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Kozalak G, Koşar A. Bone-on-a-Chip Systems for Hematological Cancers. BIOSENSORS 2025; 15:176. [PMID: 40136973 PMCID: PMC11940066 DOI: 10.3390/bios15030176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/04/2025] [Revised: 02/28/2025] [Accepted: 03/06/2025] [Indexed: 03/27/2025]
Abstract
Hematological malignancies originating from blood, bone marrow, and lymph nodes include leukemia, lymphoma, and myeloma, which necessitate the use of a distinct chemotherapeutic approach. Drug resistance frequently complicates their treatment, highlighting the need for predictive tools to guide therapeutic decisions. Conventional 2D/3D cell cultures do not fully encompass in vivo criteria, and translating disease models from mice to humans proves challenging. Organ-on-a-chip technology presents an avenue to surmount genetic disparities between species, offering precise design, concurrent manipulation of various cell types, and extrapolation of data to human physiology. The development of bone-on-a-chip (BoC) systems is crucial for accurately representing the in vivo bone microenvironment, predicting drug responses for hematological cancers, mitigating drug resistance, and facilitating personalized therapeutic interventions. BoC systems for modeling hematological cancers and drug research can encompass intricate designs and integrated platforms for analyzing drug response data to simulate disease scenarios. This review provides a comprehensive examination of BoC systems applicable to modeling hematological cancers and visualizing drug responses within the intricate context of bone. It thoroughly discusses the materials pertinent to BoC systems, suitable in vitro techniques, the predictive capabilities of BoC systems in clinical settings, and their potential for commercialization.
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Affiliation(s)
- Gül Kozalak
- Faculty of Engineering and Natural Sciences, Sabancı University, Istanbul 34956, Turkey;
- Center of Excellence for Functional Surfaces and Interfaces for Nano Diagnostics (EFSUN), Sabancı University, Istanbul 34956, Turkey
| | - Ali Koşar
- Faculty of Engineering and Natural Sciences, Sabancı University, Istanbul 34956, Turkey;
- Center of Excellence for Functional Surfaces and Interfaces for Nano Diagnostics (EFSUN), Sabancı University, Istanbul 34956, Turkey
- Turkish Academy of Sciences (TÜBA), Çankaya, Ankara 06700, Turkey
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2
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Verdugo-Avello F, Wychowaniec JK, Villacis-Aguirre CA, D'Este M, Toledo JR. Bone microphysiological models for biomedical research. LAB ON A CHIP 2025; 25:806-836. [PMID: 39906932 DOI: 10.1039/d4lc00762j] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2025]
Abstract
Bone related disorders are highly prevalent, and many of these pathologies still do not have curative and definitive treatment methods. This is due to a complex interplay of multiple factors, such as the crosstalk between different tissues and cellular components, all of which are affected by microenvironmental factors. Moreover, these bone pathologies are specific, and current treatment results vary from patient to patient owing to their intrinsic biological variability. Current approaches in drug development to deliver new drug candidates against common bone disorders, such as standard two-dimensional (2D) cell culture and animal-based studies, are now being replaced by more relevant diseases modelling, such as three-dimension (3D) cell culture and primary cells under human-focused microphysiological systems (MPS) that can resemble human physiology by mimicking 3D tissue organization and cell microenvironmental cues. In this review, various technological advancements for in vitro bone modeling are discussed, highlighting the progress in biomaterials used as extracellular matrices, stem cell biology, and primary cell culture techniques. With emphasis on examples of modeling healthy and disease-associated bone tissues, this tutorial review aims to survey current approaches of up-to-date bone-on-chips through MPS technology, with special emphasis on the scaffold and chip capabilities for mimicking the bone extracellular matrix as this is the key environment generated for cell crosstalk and interaction. The relevant bone models are studied with critical analysis of the methods employed, aiming to serve as a tool for designing new and translational approaches. Additionally, the features reported in these state-of-the-art studies will be useful for modeling bone pathophysiology, guiding future improvements in personalized bone models that can accelerate drug discovery and clinical translation.
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Affiliation(s)
- Francisco Verdugo-Avello
- Biotechnology and Biopharmaceuticals Laboratory, Departamento de Fisiopatología, Facultad de Ciencias Biológicas, Universidad de Concepción, Víctor Lamas 1290, P.O. Box 160-C, Concepción, Chile.
| | | | - Carlos A Villacis-Aguirre
- Biotechnology and Biopharmaceuticals Laboratory, Departamento de Fisiopatología, Facultad de Ciencias Biológicas, Universidad de Concepción, Víctor Lamas 1290, P.O. Box 160-C, Concepción, Chile.
| | - Matteo D'Este
- AO Research Institute Davos, Clavadelerstrasse 8, 7270, Davos, Switzerland
| | - Jorge R Toledo
- Biotechnology and Biopharmaceuticals Laboratory, Departamento de Fisiopatología, Facultad de Ciencias Biológicas, Universidad de Concepción, Víctor Lamas 1290, P.O. Box 160-C, Concepción, Chile.
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Wu W, Zhao Z, Wang Y, Liu M, Zhu G, Li L. Mechanism research of elastic fixation promoting fracture healing based on proteomics and fracture microenvironment. Bone Joint Res 2024; 13:559-572. [PMID: 39377775 PMCID: PMC11460404 DOI: 10.1302/2046-3758.1310.bjr-2023-0257.r2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/09/2024] Open
Abstract
Aims This study aimed to demonstrate the promoting effect of elastic fixation on fracture, and further explore its mechanism at the gene and protein expression levels. Methods A closed tibial fracture model was established using 12 male Japanese white rabbits, and divided into elastic and stiff fixation groups based on different fixation methods. Two weeks after the operation, a radiograph and pathological examination of callus tissue were used to evaluate fracture healing. Then, the differentially expressed proteins (DEPs) were examined in the callus using proteomics. Finally, in vitro cell experiments were conducted to investigate hub proteins involved in this process. Results Mean callus volume was larger in the elastic fixation group (1,755 mm3 (standard error of the mean (SEM) 297)) than in the stiff fixation group (258 mm3 (SEM 65)). Pathological observation found that the expression levels of osterix (OSX), collagen, type I, alpha 1 (COL1α1), and alkaline phosphatase (ALP) in the callus of the elastic fixation group were higher than those of the stiff fixation group. The protein sequence of the callus revealed 199 DEPs, 124 of which were highly expressed in the elastic fixation group. In the in vitro study, it was observed that a stress of 200 g led to upregulation of thrombospondin 1 (THBS1) and osteoglycin (OGN) expression in bone marrow mesenchymal stem cells (BMSCs). Additionally, these genes were found to be upregulated during the osteogenic differentiation process of the BMSCs. Conclusion Elastic fixation can promote fracture healing and osteoblast differentiation in callus, and the ability of elastic fixation to promote osteogenic differentiation of BMSCs may be achieved by upregulating genes such as THBS1 and OGN.
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Affiliation(s)
- Weiyong Wu
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
| | - Zhihui Zhao
- Orthopedic Department, The Fourth Central Clinical School, Tianjin Medical University, Tianjin, China
| | - Yongqing Wang
- Orthopedic Department, The Fourth Central Clinical School, Tianjin Medical University, Tianjin, China
| | - Meiyue Liu
- Orthopedic Department, The Fourth Central Clinical School, Tianjin Medical University, Tianjin, China
| | - Genbao Zhu
- General Clinical Research Center, Anhui Wanbei Coal-Electricity Group General Hospital, Suzhou, China
| | - Lili Li
- General Clinical Research Center, Anhui Wanbei Coal-Electricity Group General Hospital, Suzhou, China
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Newton JD, Song Y, Park S, Kanagarajah KR, Wong AP, Young EWK. Tunable In Situ Synthesis of Ultrathin Extracellular Matrix-Derived Membranes in Organ-on-a-Chip Devices. Adv Healthc Mater 2024; 13:e2401158. [PMID: 38587309 DOI: 10.1002/adhm.202401158] [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] [Received: 03/27/2024] [Indexed: 04/09/2024]
Abstract
Thin cell culture membranes in organ-on-a-chip (OOC) devices are used to model a wide range of thin tissues. While early and most current platforms use microporous or fibrous elastomeric or thermoplastic membranes, there is an emerging class of devices using extra-cellular matrix (ECM) protein-based membranes to improve their biological relevance. These ECM-based membranes present physiologically relevant properties, but they are difficult to integrate into OOC devices due to their relative fragility. Additionally, the specialized fabrication methods developed to date make comparison between methods difficult. This work presents the development and characterization of a method to produce ultrathin matrix-derived membranes (UMM) in OOC devices that requires only a preassembled thermoplastic device and a micropipette, decoupling the device and UMM fabrication processes. Control over the thickness and permeability of the UMM is demonstrated, along with integration of the UMM in a device enabling high-resolution on-chip microscopy. The reliability of the UMM fabrication method is leveraged to develop a medium-throughput well-plate format device with 32 independent UMM-integrated samples. Finally, proof-of-concept cell culture experiments are demonstrated. Due to its simplicity and controllability, the presented method has the potential to overcome technical barriers preventing wider adoption of physiologically relevant ECM-based membranes in OOC devices.
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Affiliation(s)
- Jeremy D Newton
- Department of Mechanical & Industrial Engineering, University of Toronto, 5 King's College Road, Toronto, ON, M5S 3G8, Canada
| | - Yuetong Song
- Program in Developmental and Stem Cell Biology, Hospital for Sick Children, 656 Bay Street, Toronto, ON, M5G 0A4, Canada
- Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Road, Toronto, ON, M5S 1A8, Canada
| | - Siwan Park
- Institute of Biomedical Engineering, University of Toronto, 164 College Street, Toronto, ON, M5S 3G9, Canada
| | - Kayshani R Kanagarajah
- Program in Developmental and Stem Cell Biology, Hospital for Sick Children, 656 Bay Street, Toronto, ON, M5G 0A4, Canada
- Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Road, Toronto, ON, M5S 1A8, Canada
| | - Amy P Wong
- Program in Developmental and Stem Cell Biology, Hospital for Sick Children, 656 Bay Street, Toronto, ON, M5G 0A4, Canada
- Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Road, Toronto, ON, M5S 1A8, Canada
| | - Edmond W K Young
- Department of Mechanical & Industrial Engineering, University of Toronto, 5 King's College Road, Toronto, ON, M5S 3G8, Canada
- Institute of Biomedical Engineering, University of Toronto, 164 College Street, Toronto, ON, M5S 3G9, Canada
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Li X, Zhu H, Gu B, Yao C, Gu Y, Xu W, Zhang J, He J, Liu X, Li D. Advancing Intelligent Organ-on-a-Chip Systems with Comprehensive In Situ Bioanalysis. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2024; 36:e2305268. [PMID: 37688520 DOI: 10.1002/adma.202305268] [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: 06/02/2023] [Revised: 08/03/2023] [Indexed: 09/11/2023]
Abstract
In vitro models are essential to a broad range of biomedical research, such as pathological studies, drug development, and personalized medicine. As a potentially transformative paradigm for 3D in vitro models, organ-on-a-chip (OOC) technology has been extensively developed to recapitulate sophisticated architectures and dynamic microenvironments of human organs by applying the principles of life sciences and leveraging micro- and nanoscale engineering capabilities. A pivotal function of OOC devices is to support multifaceted and timely characterization of cultured cells and their microenvironments. However, in-depth analysis of OOC models typically requires biomedical assay procedures that are labor-intensive and interruptive. Herein, the latest advances toward intelligent OOC (iOOC) systems, where sensors integrated with OOC devices continuously report cellular and microenvironmental information for comprehensive in situ bioanalysis, are examined. It is proposed that the multimodal data in iOOC systems can support closed-loop control of the in vitro models and offer holistic biomedical insights for diverse applications. Essential techniques for establishing iOOC systems are surveyed, encompassing in situ sensing, data processing, and dynamic modulation. Eventually, the future development of iOOC systems featuring cross-disciplinary strategies is discussed.
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Affiliation(s)
- Xiao Li
- State Key Laboratory for Manufacturing Systems Engineering, Xi'an Jiaotong University, Xi'an, 710049, China
- NMPA Key Laboratory for Research and Evaluation of Additive Manufacturing Medical Devices, Xi'an Jiaotong University, Xi'an, 710049, China
| | - Hui Zhu
- State Key Laboratory for Manufacturing Systems Engineering, Xi'an Jiaotong University, Xi'an, 710049, China
- NMPA Key Laboratory for Research and Evaluation of Additive Manufacturing Medical Devices, Xi'an Jiaotong University, Xi'an, 710049, China
| | - Bingsong Gu
- State Key Laboratory for Manufacturing Systems Engineering, Xi'an Jiaotong University, Xi'an, 710049, China
- NMPA Key Laboratory for Research and Evaluation of Additive Manufacturing Medical Devices, Xi'an Jiaotong University, Xi'an, 710049, China
| | - Cong Yao
- State Key Laboratory for Manufacturing Systems Engineering, Xi'an Jiaotong University, Xi'an, 710049, China
- NMPA Key Laboratory for Research and Evaluation of Additive Manufacturing Medical Devices, Xi'an Jiaotong University, Xi'an, 710049, China
| | - Yuyang Gu
- State Key Laboratory for Manufacturing Systems Engineering, Xi'an Jiaotong University, Xi'an, 710049, China
- NMPA Key Laboratory for Research and Evaluation of Additive Manufacturing Medical Devices, Xi'an Jiaotong University, Xi'an, 710049, China
| | - Wangkai Xu
- State Key Laboratory for Manufacturing Systems Engineering, Xi'an Jiaotong University, Xi'an, 710049, China
- NMPA Key Laboratory for Research and Evaluation of Additive Manufacturing Medical Devices, Xi'an Jiaotong University, Xi'an, 710049, China
| | - Jia Zhang
- State Key Laboratory for Manufacturing Systems Engineering, Xi'an Jiaotong University, Xi'an, 710049, China
- NMPA Key Laboratory for Research and Evaluation of Additive Manufacturing Medical Devices, Xi'an Jiaotong University, Xi'an, 710049, China
| | - Jiankang He
- State Key Laboratory for Manufacturing Systems Engineering, Xi'an Jiaotong University, Xi'an, 710049, China
- NMPA Key Laboratory for Research and Evaluation of Additive Manufacturing Medical Devices, Xi'an Jiaotong University, Xi'an, 710049, China
| | - Xinyu Liu
- Department of Mechanical & Industrial Engineering, University of Toronto, Toronto, M5S 3G8, Canada
| | - Dichen Li
- State Key Laboratory for Manufacturing Systems Engineering, Xi'an Jiaotong University, Xi'an, 710049, China
- NMPA Key Laboratory for Research and Evaluation of Additive Manufacturing Medical Devices, Xi'an Jiaotong University, Xi'an, 710049, China
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Maita KC, Avila FR, Torres-Guzman RA, Sarabia-Estrada R, Zubair AC, Quinones-Hinojosa A, Forte AJ. In Vitro Enhanced Osteogenic Potential of Human Mesenchymal Stem Cells Seeded in a Poly (Lactic- co-Glycolic) Acid Scaffold: A Systematic Review. Craniomaxillofac Trauma Reconstr 2024; 17:61-73. [PMID: 38371215 PMCID: PMC10874209 DOI: 10.1177/19433875231157454] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/20/2024] Open
Abstract
Study Design Human bone marrow stem cells (hBMSCs) and human adipose-derived stem cells (hADSCs) have demonstrated the capability to regenerate bone once they have differentiated into osteoblasts. Objective This systematic review aimed to evaluate the in vitro osteogenic differentiation potential of these cells when seeded in a poly (lactic-co-glycolic) acid (PLGA) scaffold. Methods A literature search of 4 databases following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted in January 2021 for studies evaluating the osteogenic differentiation potential of hBMSCs and hADSCs seeded in a PLGA scaffold. Only in vitro models were included. Studies in languages other than English were excluded. Results A total of 257 studies were identified after the removal of duplicates. Seven articles fulfilled our inclusion and exclusion criteria. Four of these reviews used hADSCs and three used hBMSCs in the scaffold. Upregulation in osteogenic gene expression was seen in all the cells seeded in a 3-dimensional scaffold compared with 2-dimensional films. High angiogenic gene expression was found in hADSCs. Addition of inorganic material to the scaffold material affected cell performance. Conclusions Viability, proliferation, and differentiation of cells strongly depend on the environment where they grow. There are several factors that can enhance the differentiation capacity of stem cells. A PLGA scaffold proved to be a biocompatible material capable of boosting the osteogenic differentiation potential and mineralization capacity in hBMSCs and hADSCs.
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Affiliation(s)
- Karla C. Maita
- Division of Plastic Surgery, Mayo Clinic, Jacksonville, FL, USA
| | | | | | | | - Abba C. Zubair
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, FL, USA
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Ghasemzadeh-Hasankolaei M, Pinto CA, Jesus D, Saraiva JA, Mano JF. Effect of high cyclic hydrostatic pressure on osteogenesis of mesenchymal stem cells cultured in liquefied micro-compartments. Mater Today Bio 2023; 23:100861. [PMID: 38058695 PMCID: PMC10696388 DOI: 10.1016/j.mtbio.2023.100861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 11/04/2023] [Accepted: 11/09/2023] [Indexed: 12/08/2023] Open
Abstract
Bone resident cells are constantly subjected to a range of distinct mechanical loadings, which generates a complex microenvironment. In particular, hydrostatic pressure (HP) has a key impact on modulation of cell function and fate determination. Although HP is a constant mechanical stimulus, its role in regulating the osteogenesis process within a defined 3D microenvironment has not been comprehensively elucidated. Perceiving how environmental factors regulate the differentiation of stem cells is essential for expanding their regenerative potential. Inspired by the mechanical environment of bone, this study attempted to investigate the influence of different ranges of cyclic HP on human adipose-derived mesenchymal stem cells (MSCs) encapsulated within a compartmentalized liquefied microenvironment. Taking advantage of the liquefied environment of microcapsules, MSCs were exposed to cyclic HP of 5 or 50 MPa, 3 times/week at 37 °C. Biological tests using fluorescence staining of F-actin filaments showed a noticeable improvement in cell-cell interactions and cellular network formation of MSCs. These observations were more pronounced in osteogenic (OST) condition, as confirmed by fluorescent staining of vinculin. More interestingly, there was a significant increase in alkaline phosphatase activity of MSCs exposed to 50 MPa magnitude of HP, even in the absence of osteoinductive factors. In addition, a greater staining area of both osteopontin and hydroxyapatite was detected in the 50 MPa/OST group. These findings highlight the benefit of hydrostatic pressure to regulate osteogenesis of MSCs as well as the importance of employing simultaneous biochemical and mechanical stimulation to accelerate the osteogenic potential of MSCs for biomedical purposes.
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Affiliation(s)
| | - Carlos A. Pinto
- LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193, Aveiro, Portugal
| | - Diana Jesus
- CICECO–Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, 3810-193, Aveiro, Portugal
| | - Jorge A. Saraiva
- LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193, Aveiro, Portugal
| | - João F. Mano
- CICECO–Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, 3810-193, Aveiro, Portugal
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Cauli E, Polidoro MA, Marzorati S, Bernardi C, Rasponi M, Lleo A. Cancer-on-chip: a 3D model for the study of the tumor microenvironment. J Biol Eng 2023; 17:53. [PMID: 37592292 PMCID: PMC10436436 DOI: 10.1186/s13036-023-00372-6] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Accepted: 08/03/2023] [Indexed: 08/19/2023] Open
Abstract
The approval of anticancer therapeutic strategies is still slowed down by the lack of models able to faithfully reproduce in vivo cancer physiology. On one hand, the conventional in vitro models fail to recapitulate the organ and tissue structures, the fluid flows, and the mechanical stimuli characterizing the human body compartments. On the other hand, in vivo animal models cannot reproduce the typical human tumor microenvironment, essential to study cancer behavior and progression. This study reviews the cancer-on-chips as one of the most promising tools to model and investigate the tumor microenvironment and metastasis. We also described how cancer-on-chip devices have been developed and implemented to study the most common primary cancers and their metastatic sites. Pros and cons of this technology are then discussed highlighting the future challenges to close the gap between the pre-clinical and clinical studies and accelerate the approval of new anticancer therapies in humans.
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Affiliation(s)
- Elisa Cauli
- Department of Electronics, Information and Bioengineering, Politecnico Di Milano, Milan, Italy.
- Accelera Srl, Nerviano, Milan, Italy.
| | - Michela Anna Polidoro
- Hepatobiliary Immunopathology Laboratory, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Simona Marzorati
- Hepatobiliary Immunopathology Laboratory, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | | | - Marco Rasponi
- Department of Electronics, Information and Bioengineering, Politecnico Di Milano, Milan, Italy
| | - Ana Lleo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
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Kim MK, Paek K, Woo SM, Kim JA. Bone-on-a-Chip: Biomimetic Models Based on Microfluidic Technologies for Biomedical Applications. ACS Biomater Sci Eng 2023. [PMID: 37183366 DOI: 10.1021/acsbiomaterials.3c00066] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/16/2023]
Abstract
With the increasing importance of preclinical evaluation of newly developed drugs or treatments, in vitro organ or disease models are necessary. Although various organ-specific on-chip (organ-on-a-chip, or OOC) systems have been developed as emerging in vitro models, bone-on-a-chip (BOC) systems that recapitulate the bone microenvironment have been less developed or reviewed compared with other OOCs. The bone is one of the most dynamic organs and undergoes continuous remodeling throughout its lifetime. The aging population is growing worldwide, and healthcare costs are rising rapidly. Since in vitro BOC models that recapitulate native bone niches and pathological features can be important for studying the underlying mechanism of orthopedic diseases and predicting drug responses in preclinical trials instead of in animals, the development of biomimetic BOCs with high efficiency and fidelity will be accelerated further. Here, we review recently engineered BOCs developed using various microfluidic technologies and investigate their use to model the bone microenvironment. We have also explored various biomimetic strategies based on biological, geometrical, and biomechanical cues for biomedical applications of BOCs. Finally, we addressed the limitations and challenging issues of current BOCs that should be overcome to obtain more acceptable BOCs in the biomedical and pharmaceutical industries.
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Affiliation(s)
- Min Kyeong Kim
- Center for Scientific Instrumentation, Korea Basic Science Institute, Cheongju 28119, Republic of Korea
| | - Kyurim Paek
- Center for Scientific Instrumentation, Korea Basic Science Institute, Cheongju 28119, Republic of Korea
- Program in Biomicro System Technology, Korea University, Seoul 02841, Republic of Korea
| | - Sang-Mi Woo
- Center for Scientific Instrumentation, Korea Basic Science Institute, Cheongju 28119, Republic of Korea
| | - Jeong Ah Kim
- Center for Scientific Instrumentation, Korea Basic Science Institute, Cheongju 28119, Republic of Korea
- Department of Bio-Analytical Science, University of Science and Technology, Daejeon 34113, Republic of Korea
- Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul 06973, Republic of Korea
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Fujii Y, Hatori A, Chikazu D, Ogasawara T. Application of Dental Pulp Stem Cells for Bone and Neural Tissue Regeneration in Oral and Maxillofacial Region. Stem Cells Int 2023; 2023:2026572. [PMID: 37035445 PMCID: PMC10076122 DOI: 10.1155/2023/2026572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 10/21/2022] [Accepted: 03/18/2023] [Indexed: 03/31/2023] Open
Abstract
In the oral and maxillofacial region, the treatment of severe bone defects, caused by fractures, cancers, congenital abnormalities, etc., remains a great challenge. In addition, neurological disorders are frequently accompanied by these bone defects or the treatments for them. Therefore, novel bone regenerative techniques and methods to repair nerve injury are eagerly sought. Among them, strategies using dental pulp stem cells (DPSCs) are promising options. Human DPSCs can be collected easily from extracted teeth and are now considered a type of mesenchymal stem cell with higher clonogenic and proliferative potential. DPSCs have been getting attention as a cell source for bone and nerve regeneration. In this article, we reviewed the latest studies on osteogenic or neural differentiation of DPSCs as well as bone or neural regeneration methods using DPSCs and discussed the potential of DPSCs for bone and nerve tissue regeneration.
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11
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Mohamed Rasheed ZB, Nordin F, Wan Kamarul Zaman WS, Tan YF, Abd Aziz NH. Autologous Human Mesenchymal Stem Cell-Based Therapy in Infertility: New Strategies and Future Perspectives. BIOLOGY 2023; 12:108. [PMID: 36671799 PMCID: PMC9855776 DOI: 10.3390/biology12010108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 01/06/2023] [Accepted: 01/08/2023] [Indexed: 01/12/2023]
Abstract
Infertility could be associated with a few factors including problems with physical and mental health, hormonal imbalances, lifestyles, and genetic factors. Given that there is a concern about the rise of infertility globally, increased focus has been given to its treatment for the last several decades. Traditional assisted reproductive technology (ART) has been the prime option for many years in solving various cases of infertility; however, it contains significant risks and does not solve the fundamental problem of infertility such as genetic disorders. Attention toward the utilization of MSCs has been widely regarded as a promising option in the development of stem-cell-based infertility treatments. This narrative review briefly presents the challenges in the current ART treatment of infertility and the various potential applications of autologous MSCs in the treatment of these reproductive diseases.
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Affiliation(s)
- Zahirrah Begam Mohamed Rasheed
- UKM Medical Molecular Biology Institute (UMBI), Jalan Yaacob Latiff, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia
| | - Fazlina Nordin
- Centre for Tissue Engineering and Regenerative Medicine (CTERM), Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latiff, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia
| | | | - Yuen-Fen Tan
- PPUKM-MAKNA Cancer Center, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, WPKL, Kuala Lumpur 56000, Malaysia
- Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Sungai Long Campus, Bandar Sungai Long, Kajang 43000, Malaysia
| | - Nor Haslinda Abd Aziz
- Department of Obstetrics and Gynaecology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
- Research Laboratory of UKM Specialist Children’s Hospital, UKM Specialist Children’s Hospital, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
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Zommiti M, Connil N, Tahrioui A, Groboillot A, Barbey C, Konto-Ghiorghi Y, Lesouhaitier O, Chevalier S, Feuilloley MGJ. Organs-on-Chips Platforms Are Everywhere: A Zoom on Biomedical Investigation. Bioengineering (Basel) 2022; 9:646. [PMID: 36354557 PMCID: PMC9687856 DOI: 10.3390/bioengineering9110646] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 10/13/2022] [Accepted: 10/27/2022] [Indexed: 08/28/2023] Open
Abstract
Over the decades, conventional in vitro culture systems and animal models have been used to study physiology, nutrient or drug metabolisms including mechanical and physiopathological aspects. However, there is an urgent need for Integrated Testing Strategies (ITS) and more sophisticated platforms and devices to approach the real complexity of human physiology and provide reliable extrapolations for clinical investigations and personalized medicine. Organ-on-a-chip (OOC), also known as a microphysiological system, is a state-of-the-art microfluidic cell culture technology that sums up cells or tissue-to-tissue interfaces, fluid flows, mechanical cues, and organ-level physiology, and it has been developed to fill the gap between in vitro experimental models and human pathophysiology. The wide range of OOC platforms involves the miniaturization of cell culture systems and enables a variety of novel experimental techniques. These range from modeling the independent effects of biophysical forces on cells to screening novel drugs in multi-organ microphysiological systems, all within microscale devices. As in living biosystems, the development of vascular structure is the salient feature common to almost all organ-on-a-chip platforms. Herein, we provide a snapshot of this fast-evolving sophisticated technology. We will review cutting-edge developments and advances in the OOC realm, discussing current applications in the biomedical field with a detailed description of how this technology has enabled the reconstruction of complex multi-scale and multifunctional matrices and platforms (at the cellular and tissular levels) leading to an acute understanding of the physiopathological features of human ailments and infections in vitro.
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Affiliation(s)
- Mohamed Zommiti
- Research Unit Bacterial Communication and Anti-infectious Strategies (CBSA, UR4312), University of Rouen Normandie, 27000 Evreux, France
| | | | | | | | | | | | | | | | - Marc G. J. Feuilloley
- Research Unit Bacterial Communication and Anti-infectious Strategies (CBSA, UR4312), University of Rouen Normandie, 27000 Evreux, France
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13
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Bagge J, Berg LC, Janes J, MacLeod JN. Donor age effects on in vitro chondrogenic and osteogenic differentiation performance of equine bone marrow- and adipose tissue-derived mesenchymal stromal cells. BMC Vet Res 2022; 18:388. [PMID: 36329434 PMCID: PMC9632053 DOI: 10.1186/s12917-022-03475-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 10/10/2022] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND Bone marrow (BM)- and adipose tissue (AT)-derived mesenchymal stromal cells (MSCs) have shown potential as cell-based therapies for cartilage and bone injuries and are used increasingly in human and veterinary practice to facilitate the treatment of orthopedic conditions. However, human and rodent studies have documented a sharp decline in chondrogenic and osteogenic differentiation potential with increasing donor age, which may be problematic for the important demographic of older orthopedic patients. The aim of this study was to identify the effect of donor age on the chondrogenic and osteogenic differentiation performance of equine BM- and AT-MSCs in vitro. BM- and AT-MSCs and dermal fibroblasts (biological negative control) were harvested from horses in five different age groups (n = 4, N = 60); newborn (0 days), yearling (15-17 months), adult (5-8 years), middle-aged (12-18 years), and geriatric (≥ 22 years). Chondrogenic differentiation performance was assessed quantitatively by measuring pellet size, matrix proteoglycan levels, and gene expression of articular cartilage biomarkers. Osteogenic differentiation performance was assessed quantitatively by measuring alkaline phosphatase activity, calcium deposition, and gene expression of bone biomarkers. RESULTS Chondrogenic and osteogenic differentiation performance of equine BM- and AT-MSCs declined with increasing donor age. BM-MSCs had a higher chondrogenic differentiation performance. AT-MSCs showed minimal chondrogenic differentiation performance in all age groups. For osteogenesis, alkaline phosphatase activity was also higher in BM-MSCs, but BM-MSCs calcium deposition was affected by donor age earlier than AT-MSCs. Chondrogenic and osteogenic differentiation performance of BM-MSCs exhibited a decline as early as between the newborn and yearling samples. Steady state levels of mRNA encoding growth factors, chondrogenic, and osteogenic biomarkers were lower with increasing donor age in both MSC types. CONCLUSIONS The data showed that chondrogenic and osteogenic differentiation performance of equine BM-MSCs declined already in yearlings, and that AT-MSCs showed minimal chondrogenic potential, but were affected later by donor age with regards to osteogenesis (calcium deposition). The results highlight the importance of donor age considerations and MSC selection for cell-based treatment of orthopedic injuries and will help inform clinicians on when to implement or potentially cryopreserve cells. Moreover, the study provides molecular targets affected by donor age.
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Affiliation(s)
- Jasmin Bagge
- grid.5254.60000 0001 0674 042XDepartment of Veterinary Clinical Sciences, University of Copenhagen, Agrovej 8, 2630 Taastrup, Denmark ,grid.266539.d0000 0004 1936 8438Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, University of Kentucky, 1400 Nicholasville Rd, Lexington, KY 40546 USA
| | - Lise Charlotte Berg
- grid.5254.60000 0001 0674 042XDepartment of Veterinary Clinical Sciences, University of Copenhagen, Agrovej 8, 2630 Taastrup, Denmark
| | - Jennifer Janes
- grid.266539.d0000 0004 1936 8438Department of Veterinary Science, University of Kentucky Veterinary Diagnostic Laboratory, University of Kentucky, 1490 Bull Lea Rd, Lexington, KY 40511 USA
| | - James N. MacLeod
- grid.266539.d0000 0004 1936 8438Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, University of Kentucky, 1400 Nicholasville Rd, Lexington, KY 40546 USA
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14
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Tahmasbpour Marzouni E, Stern C, Henrik Sinclair A, Tucker EJ. Stem Cells and Organs-on-chips: New Promising Technologies for Human Infertility Treatment. Endocr Rev 2022; 43:878-906. [PMID: 34967858 DOI: 10.1210/endrev/bnab047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Indexed: 11/19/2022]
Abstract
Having biological children remains an unattainable dream for most couples with reproductive failure or gonadal dysgenesis. The combination of stem cells with gene editing technology and organ-on-a-chip models provides a unique opportunity for infertile patients with impaired gametogenesis caused by congenital disorders in sex development or cancer survivors. But how will these technologies overcome human infertility? This review discusses the regenerative mechanisms, applications, and advantages of different types of stem cells for restoring gametogenesis in infertile patients, as well as major challenges that must be overcome before clinical application. The importance and limitations of in vitro generation of gametes from patient-specific human-induced pluripotent stem cells (hiPSCs) will be discussed in the context of human reproduction. The potential role of organ-on-a-chip models that can direct differentiation of hiPSC-derived primordial germ cell-like cells to gametes and other reproductive organoids is also explored. These rapidly evolving technologies provide prospects for improving fertility to individuals and couples who experience reproductive failure.
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Affiliation(s)
- Eisa Tahmasbpour Marzouni
- Laboratory of Regenerative Medicine & Biomedical Innovations, Pasteur Institute of Iran, Tehran, Iran
| | - Catharyn Stern
- Royal Women's Hospital, Parkville and Melbourne IVF, Melbourne, Australia
| | - Andrew Henrik Sinclair
- Reproductive Development, Murdoch Children's Research Institute, Melbourne, Australia.,Department of Paediatrics, University of Melbourne, Melbourne, Australia
| | - Elena Jane Tucker
- Reproductive Development, Murdoch Children's Research Institute, Melbourne, Australia.,Department of Paediatrics, University of Melbourne, Melbourne, Australia
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15
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Petta D, D'Amora U, D'Arrigo D, Tomasini M, Candrian C, Ambrosio L, Moretti M. Musculoskeletal tissues-on-a-chip: role of natural polymers in reproducing tissue-specific microenvironments. Biofabrication 2022; 14. [PMID: 35931043 DOI: 10.1088/1758-5090/ac8767] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Accepted: 08/05/2022] [Indexed: 11/12/2022]
Abstract
Over the past years, 3D in vitro models have been widely employed in the regenerative medicine field. Among them, organ-on-a-chip technology has the potential to elucidate cellular mechanism exploiting multichannel microfluidic devices to establish 3D co-culture systems that offer control over the cellular, physico-chemical and biochemical microenvironments. To deliver the most relevant cues to cells, it is of paramount importance to select the most appropriate matrix for mimicking the extracellular matrix of the native tissue. Natural polymers-based hydrogels are the elected candidates for reproducing tissue-specific microenvironments in musculoskeletal tissue-on-a-chip models owning to their interesting and peculiar physico-chemical, mechanical and biological properties. Despite these advantages, there is still a gap between the biomaterials complexity in conventional tissue engineering and the application of these biomaterials in 3D in vitro microfluidic models. In this review, the aim is to suggest the adoption of more suitable biomaterials, alternative crosslinking strategies and tissue engineered-inspired approaches in organ-on-a-chip to better mimic the complexity of physiological musculoskeletal tissues. Accordingly, after giving an overview of the musculoskeletal tissue compositions, the properties of the main natural polymers employed in microfluidic systems are investigated, together with the main musculoskeletal tissues-on-a-chip devices.
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Affiliation(s)
- Dalila Petta
- Regenerative Medicine Technologis Lab, Repubblica e Cantone Ticino Ente Ospedaliero Cantonale, Via Francesco Chiesa 5, Bellinzona, Ticino, 6500, SWITZERLAND
| | - Ugo D'Amora
- Institute of Polymers, Composites and Biomaterials, National Research Council, V.le J.F. Kennedy 54 Mostra d'Oltremare Pad 20, Naples, 80125, ITALY
| | - Daniele D'Arrigo
- Repubblica e Cantone Ticino Ente Ospedaliero Cantonale, Via Francesco Chiesa 5, Bellinzona, Ticino, 6500, SWITZERLAND
| | - Marta Tomasini
- Repubblica e Cantone Ticino Ente Ospedaliero Cantonale, Via Francesco chies 5, Bellinzona, Ticino, 6500, SWITZERLAND
| | - Christian Candrian
- Unità di Traumatologia e Ortopedia, Ente Ospedaliero Cantonale, via Tesserete 46, Lugano, 6900, SWITZERLAND
| | - Luigi Ambrosio
- Institute of Polymers Composites and Biomaterials National Research Council, Viale Kennedy, Pozzuoli, Campania, 80078, ITALY
| | - Matteo Moretti
- Regenerative Medicine Technologies Laboratory, Repubblica e Cantone Ticino Ente Ospedaliero Cantonale, Via Francesco Chiesa 5, Bellinzona, Ticino, 6500, SWITZERLAND
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16
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Amiri MA, Farshidfar N, Hamedani S. The feasibility of craniofacial-derived bone marrow stem cells for the treatment of oral and maxillofacial hard tissue defects. J Dent Sci 2022; 17:1445-1447. [PMID: 35784165 PMCID: PMC9236948 DOI: 10.1016/j.jds.2022.01.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 01/11/2022] [Indexed: 11/23/2022] Open
Affiliation(s)
- Mohammad Amin Amiri
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Nima Farshidfar
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
- Orthodontic Research Center, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Shahram Hamedani
- Oral and Dental Disease Research Center, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran
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17
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Labusca L. Adipose tissue in bone regeneration - stem cell source and beyond. World J Stem Cells 2022; 14:372-392. [PMID: 35949397 PMCID: PMC9244952 DOI: 10.4252/wjsc.v14.i6.372] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2021] [Revised: 08/30/2021] [Accepted: 05/27/2022] [Indexed: 02/06/2023] Open
Abstract
Adipose tissue (AT) is recognized as a complex organ involved in major home-ostatic body functions, such as food intake, energy balance, immunomodulation, development and growth, and functioning of the reproductive organs. The role of AT in tissue and organ homeostasis, repair and regeneration is increasingly recognized. Different AT compartments (white AT, brown AT and bone marrow AT) and their interrelation with bone metabolism will be presented. AT-derived stem cell populations - adipose-derived mesenchymal stem cells and pluripotent-like stem cells. Multilineage differentiating stress-enduring and dedifferentiated fat cells can be obtained in relatively high quantities compared to other sources. Their role in different strategies of bone and fracture healing tissue engineering and cell therapy will be described. The current use of AT- or AT-derived stem cell populations for fracture healing and bone regenerative strategies will be presented, as well as major challenges in furthering bone regenerative strategies to clinical settings.
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Affiliation(s)
- Luminita Labusca
- Magnetic Materials and Sensors, National Institute of Research and Development for Technical Physics, Iasi 700050, Romania
- Orthopedics and Traumatology, County Emergency Hospital Saint Spiridon Iasi, Iasi 700050, Romania.
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18
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Yen BL, Liu K, Sytwu H, Yen M. Clinical implications of differential functional capacity between tissue‐specific human mesenchymal stromal/stem cells. FEBS J 2022. [DOI: 10.1111/febs.16438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 01/30/2022] [Accepted: 03/16/2022] [Indexed: 11/28/2022]
Affiliation(s)
- B. Linju Yen
- Regenerative Medicine Research Group Institute of Cellular & System Medicine National Health Research Institutes (NHRI) Zhunan Taiwan
- Department of Obstetrics & Gynecology Cathay General Hospital Shiji New Taipei City Taiwan
| | - Ko‐Jiunn Liu
- National Institute of Cancer Research NHRI Zhunan Taiwan
- Institute of Clinical Pharmacy & Pharmaceutical Sciences National Cheng Kung University Tainan Taiwan
- School of Medical Laboratory Science and Biotechnology Taipei Medical University Taiwan
| | - Huey‐Kang Sytwu
- National Institute of Infectious Diseases & Vaccinology NHRI Zhunan Taiwan
- Graduate Institute of Microbiology & Immunology National Defense Medical Center Taipei Taiwan
| | - Men‐Luh Yen
- Department of Obstetrics & Gynecology National Taiwan University (NTU) Hospital & College of Medicine NTU Taipei Taiwan
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19
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Prajwal GS, Jeyaraman N, Kanth V K, Jeyaraman M, Muthu S, Rajendran SNS, Rajendran RL, Khanna M, Oh EJ, Choi KY, Chung HY, Ahn BC, Gangadaran P. Lineage Differentiation Potential of Different Sources of Mesenchymal Stem Cells for Osteoarthritis Knee. Pharmaceuticals (Basel) 2022; 15:386. [PMID: 35455383 PMCID: PMC9028477 DOI: 10.3390/ph15040386] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 03/11/2022] [Accepted: 03/17/2022] [Indexed: 02/05/2023] Open
Abstract
Tissue engineering and regenerative medicine (TERM) have paved a way for treating musculoskeletal diseases in a minimally invasive manner. The regenerative medicine cocktail involves the usage of mesenchymal stem/stromal cells (MSCs), either uncultured or culture-expanded cells along with growth factors, cytokines, exosomes, and secretomes to provide a better regenerative milieu in degenerative diseases. The successful regeneration of cartilage depends on the selection of the appropriate source of MSCs, the quality, quantity, and frequency of MSCs to be injected, and the selection of the patient at an appropriate stage of the disease. However, confirmation on the most favorable source of MSCs remains uncertain to clinicians. The lack of knowledge in the current cellular treatment is uncertain in terms of how beneficial MSCs are in the long-term or short-term (resolution of pain) and improved quality of life. Whether MSCs treatments have any superiority, exists due to sources of MSCs utilized in their potential to objectively regenerate the cartilage at the target area. Many questions on source and condition remain unanswered. Hence, in this review, we discuss the lineage differentiation potentials of various sources of MSCs used in the management of knee osteoarthritis and emphasize the role of tissue engineering in cartilage regeneration.
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Affiliation(s)
- Gollahalli Shivashankar Prajwal
- Research Fellow, Fellowship in Orthopaedic Rheumatology (FEIORA), Dr. Ram Manohar Lohiya National Law University, Lucknow 226010, Uttar Pradesh, India; (G.S.P.); (N.J.)
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow 110048, Uttar Pradesh, India; (S.M.); (M.K.)
- Department of Orthopaedics, Mallika Spine Centre, Guntur 522001, Andhra Pradesh, India
| | - Naveen Jeyaraman
- Research Fellow, Fellowship in Orthopaedic Rheumatology (FEIORA), Dr. Ram Manohar Lohiya National Law University, Lucknow 226010, Uttar Pradesh, India; (G.S.P.); (N.J.)
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow 110048, Uttar Pradesh, India; (S.M.); (M.K.)
- Department of Orthopaedics, Atlas Hospitals, Tiruchirappalli 620002, Tamil Nadu, India
| | - Krishna Kanth V
- Department of Orthopaedics, Government Medical College, Mahabubabad 506104, Telangana, India;
| | - Madhan Jeyaraman
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow 110048, Uttar Pradesh, India; (S.M.); (M.K.)
- Department of Orthopaedics, Faculty of Medicine—Sri Lalithambigai Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai 600095, Tamil Nadu, India
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida 201306, Uttar Pradesh, India
- Orthopaedic Research Group, Coimbatore 641001, Tamil Nadu, India
| | - Sathish Muthu
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow 110048, Uttar Pradesh, India; (S.M.); (M.K.)
- Department of Orthopaedics, Government Medical College, Mahabubabad 506104, Telangana, India;
- Department of Orthopaedics, Faculty of Medicine—Sri Lalithambigai Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai 600095, Tamil Nadu, India
- Orthopaedic Research Group, Coimbatore 641001, Tamil Nadu, India
| | - Sree Naga Sowndary Rajendran
- Department of Medicine, Sri Venkateshwaraa Medical College Hospital and Research Centre, Puducherry 605102, Puducherry, India;
| | - Ramya Lakshmi Rajendran
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea;
| | - Manish Khanna
- Indian Stem Cell Study Group (ISCSG) Association, Lucknow 110048, Uttar Pradesh, India; (S.M.); (M.K.)
- Department of Orthopaedics, Government Medical College and Hospital, Dindigul 624001, Tamil Nadu, India
- Department of Orthopaedics, Prasad Institute of Medical Sciences, Lucknow 226010, Uttar Pradesh, India
| | - Eun Jung Oh
- Department of Plastic and Reconstructive Surgery, CMRI, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea; (E.J.O.); (K.Y.C.); (H.Y.C.)
| | - Kang Young Choi
- Department of Plastic and Reconstructive Surgery, CMRI, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea; (E.J.O.); (K.Y.C.); (H.Y.C.)
| | - Ho Yun Chung
- Department of Plastic and Reconstructive Surgery, CMRI, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea; (E.J.O.); (K.Y.C.); (H.Y.C.)
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu 41944, Korea
| | - Byeong-Cheol Ahn
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea;
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu 41944, Korea
| | - Prakash Gangadaran
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea;
- BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu 41944, Korea
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20
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Özkayar G, Lötters JC, Tichem M, Ghatkesar MK. Toward a modular, integrated, miniaturized, and portable microfluidic flow control architecture for organs-on-chips applications. BIOMICROFLUIDICS 2022; 16:021302. [PMID: 35464136 PMCID: PMC9018096 DOI: 10.1063/5.0074156] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Accepted: 03/23/2022] [Indexed: 05/08/2023]
Abstract
Microfluidic organs-on-chips (OoCs) technology has emerged as the trend for in vitro functional modeling of organs in recent years. Simplifying the complexities of the human organs under controlled perfusion of required fluids paves the way for accurate prediction of human organ functionalities and their response to interventions like exposure to drugs. However, in the state-of-the-art OoC, the existing methods to control fluids use external bulky peripheral components and systems much larger than the chips used in experiments. A new generation of compact microfluidic flow control systems is needed to overcome this challenge. This study first presents a structured classification of OoC devices according to their types and microfluidic complexities. Next, we suggest three fundamental fluid flow control mechanisms and define component configurations for different levels of OoC complexity for each respective mechanism. Finally, we propose an architecture integrating modular microfluidic flow control components and OoC devices on a single platform. We emphasize the need for miniaturization of flow control components to achieve portability, minimize sample usage, minimize dead volume, improve the flowing time of fluids to the OoC cell chamber, and enable long-duration experiments.
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Affiliation(s)
- Gürhan Özkayar
- Department of Precision and Microsystems Engineering, Delft University of Technology, Delft, The Netherlands
| | | | - Marcel Tichem
- Department of Precision and Microsystems Engineering, Delft University of Technology, Delft, The Netherlands
| | - Murali K. Ghatkesar
- Department of Precision and Microsystems Engineering, Delft University of Technology, Delft, The Netherlands
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21
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Hodgkinson T, Amado IN, O'Brien FJ, Kennedy OD. The role of mechanobiology in bone and cartilage model systems in characterizing initiation and progression of osteoarthritis. APL Bioeng 2022. [DOI: 10.1063/5.0068277] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Affiliation(s)
- Tom Hodgkinson
- Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Isabel N. Amado
- Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Fergal J. O'Brien
- Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland
- Advanced Materials Bio-Engineering Research Centre (AMBER), Dublin, Ireland
- Trinity Centre for Biomedical Engineering, Trinity College Dublin, Dublin, Ireland
| | - Oran D. Kennedy
- Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland
- Advanced Materials Bio-Engineering Research Centre (AMBER), Dublin, Ireland
- Trinity Centre for Biomedical Engineering, Trinity College Dublin, Dublin, Ireland
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22
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Zhang J, Zhang M, Lin R, Du Y, Wang L, Yao Q, Zannettino A, Zhang H. Chondrogenic preconditioning of mesenchymal stem/stromal cells within a magnetic scaffold for osteochondral repair. Biofabrication 2022; 14. [PMID: 35226893 DOI: 10.1088/1758-5090/ac5935] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Accepted: 02/28/2022] [Indexed: 12/11/2022]
Abstract
Stem cell therapy using mesenchymal stromal/stem cells (MSCs) represents a novel approach to treating severe diseases, including osteoarthritis (OA). However, the therapeutic benefit of MSCs is highly dependent on their differentiation state, which can be regulated by many factors. Herein, three-dimensional (3D) magnetic scaffolds were successfully fabricated by incorporating magnetic nanoparticles (MNPs) into electrospun gelatin nanofibers. When positioned near a rotating magnet (f= 0.5 Hz), the magnetic scaffolds with the embedded MSCs were driven upward/downward in the culture container to induce mechanical stimulation to MSCs due to spatial confinement and fluid flow. The extracellular matrix-mimicking scaffold and the alternating magnetic field significantly enhanced chondrogenesis instead of osteogenesis. Furthermore, the fibre topography could be tuned with different compositions of the coating layer on MNPs, and the topography had a significant impact on MSC differentiation. Selective up-regulation of chondrogenesis-related genes (COL2A1andACAN) was found for the magnetic scaffolds with citric acid-coated MNPs (CAG). In contrast, osteogenesis-related genes (RUNX2andSPARC) were selectively and significantly up-regulated for the magnetic scaffolds with polyvinylpyrrolidone-coated MNPs (PVPG). Prior to implantation in vivo, chondrogenic preconditioning of MSCs within the CAG scaffolds under a dynamic magnetic field resulted in superior osteochondral repair. Hence, the magnetic scaffolds together with an in-house rotating magnet device could be a novel platform to initiate multiple stimuli on stem cell differentiation for effective repair of osteochondral defects.
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Affiliation(s)
- Jiabin Zhang
- Sun Yat-Sen University, Sun Yat-Sen University, Guangzhou, 510275, CHINA
| | - Ming Zhang
- Department of Orthopedics, Zhongda Hospital, School of Medicine, Southeast University, Department of Orthopedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing , Jiangsu Province, China, Nangjing, Jiangsu, 210009, CHINA
| | - Rongcai Lin
- Department of Orthopaedic Surgery, Institute of Digital Medicine, Nanjing First Hospital, Nanjing Medical University, Department of Orthopaedic Surgery, Institute of Digital Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China, Nanjing, 210006, CHINA
| | - Yuguang Du
- Institute of Process Engineering Chinese Academy of Sciences, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China, Beijing, Beijing, 100190, CHINA
| | - Liming Wang
- Department of Orthopaedic Surgery Nanjing First Hospital, Nanjing Medical University, Department of Orthopaedic Surgery, Institute of Digital Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China, Nanjing, Jiangsu Province, 210006, CHINA
| | - Qingqiang Yao
- Department of Orthopaedic Surgery, Institute of Digital Medicine, Nanjing First Hospital, Nanjing Medical University, Department of Orthopaedic Surgery, Institute of Digital Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China, Nanjing, 210006, CHINA
| | - Andrew Zannettino
- Adelaide Medical School Research, The University of Adelaide, Adelaide, Australia, Adelaide, South Australia, 5005, AUSTRALIA
| | - Hu Zhang
- Amgen Bioprocessing Centre, Keck Graduate Institute, CA 91711, USA, 535 Watson Drive, Claremont, CA, USA, Claremont, California, 91711, UNITED STATES
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23
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Lipreri MV, Baldini N, Graziani G, Avnet S. Perfused Platforms to Mimic Bone Microenvironment at the Macro/Milli/Microscale: Pros and Cons. Front Cell Dev Biol 2022; 9:760667. [PMID: 35047495 PMCID: PMC8762164 DOI: 10.3389/fcell.2021.760667] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Accepted: 11/30/2021] [Indexed: 11/26/2022] Open
Abstract
As life expectancy increases, the population experiences progressive ageing. Ageing, in turn, is connected to an increase in bone-related diseases (i.e., osteoporosis and increased risk of fractures). Hence, the search for new approaches to study the occurrence of bone-related diseases and to develop new drugs for their prevention and treatment becomes more pressing. However, to date, a reliable in vitro model that can fully recapitulate the characteristics of bone tissue, either in physiological or altered conditions, is not available. Indeed, current methods for modelling normal and pathological bone are poor predictors of treatment outcomes in humans, as they fail to mimic the in vivo cellular microenvironment and tissue complexity. Bone, in fact, is a dynamic network including differently specialized cells and the extracellular matrix, constantly subjected to external and internal stimuli. To this regard, perfused vascularized models are a novel field of investigation that can offer a new technological approach to overcome the limitations of traditional cell culture methods. It allows the combination of perfusion, mechanical and biochemical stimuli, biological cues, biomaterials (mimicking the extracellular matrix of bone), and multiple cell types. This review will discuss macro, milli, and microscale perfused devices designed to model bone structure and microenvironment, focusing on the role of perfusion and encompassing different degrees of complexity. These devices are a very first, though promising, step for the development of 3D in vitro platforms for preclinical screening of novel anabolic or anti-catabolic therapeutic approaches to improve bone health.
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Affiliation(s)
| | - Nicola Baldini
- Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.,Biomedical Science and Technologies Lab, IRCSS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Gabriela Graziani
- Laboratory for NanoBiotechnology (NaBi), IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Sofia Avnet
- Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy
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24
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Ching T, Toh YC, Hashimoto M. Design and fabrication of micro/nanofluidics devices and systems. PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE 2022; 186:15-58. [PMID: 35033282 DOI: 10.1016/bs.pmbts.2021.07.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
This chapter provides an overview of the science, engineering, and design methods required in the development of micro/nanofluidic devices. Section 2 provides the scientific background of fluid mechanics and physical phenomena in micro/nanoscale. Section 3 gives a brief overview of the existing fabrication techniques employed in micro/nanofluidics. The techniques are grouped into three categories: (1) subtractive manufacturing, (2) formative manufacturing, and (3) additive manufacturing. The advantages and disadvantages of each manufacturing technique are also discussed. Implementation of the fluidic devices beyond laboratory demonstrations is not trivial, which requires a good understanding of the problems of interest and the end-users. To that end, Section 4 introduces the design thinking approach and its application to develop micro/nanofluidic devices. Finally, Section 5 concludes the chapter with future outlooks.
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Affiliation(s)
- Terry Ching
- Pillar of Engineering Product Development, Singapore University of Technology and Design, Singapore, Singapore; Digital Manufacturing and Design Centre, Singapore University of Technology and Design, Singapore, Singapore; Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore
| | - Yi-Chin Toh
- School of Mechanical, Medical and Process Engineering, Queensland University of Technology, Brisbane, QLD, Australia; Centre for Biomedical Technologies, Queensland University of Technology, Kelvin Grove, QLD, Australia
| | - Michinao Hashimoto
- Pillar of Engineering Product Development, Singapore University of Technology and Design, Singapore, Singapore; Digital Manufacturing and Design Centre, Singapore University of Technology and Design, Singapore, Singapore.
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25
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Zarrintaj P, Saeb MR, Stadler FJ, Yazdi MK, Nezhad MN, Mohebbi S, Seidi F, Ganjali MR, Mozafari M. Human Organs-on-Chips: A Review of the State-of-the-Art, Current Prospects, and Future Challenges. Adv Biol (Weinh) 2022; 6:e2000526. [PMID: 34837667 DOI: 10.1002/adbi.202000526] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Revised: 08/03/2021] [Indexed: 01/09/2023]
Abstract
New emerging technologies, remarkably miniaturized 3D organ models and microfluidics, enable simulation of the real in vitro microenvironment ex vivo more closely. There are many fascinating features of innovative organ-on-a-chip (OOC) technology, including the possibility of integrating semipermeable and/or stretchable membranes, creating continuous perfusion of fluids into microchannels and chambers (while maintaining laminar flow regime), embedding microdevices like microsensors, microstimulators, micro heaters, or different cell lines, along with other 3D cell culture technologies. OOC systems are designed to imitate the structure and function of human organs, ranging from breathing lungs to beating hearts. This technology is expected to be able to revolutionize cell biology studies, personalized precision medicine, drug development process, and cancer diagnosis/treatment. OOC systems can significantly reduce the cost associated with tedious drug development processes and the risk of adverse drug reactions in the body, which makes drug screening more effective. The review mainly focus on presenting an overview of the several previously developed OOC systems accompanied by subjects relevant to pharmacy-, cancer-, and placenta-on-a-chip. The challenging issues and opportunities related to these systems are discussed, along with a future perspective for this technology.
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Affiliation(s)
- Payam Zarrintaj
- School of Chemical Engineering, Oklahoma State University, 420 Engineering North, Stillwater, OK, 74078, USA
| | - Mohammad Reza Saeb
- Department of Polymer Technology, Faculty of Chemistry, Gdańsk University of Technology, G. Narutowicza 11/12, Gdańsk, 80-233, Poland
| | - Florian J Stadler
- College of Materials Science and Engineering, Shenzhen Key Laboratory of Polymer Science and Technology, Guangdong Research Center for Interfacial Engineering of Functional Materials, Shenzhen University, Shenzhen, 518060, China
| | - Mohsen Khodadadi Yazdi
- Center of Excellence in Electrochemistry, School of Chemistry, College of Science, University of Tehran, Tehran, 1417466191, Iran
| | - Mojtaba Nasiri Nezhad
- Department of Chemical Engineering, Urmia University of Technology, Urmia, 57166-419, Iran
| | - Shabnam Mohebbi
- Department of Chemical Engineering, Tabriz University, Tabriz, 51335-1996, Iran
| | - Farzad Seidi
- Joint International Research Lab of Lignocellulosic Functional Materials, Nanjing Forestry University, Nanjing, 210037, China
| | - Mohammad Reza Ganjali
- Center of Excellence in Electrochemistry, School of Chemistry, College of Science, University of Tehran, Tehran, 1417466191, Iran
- Biosensor Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, 14395-1179, Iran
| | - Masoud Mozafari
- Department of Tissue Engineering & Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, 1449614535, Iran
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Ajalik RE, Alenchery RG, Cognetti JS, Zhang VZ, McGrath JL, Miller BL, Awad HA. Human Organ-on-a-Chip Microphysiological Systems to Model Musculoskeletal Pathologies and Accelerate Therapeutic Discovery. Front Bioeng Biotechnol 2022; 10:846230. [PMID: 35360391 PMCID: PMC8964284 DOI: 10.3389/fbioe.2022.846230] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Accepted: 02/21/2022] [Indexed: 12/12/2022] Open
Abstract
Human Microphysiological Systems (hMPS), otherwise known as organ- and tissue-on-a-chip models, are an emerging technology with the potential to replace in vivo animal studies with in vitro models that emulate human physiology at basic levels. hMPS platforms are designed to overcome limitations of two-dimensional (2D) cell culture systems by mimicking 3D tissue organization and microenvironmental cues that are physiologically and clinically relevant. Unlike animal studies, hMPS models can be configured for high content or high throughput screening in preclinical drug development. Applications in modeling acute and chronic injuries in the musculoskeletal system are slowly developing. However, the complexity and load bearing nature of musculoskeletal tissues and joints present unique challenges related to our limited understanding of disease mechanisms and the lack of consensus biomarkers to guide biological therapy development. With emphasis on examples of modeling musculoskeletal tissues, joints on chips, and organoids, this review highlights current trends of microphysiological systems technology. The review surveys state-of-the-art design and fabrication considerations inspired by lessons from bioreactors and biological variables emphasizing the role of induced pluripotent stem cells and genetic engineering in creating isogenic, patient-specific multicellular hMPS. The major challenges in modeling musculoskeletal tissues using hMPS chips are identified, including incorporating biological barriers, simulating joint compartments and heterogenous tissue interfaces, simulating immune interactions and inflammatory factors, simulating effects of in vivo loading, recording nociceptors responses as surrogates for pain outcomes, modeling the dynamic injury and healing responses by monitoring secreted proteins in real time, and creating arrayed formats for robotic high throughput screens. Overcoming these barriers will revolutionize musculoskeletal research by enabling physiologically relevant, predictive models of human tissues and joint diseases to accelerate and de-risk therapeutic discovery and translation to the clinic.
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Affiliation(s)
- Raquel E. Ajalik
- Center for Musculoskeletal Research, University of Rochester, Rochester, NY, United States
- Department of Biomedical Engineering, University of Rochester, Rochester, NY, United States
| | - Rahul G. Alenchery
- Center for Musculoskeletal Research, University of Rochester, Rochester, NY, United States
- Department of Biomedical Engineering, University of Rochester, Rochester, NY, United States
| | - John S. Cognetti
- Department of Biomedical Engineering, University of Rochester, Rochester, NY, United States
| | - Victor Z. Zhang
- Center for Musculoskeletal Research, University of Rochester, Rochester, NY, United States
- Department of Biomedical Engineering, University of Rochester, Rochester, NY, United States
| | - James L. McGrath
- Department of Biomedical Engineering, University of Rochester, Rochester, NY, United States
| | - Benjamin L. Miller
- Department of Biomedical Engineering, University of Rochester, Rochester, NY, United States
- Department of Dermatology, University of Rochester, Rochester, NY, United States
| | - Hani A. Awad
- Center for Musculoskeletal Research, University of Rochester, Rochester, NY, United States
- Department of Biomedical Engineering, University of Rochester, Rochester, NY, United States
- *Correspondence: Hani A. Awad,
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28
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Jeyaraman M, Muthu S, Sharma S, Ganta C, Ranjan R, Jha SK. Nanofat: A therapeutic paradigm in regenerative medicine. World J Stem Cells 2021; 13:1733-1746. [PMID: 34909120 PMCID: PMC8641019 DOI: 10.4252/wjsc.v13.i11.1733] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 05/15/2021] [Accepted: 10/27/2021] [Indexed: 02/06/2023] Open
Abstract
Adipose tissue is a compact and well-organized tissue containing a heterogeneous cellular population of progenitor cells, including mesenchymal stromal cells. Due to its availability and accessibility, adipose tissue is considered a "stem cell depot." Adipose tissue products possess anti-inflammatory, anti-fibrotic, anti-apoptotic, and immunomodulatory effects. Nanofat, being a compact bundle of stem cells with regenerative and tissue remodeling potential, has potential in translational and regenerative medicine. Considering the wide range of applicability of its reconstructive and regenerative potential, the applications of nanofat can be used in various disciplines. Nanofat behaves on the line of adipose tissue-derived mesenchymal stromal cells. At the site of injury, these stromal cells initiate a site-specific reparative response comprised of remodeling of the extracellular matrix, enhanced and sustained angiogenesis, and immune system modulation. These properties of stromal cells provide a platform for the usage of regenerative medicine principles in curbing various diseases. Details about nanofat, including various preparation methods, characterization, delivery methods, evidence on practical applications, and ethical concerns are included in this review. However, appropriate guidelines and preparation protocols for its optimal use in a wide range of clinical applications have yet to be standardized.
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Affiliation(s)
- Madhan Jeyaraman
- Department of Biotechnology, School of Engineering and Technology, Sharda University , Greater Noida 201306, Uttar Pradesh, India
| | - Sathish Muthu
- Department of Biotechnology, School of Engineering and Technology, Sharda University , Greater Noida 201306, Uttar Pradesh, India
| | - Shilpa Sharma
- Indian Stem Cell Study Group, Lucknow 226010, Uttar Pradesh, India
| | - Charan Ganta
- Indian Stem Cell Study Group, Lucknow 226010, Uttar Pradesh, India
| | - Rajni Ranjan
- Department of Orthopaedics, School of Medical Sciences and Research, Sharda University, Greater Noida 201306, Uttar Pradesh, India
| | - Saurabh Kumar Jha
- Department of Biotechnology, School of Engineering and Technology, Sharda University , Greater Noida 201306, Uttar Pradesh, India
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29
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Hamed GM, Nassef NA, Mansour RSAE, Shawky MKE, Zeid AAA, Hassan AA. The Effect of Early Application of a Combined Therapy of Bone Marrow Mesenchymal Stem Cells and Platelet-Rich Plasma on Blood and Bone Parameters in Ovariectomized Rats. J EVOL BIOCHEM PHYS+ 2021. [DOI: 10.1134/s0022093021040219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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30
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Ahmed HMMAM, Moreira Teixeira LS. New Endeavors of (Micro)Tissue Engineering: Cells Tissues Organs on-Chip and Communication Thereof. Cells Tissues Organs 2021; 211:721-735. [PMID: 34198305 DOI: 10.1159/000516356] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Accepted: 03/30/2021] [Indexed: 01/25/2023] Open
Abstract
The development of new therapies is tremendously hampered by the insufficient availability of human model systems suitable for preclinical research on disease target identification, drug efficacy, and toxicity. Thus, drug failures in clinical trials are too common and too costly. Animal models or standard 2D in vitro tissue cultures, regardless of whether they are human based, are regularly not representative of specific human responses. Approaching near human tissues and organs test systems is the key goal of organs-on-chips (OoC) technology. This technology is currently showing its potential to reduce both drug development costs and time-to-market, while critically lessening animal testing. OoC are based on human (stem) cells, potentially derived from healthy or disease-affected patients, thereby amenable to personalized therapy development. It is noteworthy that the OoC market potential goes beyond pharma, with the possibility to test cosmetics, food additives, or environmental contaminants. This (micro)tissue engineering-based technology is highly multidisciplinary, combining fields such as (developmental) biology, (bio)materials, microfluidics, sensors, and imaging. The enormous potential of OoC is currently facing an exciting new challenge: emulating cross-communication between tissues and organs, to simulate more complex systemic responses, such as in cancer, or restricted to confined environments, as occurs in osteoarthritis. This review describes key examples of multiorgan/tissue-on-chip approaches, or linked organs/tissues-on-chip, focusing on challenges and promising new avenues of this advanced model system. Additionally, major emphasis is given to the translation of established tissue engineering approaches, bottom up and top down, towards the development of more complex, robust, and representative (multi)organ/tissue-on-chip approaches.
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Affiliation(s)
- Haysam M M A M Ahmed
- Department of Developmental Bioengineering, Technical Medical Centre, University of Twente, Enschede, The Netherlands,
| | - Liliana S Moreira Teixeira
- Department of Developmental Bioengineering, Technical Medical Centre, University of Twente, Enschede, The Netherlands.,Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
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31
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Zhao Q, Cole T, Zhang Y, Tang SY. Mechanical Strain-Enabled Reconstitution of Dynamic Environment in Organ-on-a-Chip Platforms: A Review. MICROMACHINES 2021; 12:765. [PMID: 34203533 PMCID: PMC8304354 DOI: 10.3390/mi12070765] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Revised: 06/23/2021] [Accepted: 06/25/2021] [Indexed: 12/11/2022]
Abstract
Organ-on-a-chip (OOC) uses the microfluidic 3D cell culture principle to reproduce organ- or tissue-level functionality at a small scale instead of replicating the entire human organ. This provides an alternative to animal models for drug development and environmental toxicology screening. In addition to the biomimetic 3D microarchitecture and cell-cell interactions, it has been demonstrated that mechanical stimuli such as shear stress and mechanical strain significantly influence cell behavior and their response to pharmaceuticals. Microfluidics is capable of precisely manipulating the fluid of a microenvironment within a 3D cell culture platform. As a result, many OOC prototypes leverage microfluidic technology to reproduce the mechanically dynamic microenvironment on-chip and achieve enhanced in vitro functional organ models. Unlike shear stress that can be readily generated and precisely controlled using commercial pumping systems, dynamic systems for generating proper levels of mechanical strains are more complicated, and often require miniaturization and specialized designs. As such, this review proposes to summarize innovative microfluidic OOC platforms utilizing mechanical actuators that induce deflection of cultured cells/tissues for replicating the dynamic microenvironment of human organs.
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Affiliation(s)
- Qianbin Zhao
- School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore 639798, Singapore
| | - Tim Cole
- Department of Electronic, Electrical and Systems Engineering, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK; (T.C.); (Y.Z.)
| | - Yuxin Zhang
- Department of Electronic, Electrical and Systems Engineering, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK; (T.C.); (Y.Z.)
| | - Shi-Yang Tang
- Department of Electronic, Electrical and Systems Engineering, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK; (T.C.); (Y.Z.)
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32
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Murray BO, Flores C, Williams C, Flusberg DA, Marr EE, Kwiatkowska KM, Charest JL, Isenberg BC, Rohn JL. Recurrent Urinary Tract Infection: A Mystery in Search of Better Model Systems. Front Cell Infect Microbiol 2021; 11:691210. [PMID: 34123879 PMCID: PMC8188986 DOI: 10.3389/fcimb.2021.691210] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Accepted: 05/04/2021] [Indexed: 12/12/2022] Open
Abstract
Urinary tract infections (UTIs) are among the most common infectious diseases worldwide but are significantly understudied. Uropathogenic E. coli (UPEC) accounts for a significant proportion of UTI, but a large number of other species can infect the urinary tract, each of which will have unique host-pathogen interactions with the bladder environment. Given the substantial economic burden of UTI and its increasing antibiotic resistance, there is an urgent need to better understand UTI pathophysiology - especially its tendency to relapse and recur. Most models developed to date use murine infection; few human-relevant models exist. Of these, the majority of in vitro UTI models have utilized cells in static culture, but UTI needs to be studied in the context of the unique aspects of the bladder's biophysical environment (e.g., tissue architecture, urine, fluid flow, and stretch). In this review, we summarize the complexities of recurrent UTI, critically assess current infection models and discuss potential improvements. More advanced human cell-based in vitro models have the potential to enable a better understanding of the etiology of UTI disease and to provide a complementary platform alongside animals for drug screening and the search for better treatments.
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Affiliation(s)
- Benjamin O. Murray
- Centre for Urological Biology, Department of Renal Medicine, University College London, London, United Kingdom
| | - Carlos Flores
- Centre for Urological Biology, Department of Renal Medicine, University College London, London, United Kingdom
| | - Corin Williams
- Department of Bioengineering, Charles Stark Draper Laboratory, Inc., Cambridge, MA, United States
| | - Deborah A. Flusberg
- Department of Bioengineering, Charles Stark Draper Laboratory, Inc., Cambridge, MA, United States
| | - Elizabeth E. Marr
- Department of Bioengineering, Charles Stark Draper Laboratory, Inc., Cambridge, MA, United States
| | - Karolina M. Kwiatkowska
- Centre for Urological Biology, Department of Renal Medicine, University College London, London, United Kingdom
| | - Joseph L. Charest
- Department of Bioengineering, Charles Stark Draper Laboratory, Inc., Cambridge, MA, United States
| | - Brett C. Isenberg
- Department of Bioengineering, Charles Stark Draper Laboratory, Inc., Cambridge, MA, United States
| | - Jennifer L. Rohn
- Centre for Urological Biology, Department of Renal Medicine, University College London, London, United Kingdom
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Schneider S, Gruner D, Richter A, Loskill P. Membrane integration into PDMS-free microfluidic platforms for organ-on-chip and analytical chemistry applications. LAB ON A CHIP 2021; 21:1866-1885. [PMID: 33949565 DOI: 10.1039/d1lc00188d] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Membranes play a crucial role in many microfluidic systems, enabling versatile applications in highly diverse research fields. However, the tight and robust integration of membranes into microfluidic systems requires complex fabrication processes. Most integration approaches, so far, rely on polydimethylsiloxane (PDMS) as base material for the microfluidic chips. Several limitations of PDMS have resulted in the transition of many microfluidic approaches to PDMS-free systems using alternative materials such as thermoplastics. To integrate membranes in those PDMS-free systems, novel alternative approaches are required. This review provides an introduction into microfluidic systems applying membrane technology for analytical systems and organ-on-chip as well as a comprehensive overview of methods for the integration of membranes into PDMS-free systems. The overview and examples will provide a valuable resource and starting point for any researcher that is aiming at implementing membranes in microfluidic systems without using PDMS.
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Affiliation(s)
- Stefan Schneider
- Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, 70569 Stuttgart, Germany
| | - Denise Gruner
- Institut für Halbleiter- und Mikrosystemtechnik, Technische Universität Dresden, 01062 Dresden, Germany and Universitätsklinikum Carl Gustav Carus Dresden, Institut für Klinische Chemie und Laboratoriumsmedizin, 01307 Dresden, Germany
| | - Andreas Richter
- Institut für Halbleiter- und Mikrosystemtechnik, Technische Universität Dresden, 01062 Dresden, Germany
| | - Peter Loskill
- Department of Biomedical Science, Faculty of Medicine, Eberhard Karls University Tübingen, 72076 Tübingen, Germany. and NMI Natural and Medical Sciences Institute at the University of Tübingen, 72770 Reutlingen, Germany
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Yang L, Pijuan-Galito S, Rho HS, Vasilevich AS, Eren AD, Ge L, Habibović P, Alexander MR, de Boer J, Carlier A, van Rijn P, Zhou Q. High-Throughput Methods in the Discovery and Study of Biomaterials and Materiobiology. Chem Rev 2021; 121:4561-4677. [PMID: 33705116 PMCID: PMC8154331 DOI: 10.1021/acs.chemrev.0c00752] [Citation(s) in RCA: 94] [Impact Index Per Article: 23.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Indexed: 02/07/2023]
Abstract
The complex interaction of cells with biomaterials (i.e., materiobiology) plays an increasingly pivotal role in the development of novel implants, biomedical devices, and tissue engineering scaffolds to treat diseases, aid in the restoration of bodily functions, construct healthy tissues, or regenerate diseased ones. However, the conventional approaches are incapable of screening the huge amount of potential material parameter combinations to identify the optimal cell responses and involve a combination of serendipity and many series of trial-and-error experiments. For advanced tissue engineering and regenerative medicine, highly efficient and complex bioanalysis platforms are expected to explore the complex interaction of cells with biomaterials using combinatorial approaches that offer desired complex microenvironments during healing, development, and homeostasis. In this review, we first introduce materiobiology and its high-throughput screening (HTS). Then we present an in-depth of the recent progress of 2D/3D HTS platforms (i.e., gradient and microarray) in the principle, preparation, screening for materiobiology, and combination with other advanced technologies. The Compendium for Biomaterial Transcriptomics and high content imaging, computational simulations, and their translation toward commercial and clinical uses are highlighted. In the final section, current challenges and future perspectives are discussed. High-throughput experimentation within the field of materiobiology enables the elucidation of the relationships between biomaterial properties and biological behavior and thereby serves as a potential tool for accelerating the development of high-performance biomaterials.
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Affiliation(s)
- Liangliang Yang
- University
of Groningen, W. J. Kolff Institute for Biomedical Engineering and
Materials Science, Department of Biomedical Engineering, University Medical Center Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands
| | - Sara Pijuan-Galito
- School
of Pharmacy, Biodiscovery Institute, University
of Nottingham, University Park, Nottingham NG7 2RD, U.K.
| | - Hoon Suk Rho
- Department
of Instructive Biomaterials Engineering, MERLN Institute for Technology-Inspired
Regenerative Medicine, Maastricht University, 6229 ER Maastricht, The Netherlands
| | - Aliaksei S. Vasilevich
- Department
of Biomedical Engineering, Eindhoven University
of Technology, 5600 MB Eindhoven, The Netherlands
| | - Aysegul Dede Eren
- Department
of Biomedical Engineering, Eindhoven University
of Technology, 5600 MB Eindhoven, The Netherlands
| | - Lu Ge
- University
of Groningen, W. J. Kolff Institute for Biomedical Engineering and
Materials Science, Department of Biomedical Engineering, University Medical Center Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands
| | - Pamela Habibović
- Department
of Instructive Biomaterials Engineering, MERLN Institute for Technology-Inspired
Regenerative Medicine, Maastricht University, 6229 ER Maastricht, The Netherlands
| | - Morgan R. Alexander
- School
of Pharmacy, Boots Science Building, University
of Nottingham, University Park, Nottingham NG7 2RD, U.K.
| | - Jan de Boer
- Department
of Biomedical Engineering, Eindhoven University
of Technology, 5600 MB Eindhoven, The Netherlands
| | - Aurélie Carlier
- Department
of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired
Regenerative Medicine, Maastricht University, 6229 ER Maastricht, The Netherlands
| | - Patrick van Rijn
- University
of Groningen, W. J. Kolff Institute for Biomedical Engineering and
Materials Science, Department of Biomedical Engineering, University Medical Center Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands
| | - Qihui Zhou
- Institute
for Translational Medicine, Department of Stomatology, The Affiliated
Hospital of Qingdao University, Qingdao
University, Qingdao 266003, China
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Rothbauer M, Bachmann BE, Eilenberger C, Kratz SR, Spitz S, Höll G, Ertl P. A Decade of Organs-on-a-Chip Emulating Human Physiology at the Microscale: A Critical Status Report on Progress in Toxicology and Pharmacology. MICROMACHINES 2021; 12:470. [PMID: 33919242 PMCID: PMC8143089 DOI: 10.3390/mi12050470] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 04/16/2021] [Accepted: 04/19/2021] [Indexed: 12/22/2022]
Abstract
Organ-on-a-chip technology has the potential to accelerate pharmaceutical drug development, improve the clinical translation of basic research, and provide personalized intervention strategies. In the last decade, big pharma has engaged in many academic research cooperations to develop organ-on-a-chip systems for future drug discoveries. Although most organ-on-a-chip systems present proof-of-concept studies, miniaturized organ systems still need to demonstrate translational relevance and predictive power in clinical and pharmaceutical settings. This review explores whether microfluidic technology succeeded in paving the way for developing physiologically relevant human in vitro models for pharmacology and toxicology in biomedical research within the last decade. Individual organ-on-a-chip systems are discussed, focusing on relevant applications and highlighting their ability to tackle current challenges in pharmacological research.
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Affiliation(s)
- Mario Rothbauer
- Faculty of Technical Chemistry, Institute of Applied Synthetic Chemistry and Institute of Chemical Technologies and Analytics, Vienna University of Technology, Getreidemarkt 9/163-164, 1060 Vienna, Austria; (B.E.M.B.); (C.E.); (S.R.A.K.); (S.S.); (G.H.)
- Austrian Cluster for Tissue Regeneration, 1200 Vienna, Austria
- Karl Chiari Lab for Orthopaedic Biology, Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Währinger Gürtel 18-22, 1090 Vienna, Austria
| | - Barbara E.M. Bachmann
- Faculty of Technical Chemistry, Institute of Applied Synthetic Chemistry and Institute of Chemical Technologies and Analytics, Vienna University of Technology, Getreidemarkt 9/163-164, 1060 Vienna, Austria; (B.E.M.B.); (C.E.); (S.R.A.K.); (S.S.); (G.H.)
- Austrian Cluster for Tissue Regeneration, 1200 Vienna, Austria
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Allgemeine Unfallversicherungsanstalt (AUVA) Research Centre, Donaueschingenstraße 13, 1200 Vienna, Austria
| | - Christoph Eilenberger
- Faculty of Technical Chemistry, Institute of Applied Synthetic Chemistry and Institute of Chemical Technologies and Analytics, Vienna University of Technology, Getreidemarkt 9/163-164, 1060 Vienna, Austria; (B.E.M.B.); (C.E.); (S.R.A.K.); (S.S.); (G.H.)
- Austrian Cluster for Tissue Regeneration, 1200 Vienna, Austria
| | - Sebastian R.A. Kratz
- Faculty of Technical Chemistry, Institute of Applied Synthetic Chemistry and Institute of Chemical Technologies and Analytics, Vienna University of Technology, Getreidemarkt 9/163-164, 1060 Vienna, Austria; (B.E.M.B.); (C.E.); (S.R.A.K.); (S.S.); (G.H.)
- Austrian Cluster for Tissue Regeneration, 1200 Vienna, Austria
- Drug Delivery and 3R-Models Group, Buchmann Institute for Molecular Life Sciences & Institute for Pharmaceutical Technology, Goethe University Frankfurt Am Main, 60438 Frankfurt, Germany
| | - Sarah Spitz
- Faculty of Technical Chemistry, Institute of Applied Synthetic Chemistry and Institute of Chemical Technologies and Analytics, Vienna University of Technology, Getreidemarkt 9/163-164, 1060 Vienna, Austria; (B.E.M.B.); (C.E.); (S.R.A.K.); (S.S.); (G.H.)
- Austrian Cluster for Tissue Regeneration, 1200 Vienna, Austria
| | - Gregor Höll
- Faculty of Technical Chemistry, Institute of Applied Synthetic Chemistry and Institute of Chemical Technologies and Analytics, Vienna University of Technology, Getreidemarkt 9/163-164, 1060 Vienna, Austria; (B.E.M.B.); (C.E.); (S.R.A.K.); (S.S.); (G.H.)
- Austrian Cluster for Tissue Regeneration, 1200 Vienna, Austria
| | - Peter Ertl
- Faculty of Technical Chemistry, Institute of Applied Synthetic Chemistry and Institute of Chemical Technologies and Analytics, Vienna University of Technology, Getreidemarkt 9/163-164, 1060 Vienna, Austria; (B.E.M.B.); (C.E.); (S.R.A.K.); (S.S.); (G.H.)
- Austrian Cluster for Tissue Regeneration, 1200 Vienna, Austria
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Liu Y, Holmes C. Tissue Regeneration Capacity of Extracellular Vesicles Isolated From Bone Marrow-Derived and Adipose-Derived Mesenchymal Stromal/Stem Cells. Front Cell Dev Biol 2021; 9:648098. [PMID: 33718390 PMCID: PMC7952527 DOI: 10.3389/fcell.2021.648098] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Accepted: 02/02/2021] [Indexed: 12/12/2022] Open
Abstract
Mesenchymal stem cell (MSC)-based therapies have demonstrated tissue repair and regeneration capacity in various preclinical models. These therapeutic effects have recently been largely attributed to the paracrine effects of the MSC secretome, including proteins and extracellular vesicles (EVs). EVs are cell-secreted nano-sized vesicles with lipid bilayer membranes that facilitate cell–cell signaling. Treatments based on MSC-derived EVs are beginning to be explored as an alternative to MSC transplantation-based therapies. However, it remains to be determined which MSC source produces EVs with the greatest therapeutic potential. This review compares the tissue regeneration capacity of EVs isolated from the two most common clinical sources of adult MSCs, bone marrow and adipose tissue, with a particular focus on their angiogenic, osteogenic, and immunomodulatory potentials. Other important issues in the development of MSC-derived EV based therapies are also discussed.
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Affiliation(s)
- Yuan Liu
- Department of Chemical and Biomedical Engineering, Florida A&M University-Florida State University College of Engineering, Tallhassee, FL, United States
| | - Christina Holmes
- Department of Chemical and Biomedical Engineering, Florida A&M University-Florida State University College of Engineering, Tallhassee, FL, United States
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Manokawinchoke J, Pavasant P, Limjeerajarus CN, Limjeerajarus N, Osathanon T, Egusa H. Mechanical loading and the control of stem cell behavior. Arch Oral Biol 2021; 125:105092. [PMID: 33652301 DOI: 10.1016/j.archoralbio.2021.105092] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Revised: 01/08/2021] [Accepted: 02/21/2021] [Indexed: 12/14/2022]
Abstract
OBJECTIVE Mechanical stimulation regulates many cell responses. The present study describes the effects of different in vitro mechanical stimulation approaches on stem cell behavior. DESIGN The narrative review approach was performed. The articles published in English language that addressed the effects of mechanical force on stem cells were searched on Pubmed and Scopus database. The effects of extrinsic mechanical force on stem cell response was reviewed and discussed. RESULTS Cells sense mechanical stimuli by the function of mechanoreceptors and further transduce force stimulation into intracellular signaling. Cell responses to mechanical stimuli depend on several factors including type, magnitude, and duration. Further, similar mechanical stimuli exhibit distinct cell responses based on numerous factors including cell type and differentiation stage. Various mechanical applications modulate stemness maintenance and cell differentiation toward specific lineages. CONCLUSIONS Mechanical force application modulates stemness maintenance and differentiation. Modification of force regimens could be utilized to precisely control appropriate stem cell behavior toward specific applications.
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Affiliation(s)
- Jeeranan Manokawinchoke
- Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand; Dental Stem Cell Biology Research Unit, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand; Division of Molecular and Regenerative Prosthodontics, Tohoku University Graduate School of Dentistry, Sendai, 980-8575, Japan.
| | - Prasit Pavasant
- Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand.
| | - Chalida Nakalekha Limjeerajarus
- Dental Stem Cell Biology Research Unit, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand; Department of Physiology, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand.
| | - Nuttapol Limjeerajarus
- Research Center for Advanced Energy Technology, Faculty of Engineering, Thai-Nichi Institute of Technology, Bangkok, 10250, Thailand.
| | - Thanaphum Osathanon
- Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand; Dental Stem Cell Biology Research Unit, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand.
| | - Hiroshi Egusa
- Division of Molecular and Regenerative Prosthodontics, Tohoku University Graduate School of Dentistry, Sendai, 980-8575, Japan.
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Bagge J, MacLeod JN, Berg LC. Cellular Proliferation of Equine Bone Marrow- and Adipose Tissue-Derived Mesenchymal Stem Cells Decline With Increasing Donor Age. Front Vet Sci 2020; 7:602403. [PMID: 33363241 PMCID: PMC7758322 DOI: 10.3389/fvets.2020.602403] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Accepted: 10/19/2020] [Indexed: 11/15/2022] Open
Abstract
Background: Bone marrow (BM)- and adipose tissue (AT)-derived mesenchymal stem cells (MSCs) are used increasingly for autologous cell therapy in equine practice to treat musculoskeletal and other injuries. Current recommendations often call for 10–100 million MSCs per treatment, necessitating the expansion of primary cells in culture prior to therapeutic use. Of concern, human and rodent studies have shown a decline of both MSC recovery from sampled tissue and in vitro proliferative capacity with increasing donor age. This may be problematic for applications of autologous cell-based therapies in the important equine demographic of older patients. Objectives: To investigate the effect of donor age on the cellular proliferation of equine BM- and AT-MSCs. Study Design:In vitro study. Methods: BM- and AT-MSCs and dermal fibroblasts (biological control) were harvested from horses in five different age groups (n = 4, N = 60); newborn (0 days), yearling (15–17 months), adult (5–8 years), middle-aged (12–18 years), and geriatric (≥22 years). Proliferation of the cells was tested using an EdU incorporation assay and steady state mRNA levels measured for targeted proliferation, aging, and senescence biomarkers. Results: The cellular proliferation of equine BM- and AT-MSCs declined significantly in the geriatric cohort relative to the younger age groups. Proliferation levels in the two MSC types were equally affected by donor age. Analysis of steady state mRNA levels showed an up-regulation in tumor suppressors, apoptotic genes, and multiple growth factors in MSCs from old horses, and a down-regulation of some pro-cycling genes with a few differences between cell types. Main Limitations: Potential age-dependent differences in cell function parameters relevant to cell-therapy application were not investigated. Conclusions: The cellular proliferation of equine BM- and AT-MSCs declined at advanced donor ages. High levels of in vitro proliferation were observed in both MSC types from horses in the age groups below 18 years of age.
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Affiliation(s)
- Jasmin Bagge
- Department of Veterinary Clinical Sciences, University of Copenhagen, Copenhagen, Denmark.,Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, United States
| | - James N MacLeod
- Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, United States
| | - Lise C Berg
- Department of Veterinary Clinical Sciences, University of Copenhagen, Copenhagen, Denmark
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Quan Y, Sun M, Tan Z, Eijkel JCT, van den Berg A, van der Meer A, Xie Y. Organ-on-a-chip: the next generation platform for risk assessment of radiobiology. RSC Adv 2020; 10:39521-39530. [PMID: 35515392 PMCID: PMC9057494 DOI: 10.1039/d0ra05173j] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Accepted: 09/16/2020] [Indexed: 01/04/2023] Open
Abstract
Organ-on-a-chip devices have been widely used in biomedical science and technology, for example for experimental regenerative medicine and precision healthcare. The main advantage of organ-on-a-chip technology is the facility to build a specific human model that has functional responses on the level of organs or tissues, thereby avoiding the use of animal models, as well as greatly improving new drug discovery processes for personal healthcare. An emerging application domain for organs-on-chips is the study of internal irradiation for humans, which faces the challenges of the lack of a clear model for risk estimation of internal irradiation. We believe that radiobiology studies will benefit from organ-on-a-chip technology by building specific human organ/tissues in vitro. In this paper, we briefly reviewed the state-of-the-art in organ-on-a-chip research in different domains, and conclude with the challenges of radiobiology studies at internal low-dose irradiation. Organ-on-a-chip technology has the potential to significantly improve the radiobiology study as it can mimic the function of human organs or tissues, and here we summarize its potential benefits and possible breakthrough areas, as well as its limitations in internal low-dose radiation studies. Organ-on-a-chip technology has great potential for the next generation risk estimation of low dose internal irradiation, due to its success in mimicking human organs/tissues, which possibly can significantly improve on current animal models.![]()
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Affiliation(s)
- Yi Quan
- Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics (CAEP) Mianyang Sichuan 621000 China
| | - Miao Sun
- Joint Laboratory of Nanofluidics and Interfaces, School of Physical and Technology, Northwestern Polytechnical University Xi'an Shaanxi 710072 China
| | - Zhaoyi Tan
- Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics (CAEP) Mianyang Sichuan 621000 China
| | - Jan C T Eijkel
- BIOS, Lab on a Chip Group, MESA+ Institution for Nanotechnology, University of Twente 7522 NB Enschede The Netherlands
| | - Albert van den Berg
- BIOS, Lab on a Chip Group, MESA+ Institution for Nanotechnology, University of Twente 7522 NB Enschede The Netherlands
| | - Andries van der Meer
- Department of Applied Stem Cell Technologies, University of Twente 7522 NB Enschede The Netherlands
| | - Yanbo Xie
- Joint Laboratory of Nanofluidics and Interfaces, School of Physical and Technology, Northwestern Polytechnical University Xi'an Shaanxi 710072 China
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Luo Y, Ding X, Ji H, Li M, Song H, Li S, Wang C, Wu H, Du H. MicroRNA-503-3p affects osteogenic differentiation of human adipose-derived stem cells by regulation of Wnt2 and Wnt7b under cyclic strain. Stem Cell Res Ther 2020; 11:318. [PMID: 32711579 PMCID: PMC7382842 DOI: 10.1186/s13287-020-01842-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Revised: 07/05/2020] [Accepted: 07/20/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND MicroRNAs (miRNAs) play a role in regulating osteogenic differentiation (OD) of mesenchymal stem cells by inhibiting mRNAs translation under cyclic strain. miR-503-3p was downregulated in OD of human adipose-derived stem cells (hASCs) in vivo under cyclic strain in our previous study, while it might target the Wnt/β-catenin (W-β) pathway. In this study, we explored miR-503-3p's role in OD of hASCs under cyclic strain. METHODS OD of hASCs was induced by cyclic strain. Bioinformatic and dual luciferase analyses were used to confirm the relationship between Wnt2/Wnt7b and miR-503-3p. Immunofluorescence was used to detect the effect of miR-503-3p on Wnt2/Wnt7b and β-catenin in hASCs transfected with miR-503-3p mimic and inhibitor. Mimic, inhibitor, and small interfering RNA (siRNA) transfected in hASCs to against Wnt2 and Wnt7b. Quantitative real-time PCR (RT-PCR) and western blot were used to examine the OD and W-β pathway at the mRNA and protein levels, respectively. Immunofluorescence was performed to locate β-catenin. ALP activity and calcium were detected by colorimetric assay. RESULTS Results of immunophenotypes by flow cytometry and multi-lineage potential confirmed that the cultured cells were hASCs. Results of luciferase reporter assay indicated that miR-503-3p could regulate the expression levels of Wnt2 and Wnt7b by targeting their respective 3'-untranslated region (UTR). Under cyclic strain, gain- or loss-function of miR-503-3p studies by mimic and inhibitor revealed that decreasing expression of miR-503-3p could significantly bring about promotion of OD of hASCs, whereas increased expression of miR-503-3p inhibited OD. Furthermore, miR-503-3p high-expression reduced the activity of the W-β pathway, as indicated by lowering expression of Wnt2 and Wnt7b, inactive β-catenin in miR-503-3p-treated hASCs. By contrast, miR-503-3p inhibition activated the W-β pathway. CONCLUSIONS Collectively, our findings indicate that miR-503-3p is a negative factor in regulating W-β pathway by Wnt2 and Wnt7b, which inhibit the OD of hASCs under cyclic strain.
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Affiliation(s)
- Yadong Luo
- Department of Oral and Maxillofacial Surgery, Affiliated Stomatological Hospital of Nanjing Medical University, Hanzhong Road No.136, Nanjing, 210029, Jiangsu Province, People's Republic of China.,Jiangsu Key Laboratory of Oral Disease, Nanjing Medical University, Nanjing, 210029, Jiangsu Province, People's Republic of China
| | - Xu Ding
- Department of Oral and Maxillofacial Surgery, Affiliated Stomatological Hospital of Nanjing Medical University, Hanzhong Road No.136, Nanjing, 210029, Jiangsu Province, People's Republic of China.,Jiangsu Key Laboratory of Oral Disease, Nanjing Medical University, Nanjing, 210029, Jiangsu Province, People's Republic of China
| | - Huan Ji
- Department of Oral and Maxillofacial Surgery, Affiliated Stomatological Hospital of Nanjing Medical University, Hanzhong Road No.136, Nanjing, 210029, Jiangsu Province, People's Republic of China.,Jiangsu Key Laboratory of Oral Disease, Nanjing Medical University, Nanjing, 210029, Jiangsu Province, People's Republic of China
| | - Meng Li
- Department of Oral and Maxillofacial Surgery, Affiliated Stomatological Hospital of Nanjing Medical University, Hanzhong Road No.136, Nanjing, 210029, Jiangsu Province, People's Republic of China.,Jiangsu Key Laboratory of Oral Disease, Nanjing Medical University, Nanjing, 210029, Jiangsu Province, People's Republic of China
| | - Haiyang Song
- Department of Oral and Maxillofacial Surgery, Affiliated Stomatological Hospital of Nanjing Medical University, Hanzhong Road No.136, Nanjing, 210029, Jiangsu Province, People's Republic of China.,Jiangsu Key Laboratory of Oral Disease, Nanjing Medical University, Nanjing, 210029, Jiangsu Province, People's Republic of China
| | - Sheng Li
- Department of Oral and Maxillofacial Surgery, Affiliated Stomatological Hospital of Nanjing Medical University, Hanzhong Road No.136, Nanjing, 210029, Jiangsu Province, People's Republic of China.,Jiangsu Key Laboratory of Oral Disease, Nanjing Medical University, Nanjing, 210029, Jiangsu Province, People's Republic of China
| | - Chenxing Wang
- Department of Oral and Maxillofacial Surgery, Affiliated Stomatological Hospital of Nanjing Medical University, Hanzhong Road No.136, Nanjing, 210029, Jiangsu Province, People's Republic of China.,Jiangsu Key Laboratory of Oral Disease, Nanjing Medical University, Nanjing, 210029, Jiangsu Province, People's Republic of China
| | - Heming Wu
- Department of Oral and Maxillofacial Surgery, Affiliated Stomatological Hospital of Nanjing Medical University, Hanzhong Road No.136, Nanjing, 210029, Jiangsu Province, People's Republic of China.,Jiangsu Key Laboratory of Oral Disease, Nanjing Medical University, Nanjing, 210029, Jiangsu Province, People's Republic of China
| | - Hongming Du
- Department of Oral and Maxillofacial Surgery, Affiliated Stomatological Hospital of Nanjing Medical University, Hanzhong Road No.136, Nanjing, 210029, Jiangsu Province, People's Republic of China. .,Jiangsu Key Laboratory of Oral Disease, Nanjing Medical University, Nanjing, 210029, Jiangsu Province, People's Republic of China.
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Ramadan Q, Zourob M. Organ-on-a-chip engineering: Toward bridging the gap between lab and industry. BIOMICROFLUIDICS 2020; 14:041501. [PMID: 32699563 PMCID: PMC7367691 DOI: 10.1063/5.0011583] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Accepted: 06/22/2020] [Indexed: 05/03/2023]
Abstract
Organ-on-a-chip (OOC) is a very ambitious emerging technology with a high potential to revolutionize many medical and industrial sectors, particularly in preclinical-to-clinical translation in the pharmaceutical arena. In vivo, the function of the organ(s) is orchestrated by a complex cellular structure and physiochemical factors within the extracellular matrix and secreted by various types of cells. The trend in in vitro modeling is to simplify the complex anatomy of the human organ(s) to the minimal essential cellular structure "micro-anatomy" instead of recapitulating the full cellular milieu that enables studying the absorption, metabolism, as well as the mechanistic investigation of drug compounds in a "systemic manner." However, in order to reflect the human physiology in vitro and hence to be able to bridge the gap between the in vivo and in vitro data, simplification should not compromise the physiological relevance. Engineering principles have long been applied to solve medical challenges, and at this stage of organ-on-a-chip technology development, the work of biomedical engineers, focusing on device engineering, is more important than ever to accelerate the technology transfer from the academic lab bench to specialized product development institutions and to the increasingly demanding market. In this paper, instead of presenting a narrative review of the literature, we systemically present a synthesis of the best available organ-on-a-chip technology from what is found, what has been achieved, and what yet needs to be done. We emphasized mainly on the requirements of a "good in vitro model that meets the industrial need" in terms of the structure (micro-anatomy), functions (micro-physiology), and characteristics of the device that hosts the biological model. Finally, we discuss the biological model-device integration supported by an example and the major challenges that delay the OOC technology transfer to the industry and recommended possible options to realize a functional organ-on-a-chip system.
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Affiliation(s)
- Qasem Ramadan
- Alfaisal University, Al Zahrawi Street, Riyadh 11533, Kingdom of Saudi Arabia
| | - Mohammed Zourob
- Alfaisal University, Al Zahrawi Street, Riyadh 11533, Kingdom of Saudi Arabia
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Xu GP, Zhang XF, Sun L, Chen EM. Current and future uses of skeletal stem cells for bone regeneration. World J Stem Cells 2020; 12:339-350. [PMID: 32547682 PMCID: PMC7280866 DOI: 10.4252/wjsc.v12.i5.339] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2020] [Revised: 04/07/2020] [Accepted: 04/18/2020] [Indexed: 02/06/2023] Open
Abstract
The postnatal skeleton undergoes growth, modeling, and remodeling. The human skeleton is a composite of diverse tissue types, including bone, cartilage, fat, fibroblasts, nerves, blood vessels, and hematopoietic cells. Fracture nonunion and bone defects are among the most challenging clinical problems in orthopedic trauma. The incidence of nonunion or bone defects following fractures is increasing. Stem and progenitor cells mediate homeostasis and regeneration in postnatal tissue, including bone tissue. As multipotent stem cells, skeletal stem cells (SSCs) have a strong effect on the growth, differentiation, and repair of bone regeneration. In recent years, a number of important studies have characterized the hierarchy, differential potential, and bone formation of SSCs. Here, we describe studies on and applications of SSCs and/or mesenchymal stem cells for bone regeneration.
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Affiliation(s)
- Guo-Ping Xu
- Department of Orthopedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
| | - Xiang-Feng Zhang
- Department of Orthopedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
| | - Lu Sun
- Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Harvard University, Boston, MA 02115, United States
| | - Er-Man Chen
- Department of Orthopedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
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Pinheiro CCG, Leyendecker Junior A, Tanikawa DYS, Ferreira JRM, Jarrahy R, Bueno DF. Is There a Noninvasive Source of MSCs Isolated with GMP Methods with Better Osteogenic Potential? Stem Cells Int 2019; 2019:7951696. [PMID: 31781247 PMCID: PMC6875366 DOI: 10.1155/2019/7951696] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Revised: 08/11/2019] [Accepted: 09/11/2019] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND A new trend in the treatment for alveolar clefts in patients with cleft lip and palate involves the use of bone tissue engineering strategies to reduce or eliminate the morbidity associated with autologous bone grafting. The use of mesenchymal stem cells-autologous cells obtained from tissues such as bone marrow and fat-combined with various biomaterials has been proposed as a viable option for use in cleft patients. However, invasive procedures are necessary to obtain the mesenchymal stem cells from these two sources. To eliminate donor site morbidity, noninvasive stem cell sources such as the umbilical cord, orbicularis oris muscle, and deciduous dental pulp have been studied for use in alveolar cleft bone tissue engineering. In this study, we evaluate the osteogenic potential of these various stem cell types. METHODS Ten cellular strains obtained from each different source (umbilical cord, orbicularis oris muscle, or deciduous dental pulp) were induced to osteogenic differentiation in vitro, and the bone matrix deposition of each primary culture was quantified. To evaluate whether greater osteogenic potential of the established mesenchymal stem cell strains was associated with an increase in the expression profile of neural crest genes, real-time qPCR was performed on the following genes: SRY-box 9, SRY-box 10, nerve growth factor receptor, transcription factor AP-2 alpha, and paired box 3. RESULTS The mesenchymal stem cells obtained from deciduous dental pulp and orbicularis oris muscle demonstrated increased osteogenic potential with significantly more extracellular bone matrix deposition when compared to primary cultures obtained from the umbilical cord after twenty-one days in culture (p = 0.007 and p = 0.005, respectively). The paired box 3 gene was more highly expressed in the MSCs obtained from deciduous dental pulp and orbicularis oris muscle than in those obtained from the umbilical cord. CONCLUSION These results suggest that deciduous dental pulp and orbicularis oris muscle stem cells demonstrate superior osteogenic differentiation potential relative to umbilical cord-derived stem cells and that this increased potential is related to their neural crest origins. Based on these observations, and the distinct translational advantage of incorporating stem cells from noninvasive tissue sources into tissue engineering protocols, greater study of these specific cell lines in the setting of alveolar cleft repair is indicated.
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Affiliation(s)
- Carla C. G. Pinheiro
- Hospital Sírio-Libanês-Instituto de Ensino e Pesquisa, São Paulo, SP 01308-050, Brazil
| | | | | | - José Ricardo Muniz Ferreira
- Instituto Militar de Engenharia (IME), Departamento de Ciências de Materiais, Programa de Pós Graduação em Ciências de Materiais, Rio de Janeiro, RJ 22290-270, Brazil
| | - Reza Jarrahy
- David Geffen School of Medicine, Division of Plastic and Reconstructive Surgery, University of California Los Angeles (UCLA), Los Angeles, CA, USA
| | - Daniela F. Bueno
- Hospital Sírio-Libanês-Instituto de Ensino e Pesquisa, São Paulo, SP 01308-050, Brazil
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Methods of Delivering Mechanical Stimuli to Organ-on-a-Chip. MICROMACHINES 2019; 10:mi10100700. [PMID: 31615136 PMCID: PMC6843435 DOI: 10.3390/mi10100700] [Citation(s) in RCA: 88] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/07/2019] [Revised: 10/06/2019] [Accepted: 10/10/2019] [Indexed: 12/19/2022]
Abstract
Recent advances in integrating microengineering and tissue engineering have enabled the creation of promising microengineered physiological models, known as organ-on-a-chip (OOC), for experimental medicine and pharmaceutical research. OOCs have been used to recapitulate the physiologically critical features of specific human tissues and organs and their interactions. Application of chemical and mechanical stimuli is critical for tissue development and behavior, and they were also applied to OOC systems. Mechanical stimuli applied to tissues and organs are quite complex in vivo, which have not adequately recapitulated in OOCs. Due to the recent advancement of microengineering, more complicated and physiologically relevant mechanical stimuli are being introduced to OOC systems, and this is the right time to assess the published literature on this topic, especially focusing on the technical details of device design and equipment used. We first discuss the different types of mechanical stimuli applied to OOC systems: shear flow, compression, and stretch/strain. This is followed by the examples of mechanical stimuli-incorporated OOC systems. Finally, we discuss the potential OOC systems where various types of mechanical stimuli can be applied to a single OOC device, as a better, physiologically relevant recapitulation model, towards studying and evaluating experimental medicine, human disease modeling, drug development, and toxicology.
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Sidar B, Jenkins BR, Huang S, Spence JR, Walk ST, Wilking JN. Long-term flow through human intestinal organoids with the gut organoid flow chip (GOFlowChip). LAB ON A CHIP 2019; 19:3552-3562. [PMID: 31556415 PMCID: PMC8327675 DOI: 10.1039/c9lc00653b] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/10/2023]
Abstract
Human intestinal organoids (HIOs) are millimeter-scale models of the human intestinal epithelium and hold tremendous potential for advancing fundamental and applied biomedical research. HIOs resemble the native gut in that they consist of a fluid-filled lumen surrounded by a polarized epithelium and associated mesenchyme; however, their topologically-closed, spherical shape prevents flow through the interior luminal space, making the system less physiological and leading to the buildup of cellular and metabolic waste. These factors ultimately limit experimentation inside the HIOs. Here, we present a millifluidic device called the gut organoid flow chip (GOFlowChip), which we use to "port" HIOs and establish steady-state liquid flow through the lumen for multiple days. This long-term flow is enabled by the use of laser-cut silicone gaskets, which allow liquid in the device to be slightly pressurized, suppressing bubble formation. To demonstrate the utility of the device, we establish separate luminal and extraluminal flow and use luminal flow to remove accumulated waste. This represents the first demonstration of established liquid flow through the luminal space of a gastrointestinal organoid over physiologically relevant time scales. Flow cytometry results reveal that HIO cell viability is unaffected by long-term porting and luminal flow. We expect the real-time, long-term control over luminal and extraluminal contents provided by the GOFlowChip will enable a wide variety of studies including intestinal secretion, absorption, transport, and co-culture with intestinal microorganisms.
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Affiliation(s)
- Barkan Sidar
- Department of Chemical and Biological Engineering, Montana State University, Bozeman, MT, USA.
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Beca BM, Sun Y, Wong E, Moraes C, Simmons CA. Dynamic Bioreactors with Integrated Microfabricated Devices for Mechanobiological Screening. Tissue Eng Part C Methods 2019; 25:581-592. [DOI: 10.1089/ten.tec.2019.0121] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Affiliation(s)
- Bogdan M. Beca
- Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, Canada
| | - Yu Sun
- Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, Canada
- Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada
- Department of Electrical and Computer Engineering, University of Toronto, Toronto, Canada
| | - Edwin Wong
- Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, Canada
- Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research, University of Toronto, Toronto, Canada
| | | | - Craig A. Simmons
- Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, Canada
- Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada
- Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research, University of Toronto, Toronto, Canada
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48
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Osagie-Clouard L, Sanghani-Kerai A, Coathup M, Meeson R, Briggs T, Blunn G. The influence of parathyroid hormone 1-34 on the osteogenic characteristics of adipose- and bone-marrow-derived mesenchymal stem cells from juvenile and ovarectomized rats. Bone Joint Res 2019; 8:397-404. [PMID: 31537997 PMCID: PMC6719529 DOI: 10.1302/2046-3758.88.bjr-2019-0018.r1] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
Objectives Mesenchymal stem cells (MSCs) are of growing interest in terms of bone regeneration. Most preclinical trials utilize bone-marrow-derived mesenchymal stem cells (bMSCs), although this is not without isolation and expansion difficulties. The aim of this study was: to compare the characteristics of bMSCs and adipose-derived mesenchymal stem cells (AdMSCs) from juvenile, adult, and ovarectomized (OVX) rats; and to assess the effect of human parathyroid hormone (hPTH) 1-34 on their osteogenic potential and migration to stromal cell-derived factor-1 (SDF-1). Methods Cells were isolated from the adipose and bone marrow of juvenile, adult, and previously OVX Wistar rats, and were characterized with flow cytometry, proliferation assays, osteogenic and adipogenic differentiation, and migration to SDF-1. Experiments were repeated with and without intermittent hPTH 1-34. Results Juvenile and adult MSCs demonstrated significantly increased osteogenic and adipogenic differentiation and superior migration towards SDF-1 compared with OVX groups; this was the case for AdMSCs and bMSCs equally. Parathyroid hormone (PTH) increased parameters of osteogenic differentiation and migration to SDF-1. This was significant for all cell types, although it had the most significant effect on cells derived from OVX animals. bMSCs from all groups showed increased mineralization and migration to SDF-1 compared with AdMSCs. Conclusion Juvenile MSCs showed significantly greater migration to SDF-1 and significantly greater osteogenic and adipogenic differentiation compared with cells from osteopenic rats; this was true for bMSCs and AdMSCs. The addition of PTH increased these characteristics, with the most significant effect on cells derived from OVX animals, further illustrating possible clinical application of both PTH and MSCs in bone regenerative therapies. Cite this article:L. Osagie-Clouard, A. Sanghani-Kerai, M. Coathup, R. Meeson, T. Briggs, G. Blunn. The influence of parathyroid hormone 1-34 on the osteogenic characteristics of adipose- and bone-marrow-derived mesenchymal stem cells from juvenile and ovarectomized rats. Bone Joint Res 2019;8:397–404. DOI: 10.1302/2046-3758.88.BJR-2019-0018.R1.
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Affiliation(s)
- Liza Osagie-Clouard
- Royal Free Hospital, London, UK; Honorary Lecturer, Institute of Orthopaedics and Musculoskeletal Sciences, Royal National Orthopaedic Hospital, Stanmore, UK
| | - Anita Sanghani-Kerai
- Institute of Orthopaedics and Musculoskeletal Sciences, Royal National Orthopaedic Hospital, Stanmore, UK
| | - Melanie Coathup
- University of Central Florida College of Medicine, Orlando, Florida, USA; Honorary Lecturer, Institute of Orthopaedics and Musculoskeletal Sciences, Royal National Orthopaedic Hospital, Stanmore, UK
| | - Richard Meeson
- Institute of Orthopaedics and Musculoskeletal Sciences, Royal National Orthopaedic Hospital, Stanmore, UK
| | - Timothy Briggs
- Institute of Orthopaedics and Musculoskeletal Sciences, Royal National Orthopaedic Hospital, Stanmore, UK
| | - Gordon Blunn
- Institute of Orthopaedics and Musculoskeletal Sciences, Royal National Orthopaedic Hospital, Stanmore, UK
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Wang J, Khodabukus A, Rao L, Vandusen K, Abutaleb N, Bursac N. Engineered skeletal muscles for disease modeling and drug discovery. Biomaterials 2019; 221:119416. [PMID: 31419653 DOI: 10.1016/j.biomaterials.2019.119416] [Citation(s) in RCA: 71] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2019] [Revised: 08/01/2019] [Accepted: 08/05/2019] [Indexed: 01/04/2023]
Abstract
Skeletal muscle is the largest organ of human body with several important roles in everyday movement and metabolic homeostasis. The limited ability of small animal models of muscle disease to accurately predict drug efficacy and toxicity in humans has prompted the development in vitro models of human skeletal muscle that fatefully recapitulate cell and tissue level functions and drug responses. We first review methods for development of three-dimensional engineered muscle tissues and organ-on-a-chip microphysiological systems and discuss their potential utility in drug discovery research and development of new regenerative therapies. Furthermore, we describe strategies to increase the functional maturation of engineered muscle, and motivate the importance of incorporating multiple tissue types on the same chip to model organ cross-talk and generate more predictive drug development platforms. Finally, we review the ability of available in vitro systems to model diseases such as type II diabetes, Duchenne muscular dystrophy, Pompe disease, and dysferlinopathy.
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Affiliation(s)
- Jason Wang
- Department of Biomedical Engineering, Duke University, Durham, NC, USA
| | | | - Lingjun Rao
- Department of Biomedical Engineering, Duke University, Durham, NC, USA
| | - Keith Vandusen
- Department of Biomedical Engineering, Duke University, Durham, NC, USA
| | - Nadia Abutaleb
- Department of Biomedical Engineering, Duke University, Durham, NC, USA
| | - Nenad Bursac
- Department of Biomedical Engineering, Duke University, Durham, NC, USA.
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Abstract
Mesenchymal stem cells (MSCs) are capable of differentiating into osteoblasts, chondrocytes, and adipocytes, each of which is important for musculoskeletal tissue regeneration and repair. Reconstruction and healing of bony defects remains a major clinical challenge. Even as surgical practices advance, some severe cases of bone loss do not yield optimal recovery results. New techniques involving implantation of stem cells and tissue-engineered scaffolds are being developed to help improve bone and cartilage repair. The invasiveness and low yield of harvesting MSCs from the bone marrow (BMSCs) has led to the investigation of alternatives, including adipose-derived mesenchymal stem cells (ASCs). A review of the literature yielded several studies concerning the use of BMSCs and ASCs for the treatment of bone defects in both in vitro and in vivo models. Although both ASCs and BMSCs have demonstrated bone regenerative capabilities, BMSCs have outperformed ASCs in vitro. Despite these in vitro study findings, in vivo study results remain variable. Analysis of the literature seems to conclude there is no significant difference between bone regeneration using ASCs or BMSCs in vivo. Improved study design and standardization may enhance the application of these studies to patient care in the clinical setting.
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