2021 Issue 4 (Available Online: 2021-12-28)

    Application of stem cells in translational medicine
    James T. Triffitt, Qian Wang
    2021, 2(4):  285-286.  doi:10.12336/biomatertransl.2021.04.002
    Abstract ( 152 )   HTML ( 37)   PDF (1038KB) ( 362 )  
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    Peter W. Andrews
    2021, 2(4):  294-300.  doi:10.12336/biomatertransl.2021.04.004
    Human pluripotent stem cells can differentiate into a range of cell types, with applications for regenerative medicine. Several clinical trials of regenerative medicine based upon transplanting differentiated derivatives of these cells have begun, and their long term safety is critical for regenerative medicine.
    Abstract ( 241 )   HTML ( 34)   PDF (247KB) ( 441 )  
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    Human embryonic stem cells and induced pluripotent stem cells, together denoted as pluripotent stem cells have opened up unprecedented opportunities for developments in human healthcare over the past 20 years. Although much about the properties and behaviour of these cells required to underpin their applications has been discovered over this time, a number of issues remain. This brief review considers the history of these developments and some of the underlying biology, pointing out some of the problems still to be resolved, particularly in relation to their genetic stability and possible malignancy.

    Trivia P. Frazier, Katie Hamel, Xiying Wu, Emma Rogers, Haley Lassiter, Jordan Robinson, Omair Mohiuddin, Michael Henderson, Jeffrey M. Gimble
    2021, 2(4):  301-306.  doi:10.12336/biomatertransl.2021.04.005
    Adipose tissue is a rich source of primary cells that, together with biomaterial scaffolds, can be deployed to create humanized three-dimensional microphysiological systems with the potential to improve the accuracy of drug discovery and clinical translation relevant to cancer, cardiovascular disease, metabolism/obesity, and regenerative medicine.
    Abstract ( 208 )   HTML ( 26)   PDF (262KB) ( 525 )  
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    Microphysiological systems (MPS) created with human-derived cells and biomaterial scaffolds offer a potential in vitro alternative to in vivo animal models. The adoption of three-dimensional MPS models has economic, ethical, regulatory, and scientific implications for the fields of regenerative medicine, metabolism/obesity, oncology, and pharmaceutical drug discovery. Key opinion leaders acknowledge that MPS tools are uniquely positioned to aid in the objective to reduce, refine, and eventually replace animal experimentation while improving the accuracy of the finding’s clinical translation. Adipose tissue has proven to be an accessible and available source of human-derived stromal vascular fraction (SVF) cells, a heterogeneous population available at point of care, and adipose-derived stromal/stem cells, a relatively homogeneous population requiring plastic adherence and culture expansion of the SVF cells. The adipose-derived stromal/stem cells or SVF cells, in combination with human tissue or synthetic biomaterial scaffolds, can be maintained for extended culture periods as three-dimensional MPS models under angiogenic, stromal, adipogenic, or osteogenic conditions. This review highlights recent literature relating to the versatile use of adipose-derived cells as fundamental components of three-dimensional MPS models for discovery research and development. In this context, it compares the merits and limitations of the adipose-derived stromal/stem cells relative to SVF cell models and considers the likely directions that this emerging field of scientific discovery will take in the near future.

    Arnold I. Caplan
    2021, 2(4):  307-311.  doi:10.12336/biomatertransl.2021.04.006
    Medicinal Signaling Cells (MSCs) secrete antibacterial/antiviral proteins, such as human beta definsin-2 and defensin LL-37, that bind to the receptor binding domain (RBD) in the spike protein of SARS-CoV-2.
    Abstract ( 132 )   HTML ( 19)   PDF (238KB) ( 327 )  
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    Mesenchymal stem cells were developed as a cell-based therapeutic in the 1990’s. The translation of culture expanded mesenchymal stem cells from a basic science focus into a modern therapeutic has taken 30 years. The current state of the basic science information argues that mesenchymal stem cells may be curative for coronavirus disease 2019 (COVID-19). Indeed, early small-scale clinical trials have shown positive results. The issue raised is how to assemble the resources to get this cell-based therapy approved for clinical use. The technology is complex, the COVID-19 viral infections are life threatening, the cost is high, but human life is precious. What will it take to perfect this potentially curative technology?

    Yang Zhao, Qing Sun, Bo Huo
    2021, 2(4):  312-322.  doi:10.12336/biomatertransl.2021.04.007
    Mesenchymal stem cells (MSCs) and MC3T3-E1 cells were seeded onto three kinds of micropatterns [large circles with large spacing (LL), small circles with small spacing (SS), and small circles with large spacing (SL)]. At different time points, changes 
    in the expression and distribution of the cytoskeleton protein F-actin had regulatory effects on osteogenic differentiation, and this process was strongly correlated with the yes-associated protein (YAP) pathway.
    Abstract ( 237 )   HTML ( 36)   PDF (47387KB) ( 284 )  
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    Focal adhesions are large macromolecular assemblies through which cells are connected with the extracellular matrix so that extracellular signals can be transmitted inside cells. Some studies have focused on the effect of cell shape on the differentiation of stem cells, but little attention has been paid to focal adhesion. In the present study, mesenchymal stem cells (MSCs) and osteoblast-like MC3T3-E1 cells were seeded onto micropatterned substrates on which circular adhesive islands with different spacing and area were created for focal adhesion. Results showed that the patterns of focal adhesion changed cell morphology but did not affect cell survival. For MSCs cultured for 3 days, patterns with small circles and large spacing promoted osteogenesis. For MSCs cultured for 7 days, patterns with large circles and spacing enhanced osteogenesis. For MC3T3-E1 cells, the patterns of focal adhesion had no effect on cell differentiation after 3 days of culture, but patterns with small circles and spacing improved osteogenic differentiation after 7 days. Moreover, the assembly of F-actin, phosphorylation of myosin, and nuclear translocation of yes-associated proteins (YAP) were consistent with the expression of differentiation markers, indicating that the pattern of focal adhesion may affect the osteogenesis of MSCs and osteoblasts through changes in cytoskeletal tension and nuclear localisation of YAP.

    Qiang Wei, Shenghao Wang, Feng Han, Huan Wang, Weidong Zhang, Qifan Yu, Changjiang Liu, Luguang Ding, Jiayuan Wang, Lili Yu, Caihong Zhu, Bin Li
    2021, 2(4):  323-342.  doi:10.12336/biomatertransl.2021.04.001
    Biomaterials that mimic the mechanical properties of native extracellular matrix greatly help guide cell functions. In this review, various mechanical cues from biomaterials and their interplay effects on cell behaviours were introduced. In addition, the underlying principles for development of suitable mechanical biomaterials are discussed. This will provide guidance for researchers to explore how multimodal mechanics of biomaterials may promotetissue regeneration.
    Abstract ( 797 )   HTML ( 82)   PDF (77197KB) ( 1233 )  
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    Mechanical cues from the extracellular matrix (ECM) microenvironment are known to be significant in modulating the fate of stem cells to guide developmental processes and maintain bodily homeostasis. Tissue engineering has provided a promising approach to the repair or regeneration of damaged tissues. Scaffolds are fundamental in cell-based regenerative therapies. Developing artificial ECM that mimics the mechanical properties of native ECM would greatly help to guide cell functions and thus promote tissue regeneration. In this review, we introduce various mechanical cues provided by the ECM including elasticity, viscoelasticity, topography, and external stimuli, and their effects on cell behaviours. Meanwhile, we discuss the underlying principles and strategies to develop natural or synthetic biomaterials with different mechanical properties for cellular modulation, and explore the mechanism by which the mechanical cues from biomaterials regulate cell function toward tissue regeneration. We also discuss the challenges in multimodal mechanical modulation of cell behaviours and the interplay between mechanical cues and other microenvironmental factors.

    Yizhong Peng, Jinye Li, Hui Lin, Shuo Tian, Sheng Liu, Feifei Pu, Lei Zhao, Kaige Ma, Xiangcheng Qing, Zengwu Shao
    2021, 2(4):  343-360.  doi:10.12336/biomatertransl.2021.04.008
    After tissue damage or degeneration, the resulting unfavourable microenvironment, including inflammation, etc., imposes a great burden on the endogenous cells and non-cellular components. Tissue engineering materials are efficient in relieving the pathological changes and their damaging impact on cells and extracellular components, which may help re-establish endogenous repair mechanisms and alleviate tissue damage or degeneration.
    Abstract ( 203 )   HTML ( 26)   PDF (28393KB) ( 620 )  
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    The development of tissue engineering has led to new strategies for mitigating clinical problems; however, the design of the tissue engineering materials remains a challenge. The limited sources and inadequate function, potential risk of microbial or pathogen contamination, and high cost of cell expansion impair the efficacy and limit the application of exogenous cells in tissue engineering. However, endogenous cells in native tissues have been reported to be capable of spontaneous repair of the damaged tissue. These cells exhibit remarkable plasticity, and thus can differentiate or be reprogrammed to alter their phenotype and function after stimulation. After a comprehensive review, we found that the plasticity of these cells plays a major role in establishing the cell source in the mechanism involved in tissue regeneration. Tissue engineering materials that focus on assisting and promoting the natural self-repair function of endogenous cells may break through the limitations of exogenous seed cells and further expand the applications of tissue engineering materials in tissue repair. This review discusses the effects of endogenous cells, especially stem cells, on injured tissue repairing, and highlights the potential utilisation of endogenous repair in orthopaedic biomaterial constructions for bone, cartilage, and intervertebral disc regeneration.

    Ge Yan, Yuqi Liu, Minghui Xie, Jiawei Shi, Weihua Qiao, Nianguo Dong
    2021, 2(4):  361-375.  doi:10.12336/biomatertransl.2021.04.009
    Experimental and computational models for testing tissue-engineered heart valves are summarised. Such animal and non-animal models, supply approaches for accessing tissue-engineered heart valves from design to assessment, and guide construction of future artificial valves.
    Abstract ( 247 )   HTML ( 34)   PDF (71332KB) ( 408 )  
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    Valvular heart disease is currently a common problem which causes high morbidity and mortality worldwide. Prosthetic valve replacements are widely needed to correct narrowing or backflow through the valvular orifice. Compared to mechanical valves and biological valves, tissue-engineered heart valves can be an ideal substitute because they have a low risk of thromboembolism and calcification, and the potential for remodelling, regeneration, and growth. In order to test the performance of these heart valves, various animal models and other models are needed to optimise the structure and function of tissue-engineered heart valves, which may provide a potential mechanism responsible for substantial enhancement in tissue-engineered heart valves. Choosing the appropriate model for evaluating the performance of the tissue-engineered valve is important, as different models have their own advantages and disadvantages. In this review, we summarise the current state-of-the-art animal models, bioreactors, and computational simulation models with the aim of creating more strategies for better development of tissue-engineered heart valves. This review provides an overview of major factors that influence the selection and design of a model for tissue-engineered heart valve. Continued efforts in improving and testing models for valve regeneration remain crucial in basic science and translational researches. Future research should focus on finding the right animal model and developing better in vitro testing systems for tissue-engineered heart valve.