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Basu B, Aditya D, Kumaran V, Ravikumar K. Biophysical insights into the impact of lateral electric field stimulation to cellular microenvironment: Implications for bioelectronic medicine applications. Biomaterials 2025; 319:123132. [PMID: 40023129 DOI: 10.1016/j.biomaterials.2025.123132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2024] [Revised: 12/29/2024] [Accepted: 01/23/2025] [Indexed: 03/04/2025]
Abstract
In the last few decades, electrical stimulation devices have been clinically used for a wide spectrum of applications, ranging from deep brain stimulation to drug and gene delivery. Despite such clinical relevance, the impact of electrical stimulation on the cellular biophysical processes has not been explored significantly. We report here the analytical results to develop quantitative biophysical insights into the influence of lateral electric field stimulation on bioelectric stresses in the intercellular/extracellular region and the membrane tension. In developing quantitative insights, we solved Laplace equation with appropriate boundary conditions in an azimuthally asymmetric system with a single cell. The magnitude of the stresses increases with the electric field strength in a parabolic manner. In case of cell without surface charges, the intracellular stress field is predicted to have both compressive and tensile regions with a maximum of 2 μPa, while a maximum tensile stress of 20 μPa in extracellular region could be predicted, at field strength of 300 V/m. While considering surface charges, the magnitude of extracellular normal and shear stresses at the cell membrane is an order of magnitude higher when compared to without surface charges. Based on the variation of shear stress tensors at cell membrane, the critical field strength for membrane rupture was found to be 5.3 kV/mm and 20 kV/mm for a cell without and with surface charges respectively. The impact of the bioelectric stresses on the mechanotransduction induced cytoskeletal reorganization and stress driven cellular signalling modulation were substantiated using quantitative results from the study.
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Affiliation(s)
- Bikramjit Basu
- Laboratory for Biomaterials Science and Translational Research, Materials Research Centre, Indian Institute of Science, Bangalore, 560012, India.
| | - Dhanush Aditya
- Laboratory for Biomaterials Science and Translational Research, Materials Research Centre, Indian Institute of Science, Bangalore, 560012, India
| | - V Kumaran
- Laboratory for Biomaterials Science and Translational Research, Materials Research Centre, Indian Institute of Science, Bangalore, 560012, India
| | - K Ravikumar
- Laboratory for Biomaterials Science and Translational Research, Materials Research Centre, Indian Institute of Science, Bangalore, 560012, India.
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Xu L, Ren W, Long Y, Yang B, Chen L, Chen W, Chen S, Cao Y, Wu D, Qu J, Li H, Yu Y, Zhang A, Wang S, Wang H, Chen T, Fan G, Li Q, Chen Z. Antisenescence Expansion of Mesenchymal Stem Cells Using Piezoelectric β-Poly(vinylidene fluoride) Film-Based Culture. ACS APPLIED MATERIALS & INTERFACES 2024; 16:63207-63224. [PMID: 39503875 DOI: 10.1021/acsami.4c12725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2024]
Abstract
Regenerative therapies based on mesenchymal stem cells (MSCs) show promise in treating a wide range of disorders. However, the replicative senescence of MSCs during in vitro expansion poses a challenge to obtaining a substantial quantity of high-quality MSCs. In this investigation, a piezoelectric β-poly(vinylidene fluoride) film-based culture plate (β-CP) was developed with an antisenescence effect on cultured human umbilical cord-derived MSCs. Compared to traditional tissue culture plates (TCPs) and α-poly(vinylidene fluoride) film-based culture plates, the senescence markers of p21, p53, interleukin-6 and insulin-like growth factor-binding protein-7, stemness markers of OCT4 and NANOG, and telomere length of MSCs cultured on β-CPs were significantly improved. Additionally, MSCs at passage 18 cultured on β-CPs showed significantly better multipotency and pro-angiogenic capacities in vitro, and higher wound healing abilities in a mouse model. Mechanistically, β-CPs rejuvenated senescent MSCs by improving mitochondrial functions and mitigating oxidative and glycoxidative stresses. Overall, this study presents β-CPs as a promising approach for efficient and straightforward antisenescence expansion of MSCs while preserving their stemness, thereby holding great potential for large-scale production of MSCs for clinical application in cell therapies.
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Affiliation(s)
- Liuyue Xu
- Department of Rheumatology and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Wenxiang Ren
- Center for Hematology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China
| | - Yaoying Long
- Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Bianlei Yang
- Department of Rheumatology and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Li Chen
- Department of Hematology, Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China
| | - Wenlan Chen
- Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Siyi Chen
- Department of Rheumatology and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Yulin Cao
- Department of Rheumatology and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Di Wu
- Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Jiao Qu
- Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - He Li
- Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Yali Yu
- Department of Rheumatology and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Anyuan Zhang
- Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Shan Wang
- Department of Rheumatology and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Hongxiang Wang
- Department of Hematology, Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China
| | - Ting Chen
- Hubei Engineering Research Center for Application of Extracellular Vesicles, Hubei University of Science and Technology, Xianning 437100, China
| | - Guifen Fan
- School of Optical and Electronic Information, Key Lab of Functional Materials for Electronic Information(B), MOE, Huazhong University of Science and Technology, Wuhan 430074, China
- Wenzhou Advanced Manufacturing Institute, Huazhong University of Science and Technology, Wenzhou 325035, China
| | - Qiubai Li
- Department of Rheumatology and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Hubei Engineering Research Center for Application of Extracellular Vesicles, Hubei University of Science and Technology, Xianning 437100, China
| | - Zhichao Chen
- Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
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Zironi I, Cramer T, Fuschi A, Cioni M, Guerra G, Giuliani G, Calienni M, Caramazza L, Liberti M, Apollonio F, Remondini D, Castellani G. Enhancing cell motility via non-contact capacitively coupled electrostatic field. Sci Rep 2024; 14:28085. [PMID: 39543219 PMCID: PMC11564694 DOI: 10.1038/s41598-024-77384-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Accepted: 10/22/2024] [Indexed: 11/17/2024] Open
Abstract
Cellular motility is essential for making and maintaining multicellular organisms throughout their lifespan. Migrating cells can move either individually or collectively by a crawling movement that links the cytoskeletal activity to the adhesion surface. In vitro stimulation by electric fields can be achieved by direct, capacitive or inductive coupled setups. We tested the effects of electrical stimulation provided by capacitive coupling on glioma cells, using a capacitive-coupled system powered by a potential difference of 35 V between two electrodes placed outside the culture dish. Numerical dosimetry identified two different fields: (i) in the order of 103 V/m at the level of the dielectric substrates, with almost uniform distribution; (ii) in the order of 10-1 V/m at the level of the culture medium, with spatial and material-dependent distribution. The scratch assay and the tracking of single-cell movement showed a boosted motility when crawling occurs on polystyrene surfaces, demonstrating the feasibility of this peculiar exposure system to generate forces capable of influencing cell behavior.
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Affiliation(s)
- Isabella Zironi
- Department of Physics and Astronomy (DIFA), Alma Mater Studiorum University of Bologna, Viale Berti Pichat 6/2, Bologna, 40127, Italy.
- National Institute for Nuclear Physics (INFN BO), Bologna section, Viale Berti Pichat 6/2, Bologna, 40127, Italy.
| | - Tobias Cramer
- Department of Physics and Astronomy (DIFA), Alma Mater Studiorum University of Bologna, Viale Berti Pichat 6/2, Bologna, 40127, Italy
| | - Alessandro Fuschi
- Department of Physics and Astronomy (DIFA), Alma Mater Studiorum University of Bologna, Viale Berti Pichat 6/2, Bologna, 40127, Italy
| | - Margherita Cioni
- Department of Physics and Astronomy (DIFA), Alma Mater Studiorum University of Bologna, Viale Berti Pichat 6/2, Bologna, 40127, Italy.
| | - Giada Guerra
- Department for Life Quality Studies (QUVI), Alma Mater Studiorum University of Bologna, C.so d'Augusto, 237, Rimini, 47921, Italy
| | - Giacomo Giuliani
- Department of Physics and Astronomy (DIFA), Alma Mater Studiorum University of Bologna, Viale Berti Pichat 6/2, Bologna, 40127, Italy
| | - Maria Calienni
- Centro Laboratori di Didattica Chimica (CILDIC), Alma Mater Studiorum University of Bologna, Via Gobetti 87, Bologna, 40129, Italy
| | - Laura Caramazza
- BioEM Lab, Department of Information Engineering, Electronics and Telecommunications (DIET), Sapienza University of Rome, Via Eudossiana 18, Rome, 00184, Italy
| | - Micaela Liberti
- BioEM Lab, Department of Information Engineering, Electronics and Telecommunications (DIET), Sapienza University of Rome, Via Eudossiana 18, Rome, 00184, Italy
| | - Francesca Apollonio
- BioEM Lab, Department of Information Engineering, Electronics and Telecommunications (DIET), Sapienza University of Rome, Via Eudossiana 18, Rome, 00184, Italy
| | - Daniel Remondini
- Department of Physics and Astronomy (DIFA), Alma Mater Studiorum University of Bologna, Viale Berti Pichat 6/2, Bologna, 40127, Italy
- National Institute for Nuclear Physics (INFN BO), Bologna section, Viale Berti Pichat 6/2, Bologna, 40127, Italy
| | - Gastone Castellani
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Via Massarenti 9, Bologna, 40138, Italy
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Massarenti, 9, Bologna, 40138, Italy
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Augustine R, Gezek M, Nikolopoulos VK, Buck PL, Bostanci NS, Camci-Unal G. Stem Cells in Bone Tissue Engineering: Progress, Promises and Challenges. Stem Cell Rev Rep 2024; 20:1692-1731. [PMID: 39028416 DOI: 10.1007/s12015-024-10738-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/17/2024] [Indexed: 07/20/2024]
Abstract
Bone defects from accidents, congenital conditions, and age-related diseases significantly impact quality of life. Recent advancements in bone tissue engineering (TE) involve biomaterial scaffolds, patient-derived cells, and bioactive agents, enabling functional bone regeneration. Stem cells, obtained from numerous sources including umbilical cord blood, adipose tissue, bone marrow, and dental pulp, hold immense potential in bone TE. Induced pluripotent stem cells and genetically modified stem cells can also be used. Proper manipulation of physical, chemical, and biological stimulation is crucial for their proliferation, maintenance, and differentiation. Stem cells contribute to osteogenesis, osteoinduction, angiogenesis, and mineralization, essential for bone regeneration. This review provides an overview of the latest developments in stem cell-based TE for repairing and regenerating defective bones.
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Affiliation(s)
- Robin Augustine
- Department of Radiology, Stanford Medicine, Stanford University, Palo Alto, CA, 94304, USA
- Department of Chemical Engineering, University of Massachusetts, Lowell, MA, 01854, USA
| | - Mert Gezek
- Department of Chemical Engineering, University of Massachusetts, Lowell, MA, 01854, USA
- Biomedical Engineering and Biotechnology Graduate Program, University of Massachusetts, Lowell, MA, 01854, USA
| | | | - Paige Lauren Buck
- Department of Chemical Engineering, University of Massachusetts, Lowell, MA, 01854, USA
- Biomedical Engineering and Biotechnology Graduate Program, University of Massachusetts, Lowell, MA, 01854, USA
| | - Nazli Seray Bostanci
- Department of Chemical Engineering, University of Massachusetts, Lowell, MA, 01854, USA
- Biomedical Engineering and Biotechnology Graduate Program, University of Massachusetts, Lowell, MA, 01854, USA
| | - Gulden Camci-Unal
- Department of Chemical Engineering, University of Massachusetts, Lowell, MA, 01854, USA.
- Department of Surgery, University of Massachusetts Medical School, Worcester, MA, 01605, USA.
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Huang Y, Yao K, Zhang Q, Huang X, Chen Z, Zhou Y, Yu X. Bioelectronics for electrical stimulation: materials, devices and biomedical applications. Chem Soc Rev 2024; 53:8632-8712. [PMID: 39132912 DOI: 10.1039/d4cs00413b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/13/2024]
Abstract
Bioelectronics is a hot research topic, yet an important tool, as it facilitates the creation of advanced medical devices that interact with biological systems to effectively diagnose, monitor and treat a broad spectrum of health conditions. Electrical stimulation (ES) is a pivotal technique in bioelectronics, offering a precise, non-pharmacological means to modulate and control biological processes across molecular, cellular, tissue, and organ levels. This method holds the potential to restore or enhance physiological functions compromised by diseases or injuries by integrating sophisticated electrical signals, device interfaces, and designs tailored to specific biological mechanisms. This review explains the mechanisms by which ES influences cellular behaviors, introduces the essential stimulation principles, discusses the performance requirements for optimal ES systems, and highlights the representative applications. From this review, we can realize the potential of ES based bioelectronics in therapy, regenerative medicine and rehabilitation engineering technologies, ranging from tissue engineering to neurological technologies, and the modulation of cardiovascular and cognitive functions. This review underscores the versatility of ES in various biomedical contexts and emphasizes the need to adapt to complex biological and clinical landscapes it addresses.
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Affiliation(s)
- Ya Huang
- Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China
| | - Kuanming Yao
- Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China
| | - Qiang Zhang
- Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China
| | - Xingcan Huang
- Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China
| | - Zhenlin Chen
- Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China
| | - Yu Zhou
- Department of Electronic and Computer Engineering, The Hong Kong University of Science and Technology, Hong Kong, China.
| | - Xinge Yu
- Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China
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6
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Tian JS, Tay A. Progress on Electro-Enhancement of Cell Manufacturing. SMALL METHODS 2024; 8:e2301281. [PMID: 38059759 DOI: 10.1002/smtd.202301281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Revised: 11/09/2023] [Indexed: 12/08/2023]
Abstract
With the long persistence of complex, chronic diseases in society, there is increasing motivation to develop cells as living medicine to treat diseases ranging from cancer to wounds. While cell therapies can significantly impact healthcare, the shortage of starter cells meant that considerable raw materials must be channeled solely for cell expansion, leading to expensive products with long manufacturing time which can prevent accessibility by patients who either cannot afford the treatment or have highly aggressive diseases and cannot wait that long. Over the last three decades, there has been increasing knowledge on the effects of electrical modulation on proliferation, but to the best of the knowledge, none of these studies went beyond how electro-control of cell proliferation may be extended to enhance industrial scale cell manufacturing. Here, this review is started by discussing the importance of maximizing cell yield during manufacturing before comparing strategies spanning biomolecular/chemical/physical to modulate cell proliferation. Next, the authors describe how factors governing invasive and non-invasive electrical stimulation (ES) including capacitive coupling electric field may be modified to boost cell manufacturing. This review concludes by describing what needs to be urgently performed to bridge the gap between academic investigation of ES to industrial applications.
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Affiliation(s)
- Johann Shane Tian
- Department of Biomedical Engineering, National University of Singapore, Singapore, 117583, Singapore
| | - Andy Tay
- Department of Biomedical Engineering, National University of Singapore, Singapore, 117583, Singapore
- Institute for Health Innovation and Technology, National University of Singapore, Singapore, 117599, Singapore
- NUS Tissue Engineering Program, National University of Singapore, Singapore, 117510, Singapore
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Di Martino A, Villari E, Poluzzi R, Brunello M, Rossomando V, D’Agostino C, Ruta F, Faldini C. Role of biophysical stimulation in multimodal management of vertebral compression fractures. Comput Struct Biotechnol J 2023; 21:5650-5661. [PMID: 38047233 PMCID: PMC10692617 DOI: 10.1016/j.csbj.2023.11.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Revised: 11/10/2023] [Accepted: 11/10/2023] [Indexed: 12/05/2023] Open
Abstract
Raised life expectancy and aging of the general population are associated with an increased concern for fragility fractures due to factors such as osteoporosis, reduced bone density, and an higher risk of falls. Among these, the most frequent are vertebral compression fractures (VCF), which can be clinically occult. Once the diagnosis is made, generally thorough antero-posterior and lateral views of the affected spine at the radiographs, a comprehensive workup to assess the presence of a metabolic bone disease or secondary causes of osteoporosis and bone frailty is required. Treatment uses a multimodal management consisting of a combination of brace, pain management, bone metabolism evaluation, osteoporosis medication and has recently incorporated biophysical stimulation, a noninvasive technique that uses induced electric stimulation to improve bone recovery through the direct and indirect upregulation of bone morphogenic proteins, stimulating bone formation and remodeling. It contributes to the effectiveness of the therapy, promoting accelerated healing, supporting the reduction of bed rest and pain medications, improving patients' quality of life, and reducing the risk to undergo surgery in patients affected by VCFs. Therefore, the aim of this review is to outline the fundamental concepts of multimodal treatment for VCF, as well as the present function and significance of biophysical stimulation in the treatment of VCF patients.
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Affiliation(s)
- Alberto Di Martino
- 1st Orthopaedic and Traumatologic Department, IRCCS Istituto Ortopedico Rizzoli, Via G.B. Pupilli 1, 40136 Bologna, Italy
- Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy
| | - Eleonora Villari
- 1st Orthopaedic and Traumatologic Department, IRCCS Istituto Ortopedico Rizzoli, Via G.B. Pupilli 1, 40136 Bologna, Italy
- Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy
| | - Riccardo Poluzzi
- 1st Orthopaedic and Traumatologic Department, IRCCS Istituto Ortopedico Rizzoli, Via G.B. Pupilli 1, 40136 Bologna, Italy
- Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy
| | - Matteo Brunello
- 1st Orthopaedic and Traumatologic Department, IRCCS Istituto Ortopedico Rizzoli, Via G.B. Pupilli 1, 40136 Bologna, Italy
- Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy
| | - Valentino Rossomando
- 1st Orthopaedic and Traumatologic Department, IRCCS Istituto Ortopedico Rizzoli, Via G.B. Pupilli 1, 40136 Bologna, Italy
- Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy
| | - Claudio D’Agostino
- 1st Orthopaedic and Traumatologic Department, IRCCS Istituto Ortopedico Rizzoli, Via G.B. Pupilli 1, 40136 Bologna, Italy
- Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy
| | - Federico Ruta
- 1st Orthopaedic and Traumatologic Department, IRCCS Istituto Ortopedico Rizzoli, Via G.B. Pupilli 1, 40136 Bologna, Italy
- Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy
| | - Cesare Faldini
- 1st Orthopaedic and Traumatologic Department, IRCCS Istituto Ortopedico Rizzoli, Via G.B. Pupilli 1, 40136 Bologna, Italy
- Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy
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Singh P, Dubey AK. Accelerated Osteogenic Response of Electrodynamically Stimulated Mg 1-xCa xSi 1-xZr xO 3 ( x = 0-0.4) Bioelectrets. ACS Biomater Sci Eng 2023; 9:6293-6308. [PMID: 37877692 DOI: 10.1021/acsbiomaterials.3c00955] [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: 10/26/2023]
Abstract
MgSiO3-based biodegradable ceramics demonstrated remarkable potential for treating small-scale bone defects and temporary bone replacement. In addition, the dissolution behavior of MgSiO3 bioceramics can be tuned by doping of Ca and Zr elements at Mg and Si sites, respectively. The present study reported the influence of formation of Ca- and Zr-codoped Mg1-xCaxSi1-xZrxO3 (x = 0, 0.1, 0.2, 0.3, and 0.4) bioelectrets and electrodynamic stimulation toward improving their osteogenic response. Mg1-xCaxSi1-xZrxO3 electrets were successfully synthesized by a solid-state route. A detailed X-ray photoelectron spectroscopy (XPS) analyses revealed that the electrets produced oxygen-deficient active sites. The formation of Mg1-xCaxSi1-xZrxO3 electrets significantly increased the surface hydrophilicity. Inductively coupled plasma (ICP) analyses were used to examine the leaching behavior of Ca/Zr-codoped MgSiO3 bioceramics. In vitro cell culture analyses indicated that the osteogenesis of MG-63 cells was remarkably enhanced on the electrodynamic field-treated Mg1-xCaxSi1-xZrxO3 bioelectrets as compared to hydroxyapatite (HA). Moreover, a better osteogenic response was observed for higher concentrations of Ca (0.3 and 0.4) and Zr (0.3 and 0.4) doping in the MgSiO3 bioelectrets. Further, the mechanism of enhanced cellular functionality was revealed by the measurement of intracellular Ca2+.
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Affiliation(s)
- Priya Singh
- Department of Ceramic Engineering, Indian Institute of Technology (BHU) Varanasi, Varanasi 221005, India
| | - Ashutosh Kumar Dubey
- Department of Ceramic Engineering, Indian Institute of Technology (BHU) Varanasi, Varanasi 221005, India
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Sahm F, Freiin Grote V, Zimmermann J, Haack F, Uhrmacher AM, van Rienen U, Bader R, Detsch R, Jonitz-Heincke A. Long-term stimulation with alternating electric fields modulates the differentiation and mineralization of human pre-osteoblasts. Front Physiol 2022; 13:965181. [PMID: 36246121 PMCID: PMC9562827 DOI: 10.3389/fphys.2022.965181] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Accepted: 09/13/2022] [Indexed: 11/17/2022] Open
Abstract
Biophysical stimulation by electric fields can promote bone formation in bone defects of critical size. Even though, long-term effects of alternating electric fields on the differentiation of osteoblasts are not fully understood. Human pre-osteoblasts were stimulated over 31 days to gain more information about these cellular processes. An alternating electric field with 0.7 Vrms and 20 Hz at two distances was applied and viability, mineralization, gene expression, and protein release of differentiation factors were analyzed. The viability was enhanced during the first days of stimulation. A higher electric field resulted in upregulation of typical osteogenic markers like osteoprotegerin, osteopontin, and interleukin-6, but no significant changes in mineralization. Upregulation of the osteogenic markers could be detected with a lower electric field after the first days of stimulation. As a significant increase in the mineralized matrix was identified, an enhanced osteogenesis due to low alternating electric fields can be assumed.
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Affiliation(s)
- Franziska Sahm
- Biomechanics and Implant Technology Research Laboratory, Department of Orthopedics, Rostock University Medical Centre, Rostock, Germany
- *Correspondence: Franziska Sahm, ; Anika Jonitz-Heincke,
| | - Vivica Freiin Grote
- Biomechanics and Implant Technology Research Laboratory, Department of Orthopedics, Rostock University Medical Centre, Rostock, Germany
| | - Julius Zimmermann
- Chair of Theoretical Electrical Engineering, Institute for General Electrical Engineering, University of Rostock, Rostock, Germany
| | - Fiete Haack
- Institute for Visual and Analytic Computing, University of Rostock, Rostock, Germany
| | - Adelinde M. Uhrmacher
- Institute for Visual and Analytic Computing, University of Rostock, Rostock, Germany
| | - Ursula van Rienen
- Chair of Theoretical Electrical Engineering, Institute for General Electrical Engineering, University of Rostock, Rostock, Germany
- Department Life, Light and Matter, University of Rostock, Rostock, Germany
- Department Ageing of Individuals and Society, University of Rostock, Rostock, Germany
| | - Rainer Bader
- Biomechanics and Implant Technology Research Laboratory, Department of Orthopedics, Rostock University Medical Centre, Rostock, Germany
| | - Rainer Detsch
- Department of Materials Science and Engineering, Institute of Biomaterials, Friedrich Alexander-University Erlangen-Nuremberg, Erlangen, Germany
| | - Anika Jonitz-Heincke
- Biomechanics and Implant Technology Research Laboratory, Department of Orthopedics, Rostock University Medical Centre, Rostock, Germany
- *Correspondence: Franziska Sahm, ; Anika Jonitz-Heincke,
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10
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Lee PS, Heinemann C, Zheng K, Appali R, Alt F, Krieghoff J, Bernhardt A, Boccaccini AR, van Rienen U, Hintze V. The interplay of collagen/bioactive glass nanoparticle coatings and electrical stimulation regimes distinctly enhanced osteogenic differentiation of human mesenchymal stem cells. Acta Biomater 2022; 149:373-386. [PMID: 35817340 DOI: 10.1016/j.actbio.2022.06.045] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 06/24/2022] [Accepted: 06/30/2022] [Indexed: 12/25/2022]
Abstract
Increasing research has incorporated bioactive glass nanoparticles (BGN) and electric field (EF) stimulation for bone tissue engineering and regeneration applications. However, their interplay and the effects of different EF stimulation regimes on osteogenic differentiation of human mesenchymal stem cells (hMSC) are less investigated. In this study, we introduced EF with negligible magnetic field strength through a well-characterized transformer-like coupling (TLC) system, and applied EF disrupted (4/4) or consecutive (12/12) regime on type I collagen (Col) coatings with/without BGN over 28 days. Additionally, dexamethasone was excluded to enable an accurate interpretation of BGN and EF in supporting osteogenic differentiation. Here, we demonstrated the influences of BGN and EF on collagen topography and maintaining coating stability. Coupled with the release profile of Si ions from the BGN, cell proliferation and calcium deposition were enhanced in the Col-BGN samples after 28 days. Further, osteogenic differentiation was initiated as early as d 7, and each EF regime was shown to activate distinct pathways. The disrupted (4/4) regime was associated with the BMP/Smad4 pathways that up-regulate Runx2/OCN gene expression on d 7, with a lesser effect on ALP activity. In contrast, the canonical Wnt/β-Catenin signaling pathway activated through mechanotransduction cues is associated with the consecutive (12/12) regime, with significantly elevated ALP activity and Sp7 gene expression reported on d 7. In summary, our results illustrated the synergistic effects of BGN and EF in different stimulation regimes on osteogenic differentiation that can be further exploited to enhance current bone tissue engineering and regeneration approaches. STATEMENT OF SIGNIFICANCE: The unique release mechanisms of silica from bioactive glass nanoparticles (BGN) were coupled with pulsatile electric field (EF) stimulation to support hMSC osteogenic differentiation, in the absence of dexamethasone. Furthermore, the interplay with consecutive (12/12) and disrupted (4/4) stimulation regimes was investigated. The reported physical, mechanical and topographical effects of BGN and EF on the collagen coating, hMSC and the distinct progression of osteogenic differentiation (canonical Wnt/β-Catenin and BMP/Smad) triggered by respective stimulation regime were not explicitly reported previously. These results provide the fundamentals for further exploitations on BGN composites with metal ions and rotation of EF regimes to enhance osteogenic differentiation. The goal is sustaining continual osteogenic differentiation and achieving a more physiologically-relevant state and bone constructs in vitro.
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Affiliation(s)
- Poh Soo Lee
- Institute of General Electrical Engineering, Faculty of Computer Science and Electrical Engineering, University of Rostock, Albert-Einstein-Straße 2, Rostock 18059, Germany; Max Bergmann Centre of Biomaterials, Institute of Materials Science, Faculty of Mechanical Science and Engineering, Technische Universität Dresden, Budapesterstraße 27, Dresden, Saxony 01069, Germany.
| | - Christiane Heinemann
- Max Bergmann Centre of Biomaterials, Institute of Materials Science, Faculty of Mechanical Science and Engineering, Technische Universität Dresden, Budapesterstraße 27, Dresden, Saxony 01069, Germany
| | - Kai Zheng
- Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing Medical University, Nanjing 210029, China; Department of Material Science and Engineering, Institute of Biomaterials, University of Erlangen-Nuremburg, Cauerstraße 6, Erlangen 91058, Germany
| | - Revathi Appali
- Institute of General Electrical Engineering, Faculty of Computer Science and Electrical Engineering, University of Rostock, Albert-Einstein-Straße 2, Rostock 18059, Germany; Department of Ageing of Individuals and Society, Interdisciplinary Faculty, University of Rostock, Albert-Einstein-Straße 21, Rostock 18059, Germany
| | - Franziska Alt
- Max Bergmann Centre of Biomaterials, Institute of Materials Science, Faculty of Mechanical Science and Engineering, Technische Universität Dresden, Budapesterstraße 27, Dresden, Saxony 01069, Germany
| | - Jan Krieghoff
- Institute of Pharmacy, Pharmaceutical Technology, Faculty of Medicine, University Leipzig. Eilenburgerstraße 15a, Leipzig 04317, Germany
| | - Anne Bernhardt
- Centre for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus and Faculty of Medicine, Technische Universität Dresden, Fetscherstraße 74, Dresden 01307, Germany
| | - Aldo R Boccaccini
- Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing Medical University, Nanjing 210029, China; Department of Material Science and Engineering, Institute of Biomaterials, University of Erlangen-Nuremburg, Cauerstraße 6, Erlangen 91058, Germany
| | - Ursula van Rienen
- Institute of General Electrical Engineering, Faculty of Computer Science and Electrical Engineering, University of Rostock, Albert-Einstein-Straße 2, Rostock 18059, Germany; Department of Ageing of Individuals and Society, Interdisciplinary Faculty, University of Rostock, Albert-Einstein-Straße 21, Rostock 18059, Germany; Department of Life, Light and Matter, Interdisciplinary Faculty, University of Rostock, Albert-Einstein-Straße 25, Rostock 18059, Germany
| | - Vera Hintze
- Max Bergmann Centre of Biomaterials, Institute of Materials Science, Faculty of Mechanical Science and Engineering, Technische Universität Dresden, Budapesterstraße 27, Dresden, Saxony 01069, Germany.
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11
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Guillot-Ferriols M, Lanceros-Méndez S, Gómez Ribelles JL, Gallego Ferrer G. Electrical stimulation: Effective cue to direct osteogenic differentiation of mesenchymal stem cells? BIOMATERIALS ADVANCES 2022; 138:212918. [PMID: 35913228 DOI: 10.1016/j.bioadv.2022.212918] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 05/02/2022] [Accepted: 05/20/2022] [Indexed: 06/15/2023]
Abstract
Mesenchymal stem cells (MSCs) play a major role in bone tissue engineering (BTE) thanks to their capacity for osteogenic differentiation and being easily available. In vivo, MSCs are exposed to an electroactive microenvironment in the bone niche, which has piezoelectric properties. The correlation between the electrically active milieu and bone's ability to adapt to mechanical stress and self-regenerate has led to using electrical stimulation (ES) as physical cue to direct MSCs differentiation towards the osteogenic lineage in BTE. This review summarizes the different techniques to electrically stimulate MSCs to induce their osteoblastogenesis in vitro, including general electrical stimulation and substrate mediated stimulation by means of conductive or piezoelectric cell culture supports. Several aspects are covered, including stimulation parameters, treatment times and cell culture media to summarize the best conditions for inducing MSCs osteogenic commitment by electrical stimulation, from a critical point of view. Electrical stimulation activates different signaling pathways, including bone morphogenetic protein (BMP) Smad-dependent or independent, regulated by mitogen activated protein kinases (MAPK), extracellular signal-regulated kinases (ERK) and p38. The roles of voltage gate calcium channels (VGCC) and integrins are also highlighted according to their application technique and parameters, mainly converging in the expression of RUNX2, the master regulator of the osteogenic differentiation pathway. Despite the evident lack of homogeneity in the approaches used, the ever-increasing scientific evidence confirms ES potential as an osteoinductive cue, mimicking aspects of the in vivo microenvironment and moving one step forward to the translation of this approach into clinic.
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Affiliation(s)
- M Guillot-Ferriols
- Centre for Biomaterials and Tissue Engineering (CBIT), Universitat Politècnica de València, 46022 Valencia, Spain; Biomedical Research Networking Centre on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Valencia, Spain.
| | - S Lanceros-Méndez
- Centre of Physics of Minho and Porto Universities, Universidade do Minho, 4710-058 Braga, Portugal; BCMaterials, Basque Centre for Materials, Applications and Nanostructures, UPV/EHU Science Park, 48940 Leioa, Spain; IKERBASQUE, Basque Foundation for Science, 48009 Bilbao, Spain
| | - J L Gómez Ribelles
- Centre for Biomaterials and Tissue Engineering (CBIT), Universitat Politècnica de València, 46022 Valencia, Spain; Biomedical Research Networking Centre on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Valencia, Spain
| | - G Gallego Ferrer
- Centre for Biomaterials and Tissue Engineering (CBIT), Universitat Politècnica de València, 46022 Valencia, Spain; Biomedical Research Networking Centre on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Valencia, Spain
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12
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How to correctly estimate the electric field in capacitively coupled systems for tissue engineering: a comparative study. Sci Rep 2022; 12:11049. [PMID: 35773278 PMCID: PMC9247067 DOI: 10.1038/s41598-022-14834-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Accepted: 06/13/2022] [Indexed: 12/31/2022] Open
Abstract
Capacitively Coupled (CCoupled) electric fields are used to stimulate cell cultures in Tissue Engineering. Knowing the electric field (E-Field) magnitude in the culture medium is fundamental to establish a relationship between stimulus strength and cellular effects. We analysed eight CCoupled studies and sought to corroborate the reported estimates of the E-Field in the culture medium. First, we reviewed the basic physics underlying CCoupled stimulation and delineated three approaches to estimate the E-field. Using these approaches, we found that the reported values were overestimated in five studies, four of which were based on incorrect assumptions. In all studies, insufficient information was provided to reproduce the setup exactly. Creating electrical models of the experimental setup should improve the accuracy of the E-field estimates and enhance reproducibility. For this purpose, we developed a free open-source tool, the E-field Calculator for CCoupled systems, which is available for download from an internet hosting platform.
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13
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Afjeh-Dana E, Naserzadeh P, Moradi E, Hosseini N, Seifalian AM, Ashtari B. Stem Cell Differentiation into Cardiomyocytes: Current Methods and Emerging Approaches. Stem Cell Rev Rep 2022; 18:2566-2592. [PMID: 35508757 DOI: 10.1007/s12015-021-10280-1] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/05/2021] [Indexed: 12/26/2022]
Abstract
Cardiovascular diseases (CVDs) are globally known to be important causes of mortality and disabilities. Common treatment strategies for CVDs, such as pharmacological therapeutics impose serious challenges due to the failure of treatments for myocardial necrosis. By contrast, stem cells (SCs) based therapies are seen to be promising approaches to CVDs treatment. In such approaches, cardiomyocytes are differentiated from SCs. To fulfill SCs complete potential, the method should be appointed to generate cardiomyocytes with more mature structure and well-functioning operations. For heart repairing applications, a greatly scalable and medical-grade cardiomyocyte generation must be used. Nonetheless, there are some challenges such as immune rejection, arrhythmogenesis, tumorigenesis, and graft cell death potential. Herein, we discuss the types of potential SCs, and commonly used methods including embryoid bodies related techniques, co-culture, mechanical stimulation, and electrical stimulation and their applications, advantages and limitations in this field. An estimated 17.9 million people died from CVDs in 2019, representing 32 % of all global deaths. Of these deaths, 85 % were due to heart attack and stroke.
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Affiliation(s)
- Elham Afjeh-Dana
- Radiation Biology Research Centre, Iran University of Medical Sciences, Tehran, Iran
| | - Parvaneh Naserzadeh
- Radiation Biology Research Centre, Iran University of Medical Sciences, Tehran, Iran
| | - Elham Moradi
- Radiation Biology Research Centre, Iran University of Medical Sciences, Tehran, Iran.,Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran
| | - Nasrin Hosseini
- Neuroscience Research Centre, Iran University of Medical Sciences, Tehran, Iran.
| | - Alexander Marcus Seifalian
- Nanotechnology & Regenerative Medicine Commercialisation Centre (NanoRegMed Ltd), London BioScience Innovation Centre, London, UK
| | - Behnaz Ashtari
- Radiation Biology Research Centre, Iran University of Medical Sciences, Tehran, Iran. .,Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran. .,Cellular and Molecular Research Centre, Iran University of Medical Sciences, Tehran, Iran.
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14
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Dittmann KH, Mayer C, Stephan H, Mieth C, Bonin M, Lechmann B, Rodemann HP. Exposure of primary osteoblasts to combined magnetic and electric fields induced spatiotemporal endochondral ossification characteristic gene- and protein expression profiles. J Exp Orthop 2022; 9:39. [PMID: 35499653 PMCID: PMC9061914 DOI: 10.1186/s40634-022-00477-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Accepted: 04/20/2022] [Indexed: 11/30/2022] Open
Abstract
Purpose Molecular processes in primary osteoblasts were analyzed in response to magnetic and electric field exposure to examine its potential impact on bone healing. Methods Primary osteoblasts were exposed to a combination of a magnetic field and an additional electric field (EFMF) (20 Hz, 700 mV, 5 mT, continuous sinusoids) in vitro. mRNA- and protein-expressions were assessed during a time interval of 21 days and compared with expression data obtained from control osteoblasts. Results We observed an autonomous osteoblast differentiation process in vitro under the chosen cultivation conditions. The initial proliferative phase was characterized by a constitutively high mRNA expression of extracellular matrix proteins. Concurrent EFMF exposure resulted in significanly increased cell proliferation (fold change: 1.25) and reduced mRNA-expressions of matrix components (0.5–0.75). The following reorganization of the extracellular matrix is prerequisite for matrix mineralization and is characterised by increased Ca2+ deposition (1.44). On molecular level EFMF exposure led to a significant decreased thrombospondin 1 (THBS1) mRNA- (0.81) and protein- (0.54) expression, which in turn reduced the TGFß1-dependent mRNA- (0.68) and protein- (0.5) expression of transforming growth factor beta induced (ßIG-H3) significantly, an inhibitor of endochondral ossification. Consequently, EFMF exposure stimulated the expression of genes characteristic for endochondral ossification, such as collagen type 10, A1 (1.50), osteopontin (1.50) and acellular communication network factor 3 (NOV) (1.45). Conclusions In vitro exposure of osteoblasts to EFMF supports cell differentiation and induces gene- and protein-expression patterns characteristic for endochondral ossification during bone fracture healing in vivo. Supplementary Information The online version contains supplementary material available at 10.1186/s40634-022-00477-9.
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15
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Interfaces Based on Laser-Structured Arrays of Carbon Nanotubes with Albumin for Electrical Stimulation of Heart Cell Growth. Polymers (Basel) 2022; 14:polym14091866. [PMID: 35567036 PMCID: PMC9102927 DOI: 10.3390/polym14091866] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 04/24/2022] [Accepted: 04/28/2022] [Indexed: 12/12/2022] Open
Abstract
Successful formation of electronic interfaces between living cells and electronic components requires both good cell viability and performance level. This paper presents a technology for the formation of nanostructured arrays of multi-walled carbon nanotubes (MWCNT) in biopolymer (albumin) layer for higher biocompatibility. The layer of liquid albumin dispersion was sprayed on synthesized MWCNT arrays by deposition system. These nanostructures were engineered using the nanosecond pulsed laser radiation mapping in the near-IR spectral range (λ = 1064 nm). It was determined that the energy density of 0.015 J/cm2 provided a sufficient structuring of MWCNT. The structuring effect occurred during the formation of C–C bonds simultaneously with the formation of a cellular structure of nanotubes in the albumin matrix. It led to a decrease in the nanotube defectiveness, which was observed during the Raman spectroscopy. In addition, laser structuring led to a more than twofold increase in the electrical conductivity of MWCNT arrays with albumin (215.8 ± 10 S/m). Successful electric stimulation of cells on the interfaces with the system based on a culture plate was performed, resulting in the enhanced cell proliferation. Overall, the MWCNT laser-structured arrays with biopolymers might be a promising material for extended biomedical applications.
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16
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Jia Y, Xu J, Shi Q, Zheng L, Liu M, Wang M, Li P, Fan Y. Study on the effects of alternating capacitive electric fields with different frequencies on promoting wound healing. MEDICINE IN NOVEL TECHNOLOGY AND DEVICES 2022. [DOI: 10.1016/j.medntd.2022.100142] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
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17
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Non-contact electrical stimulation as an effective means to promote wound healing. Bioelectrochemistry 2022; 146:108108. [DOI: 10.1016/j.bioelechem.2022.108108] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2021] [Revised: 03/20/2022] [Accepted: 03/21/2022] [Indexed: 12/17/2022]
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18
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Guo R, Liao M, Ma X, Hu Y, Qian X, Xiao M, Gao X, Chai R, Tang M. Cochlear implant-based electric-acoustic stimulation modulates neural stem cell-derived neural regeneration. J Mater Chem B 2021; 9:7793-7804. [PMID: 34586130 DOI: 10.1039/d1tb01029h] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Cochlear implantation is considered to be the best therapeutic method for profound sensorineural hearing loss, but insufficient numbers of functional spiral ganglion neurons hinder the clinical effects of cochlear implantation. Stem cell transplantation has the potential to provide novel strategies for spiral ganglion neuron regeneration after injury. However, some obstacles still need to be overcome, such as low survival and uncontrolled differentiation. Several novel technologies show promise for modulating neural stem cell behaviors to address these issues. Here, a device capable of electrical stimulation was designed by combining a cochlear implant with a graphene substrate. Neural stem cells (NSCs) were cultured on the graphene substrate and subjected to electrical stimulation transduced from sound waves detected by the cochlear implant. Cell behaviors were studied, and this device showed good biocompatibility for NSCs. More importantly, electric-acoustic stimulation with higher frequencies and amplitudes induced NSC death and apoptosis, and electric-acoustic stimulation could promote NSCs to proliferate and differentiate into neurons only when low-frequency stimulation was supplied. The present study provides experimental evidence for understanding the regulatory role of electric-acoustic stimulation on NSCs and highlights the potentials of the above-mentioned device in stem cell therapy for hearing loss treatment.
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Affiliation(s)
- Rongrong Guo
- Institute for Cardiovascular Science & Department of Cardiovascular Surgery of the First Affiliated Hospital, Medical College, Soochow University, Suzhou, 215000, China. .,State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, 650500, China.,Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, School of Life Science and Technology, Southeast University, Nanjing 210096, China.
| | - Menghui Liao
- Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, School of Life Science and Technology, Southeast University, Nanjing 210096, China. .,Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China
| | - Xiaofeng Ma
- Department of Otorhinolaryngology-Head and Neck Surgery, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, Jiangsu 210008, China.,Department of Otorhinolaryngology-Head and Neck Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Jiangsu Provincial Key Medical Discipline (Laboratory), Nanjing, Jiangsu 210008, China. .,Research Institution of Otorhinolaryngology, Nanjing, Jiangsu 210008, P. R. China
| | - Yangnan Hu
- Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, School of Life Science and Technology, Southeast University, Nanjing 210096, China. .,Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China
| | - Xiaoyun Qian
- Department of Otorhinolaryngology-Head and Neck Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Jiangsu Provincial Key Medical Discipline (Laboratory), Nanjing, Jiangsu 210008, China. .,Research Institution of Otorhinolaryngology, Nanjing, Jiangsu 210008, P. R. China
| | - Miao Xiao
- Institute for Cardiovascular Science & Department of Cardiovascular Surgery of the First Affiliated Hospital, Medical College, Soochow University, Suzhou, 215000, China.
| | - Xia Gao
- Department of Otorhinolaryngology-Head and Neck Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Jiangsu Provincial Key Medical Discipline (Laboratory), Nanjing, Jiangsu 210008, China. .,Research Institution of Otorhinolaryngology, Nanjing, Jiangsu 210008, P. R. China
| | - Renjie Chai
- Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, School of Life Science and Technology, Southeast University, Nanjing 210096, China. .,Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China
| | - Mingliang Tang
- Institute for Cardiovascular Science & Department of Cardiovascular Surgery of the First Affiliated Hospital, Medical College, Soochow University, Suzhou, 215000, China. .,Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, School of Life Science and Technology, Southeast University, Nanjing 210096, China. .,Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China
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19
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Chen ST, Li Y, He SY, Zhou P, Lu J, Gu N. Microscopic Volta potential difference on metallic surface promotes the osteogenic differentiation and proliferation of human mesenchymal stem cells. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2021; 128:112325. [PMID: 34474876 DOI: 10.1016/j.msec.2021.112325] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 06/29/2021] [Accepted: 07/12/2021] [Indexed: 11/25/2022]
Abstract
Endogenous microscopic electric cues play an essential role in bone's remodeling and self-repair. Modulating the extracellular electrical environment, by means of external electric stimulation or changing surface potential of implants, was manifested to facilitate the osteointegration. The microscopic potential difference, originating from heterogeneous microstructures of materials, may mimic the endogenous electric signals to stimulate surrounding cells. In this study, the spark-plasma sintered Ti/Ta hybrid metal was fabricated and utilized to realize a surface microscopic potential difference at the same magnitude as endogenous potentials. Activated by the electric stimulation, the mesenchymal stem cells exhibited the anisotropic and polygonal cellular morphology on the Ti/Ta hybrid metal. The microscopic electric potential difference coordinated the cells proliferation on the subsequent days. Moreover, the results showed that the osteo-lineage differentiation on Ti/Ta hybrid metal were in vitro boosted over the control groups. Tailoring microstructures of material to obtain a reasonable electric microenvironment may be a necessary principle to achieve more favorable cell responses to implants, suggesting an extra degree of freedom in bone-repairing material design.
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Affiliation(s)
- Shi-Ting Chen
- State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, China
| | - Yan Li
- State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, China
| | - Si-Yuan He
- State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, China.
| | - Ping Zhou
- State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, China
| | - Jian Lu
- Department of Mechanical Engineering, City University of Hong Kong, Hong Kong, China
| | - Ning Gu
- State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, China.
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20
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Mansourian M, Shanei A. Evaluation of Pulsed Electromagnetic Field Effects: A Systematic Review and Meta-Analysis on Highlights of Two Decades of Research In Vitro Studies. BIOMED RESEARCH INTERNATIONAL 2021; 2021:6647497. [PMID: 34368353 PMCID: PMC8342182 DOI: 10.1155/2021/6647497] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/04/2020] [Revised: 05/30/2021] [Accepted: 06/27/2021] [Indexed: 12/13/2022]
Abstract
Pulsed electromagnetic field (PEMF) therapy is a type of physical stimulation that affects biological systems by producing interfering or coherent fields. Given that cell types are significantly distinct, which represents an important factor in stimulation, and that PEMFs can have different effects in terms of frequency and intensity, time of exposure, and waveform. This study is aimed at investigating if distinct positive and negative responses would correspond to specific characteristics of cells, frequency and flux density, time of exposure, and waveform. Necessary data were abstracted from the experimental observations of cell-based in vitro models. The observations were obtained from 92 publications between the years 1999 and 2019, which are available on PubMed and Web of Science databases. From each of the included studies, type of cells, pulse frequency of exposure, exposure flux density, and assayed cell responses were extracted. According to the obtained data, most of the experiments were carried out on human cells, and out of 2421 human cell experiments, cell changes were observed only in 51.05% of the data. In addition, the results pointed out the potential effects of PEMFs on some human cell types such as MG-63 human osteosarcoma cells (p value < 0.001) and bone marrow mesenchymal stem cells. However, human osteogenic sarcoma SaOS-2 (p < 0.001) and human adipose-derived mesenchymal stem cells (AD-MSCs) showed less sensitivity to PEMFs. Nevertheless, the evidence suggests that frequencies higher than 100 Hz, flux densities between 1 and 10 mT, and chronic exposure more than 10 days would be more effective in establishing a cellular response. This study successfully reported useful information about the role of cell type and signal characteristic parameters, which were of high importance for targeted therapies using PEMFs. Our findings would provide a deeper understanding about the effect of PEMFs in vitro, which could be useful as a reference for many in vivo experiments or preclinical trials.
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Affiliation(s)
- Mahsa Mansourian
- Department of Medical Physics, Faculty of Medicine, Isfahan University of Medical Science, Isfahan, Hezar Jerib Avenue, Isfahan, Iran
| | - Ahmad Shanei
- Department of Medical Physics, Faculty of Medical Science, Isfahan University of Medical Science, Isfahan, Hezar Jerib Street, Isfahan, Iran
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21
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Imbarak N, Abdel-Aziz HI, Farghaly LM, Hosny S. Effect of mesenchymal stem cells versus aloe vera on healing of deep second-degree burn. Stem Cell Investig 2021; 8:12. [PMID: 34268441 DOI: 10.21037/sci-2020-030] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Accepted: 03/25/2021] [Indexed: 01/09/2023]
Abstract
Background Burn injuries constitute a major health problem which cause more severe physiological stress than other traumas. Aloe vera has been used in traditional medicine for a long time for burn treatment. Mesenchymal stem cells (MSCs) have delivered new approaches to the management of deep burns. The present study assessed the effect of aloe vera versus MSCs on experimentally induced deep second-degree burn. Methods Sixty adult female albino rats randomized into 6 groups: group I served as negative control, group II received topical aloe vera only, group III were injected intradermally with MSCs, group IV subjected to burn injury, group V received topical aloe vera post burn and group VI were injected intradermally with MSCs post burn. Healing of burn injury was evaluated grossly. Skin specimens were obtained after 14 & 21-days post-burn induction and prepared for histological techniques (H&E and Masson's trichrome stain). Polymerase chain reaction (PCR) analysis of Sry gene for group VI was done. Results After 14 days, groups V&VI showed fully regenerated epidermis with a significant increase in the epidermal thickness and a significant decrease in the optical density of collagen fibers compared to control groups. After 21 days, group V showed less epidermal thickness compared to that of day 14 and nearly normal collagen fibers arrangement. However, group VI showed a significant increase in the epidermal thickness compared to groups V&I and an interwoven collagen fibers arrangement with a significant decrease in the optical density of collagen fibers in comparison to control groups. PCR results of the tested samples revealed that 100% of the recipient rats contain Sry positive gene. Conclusions Topical aloe vera promoted burn wound healing faster and better than intradermal injection of MSCs.
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Affiliation(s)
- Nahla Imbarak
- Department of Histology and Cell Biology, Faculty of Medicine, Suez Canal University Ismailia, Egypt.,Tissue Culture Unit, Center of Excellence in Molecular and Cellular Medicine, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
| | - H Ismail Abdel-Aziz
- Department of Histology and Cell Biology, Faculty of Medicine, Suez Canal University Ismailia, Egypt
| | - Lamiaa M Farghaly
- Department of Histology and Cell Biology, Faculty of Medicine, Suez Canal University Ismailia, Egypt
| | - Somaya Hosny
- Department of Histology and Cell Biology, Faculty of Medicine, Suez Canal University Ismailia, Egypt.,Tissue Culture Unit, Center of Excellence in Molecular and Cellular Medicine, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
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22
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Srirussamee K, Xue R, Mobini S, Cassidy NJ, Cartmell SH. Changes in the extracellular microenvironment and osteogenic responses of mesenchymal stem/stromal cells induced by in vitro direct electrical stimulation. J Tissue Eng 2021; 12:2041731420974147. [PMID: 33643602 PMCID: PMC7894594 DOI: 10.1177/2041731420974147] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Accepted: 10/28/2020] [Indexed: 12/26/2022] Open
Abstract
Electrical stimulation (ES) has potential to be an effective tool for bone injury treatment in clinics. However, the therapeutic mechanism associated with ES is still being discussed. This study aims to investigate the initial mechanism of action by characterising the physical and chemical changes in the extracellular environment during ES and correlate them with the responses of mesenchymal stem/stromal cells (MSCs). Computational modelling was used to estimate the electrical potentials relative to the cathode and the current density across the cell monolayer. We showed expression of phosphorylated ERK1/2, c-FOS, c-JUN, and SPP1 mRNAs, as well as the increased metabolic activities of MSCs at different time points. Moreover, the average of 2.5 μM of H2O2 and 34 μg/L of dissolved Pt were measured from the electrically stimulated media (ES media), which also corresponded with the increases in SPP1 mRNA expression and cell metabolic activities. The addition of sodium pyruvate to the ES media as an antioxidant did not alter the SPP1 mRNA expression, but eliminated an increase in cell metabolic activities induced by ES media treatment. These findings suggest that H2O2 was influencing cell metabolic activity, whereas SPP1 mRNA expression was regulated by other faradic by-products. This study reveals how different electrical stimulation regime alters cellular regenerative responses and the roles of faradic by-products, that might be used as a physical tool to guide and control cell behaviour.
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Affiliation(s)
- Kasama Srirussamee
- Department of Materials, The University of Manchester, Manchester, UK.,Department of Biomedical Engineering, Faculty of Engineering, King Mongkut's Institute of Technology Ladkrabang (KMITL), Bangkok, Thailand
| | - Ruikang Xue
- Department of Materials, The University of Manchester, Manchester, UK
| | - Sahba Mobini
- Department of Materials, The University of Manchester, Manchester, UK.,Instituto de Micro y Nanotecnología IMN-CNM, The Spanish National Research Council (CSIC), Madrid, Comunidad de Madrid, Spain.,Departamento de Biología Molecular and Centro de Biología Molecular "Severo Ochoa" (UAM-CSIC), Universidad Autónoma de Madrid, Madrid, Spain
| | - Nigel J Cassidy
- Department of Civil Engineering, University of Birmingham, Birmingham, UK
| | - Sarah H Cartmell
- Department of Materials, The University of Manchester, Manchester, UK
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Ye D, Chen C, Wang Q, Zhang Q, Li S, Liu H. Short-wave enhances mesenchymal stem cell recruitment in fracture healing by increasing HIF-1 in callus. Stem Cell Res Ther 2020; 11:382. [PMID: 32894200 PMCID: PMC7487968 DOI: 10.1186/s13287-020-01888-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Revised: 08/12/2020] [Accepted: 08/17/2020] [Indexed: 01/14/2023] Open
Abstract
Background As a type of high-frequency electrotherapy, a short-wave can promote the fracture healing process; yet, its underlying therapeutic mechanisms remain unclear. Purpose To observe the effect of Short-Wave therapy on mesenchymal stem cell (MSC) homing and relative mechanisms associated with fracture healing. Materials and methods For in vivo study, the effect of Short-Wave therapy to fracture healing was examined in a stabilized femur fracture model of 40 SD rats. Radiography was used to analyze the morphology and microarchitecture of the callus. Additionally, fluorescence assays were used to analyze the GFP-labeled MSC homing after treatment in 20 nude mice with a femoral fracture. For in vitro study, osteoblast from newborn rats simulated fracture site was first irradiated by the Short-Wave; siRNA targeting HIF-1 was used to investigate the role of HIF-1. Osteoblast culture medium was then collected as chemotaxis content of MSC, and the migration of MSC from rats was evaluated using wound healing assay and trans-well chamber test. The expression of HIF-1 and its related factors were quantified by q RT-PCR, ELISA, and Western blot. Results Our in vivo experiment indicated that Short-Wave therapy could promote MSC migration, increase local and serum HIF-1 and SDF-1 levels, induce changes in callus formation, and improve callus microarchitecture and mechanical properties, thus speeding up the healing process of the fracture site. Moreover, the in vitro results further indicated that Short-Wave therapy upregulated HIF-1 and SDF-1 expression in osteoblast and its cultured medium, as well as the expression of CXCR-4, β-catenin, F-actin, and phosphorylation levels of FAK in MSC. On the other hand, the inhibition of HIF-1α was significantly restrained by the inhibition of HIF-1α in osteoblast, and it partially inhibited the migration of MSC. Conclusions These results suggested that Short-Wave therapy could increase HIF-1 in callus, which is one of the crucial mechanisms of chemotaxis MSC homing in fracture healing.
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Affiliation(s)
- Dongmei Ye
- Department of Rehabilitation, Affiliated Zhongshan Hospital of Dalian University, Dalian, 116001, China.
| | - Chen Chen
- Department of Anatomy, Medical College of Dalian University, Dalian, China
| | - Qiwen Wang
- Department of Rehabilitation, Affiliated Zhongshan Hospital of Dalian University, Dalian, 116001, China.,Department of Rehabilitation, The people's Hospital of Longhua District, Shenzhen, China
| | - Qi Zhang
- Department of Rehabilitation, Affiliated Zhongshan Hospital of Dalian University, Dalian, 116001, China
| | - Sha Li
- Department of Rehabilitation, Affiliated Zhongshan Hospital of Dalian University, Dalian, 116001, China
| | - Hongwei Liu
- Department of Rehabilitation, Affiliated Zhongshan Hospital of Dalian University, Dalian, 116001, China
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Verma AS, Sharma A, Kumar A, Mukhopadhyay A, Kumar D, Dubey AK. Multifunctional Response of Piezoelectric Sodium Potassium Niobate (NKN)-Toughened Hydroxyapatite-Based Biocomposites. ACS APPLIED BIO MATERIALS 2020; 3:5287-5299. [DOI: 10.1021/acsabm.0c00642] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
- Alok Singh Verma
- Department of Ceramic Engineering, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005, India
| | - Ankur Sharma
- High Temperature and Energy Materials Laboratory, Department of Metallurgical Engineering and Materials Science, Indian Institute of Technology (IIT) Bombay, Mumbai 400076, India
| | - Ajay Kumar
- High Temperature and Energy Materials Laboratory, Department of Metallurgical Engineering and Materials Science, Indian Institute of Technology (IIT) Bombay, Mumbai 400076, India
| | - Amartya Mukhopadhyay
- High Temperature and Energy Materials Laboratory, Department of Metallurgical Engineering and Materials Science, Indian Institute of Technology (IIT) Bombay, Mumbai 400076, India
| | - Devendra Kumar
- Department of Ceramic Engineering, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005, India
| | - Ashutosh Kumar Dubey
- Department of Ceramic Engineering, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005, India
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25
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Leppik L, Oliveira KMC, Bhavsar MB, Barker JH. Electrical stimulation in bone tissue engineering treatments. Eur J Trauma Emerg Surg 2020; 46:231-244. [PMID: 32078704 PMCID: PMC7113220 DOI: 10.1007/s00068-020-01324-1] [Citation(s) in RCA: 129] [Impact Index Per Article: 25.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Accepted: 02/04/2020] [Indexed: 12/20/2022]
Abstract
Electrical stimulation (EStim) has been shown to promote bone healing and regeneration both in animal experiments and clinical treatments. Therefore, incorporating EStim into promising new bone tissue engineering (BTE) therapies is a logical next step. The goal of current BTE research is to develop combinations of cells, scaffolds, and chemical and physical stimuli that optimize treatment outcomes. Recent studies demonstrating EStim's positive osteogenic effects at the cellular and molecular level provide intriguing clues to the underlying mechanisms by which it promotes bone healing. In this review, we discuss results of recent in vitro and in vivo research focused on using EStim to promote bone healing and regeneration and consider possible strategies for its application to improve outcomes in BTE treatments. Technical aspects of exposing cells and tissues to EStim in in vitro and in vivo model systems are also discussed.
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Affiliation(s)
- Liudmila Leppik
- Frankfurt Initiative for Regenerative Medicine, Experimental Orthopedics and Trauma Surgery, J.W. Goethe University, Frankfurt/Main, Germany.
| | - Karla Mychellyne Costa Oliveira
- Frankfurt Initiative for Regenerative Medicine, Experimental Orthopedics and Trauma Surgery, J.W. Goethe University, Frankfurt/Main, Germany
| | - Mit Balvantray Bhavsar
- Frankfurt Initiative for Regenerative Medicine, Experimental Orthopedics and Trauma Surgery, J.W. Goethe University, Frankfurt/Main, Germany
| | - John Howard Barker
- Frankfurt Initiative for Regenerative Medicine, Experimental Orthopedics and Trauma Surgery, J.W. Goethe University, Frankfurt/Main, Germany
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26
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Budde K, Zimmermann J, Neuhaus E, Schroder M, Uhrmacher AM, van Rienen U. Requirements for Documenting Electrical Cell Stimulation Experiments for Replicability and Numerical Modeling ∗. ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. ANNUAL INTERNATIONAL CONFERENCE 2020; 2019:1082-1088. [PMID: 31946082 DOI: 10.1109/embc.2019.8856863] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Thorough documentation of biological experiments is necessary for their replicability. This becomes even more evident when individual steps of in vitro wet-lab experiments are to be incorporated into computer simulation models. In the highly interdisciplinary field of electrical stimulation of biological cells, not only biological but also physical aspects play a crucial role. Simulations may help to identify parameters that influence cells and thereby reveal new insights into mechanisms of the cell biological system. However, missing or misleading documentation of the electrical stimulation step within wet-lab experiments may lead to discrepancies between reported and simulated electrical quantities. In addition, this threatens the replicability of electrical stimulation experiments. Thus, we argue that a minimal set of information is needed to enable a translation of electrical stimulation experiments of biological cells into computer simulation experiments and to support replicability. This set includes detailed information about the electronic devices and components, their set-up as well as the applied stimulus and shall be integrated into an existing guideline for cell biological experiments. Ideally, the documentation should also contain measured properties of the cellular and experimental environment. Furthermore, a realization of our proposed documentation requirements within electronic lab notebooks may provide a crucial step toward a more seamless integration of wet-lab data into simulations. Based on two exemplary studies, we demonstrate the relevance of our claim.
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27
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Geng K, Wang J, Liu P, Tian X, Liu H, Wang X, Hu C, Yan H. Electrical stimulation facilitates the angiogenesis of human umbilical vein endothelial cells through MAPK/ERK signaling pathway by stimulating FGF2 secretion. Am J Physiol Cell Physiol 2019; 317:C277-C286. [PMID: 30995109 DOI: 10.1152/ajpcell.00474.2018] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Electrical stimulation (ES) is able to enhance angiogenesis by stimulating fibroblasts. Fibroblast growth factor 2 (FGF2) is an independent angiogenesis inducer. The present study aimed to evaluate the role of ES-induced FGF2 secretion in affecting angiogenesis during wound healing via the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway. Fibroblasts and human umbilical vein endothelial cells (HUVECs) were exposed to ES, and the HUVECs were cocultured with ES-treated fibroblast culture solution. ES exposure showed no toxic effects on fibroblasts or HUVECs. ES led to enhanced growth of fibroblasts and HUVECs as well as FGF2 secretion, which is induced through the NOS pathway. ES-induced FGF2 secretion was shown to increase vascular endothelial growth factor (VEGF) protein and enhance migration, invasion, and angiogenesis of HUVECs. Also, ES-induced FGF2 secretion activated the MAPK/ERK signaling pathway. However, inhibition of the MAPK/ERK signaling pathway reversed the positive effects of ES-induced FGF2 secretion. In vitro experiments showed positive effects of ES on wound healing. Taken together, the findings suggested that ES promoted FGF2 secretion and then activated the MAPK/ERK signaling pathway by facilitating angiogenesis and promoting wound healing.
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Affiliation(s)
- Kang Geng
- Department of Burns and Plastic Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Jing Wang
- Southwest Petroleum University College of Mechanical and Electrical Engineering, Chengdu, China
| | - Pengfei Liu
- Department of Orthopedics, Aerospace 731 Hospital, Beijing,China
| | - Xinli Tian
- Department of Burns and Plastic Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Hongjun Liu
- Department of Burns and Plastic Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Xue Wang
- Department of Burns and Plastic Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Chunbing Hu
- Department of Plastic Surgery, Yuehao Medical Beauty Hospital, Chengdu, China
| | - Hong Yan
- Department of Burns and Plastic Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, China
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28
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Hou J, Luo T, Chen S, Lin S, Yang MM, Li G, Sun D. Calcium Spike Patterns Reveal Linkage of Electrical Stimulus and MSC Osteogenic Differentiation. IEEE Trans Nanobioscience 2019; 18:3-9. [PMID: 30442614 DOI: 10.1109/tnb.2018.2881004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Mesenchymal stromal/stem cells (MSCs) are easily obtained multipotent cells that are widely applied in regenerative medicine. Electrical stimulation (ES) has a promoting effect on bone healing and osteogenic differentiation of MSCs. Direct and alternating currents (AC) are extensively used to promote the osteogenic differentiation of MSCs in vivo and in vitro. However, information on conducting effective differentiation remains scarce. In this paper, we propose a method to optimize ES parameters based on calcium spike patterns of MSCs. Calcium spike frequency decreases as the osteogenic differentiation of MSC progresses. Furthermore, we tested various ES parameters through the real-time monitoring of calcium spike patterns. We efficiently initiated the process of osteogenic differentiation in MSCs by using the optimal parameters of AC, including voltage, signal shapes, frequency, and duty time. This method provides a new approach to optimize osteogenic differentiation and is potentially useful in clinical treatment such as of bone fractures.
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29
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Wang X, Ren Y, Liu J. Liquid Metal Enabled Electrobiology: A New Frontier to Tackle Disease Challenges. MICROMACHINES 2018; 9:E360. [PMID: 30424293 PMCID: PMC6082282 DOI: 10.3390/mi9070360] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/14/2018] [Revised: 07/09/2018] [Accepted: 07/18/2018] [Indexed: 01/06/2023]
Abstract
In this article, a new conceptual biomedical engineering strategy to tackle modern disease challenges, called liquid metal (LM) enabled electrobiology, is proposed. This generalized and simple method is based on the physiological fact that specially administrated electricity induces a series of subsequent desired biological effects, either shortly, transitionally, or permanently. Due to high compliance within biological tissues, LM would help mold a pervasive method for treating physiological or psychological diseases. As highly conductive and non-toxic multifunctional flexible materials, such LMs can generate any requested electric treating fields (ETFields), which can adapt to various sites inside the human body. The basic mechanisms of electrobiology in delivering electricity to the target tissues and then inducing expected outputs for disease treatment are interpreted. The methods for realizing soft and conformable electronics based on LM are illustrated. Furthermore, a group of typical disease challenges are observed to illustrate the basic strategies for performing LM electrobiology therapy, which include but are not limited to: tissue electronics, brain disorder, immunotherapy, neural functional recovery, muscle stimulation, skin rejuvenation, cosmetology and dieting, artificial organs, cardiac pacing, cancer therapy, etc. Some practical issues regarding electrobiology for future disease therapy are discussed. Perspectives in this direction for incubating a simple biomedical tool for health care are pointed out.
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Affiliation(s)
- Xuelin Wang
- Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China.
| | - Yi Ren
- Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China.
| | - Jing Liu
- Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China.
- Beijing Key Lab of CryoBiomedical Engineering and Key Lab of Cryogenics, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
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30
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Qi Z, Xia P, Pan S, Zheng S, Fu C, Chang Y, Ma Y, Wang J, Yang X. Combined treatment with electrical stimulation and insulin-like growth factor-1 promotes bone regeneration in vitro. PLoS One 2018; 13:e0197006. [PMID: 29746517 PMCID: PMC5944947 DOI: 10.1371/journal.pone.0197006] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2018] [Accepted: 04/24/2018] [Indexed: 12/12/2022] Open
Abstract
Electrical stimulation (ES) and insulin-like growth factor-1 (IGF-1) are widely used in bone regeneration because of their osteogenic activity. However, the combined effects of ES and supplemental IGF-1 on the whole bone formation process remain unclear. In this study, fluorescence staining and an MTT assay were first utilized to observe the influence of ES and IGF-1 on MC3T3-E1 cell proliferation and adhesion in vitro. Subsequently, osteogenic differentiation was evaluated by the alkaline phosphatase activity (ALP) and the expression of osteogenic marker genes. In addition, cell mineralization was determined by alizarin red staining and scanning electron microscopy (SEM). We demonstrated that the MC3T3-E1 cell proliferation was significantly higher for treatments combining IGF-1 and ES than for treatments with IGF-1 alone. The combination of IGF-1 and ES increased the MC3T3-E1 cell ALP activity, the expression of osteogenesis-related genes and the calcium deposition with a clear dose-dependent effect. Our data show the synergistic effect of IGF-1 and ES in promoting the proliferation, differentiation and mineralization of MC3T3-E1 cells, which suggests that it would be more effective to combine the proper dose of IGF-1 with ES to promote local bone damage repair and regeneration.
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Affiliation(s)
- Zhiping Qi
- Department of Orthopedic Surgery, the Second Hospital of Jilin University, Changchun, PR China
| | - Peng Xia
- Department of Orthopedic Surgery, the Second Hospital of Jilin University, Changchun, PR China
| | - Su Pan
- Department of Orthopedic Surgery, the Second Hospital of Jilin University, Changchun, PR China
| | - Shuang Zheng
- Department of Orthopedic Surgery, the Second Hospital of Jilin University, Changchun, PR China
| | - Chuan Fu
- Department of Orthopedic Surgery, the Second Hospital of Jilin University, Changchun, PR China
| | - Yuxin Chang
- Department of Orthopedic Surgery, the Second Hospital of Jilin University, Changchun, PR China
| | - Yue Ma
- Department of Gynecological Oncology, the First Hospital of Jilin University, Changchun, PR China
| | - Jincheng Wang
- Department of Orthopedic Surgery, the Second Hospital of Jilin University, Changchun, PR China
- * E-mail: (JW); (XY)
| | - Xiaoyu Yang
- Department of Orthopedic Surgery, the Second Hospital of Jilin University, Changchun, PR China
- * E-mail: (JW); (XY)
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31
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Yong KW, Choi JR, Dolbashid AS, Wan Safwani WKZ. Biosafety and bioefficacy assessment of human mesenchymal stem cells: what do we know so far? Regen Med 2018; 13:219-232. [PMID: 29509072 DOI: 10.2217/rme-2017-0078] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2017] [Accepted: 12/07/2017] [Indexed: 12/13/2022] Open
Abstract
An outstanding amount of resources has been used in research on manipulation of human stem cells, especially mesenchymal stem cells (MSCs), for various clinical applications. However, human MSCs have not been fully utilized in clinical applications due to restrictions with regard to their certain biosafety and bioefficacy concerns, for example, genetic abnormality, tumor formation, induction of host immune response and failure of homing and engraftment. This review summarizes the biosafety and bioefficacy assessment of human MSCs in terms of genetic stability, tumorigenicity, immunogenicity, homing and engraftment. The strategies used to reduce the biosafety concerns and improve the bioefficacy of human MSCs are highlighted. In addition, the approaches that can be implemented to improve their biosafety and bioefficacy assessment are briefly discussed.
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Affiliation(s)
- Kar Wey Yong
- Department of Biomedical Engineering, Faculty of Engineering, University of Malaya, Kuala Lumpur 50603, Malaysia
- Department of Chemical & Petroleum Engineering, Schulich School of Engineering, University of Calgary, Calgary, AB, T2N 1N4, Canada
| | - Jane Ru Choi
- Department of Biomedical Engineering, Faculty of Engineering, University of Malaya, Kuala Lumpur 50603, Malaysia
- Department of Mechanical Engineering, University of British Columbia, 2054-6250 Applied Science Lane, Vancouver, BC, V6T 1Z4, Canada
| | - Asdani Saifullah Dolbashid
- Department of Biomedical Engineering, Faculty of Engineering, University of Malaya, Kuala Lumpur 50603, Malaysia
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Unraveling the mechanistic effects of electric field stimulation towards directing stem cell fate and function: A tissue engineering perspective. Biomaterials 2017; 150:60-86. [PMID: 29032331 DOI: 10.1016/j.biomaterials.2017.10.003] [Citation(s) in RCA: 230] [Impact Index Per Article: 28.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2017] [Revised: 09/27/2017] [Accepted: 10/02/2017] [Indexed: 02/06/2023]
Abstract
Electric field (EF) stimulation can play a vital role in eliciting appropriate stem cell response. Such an approach is recently being established to guide stem cell differentiation through osteogenesis/neurogenesis/cardiomyogenesis. Despite significant recent efforts, the biophysical mechanisms by which stem cells sense, interpret and transform electrical cues into biochemical and biological signals still remain unclear. The present review critically analyses the variety of EF stimulation approaches that can be employed to evoke appropriate stem cell response and also makes an attempt to summarize the underlying concepts of this notion, placing special emphasis on stem cell based tissue engineering and regenerative medicine. This review also discusses the major signaling pathways and cellular responses that are elicited by electric stimulation, including the participation of reactive oxygen species and heat shock proteins, modulation of intracellular calcium ion concentration, ATP production and numerous other events involving the clustering or reassembling of cell surface receptors, cytoskeletal remodeling and so on. The specific advantages of using external electric stimulation in different modalities to regulate stem cell fate processes are highlighted with explicit examples, in vitro and in vivo.
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33
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Love MR, Palee S, Chattipakorn SC, Chattipakorn N. Effects of electrical stimulation on cell proliferation and apoptosis. J Cell Physiol 2017; 233:1860-1876. [PMID: 28452188 DOI: 10.1002/jcp.25975] [Citation(s) in RCA: 93] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2017] [Accepted: 04/24/2017] [Indexed: 02/06/2023]
Abstract
The application of exogenous electrical stimulation (ES) to cells in order to manipulate cell apoptosis and proliferation has been widely investigated as a possible method of treatment in a number of diseases. Alteration of the transmembrane potential of cells via ES can affect various intracellular signaling pathways which are involved in the regulation of cellular function. Controversially, several types of ES have proved to be effective in both inhibiting or inducing apoptosis, as well as increasing proliferation. However, the mechanisms through which ES achieves this remain fairly unclear. The aim of this review was to comprehensively summarize current findings from in vitro and in vivo studies on the effects of different types of ES on cell apoptosis and proliferation, highlighting the possible mechanisms through which ES induced these effects and define the optimum parameters at which ES can be used. Through this we hope to provide a greater insight into how future studies can most effectively use ES at the clinical trial stage.
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Affiliation(s)
- Maria R Love
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.,Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
| | - Siripong Palee
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.,Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand
| | - Siriporn C Chattipakorn
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.,Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand.,Department of Oral Biology and Diagnostic Science, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand
| | - Nipon Chattipakorn
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.,Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand.,Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
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34
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Robinson VS, Garner AL, Loveless AM, Neculaes VB. Calculated plasma membrane voltage induced by applying electric pulses using capacitive coupling. Biomed Phys Eng Express 2017. [DOI: 10.1088/2057-1976/aa630a] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
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35
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New cosurface capacitive stimulators for the development of active osseointegrative implantable devices. Sci Rep 2016; 6:30231. [PMID: 27456818 PMCID: PMC4960616 DOI: 10.1038/srep30231] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2016] [Accepted: 06/28/2016] [Indexed: 12/12/2022] Open
Abstract
Non-drug strategies based on biophysical stimulation have been emphasized for the treatment and prevention of musculoskeletal conditions. However, to date, an effective stimulation system for intracorporeal therapies has not been proposed. This is particularly true for active intramedullary implants that aim to optimize osseointegration. The increasing demand for these implants, particularly for hip and knee replacements, has driven the design of innovative stimulation systems that are effective in bone-implant integration. In this paper, a new cosurface-based capacitive system concept is proposed for the design of implantable devices that deliver controllable and personalized electric field stimuli to target tissues. A prototype architecture of this system was constructed for in vitro tests, and its ability to deliver controllable stimuli was numerically analyzed. Successful results were obtained for osteoblastic proliferation and differentiation in the in vitro tests. This work provides, for the first time, a design of a stimulation system that can be embedded in active implantable devices for controllable bone-implant integration and regeneration. The proposed cosurface design holds potential for the implementation of novel and innovative personalized stimulatory therapies based on the delivery of electric fields to bone cells.
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36
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Modulation of Osteogenesis in MC3T3-E1 Cells by Different Frequency Electrical Stimulation. PLoS One 2016; 11:e0154924. [PMID: 27149625 PMCID: PMC4858221 DOI: 10.1371/journal.pone.0154924] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2016] [Accepted: 04/21/2016] [Indexed: 11/19/2022] Open
Abstract
Electrical stimulation (ES) is therapeutic to many bone diseases, from promoting fracture regeneration to orthopedic intervention. The application of ES offers substantial therapeutic potential, while optimal ES parameters and the underlying mechanisms responsible for the positive clinical impact are poorly understood. In this study, we assembled an ES cell culture and monitoring device. Mc-3T3-E1 cells were subjected to different frequency to investigate the effect of osteogenesis. Cell proliferation, DNA synthesis, the mRNA levels of osteosis-related genes, the activity of alkaline phosphatase (ALP), and intracellular concentration of Ca2+ were thoroughly evaluated. We found that 100 Hz could up-regulate the mRNA levels of collagen I, collagen II and Runx2. On the contrary, ES could down-regulate the mRNA levels of osteopontin (OPN). ALP activity assay and Fast Blue RR salt stain showed that 100 Hz could accelerate cells differentiation. Compared to the control group, 100 Hz could promote cell proliferation. Furthermore, 1 Hz to 10 Hz could improve calcium deposition in the intracellular matrix. Overall, these results indicate that 100Hz ES exhibits superior potentialities in osteogenesis, which should be beneficial for the clinical applications of ES for the treatment of bone diseases.
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The effect of capacitively coupled (CC) electrical stimulation on human disc nucleus pulposus cells and the relationship between CC and BMP-7. EUROPEAN SPINE JOURNAL : OFFICIAL PUBLICATION OF THE EUROPEAN SPINE SOCIETY, THE EUROPEAN SPINAL DEFORMITY SOCIETY, AND THE EUROPEAN SECTION OF THE CERVICAL SPINE RESEARCH SOCIETY 2016; 26:240-247. [DOI: 10.1007/s00586-016-4439-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/25/2015] [Revised: 02/04/2016] [Accepted: 02/04/2016] [Indexed: 10/22/2022]
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Leppik LP, Froemel D, Slavici A, Ovadia ZN, Hudak L, Henrich D, Marzi I, Barker JH. Effects of electrical stimulation on rat limb regeneration, a new look at an old model. Sci Rep 2015; 5:18353. [PMID: 26678416 PMCID: PMC4683620 DOI: 10.1038/srep18353] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2015] [Accepted: 11/17/2015] [Indexed: 11/09/2022] Open
Abstract
Limb loss is a devastating disability and while current treatments provide aesthetic and functional restoration, they are associated with complications and risks. The optimal solution would be to harness the body's regenerative capabilities to regrow new limbs. Several methods have been tried to regrow limbs in mammals, but none have succeeded. One such attempt, in the early 1970s, used electrical stimulation and demonstrated partial limb regeneration. Several researchers reproduced these findings, applying low voltage DC electrical stimulation to the stumps of amputated rat forelimbs reporting "blastema, and new bone, bone marrow, cartilage, nerve, skin, muscle and epiphyseal plate formation". In spite of these encouraging results this research was discontinued. Recently there has been renewed interest in studying electrical stimulation, primarily at a cellular and subcellular level, and studies have demonstrated changes in stem cell behavior with increased proliferation, differentiation, matrix formation and migration, all important in tissue regeneration. We applied electrical stimulation, in vivo, to the stumps of amputated rat limbs and observed significant new bone, cartilage and vessel formation and prevention of neuroma formation. These findings demonstrate that electricity stimulates tissue regeneration and form the basis for further research leading to possible new treatments for regenerating limbs.
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Affiliation(s)
- Liudmila P Leppik
- Frankfurt Initiative for Regenerative Medicine, Experimental Orthopedics and Trauma Surgery, J.W. Goethe University, Friedrichsheim gGmbH, Marienburgstraße 2, Frankfurt/Main, 60528, Germany
| | - Dara Froemel
- Frankfurt Initiative for Regenerative Medicine, Experimental Orthopedics and Trauma Surgery, J.W. Goethe University, Friedrichsheim gGmbH, Marienburgstraße 2, Frankfurt/Main, 60528, Germany.,Department of Orthopedics, J.W. Goethe University, Friedrichsheim gGmbH, Marienburgstraße 2, Frankfurt/Main, 60528, Germany
| | - Andrei Slavici
- Frankfurt Initiative for Regenerative Medicine, Experimental Orthopedics and Trauma Surgery, J.W. Goethe University, Friedrichsheim gGmbH, Marienburgstraße 2, Frankfurt/Main, 60528, Germany.,Department of Orthopedics, J.W. Goethe University, Friedrichsheim gGmbH, Marienburgstraße 2, Frankfurt/Main, 60528, Germany
| | - Zachri N Ovadia
- Frankfurt Initiative for Regenerative Medicine, Experimental Orthopedics and Trauma Surgery, J.W. Goethe University, Friedrichsheim gGmbH, Marienburgstraße 2, Frankfurt/Main, 60528, Germany
| | - Lukasz Hudak
- Frankfurt Initiative for Regenerative Medicine, Experimental Orthopedics and Trauma Surgery, J.W. Goethe University, Friedrichsheim gGmbH, Marienburgstraße 2, Frankfurt/Main, 60528, Germany
| | - Dirk Henrich
- Department of Trauma, Hand and Reconstructive Surgery, J.W. Goethe University, Theodor-Stern-Kai 7, Frankfurt am Main, 60590, Germany
| | - Ingo Marzi
- Department of Trauma, Hand and Reconstructive Surgery, J.W. Goethe University, Theodor-Stern-Kai 7, Frankfurt am Main, 60590, Germany
| | - John H Barker
- Frankfurt Initiative for Regenerative Medicine, Experimental Orthopedics and Trauma Surgery, J.W. Goethe University, Friedrichsheim gGmbH, Marienburgstraße 2, Frankfurt/Main, 60528, Germany
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Tschon M, Incerti-Parenti S, Cepollaro S, Checchi L, Fini M. Photobiomodulation with low-level diode laser promotes osteoblast migration in an in vitro micro wound model. JOURNAL OF BIOMEDICAL OPTICS 2015; 20:78002. [PMID: 26140461 DOI: 10.1117/1.jbo.20.7.078002] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/04/2015] [Accepted: 06/03/2015] [Indexed: 05/15/2023]
Abstract
Laser photobiomodulation can improve bone healing, but well-defined treatment parameters are lacking. Saos-2 human osteoblast-like cells were subjected to an in vitro scratch-wound healing assay and irradiated by a 915-nm gallium-aluminum-arsenide diode laser for 0, 48, 96, and 144 s using doses of, respectively, 0, 5, 10, and 15 J/cm(2) . Wound area was measured after 4, 24, 48, and 72 h. Cell viability, DNA content, gene expression, and release of bone-related proteins were evaluated after 24, 48, and 72 h. Laser significantly improved wound healing compared with nonirradiated controls. Cells treated with laser doses of 5 and 10 J/cm(2) reached wound closure after 72 h, followed by 15 J/cm(2) after 96 h. With the cell proliferation inhibitor Mitomycin C, the doses of 10 and 15 J/cm(2) maintained an improved wound healing compared with controls. Laser increased collagen type 1 gene expression with higher doses inducing a longer-lasting effect, whereas transforming growth factor-beta 1 showed comparable or decreased levels in irradiated versus nonirradiated groups, with no effect on protein release. This study demonstrated that laser photobiomodulation at 915 nm promoted wound healing mainly through stimulation of cell migration and collagen deposition by osteoblasts.
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Affiliation(s)
- Matilde Tschon
- Rizzoli Orthopaedic Institute, Laboratory of Preclinical and Surgical Studies, via di Barbiano 1/10, Bologna 40136, Italy
| | - Serena Incerti-Parenti
- University of Bologna, Unit of Orthodontics, Department of Biomedical and Neuromotor Sciences, via San Vitale 59, Bologna 40125, Italy
| | - Simona Cepollaro
- Rizzoli Orthopaedic Institute, Laboratory of Preclinical and Surgical Studies, via di Barbiano 1/10, Bologna 40136, ItalycUniversity of Bologna, Department of Medical and Surgical Sciences, via Massarenti 9, Bologna 40138, Italy
| | - Luigi Checchi
- University of Bologna, Unit of Periodontology, Department of Biomedical and Neuromotor Sciences, via San Vitale 59, Bologna 40125, Italy
| | - Milena Fini
- Rizzoli Orthopaedic Institute, Laboratory of Preclinical and Surgical Studies, via di Barbiano 1/10, Bologna 40136, Italy
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Zack-Williams SDL, Butler PE, Kalaskar DM. Current progress in use of adipose derived stem cells in peripheral nerve regeneration. World J Stem Cells 2015; 7:51-64. [PMID: 25621105 PMCID: PMC4300936 DOI: 10.4252/wjsc.v7.i1.51] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2014] [Revised: 09/25/2014] [Accepted: 10/29/2014] [Indexed: 02/06/2023] Open
Abstract
Unlike central nervous system neurons; those in the peripheral nervous system have the potential for full regeneration after injury. Following injury, recovery is controlled by schwann cells which replicate and modulate the subsequent immune response. The level of nerve recovery is strongly linked to the severity of the initial injury despite the significant advancements in imaging and surgical techniques. Multiple experimental models have been used with varying successes to augment the natural regenerative processes which occur following nerve injury. Stem cell therapy in peripheral nerve injury may be an important future intervention to improve the best attainable clinical results. In particular adipose derived stem cells (ADSCs) are multipotent mesenchymal stem cells similar to bone marrow derived stem cells, which are thought to have neurotrophic properties and the ability to differentiate into multiple lineages. They are ubiquitous within adipose tissue; they can form many structures resembling the mature adult peripheral nervous system. Following early in vitro work; multiple small and large animal in vivo models have been used in conjunction with conduits, autografts and allografts to successfully bridge the peripheral nerve gap. Some of the ADSC related neuroprotective and regenerative properties have been elucidated however much work remains before a model can be used successfully in human peripheral nerve injury (PNI). This review aims to provide a detailed overview of progress made in the use of ADSC in PNI, with discussion on the role of a tissue engineered approach for PNI repair.
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Kruger EA, Pires M, Ngann Y, Sterling M, Rubayi S. Comprehensive management of pressure ulcers in spinal cord injury: current concepts and future trends. J Spinal Cord Med 2013; 36:572-85. [PMID: 24090179 PMCID: PMC3831318 DOI: 10.1179/2045772313y.0000000093] [Citation(s) in RCA: 137] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Pressure ulcers in spinal cord injury represent a challenging problem for patients, their caregivers, and their physicians. They often lead to recurrent hospitalizations, multiple surgeries, and potentially devastating complications. They present a significant cost to the healthcare system, they require a multidisciplinary team approach to manage well, and outcomes directly depend on patients' education, prevention, and compliance with conservative and surgical protocols. With so many factors involved in the successful treatment of pressure ulcers, an update on their comprehensive management in spinal cord injury is warranted. Current concepts of local wound care, surgical options, as well as future trends from the latest wound healing research are reviewed to aid medical professionals in treating patients with this difficult problem.
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Affiliation(s)
- Erwin A. Kruger
- Department of Surgery, Pressure Ulcer Management Service, Rancho Los Amigos National Rehabilitation Center, Downey, CA, USA
| | - Marilyn Pires
- Department of Nursing, Rancho Los Amigos National Rehabilitation Center, Downey, CA, USA
| | - Yvette Ngann
- Department of Nursing, Rancho Los Amigos National Rehabilitation Center, Downey, CA, USA
| | - Michelle Sterling
- Department of Nursing, Rancho Los Amigos National Rehabilitation Center, Downey, CA, USA
| | - Salah Rubayi
- Department of Surgery, Pressure Ulcer Management Service, Rancho Los Amigos National Rehabilitation Center, Downey, CA, USA,Correspondence to: Dr Salah Rubayi, JPI 3140, Rancho Los Amigos National Rehabilitation Center, 7601 E. Imperial Highway, Downey, CA 90242, USA.
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Griffin M, Sebastian A, Colthurst J, Bayat A. Enhancement of differentiation and mineralisation of osteoblast-like cells by degenerate electrical waveform in an in vitro electrical stimulation model compared to capacitive coupling. PLoS One 2013; 8:e72978. [PMID: 24039834 PMCID: PMC3770651 DOI: 10.1371/journal.pone.0072978] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2013] [Accepted: 07/17/2013] [Indexed: 01/17/2023] Open
Abstract
Electrical stimulation (ES) is effective in enhancing bone healing, however the best electrical waveform, mode of application and mechanisms remains unclear. We recently reported the in vitro differential healing response of a novel electrical waveform called degenerate sine wave (DW) compared to other forms of ES. This study further explores this original observation on osteoblast cells. Here, we electrically stimulated SaOS-2 osteoblast-like cells with DW in an in vitro ES chamber (referred to as ‘DW stimulation’) and compared the intracellular effects to capacitive coupling (CC) stimulation. ES lasted for 4 h, followed by an incubation period of 20 h and subsequent ES for 4 additional hours. Cytotoxicity, proliferation, differentiation and mineralisation of the osteoblast-like cells were evaluated to determine the cell maturation process. DW significantly enhanced the differentiation of cells when compared to CC stimulation with increased alkaline phosphatase and collagen I gene expression by quantitative real time- polymerase chain reaction analysis (p<0.01). Moreover, DW significantly increased the mineralisation of cells compared to CC stimulation. Furthermore the transcription of osteocalcin, osteonectin, osteopontin and bone sialoprotein (p<0.05) was also up regulated by DW. However, ES did not augment the proliferation of cells. Translational analysis by immunocytochemistry and Western blotting showed increased collagen I, osteocalcin and osteonectin expression after DW than CC stimulation. In summary, we have demonstrated for the first time that DW stimulation in an in vitro ES chamber has a significant effect on maturation of osteoblast-like cells compared to CC stimulation of the same magnitude.
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Affiliation(s)
- Michelle Griffin
- Plastic and Reconstructive Surgery Research, Manchester Institute of Biotechnology, University of Manchester, Manchester, United Kingdom
| | - Anil Sebastian
- Plastic and Reconstructive Surgery Research, Manchester Institute of Biotechnology, University of Manchester, Manchester, United Kingdom
| | | | - Ardeshir Bayat
- Plastic and Reconstructive Surgery Research, Manchester Institute of Biotechnology, University of Manchester, Manchester, United Kingdom
- Department of Plastic and Reconstructive Surgery, South Manchester University Hospital Foundation Trust, Wythenshawe Hospital, Manchester, United Kingdom
- Institute of Inflammation and Repair, University of Manchester, Manchester Academic Health Science Centre, South Manchester University Hospital Foundation Trust, Wythenshawe Hospital, Manchester, United Kingdom
- * E-mail:
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Wang X, Wang Y, Gou W, Lu Q, Peng J, Lu S. Role of mesenchymal stem cells in bone regeneration and fracture repair: a review. INTERNATIONAL ORTHOPAEDICS 2013; 37:2491-8. [PMID: 23948983 DOI: 10.1007/s00264-013-2059-2] [Citation(s) in RCA: 229] [Impact Index Per Article: 19.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/12/2013] [Accepted: 07/26/2013] [Indexed: 12/15/2022]
Abstract
Mesenchymal stem cells (MSCs) are non-haematopoietic stromal stem cells that have many sources, such as bone marrow, periosteum, vessel walls, adipose, muscle, tendon, peripheral circulation, umbilical cord blood, skin and dental tissues. They are capable of self-replication and of differentiating into, and contributing to the regeneration of, mesenchymal tissues, such as bone, cartilage, ligament, tendon, muscle and adipose tissue. The homing of MSCs may play an important role in the repair of bone fractures. As a composite material, the formation and growth of bone tissue is a complex process, including molecular, cell and biochemical metabolic changes. The recruitment of factors with an adequate number of MSCs and the micro-environment around the fracture are effective for fracture repair. Several studies have investigated the functional expression of various chemokine receptors, trophic factors and adhesion molecules in human MSCs. Many external factors affect MSC homing. MSCs have been used as seed cells in building tissue-engineered bone grafts. Scaffolds seeded with MSCs are most often used in tissue engineering and include biotic and abiotic materials. This knowledge provides a platform for the development of novel therapies for bone regeneration with endogenous MSCs.
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Affiliation(s)
- Xin Wang
- Key Laboratory of Peoples Liberation Army, Institute of Orthopedics, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing, 100853, People's Republic of China
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Xue L, Xu YB, Xie JL, Tang JM, Shu B, Chen L, Qi SH, Liu XS. Effects of human bone marrow mesenchymal stem cells on burn injury healing in a mouse model. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2013; 6:1327-1336. [PMID: 23826413 PMCID: PMC3693197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 04/23/2013] [Accepted: 05/21/2013] [Indexed: 06/02/2023]
Abstract
OBJECTIVE To investigate the feasibility and safety of human bone marrow mesenchymal stem cells (BM-MSCs) transplantation on the improvement of burn wound healing. METHOD Human BM-MSCs were injected into the skin of the mouse models, and the new blood vessels growth, the engraftment of BM-MSCs and the speed of healing were observed. Moreover the body weight and activity were tested after BM-MSCs transplantation. RESULTS We found that wound surface healing was significantly accelerated when BM-MSCs were applied to the wound surface in mice. Moreover, both the number and density of new blood vessels were increased in the BM-MSC-treated group. The engraftment of BM-MSCs was also investigated using GFP-labeled cells and no GFP-positive cells were observed in tissues other than the location of BM-MSC injection. We also found that both body weight and activity were quickly restored in BM-MSC-treated mice, and no tumor growth was found. CONCLUSION The present results suggest that BM-MSC transplantation can effectively improve wound healing in a mouse model of burn injuries. Use of BM-MSCs might therefore facilitate development and improvement of burn injury treatments in future.
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Affiliation(s)
- Liang Xue
- Department of Burns, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, Guangdong, P R China
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Wang XM, Li J, Yan MX, Liu L, Jia DS, Geng Q, Lin HC, He XH, Li JJ, Yao M. Integrative analyses identify osteopontin, LAMB3 and ITGB1 as critical pro-metastatic genes for lung cancer. PLoS One 2013; 8:e55714. [PMID: 23441154 PMCID: PMC3575388 DOI: 10.1371/journal.pone.0055714] [Citation(s) in RCA: 68] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2012] [Accepted: 12/29/2012] [Indexed: 01/13/2023] Open
Abstract
OBJECTIVE To explore the key regulatory genes associated with lung cancer in order to reduce its occurrence and progress through silencing these key genes. METHODS To identify the key regulatory genes involved in lung cancer, we performed a combination of gene array and bioinformatics analyses to compare gene transcription profiles in 3 monoclonal cell strains with high, medium or low metastatic abilities, which were separated from the SPC-A-1sci and SPC-A-1 cell lines by limiting dilution monoclone assay. We then analyzed those genes' biological activities by knocking down their expression in SPC-A-1sci cells using siRNA and lenti-viral shRNA vectors, followed by determinations of the invasion and migration capabilities of the resulting cell lines in vitro as well as their potential for inducing occurrence and metastasis of lung cancer in vivo. To examine the clinical relevance of these findings, we analyzed the expression levels of the identified genes in human lung cancer tissues (n = 135) and matched adjacent normal tissues by immunohistochemical (IHC) staining. RESULTS Three monoclonal cell strains characterized with high, medium or low metastatic abilities were successfully selected. Gene array and bioinformatics analyses implied that osteopontin, LAMB3 and ITGB1 were key genes involved in lung cancer. Knockdown of these genes suppressed human lung cancer cell invasion and metastasis in vitro and in vivo. Clinical sample analyses indicated that osteopontin, LAMB3 and ITGB1 protein expression levels were higher in lung cancer patients, compared to non-cancerous adjacent tissues, and correlated with lymphatic metastasis. CONCLUSIONS We confirmed that osteopontin, LAMB3 and ITGB1 played important roles in the occurrence and metastasis of lung cancer, thus provided important clues to understanding the molecular mechanism of metastasis and contributing to the therapeutic treatment of lung cancer.
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Affiliation(s)
- Xiao-Min Wang
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jing Li
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ming-Xia Yan
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lei Liu
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - De-Shui Jia
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qin Geng
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - He-Chun Lin
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiang-Huo He
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jin-Jun Li
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ming Yao
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Luo F, Hou T, Zhang Z, Xie Z, Wu X, Xu J. Effects of pulsed electromagnetic field frequencies on the osteogenic differentiation of human mesenchymal stem cells. Orthopedics 2012; 35:e526-31. [PMID: 22495854 DOI: 10.3928/01477447-20120327-11] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
The purpose of this study was to evaluate the effect of different frequencies of pulsed electromagnetic fields on the osteogenic differentiation of human mesenchymal stem cells. Third-generation human mesenchymal stem cells were irradiated with different frequencies of pulsed electromagnetic fields, including 5, 25, 50, 75, 100, and 150 Hz, with a field intensity of 1.1 mT, for 30 minutes per day for 21 days. Changes in human mesenchymal stem cell morphology were observed using phase contrast microscopy. Alkaline phosphatase activity and osteocalcin expression were also determined to evaluate human mesenchymal stem cell osteogenic differentiation.Different effects were observed on human mesenchymal stem cell osteoblast induction following exposure to different pulsed electromagnetic field frequencies. Levels of human mesenchymal stem cell differentiation increased when the pulsed electromagnetic field frequency was increased from 5 hz to 50 hz, but the effect was weaker when the pulsed electromagnetic field frequency was increased from 50 Hz to 150 hz. The most significant effect on human mesenchymal stem cell differentiation was observed at of 50 hz.The results of the current study show that pulsed electromagnetic field frequency is an important factor with regard to the induction of human mesenchymal stem cell differentiation. Furthermore, a pulsed electromagnetic field frequency of 50 Hz was the most effective at inducing human mesenchymal stem cell osteoblast differentiation in vitro.
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Affiliation(s)
- Fei Luo
- Department of Orthopaedics, South-West Hospital, The Third Military University, Chongqing, China
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