted, paramagnetic-fluorescent double-signal molecular nanoprobe for CRC in vivo magnetic resonance imaging (MRI) diagnosis and subsequent biopsy. The unique molecular nanoprobe is composed of a fluorescent quantum dot (QD) core; a coating layer of paramagnetic DTPA-Gd coupled BSA ((Gd)DTPA∙BSA), and a surface targeting moiety of anti-Glut1 polyclonal antibody. The engineered (Gd)DTPA∙BSA@QDs-PcAb is 35 nm in diameter and colloidally stable under both basic and acidic conditions. It exhibits strong fluorescent intensities and high relaxivity (r1 and r2: 16.561 and 27.702 s(-1) per mM of Gd(3+)). Distribution and expression of Glut1 of CRC cells are investigated by in vitro cellular confocal fluorescent imaging and MR scanning upon treating with the (Gd)DTPA∙BSA@QDs-PcAb nanoprobes. In vivo MRI shows real-time imaging of CRC tumor on nude mice after intravenously injection of the (Gd)DTPA∙BSA@QDs-PcAb nanoprobes. Ex vivo biopsy is subsequently conducted for expression of Glut1 on tumor tissues. These nanoprobes are found biocompatible in vitro and in vivo. (Gd)DTPA∙BSA@QDs-PcAb targeted nanoprobe is shown to be a promising agent for CRC cancer in vivo MRI diagnosis and ex vivo biopsy analysis. The "imaging-biopsy" is a viable strategy for tumor reconfirmation with improved diagnostic accuracy and biopsy in personalized treatment.
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Affiliation(s)
- Xiaohong Xing
- Department of Radiology of the Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, PR China
| | - Bingbo Zhang
- Shanghai East Hospital, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai, 200120, PR China.
| | - Xiaohui Wang
- Department of Radiology of the Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, PR China
| | - Fengjun Liu
- Department of Radiology of the Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, PR China
| | - Donglu Shi
- Shanghai East Hospital, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai, 200120, PR China; The Materials Science and Engineering Program, Dept of Mechanical and Materials Engineering, University of Cincinnati, Cincinnati, OH, 45221-0072, USA
| | - Yingsheng Cheng
- Department of Radiology, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, 200233, PR China.
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13
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Ferreira TH, Rocca A, Marino A, Mattoli V, de Sousa EMB, Ciofani G. Evaluation of the effects of boron nitride nanotubes functionalized with gum arabic on the differentiation of rat mesenchymal stem cells. RSC Adv 2015. [DOI: 10.1039/c5ra05091j] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
The biocompatibility of boron nitride nanotubes with rat mesenchymal stem cells has been evaluated in terms of cell proliferation and differentiation.
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Affiliation(s)
- Tiago H. Ferreira
- SENAN
- Centro de Desenvolvimento da Tecnologia Nuclear
- CDTN/CNEN
- 30270-901 Belo Horizonte
- Brazil
| | - Antonella Rocca
- Center for Micro-BioRobotics @SSSA
- Istituto Italiano di Tecnologia
- 56025 Pontedera
- Italy
- The BioRobotics Institute
| | - Attilio Marino
- Center for Micro-BioRobotics @SSSA
- Istituto Italiano di Tecnologia
- 56025 Pontedera
- Italy
- The BioRobotics Institute
| | - Virgilio Mattoli
- Center for Micro-BioRobotics @SSSA
- Istituto Italiano di Tecnologia
- 56025 Pontedera
- Italy
| | - Edesia M. B. de Sousa
- SENAN
- Centro de Desenvolvimento da Tecnologia Nuclear
- CDTN/CNEN
- 30270-901 Belo Horizonte
- Brazil
| | - Gianni Ciofani
- Center for Micro-BioRobotics @SSSA
- Istituto Italiano di Tecnologia
- 56025 Pontedera
- Italy
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14
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Quantum Dots Do Not Alter the Differentiation Potential of Pancreatic Stem Cells and Are Distributed Randomly among Daughter Cells. Int J Cell Biol 2013; 2013:918242. [PMID: 23997768 PMCID: PMC3742022 DOI: 10.1155/2013/918242] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2013] [Revised: 06/21/2013] [Accepted: 06/21/2013] [Indexed: 01/08/2023] Open
Abstract
With the increasing relevance of cell-based therapies, there is a demand for cell-labeling techniques for in vitro and in vivo studies. For the reasonable tracking of transplanted stem cells in animal models, the usage of quantum dots (QDs) for sensitive cellular imaging has major advances. QDs could be delivered to the cytoplasm of the cells providing intense and stable fluorescence. Although QDs are emerging as favourable nanoparticles for bioimaging, substantial investigations are still required to consider their application for adult stem cells. Therefore, rat pancreatic stem cells (PSCs) were labeled with different concentrations of CdSe quantum dots (Qtracker 605 nanocrystals). The QD labeled PSCs showed normal proliferation and their usual spontaneous differentiation potential in vitro. The labeling of the cell population was concentration dependent, with increasing cell load from 5 nM QDs to 20 nM QDs. With time-lapse microscopy, we observed that the transmission of the QD particles during cell divisions was random, appearing as equal or unequal transmission to daughter cells. We report here that QDs offered an efficient and nontoxic way to label pancreatic stem cells without genetic modifications. In summary, QD nanocrystals are a promising tool for stem cell labeling and facilitate tracking of transplanted cells in animal models.
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15
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Mitsiadis TA, Woloszyk A, Jiménez-Rojo L. Nanodentistry: combining nanostructured materials and stem cells for dental tissue regeneration. Nanomedicine (Lond) 2012; 7:1743-53. [DOI: 10.2217/nnm.12.146] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Regenerative dentistry represents an attractive multidisciplinary therapeutic approach that complements traditional restorative/surgery techniques and benefits from recent advances in stem cell biology, molecular biology, genomics and proteomics. Materials science is important in such advances to move regenerative dentistry from the laboratory to the clinic. The design of novel nanostructured materials, such as biomimetic matrices and scaffolds for controlling cell fate and differentiation, and nanoparticles for diagnostics, imaging and targeted treatment, is needed. The combination of nanotechnology, which allows the creation of sophisticated materials with exquisite fine structural detail, and stem cell biology turns out to be increasingly useful in regenerative medicine. The administration to patients of dynamic biological agents comprising stem cells, bioactive scaffolds and/or nanoparticles will certainly increase the regenerative impact of dental pathological tissues. This overview briefly describes some of the actual benefits and future possibilities of nanomaterials in the emerging field of stem cell-based regenerative dentistry.
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Affiliation(s)
- Thimios A Mitsiadis
- Institute of Oral Biology, Department of Orofacial Development & Regeneration, ZZM, Faculty of Medicine, University of Zurich, Zurich, Switzerland
| | - Anna Woloszyk
- Institute of Oral Biology, Department of Orofacial Development & Regeneration, ZZM, Faculty of Medicine, University of Zurich, Zurich, Switzerland
| | - Lucia Jiménez-Rojo
- Institute of Oral Biology, Department of Orofacial Development & Regeneration, ZZM, Faculty of Medicine, University of Zurich, Zurich, Switzerland
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16
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Accomasso L, Cibrario Rocchietti E, Raimondo S, Catalano F, Alberto G, Giannitti A, Minieri V, Turinetto V, Orlando L, Saviozzi S, Caputo G, Geuna S, Martra G, Giachino C. Fluorescent silica nanoparticles improve optical imaging of stem cells allowing direct discrimination between live and early-stage apoptotic cells. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2012; 8:3192-200. [PMID: 22821625 DOI: 10.1002/smll.201200882] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/24/2012] [Indexed: 05/23/2023]
Abstract
Highly bright and photostable cyanine dye-doped silica nanoparticles, IRIS Dots, are developed, which can efficiently label human mesenchymal stem cells (hMSCs). The application procedure used to label hMSCs is fast (2 h), the concentration of IRIS Dots for efficient labeling is low (20 μg mL(-1) ), and the labeled cells can be visualized by flow cytometry, confocal microscopy, and transmission electron microscopy. Labeled hMSCs are unaffected in their viability and proliferation, as well as stemness surface marker expression and differentiation capability into osteocytes. Moreover, this is the first report that shows nonfunctionalized IRIS Dots can discriminate between live and early-stage apoptotic stem cells (both mesenchymal and embryonic) through a distinct external cell surface distribution. On the basis of biocompatibility, efficient labeling, and apoptotic discrimination potential, it is suggested that IRIS Dots can serve as a promising stem cell tracking agent.
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Affiliation(s)
- Lisa Accomasso
- Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043 Orbassano, Torino, Italy
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17
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Paspala SA, Vishwakarma SK, Murthy TV, Rao TN, Khan AA. Potential role of stem cells in severe spinal cord injury: current perspectives and clinical data. STEM CELLS AND CLONING-ADVANCES AND APPLICATIONS 2012; 5:15-27. [PMID: 24198535 PMCID: PMC3781762 DOI: 10.2147/sccaa.s28477] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Stem cell transplantation for spinal cord injury (SCI) along with new pharmacotherapy research offers the potential to restore function and ease the associated social and economic burden in the years ahead. Various sources of stem cells have been used in the treatment of SCI, but the most convincing results have been obtained with neural progenitor cells in preclinical models. Although the use of cell-based transplantation strategies for the repair of chronic SCI remains the long sought after holy grail, these approaches have been to date the most successful when applied in the subacute phase of injury. Application of cell-based strategies for the repair and regeneration of the chronically injured spinal cord will require a combinational strategy that may need to include approaches to overcome the effects of the glial scar, inhibitory molecules, and use of tissue engineering strategies to bridge the lesion. Nonetheless, cell transplantation strategies are promising, and it is anticipated that the Phase I clinical trials of some form of neural stem cell-based approach in SCI will commence very soon.
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Affiliation(s)
- Syed Ab Paspala
- PAN Research Foundation, CARE, Hyderabad, India ; The Institute of Medical Sciences, Hyderabad, India
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18
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de Mel A, Oh JT, Ramesh B, Seifalian AM. Biofunctionalized quantum dots for live monitoring of stem cells: applications in regenerative medicine. Regen Med 2012; 7:335-47. [PMID: 22594327 DOI: 10.2217/rme.12.21] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
AIM This study aimed to live monitor the degree of endothelial progenitor cell (EPC) integration onto tissue-engineering scaffolds by conjugating relevant antibodies to quantum dots (QDs). MATERIALS & METHODS Biocompatible mercaptosuccinic acid-coated QDs were functionalized with two different antibodies to EPC (CD133 with QDs of 640 nm wavelength [λ] and later-stage mature EPCs; and von Willebrand factor with QDs of λ595 and λ555 nm) using conventional carbomide and N-hydroxysuccinimide chemistry. Biofunctionalization was characterized with Fourier-transform infrared spectroscopy. Cell viability assays and gross morphology observations confirmed cytocompatibility and normal patterns of celluar growth. The antigens corresponding to each state of cell maturation were determined using a single excitation at λ488 nm. RESULTS The optimal concentrations of antibody-QD conjugates were biocompatible, hemocompatible and determined the state of EPC transformation to endothelial cells. CONCLUSION Antibody-functionalized QDs suggest new applications in tissue engineering of polymer-based implants where cell integration can potentially be monitored without requiring the sacrifice of implants.
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Affiliation(s)
- Achala de Mel
- UCL Centre for Nanotechnology & Regenerative Medicine, Division of Surgery & Interventional Science, University College London, London, UK
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19
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Perán M, García MA, López-Ruiz E, Bustamante M, Jiménez G, Madeddu R, Marchal JA. Functionalized nanostructures with application in regenerative medicine. Int J Mol Sci 2012; 13:3847-3886. [PMID: 22489186 PMCID: PMC3317746 DOI: 10.3390/ijms13033847] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2012] [Revised: 03/03/2012] [Accepted: 03/06/2012] [Indexed: 12/16/2022] Open
Abstract
In the last decade, both regenerative medicine and nanotechnology have been broadly developed leading important advances in biomedical research as well as in clinical practice. The manipulation on the molecular level and the use of several functionalized nanoscaled materials has application in various fields of regenerative medicine including tissue engineering, cell therapy, diagnosis and drug and gene delivery. The themes covered in this review include nanoparticle systems for tracking transplanted stem cells, self-assembling peptides, nanoparticles for gene delivery into stem cells and biomimetic scaffolds useful for 2D and 3D tissue cell cultures, transplantation and clinical application.
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Affiliation(s)
- Macarena Perán
- Department of Health Sciences, University of Jaén, Jaén E-23071, Spain; E-Mails: (M.P.); (E.L.-R.)
| | - María A. García
- Research Unit, Hospital Universitario Virgen de las Nieves, Granada E-18014, Spain; E-Mail:
| | - Elena López-Ruiz
- Department of Health Sciences, University of Jaén, Jaén E-23071, Spain; E-Mails: (M.P.); (E.L.-R.)
| | - Milán Bustamante
- Biosciences Institute, University College Cork, Cork, Ireland; E-Mail:
| | - Gema Jiménez
- Biopathology and Regenerative Medicine Institute (IBIMER), Biomedical Research Centre, University of Granada, Granada E-18100, Spain; E-Mail:
| | - Roberto Madeddu
- Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy; E-Mail:
| | - Juan A. Marchal
- Biopathology and Regenerative Medicine Institute (IBIMER), Biomedical Research Centre, University of Granada, Granada E-18100, Spain; E-Mail:
- Department of Human Anatomy and Embryology, Faculty of Medicine, University of Granada, Granada E-18012, Spain
- Author to whom correspondence should be addressed; E-Mail: ; Tel.: +34-958-249-321; Fax: +34-958-246-296
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Leung L. Cellular therapies for treating pain associated with spinal cord injury. J Transl Med 2012; 10:37. [PMID: 22394650 PMCID: PMC3320547 DOI: 10.1186/1479-5876-10-37] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2011] [Accepted: 03/06/2012] [Indexed: 12/21/2022] Open
Abstract
Spinal cord injury leads to immense disability and loss of quality of life in human with no satisfactory clinical cure. Cell-based or cell-related therapies have emerged as promising therapeutic potentials both in regeneration of spinal cord and mitigation of neuropathic pain due to spinal cord injury. This article reviews the various options and their latest developments with an update on their therapeutic potentials and clinical trialing.
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Affiliation(s)
- Lawrence Leung
- Centre of Neurosciences Study, Queen's University, 18 Stuart Street, Kingston, ON K7L 3N6, Canada.
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21
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Synthesis of a quinazoline derivative: a new α₁-adrenoceptor ligand for conjugation to quantum dots to study α₁-adrenoceptors in living cells. Bioorg Med Chem Lett 2011; 21:5905-9. [PMID: 21875797 DOI: 10.1016/j.bmcl.2011.07.122] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2011] [Revised: 07/04/2011] [Accepted: 07/23/2011] [Indexed: 11/21/2022]
Abstract
Quantum dots (QDs) that are conjugated to small molecule derivatives of drugs and endogenous ligands may be useful tools to study the distribution and dynamic of membrane bound receptors, ion channels and transporters in live cells. In order to use these tools, it is necessary to functionalize QDs with bioactive ligands. In this paper, we successfully synthesized a ligand of α(1)-adrenoceptor that could be conjugated to QDs. In addition, the conjugation of the ligands to QDs and their biological activity were evaluated through binding assay with 30 nM QD conjugates in living human embryonic kidney 293 cells.
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