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Francius G, Audoux K, Gaye I, Guedon E, Chebil L. Impact of Substrate Surface Chemistry on Wharton's Jelly Mesenchymal Stem Cell Morphological Characteristics, Adherence, and Detachment. ACS APPLIED BIO MATERIALS 2025; 8:4033-4045. [PMID: 40278837 DOI: 10.1021/acsabm.5c00160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/26/2025]
Abstract
Using a multidisciplinary approach combining cell biology assays and physicochemical analyses, the effect of surface chemistry, usually involved in 2D and 3D cell cultures, on the adherence and detachment of Wharton's jelly mesenchymal stem cells (WJ-MSC) was clearly characterized. Values calculated from AFM measurements showed that the Young's modulus of the cells depends on the coating substrate: diethylaminoethyl-dextran (DEAE-D) and carboxypolystyrene (cPS). The adhesion of WJ-MSC was influenced by the composition, charge, and Young's modulus of the surface. High adhesion was observed on DEAE-D. Increasing the wall shear stress decreased the proportion of attached cells on DEAE-D down to ∼20%. For the cPS-coated glass substrate, the fraction of detached cells was higher than that for the DEAE-D surfaces, and at the end of the experiment (maximum wall shear stress of 1 Pa), almost complete detachment was achieved. The experimental strategy used in this work provides information in the field of surface chemistry and may help in the selection and design of efficient microcarriers for cell attachment and detachment during bioreactor cultivation.
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Affiliation(s)
| | - Kévin Audoux
- Université de Lorraine, CNRS, LRGP, F-54000 Nancy, France
| | - Ibrahima Gaye
- Université de Lorraine, CNRS, LRGP, F-54000 Nancy, France
| | | | - Latifa Chebil
- Université de Lorraine, CNRS, LRGP, F-54000 Nancy, France
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Amiri F, Mistriotis P. Leveraging Cell Migration Dynamics to Discriminate Between Senescent and Presenescent Human Mesenchymal Stem Cells. Cell Mol Bioeng 2024; 17:385-399. [PMID: 39513008 PMCID: PMC11538215 DOI: 10.1007/s12195-024-00807-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Accepted: 06/11/2024] [Indexed: 11/15/2024] Open
Abstract
Purpose The suboptimal clinical performance of human mesenchymal stem cells (hMSCs) has raised concerns about their therapeutic potential. One major contributing factor to this issue is the heterogeneous nature of hMSCs. Senescent cell accumulation during stem cell expansion is a key driver of MSC heterogeneity. Current methodologies to eradicate senescent hMSCs have either shown limited success or lack clinical relevance. This study leverages the inherent capacity of hMSCs to migrate toward damaged tissues as a means to discern senescent from presenescent stem cells. Given the established deficiency of senescent cells to migrate through physiologically relevant environments, we hypothesized that a microfluidic device, designed to emulate key facets of in vivo cell motility, could serve as a platform for identifying presenescent cells. Methods We employed a Y-shaped microchannel assay, which allows fine-tuning of fluid flow rates and the degree of confinement. Results Highly migratory hMSCs detected by the device not only demonstrate increased speed, smaller size, and higher proliferative capacity but also manifest reduced DNA damage and senescence compared to non-migratory cells. Additionally, this assay detects presenescent cells in experiments with mixed early and late passage cells. The introduction of fluid flow through the device can further increase the fraction of highly motile stem cells, improving the assay's effectiveness to remove senescent hMSCs. Conclusions Collectively, this assay facilitates the detection and isolation of a highly potent stem cell subpopulation. Given the positive correlation between the migratory potential of administered MSCs and the long-term clinical outcome, delivering homogeneous, highly motile presenescent hMSCs may benefit patient outcomes. Supplementary Information The online version contains supplementary material available at 10.1007/s12195-024-00807-0.
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Affiliation(s)
- Farshad Amiri
- Department of Chemical Engineering, Auburn University, Auburn, AL USA
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Jiang Z, Chen L, Huang L, Yu S, Lin J, Li M, Gao Y, Yang L. Bioactive Materials That Promote the Homing of Endogenous Mesenchymal Stem Cells to Improve Wound Healing. Int J Nanomedicine 2024; 19:7751-7773. [PMID: 39099796 PMCID: PMC11297574 DOI: 10.2147/ijn.s455469] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Accepted: 04/23/2024] [Indexed: 08/06/2024] Open
Abstract
Endogenous stem cell homing refers to the transport of endogenous mesenchymal stem cells (MSCs) to damaged tissue. The paradigm of using well-designed biomaterials to induce resident stem cells to home in to the injured site while coordinating their behavior and function to promote tissue regeneration is known as endogenous regenerative medicine (ERM). ERM is a promising new avenue in regenerative therapy research, and it involves the mobilizing of endogenous stem cells for homing as the principal means through which to achieve it. Comprehending how mesenchymal stem cells home in and grasp the influencing factors of mesenchymal stem cell homing is essential for the understanding and design of tissue engineering. This review summarizes the process of MSC homing, the factors influencing the homing process, analyses endogenous stem cell homing studies of interest in the field of skin tissue repair, explores the integration of endogenous homing promotion strategies with cellular therapies and details tissue engineering strategies that can be used to modulate endogenous homing of stem cells. In addition to providing more systematic theories and ideas for improved materials for endogenous tissue repair, this review provides new perspectives to explore the complex process of tissue remodeling to enhance the rational design of biomaterial scaffolds and guide tissue regeneration strategies.
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Affiliation(s)
- Ziwei Jiang
- Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
| | - Lianglong Chen
- Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
| | - Lei Huang
- Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
| | - Shengxiang Yu
- Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
| | - Jiabao Lin
- Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
| | - Mengyao Li
- Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
| | - Yanbin Gao
- Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
| | - Lei Yang
- Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
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Szydlak R. Mesenchymal stem cells in ischemic tissue regeneration. World J Stem Cells 2023; 15:16-30. [PMID: 36909782 PMCID: PMC9993139 DOI: 10.4252/wjsc.v15.i2.16] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 11/10/2022] [Accepted: 01/19/2023] [Indexed: 02/21/2023] Open
Abstract
Diseases caused by ischemia are one of the leading causes of death in the world. Current therapies for treating acute myocardial infarction, ischemic stroke, and critical limb ischemia do not complete recovery. Regenerative therapies opens new therapeutic strategy in the treatment of ischemic disorders. Mesenchymal stem cells (MSCs) are the most promising option in the field of cell-based therapies, due to their secretory and immunomodulatory abilities, that contribute to ease inflammation and promote the regeneration of damaged tissues. This review presents the current knowledge of the mechanisms of action of MSCs and their therapeutic effects in the treatment of ischemic diseases, described on the basis of data from in vitro experiments and preclinical animal studies, and also summarize the effects of using these cells in clinical trial settings. Since the obtained therapeutic benefits are not always satisfactory, approaches aimed at enhancing the effect of MSCs in regenerative therapies are presented at the end.
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Affiliation(s)
- Renata Szydlak
- Chair of Medical Biochemistry, Faculty of Medicine, Jagiellonian University Medical College, Kraków 31-034, Poland
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Qin Y, Yang W, Chu H, Li Y, Cai S, Yu H, Liu L. Atomic Force Microscopy for Tumor Research at Cell and Molecule Levels. MICROSCOPY AND MICROANALYSIS : THE OFFICIAL JOURNAL OF MICROSCOPY SOCIETY OF AMERICA, MICROBEAM ANALYSIS SOCIETY, MICROSCOPICAL SOCIETY OF CANADA 2022; 28:1-18. [PMID: 35257653 DOI: 10.1017/s1431927622000290] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Tumors have posed a serious threat to human life and health. Researchers can determine whether or not cells are cancerous, whether the cancer cells are invasive or metastatic, and what the effects of drugs are on cancer cells by the physical properties such as hardness, adhesion, and Young's modulus. The atomic force microscope (AFM) has emerged as a key important tool for biomechanics research on tumor cells due to its ability to image and collect force spectroscopy information of biological samples with nano-level spatial resolution and under near-physiological conditions. This article reviews the existing results of the study of cancer cells with AFM. The main foci are the operating principle of AFM and research advances in mechanical property measurement, ultra-microtopography, and molecular recognition of tumor cells, which allows us to outline what we do know it in a systematic way and to summarize and to discuss future directions.
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Affiliation(s)
- Yitong Qin
- School of Electromechanical and Automotive Engineering, Yantai University, Yantai264005, China
| | - Wenguang Yang
- School of Electromechanical and Automotive Engineering, Yantai University, Yantai264005, China
| | - Honghui Chu
- School of Electromechanical and Automotive Engineering, Yantai University, Yantai264005, China
| | - Yan Li
- School of Electromechanical and Automotive Engineering, Yantai University, Yantai264005, China
| | - Shuxiang Cai
- School of Electromechanical and Automotive Engineering, Yantai University, Yantai264005, China
| | - Haibo Yu
- State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang110016, China
| | - Lianqing Liu
- State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang110016, China
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The Hertzian theory in AFM nanoindentation experiments regarding biological samples: Overcoming limitations in data processing. Micron 2022; 155:103228. [DOI: 10.1016/j.micron.2022.103228] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 12/09/2021] [Accepted: 01/26/2022] [Indexed: 11/21/2022]
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Quality control methods in musculoskeletal tissue engineering: from imaging to biosensors. Bone Res 2021; 9:46. [PMID: 34707086 PMCID: PMC8551153 DOI: 10.1038/s41413-021-00167-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Revised: 04/23/2021] [Accepted: 06/27/2021] [Indexed: 02/06/2023] Open
Abstract
Tissue engineering is rapidly progressing toward clinical application. In the musculoskeletal field, there has been an increasing necessity for bone and cartilage replacement. Despite the promising translational potential of tissue engineering approaches, careful attention should be given to the quality of developed constructs to increase the real applicability to patients. After a general introduction to musculoskeletal tissue engineering, this narrative review aims to offer an overview of methods, starting from classical techniques, such as gene expression analysis and histology, to less common methods, such as Raman spectroscopy, microcomputed tomography, and biosensors, that can be employed to assess the quality of constructs in terms of viability, morphology, or matrix deposition. A particular emphasis is given to standards and good practices (GXP), which can be applicable in different sectors. Moreover, a classification of the methods into destructive, noninvasive, or conservative based on the possible further development of a preimplant quality monitoring system is proposed. Biosensors in musculoskeletal tissue engineering have not yet been used but have been proposed as a novel technology that can be exploited with numerous advantages, including minimal invasiveness, making them suitable for the development of preimplant quality control systems.
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Szydlak R. Biological, chemical and mechanical factors regulating migration and homing of mesenchymal stem cells. World J Stem Cells 2021; 13:619-631. [PMID: 34249231 PMCID: PMC8246245 DOI: 10.4252/wjsc.v13.i6.619] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 04/03/2021] [Accepted: 05/17/2021] [Indexed: 02/06/2023] Open
Abstract
Mesenchymal stem cells (MSCs) are a population of primary and non-specialized cells, which can be isolated from various tissues. Currently, MSCs are key players in cellular therapy and regenerative medicine. However, the possibility of using MSCs in the treatment of many diseases needs to be preceded, though, by in-depth analysis of their properties, especially by determining the mechanism of tissue homing as well as the mechanism, due to which cells contribute to tissue regeneration. This review is intended to present information on recent findings regarding the mechanism of recruitment and tissue homing by MSCs and discuss current hypotheses for how MSCs can reach target tissues.
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Affiliation(s)
- Renata Szydlak
- Department of Medical Biochemistry, Faculty of Medicine, Jagiellonian University Medical College, Kraków 31-034, Poland
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Danalache M, Knoll J, Linzenbold W, Enderle M, Abruzzese T, Stenzl A, Aicher WK. Injection of Porcine Adipose Tissue-Derived Stromal Cells by a Novel Waterjet Technology. Int J Mol Sci 2021; 22:ijms22083958. [PMID: 33921246 PMCID: PMC8070533 DOI: 10.3390/ijms22083958] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Revised: 04/07/2021] [Accepted: 04/08/2021] [Indexed: 12/13/2022] Open
Abstract
Previously, we developed a novel, needle-free waterjet (WJ) technology capable of injecting viable cells by visual guided cystoscopy in the urethral sphincter. In the present study, we aimed to investigate the effect of WJ technology on cell viability, surface markers, differentiation and attachment capabilities, and biomechanical features. Porcine adipose tissue-derived stromal cells (pADSCs) were isolated, expanded, and injected by WJ technology. Cell attachment assays were employed to investigate cell-matrix interactions. Cell surface molecules were analyzed by flow cytometry. Cells injected by Williams Needle (WN), normal cannula, or not injected cells served as controls. Biomechanical properties were assessed by atomic force microscopy (AFM). pADSCs injected by the WJ were viable (85.9%), proliferated well, and maintained their in vitro adipogenic and osteogenic differentiation capacities. The attachment of pADSCs was not affected by WJ injection and no major changes were noted for cell surface markers. AFM measurements yielded a significant reduction of cellular stiffness after WJ injections (p < 0.001). WJ cell delivery satisfies several key considerations required in a clinical context, including the fast, simple, and reproducible delivery of viable cells. However, the optimization of the WJ device may be necessary to further reduce the effects on the biomechanical properties of cells.
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Affiliation(s)
- Marina Danalache
- Department of Orthopaedic Surgery, University Hospital Tübingen, 72072 Tübingen, Germany;
| | - Jasmin Knoll
- Department of Urology, University Hospital Tübingen, Waldhörnlestrasse 22, 72072 Tübingen, Germany; (J.K.); (T.A.); (A.S.)
| | - Walter Linzenbold
- ERBE Elektromedizin GmbH Tübingen, 72072 Tübingen, Germany; (W.L.); (M.E.)
| | - Markus Enderle
- ERBE Elektromedizin GmbH Tübingen, 72072 Tübingen, Germany; (W.L.); (M.E.)
| | - Tanja Abruzzese
- Department of Urology, University Hospital Tübingen, Waldhörnlestrasse 22, 72072 Tübingen, Germany; (J.K.); (T.A.); (A.S.)
| | - Arnulf Stenzl
- Department of Urology, University Hospital Tübingen, Waldhörnlestrasse 22, 72072 Tübingen, Germany; (J.K.); (T.A.); (A.S.)
| | - Wilhelm K. Aicher
- Department of Urology, University Hospital Tübingen, Waldhörnlestrasse 22, 72072 Tübingen, Germany; (J.K.); (T.A.); (A.S.)
- Correspondence: ; Tel.: +49-7071-298-7021; Fax: +49-7071-292-5072
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Liang W, Shi H, Yang X, Wang J, Yang W, Zhang H, Liu L. Recent advances in AFM-based biological characterization and applications at multiple levels. SOFT MATTER 2020; 16:8962-8984. [PMID: 32996549 DOI: 10.1039/d0sm01106a] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Atomic force microscopy (AFM) has found a wide range of bio-applications in the past few decades due to its ability to measure biological samples in natural environments at a high spatial resolution. AFM has become a key platform in biomedical, bioengineering and drug research fields, enabling mechanical and morphological characterization of live biological systems. Hence, we provide a comprehensive review on recent advances in the use of AFM for characterizing the biomechanical properties of multi-scale biological samples, ranging from molecule, cell to tissue levels. First, we present the fundamental principles of AFM and two AFM-based models for the characterization of biomechanical properties of biological samples, covering key AFM devices and AFM bioimaging as well as theoretical models for characterizing the elasticity and viscosity of biomaterials. Then, we elaborate on a series of new experimental findings through analysis of biomechanics. Finally, we discuss the future directions and challenges. It is envisioned that the AFM technique will enable many remarkable discoveries, and will have far-reaching impacts on bio-related studies and applications in the future.
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Affiliation(s)
- Wenfeng Liang
- School of Mechanical Engineering, Shenyang Jianzhu University, Shenyang, 110168, China.
| | - Haohao Shi
- School of Mechanical Engineering, Shenyang Jianzhu University, Shenyang, 110168, China.
| | - Xieliu Yang
- School of Mechanical Engineering, Shenyang Jianzhu University, Shenyang, 110168, China.
| | - Junhai Wang
- School of Mechanical Engineering, Shenyang Jianzhu University, Shenyang, 110168, China.
| | - Wenguang Yang
- School of Electromechanical and Automotive Engineering, Yantai University, Yantai 264005, China
| | - Hemin Zhang
- Department of Neurology, The People's Hospital of Liaoning Province, Shenyang 110016, China.
| | - Lianqing Liu
- State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016, China.
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