2022 Issue 1 (Available Online: 2022-03-28)

    Stem cell fate and microenvironment
    James T. Triffitt, Qian Wang
    2022, 3(1):  1-2.  doi:10.12336/biomatertransl.2022.01.001
    Abstract ( 78 )   HTML ( 18)   PDF (91KB) ( 195 )  
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    Deepika Arora, Pamela Gehron Robey
    2022, 3(1):  3-16.  doi:10.12336/biomatertransl.2022.01.002
    Heterogeneity in BMSCs/skeletal stem cells still remains a long-standing challenge in developing successful and reproducible tissue grafts for applications. Understanding the molecular basis of heterogeneity in skeletal stem cells is critical and so far, several intrinsic and extrinsic factors that may account for the heterogeneity have been put forth.
    Abstract ( 163 )   HTML ( 33)   PDF (2307KB) ( 425 )  
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    Based on studies over the last several decades, the self-renewing skeletal lineages derived from bone marrow stroma could be an ideal source for skeletal tissue engineering. However, the markers for osteogenic precursors; i.e., bone marrow-derived skeletal stem cells (SSCs), in association with other cells of the marrow stroma (bone marrow stromal cells, BMSCs) and their heterogeneous nature both in vivo and in vitro remain to be clarified. This review aims to highlight: i) the importance of distinguishing BMSCs/SSCs from other “mesenchymal stem/stromal cells”, and ii) factors that are responsible for their heterogeneity, and how these factors impact on the differentiation potential of SSCs towards bone. The prospective role of SSC enrichment, their expansion and its impact on SSC phenotype is explored. Emphasis has also been given to emerging single cell RNA sequencing approaches in scrutinizing the unique population of SSCs within the BMSC population, along with their committed progeny. Understanding the factors involved in heterogeneity may help researchers to improvise their strategies to isolate, characterize and adopt best culture practices and source identification to develop standard operating protocols for developing reproducible stem cells grafts. However, more scientific understanding of the molecular basis of heterogeneity is warranted that may be obtained from the robust high-throughput functional transcriptomics of single cells or clonal populations.

    Dafna Benayahu
    2022, 3(1):  17-23.  doi:10.12336/biomatertransl.2022.01.003
    Schematic illustration of mesenchymal cells, which can differentiate into various lineages, along with a scaffold which can serve as building blocks. The use of cells and scaffold in biotechnology approaches combined with fermentation in bioreactors can result in the large-scale mass production needed for tissue regenerative or food tech applications.
    Abstract ( 102 )   HTML ( 12)   PDF (199KB) ( 322 )  
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    Recent advances in the field of stem cell research now enable their utilisation for biotechnology applications in regenerative medicine and food tech. The first use of stem cells as biomedical devices employed a combination of cells and scaffold to restore, improve, or replace damaged tissues and to grow new viable tissue for replacement organs. This approach has also been adopted to replace meat production in the food industry. Mesenchymal stem cells are the source material used to induce cells to differentiate into the desired lineage. These technologies require mass propagation and rely on supplying the regulatory factors that direct differentiation. Mesenchymal stem cells can differentiate into fibroblastic and skeletal cells; fibroblastic/chondrogenic/osteogenic/myogenic and adipogenic lineages. Each differentiation fate requires specific key molecular regulators and appropriate activation conditions. Stem cell commitment determination involves a concerted effort of coordinated activation and silencing of lineage-specific genes. Transcription factors which bind gene promoters and chromatin-remodelling proteins are key players in the control process of lineage commitment and differentiation from embryogenesis through adulthood. Consequently, a major research challenge is to characterise such molecular pathways that coordinate lineage-specific differentiation and function. Revealing the mechanisms of action and the main factors will provide the knowledge necessary to control activation and regulation to achieve a specific lineage. Growing cells on a scaffold is a support system that mimics natural tissue and transduces the appropriate signals of the tissue niche for appropriate cellular function. The outcome of such research will deepen the understanding of cell differentiation to promote and advance the biotech, allowing the cell expansion required for their usage in therapy or the development of food tech.

    Xuechen Zhang, Ana Justo Caetano, Paul T. Sharpe, Ana Angelova Volponi
    2022, 3(1):  24-30.  doi:10.12336/biomatertransl.2022.01.004
    Teeth and their supporting oral tissues harbour diverse populations of stem cells that are easily accessible. The recent advancements in studying these cells in mouse models (A), as well as different human oral tissues (B), by using cell-sequencing approaches (C) reveal complex cellular architecture of different oral tissues, offering a deeper understanding of the underlying mechanisms that drive homeostasis, repair, and regeneration.
    Abstract ( 151 )   HTML ( 19)   PDF (1244KB) ( 535 )  
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    The teeth and their supporting tissues provide an easily accessible source of oral stem cells. These different stem cell populations have been extensively studied for their properties, such as high plasticity and clonogenicity, expressing stem cell markers and potency for multilineage differentiation in vitro. Such cells with stem cell properties have been derived and characterised from the dental pulp tissue, the apical papilla region of roots in development, as well as the supporting tissue of periodontal ligament that anchors the tooth within the alveolar socket and the soft gingival tissue. Studying the dental pulp stem cell populations in a continuously growing mouse incisor model, as a traceable in vivo model, enables the researchers to study the properties, origin and behaviour of mesenchymal stem cells. On the other side, the oral mucosa with its remarkable scarless wound healing phenotype, offers a model to study a well-coordinated system of healing because of coordinated actions between epithelial, mesenchymal and immune cells populations. Although described as homogeneous cell populations following their in vitro expansion, the increasing application of approaches that allow tracing of individual cells over time, along with single-cell RNA-sequencing, reveal that different oral stem cells are indeed diverse populations and there is a highly organised map of cell populations according to their location in resident tissues, elucidating diverse stem cell niches within the oral tissues. This review covers the current knowledge of diverse oral stem cells, focusing on the new approaches in studying these cells. These approaches “decode” and “map” the resident cells populations of diverse oral tissues and contribute to a better understanding of the “stem cells niche architecture and interactions. Considering the high accessibility and simplicity in obtaining these diverse stem cells, the new findings offer potential in development of translational tissue engineering approaches and innovative therapeutic solutions.

    Suzanne M. Watt
    2022, 3(1):  31-54.  doi:10.12336/biomatertransl.2022.01.005
    Some key cellular components of adult bone marrow microenvironmental haematopoietic stem cell (HSC) peri-sinusoidal niches are depicted on the left. C-X-C motif chemokine ligand 12 (CXCL-12) abundant reticular stromal cells are important elements of the HSC perisinusoidal niche, producing key cytokines and chemokines for HSC retention, and homeostatic regulation of HSC fate. Dysregulation of perivascular/endosteal niches and haematopoiesis occurs with acute or chronic inflammation or inflamm-ageing as shown on the right. The haematopoietic decline observed with ageing is potentially reversible by blocking or controlling inflamm-ageing or by reactivating skeletal stem cells.
    Abstract ( 79 )   HTML ( 16)   PDF (1774KB) ( 480 )  
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    Haematopoietic microenvironmental niches have been described as the ‘gatekeepers’ for the blood and immune systems. These niches change during ontogeny, with the bone marrow becoming the predominant site of haematopoiesis in post-natal life under steady state conditions. To determine the structure and function of different haematopoietic microenvironmental niches, it is essential to clearly define specific haematopoietic stem and progenitor cell subsets during ontogeny and to understand their temporal appearance and anatomical positioning. A variety of haematopoietic and non-haematopoietic cells contribute to haematopoietic stem and progenitor cell niches. The latter is reported to include endothelial cells and mesenchymal stromal cells (MSCs), skeletal stem cells and/or C-X-C motif chemokine ligand 12-abundant-reticular cell populations, which form crucial components of these microenvironments under homeostatic conditions. Dysregulation or deterioration of such cells contributes to significant clinical disorders and diseases worldwide and is associated with the ageing process. A critical appraisal of these issues and of the roles of MSC/C-X-C motif chemokine ligand 12-abundant-reticular cells and the more recently identified skeletal stem cell subsets in bone marrow haematopoietic niche function under homeostatic conditions and during ageing will form the basis of this research review. In the context of haematopoiesis, clinical translation will deal with lessons learned from the vast experience garnered from the development and use of MSC therapies to treat graft versus host disease in the context of allogeneic haematopoietic transplants, the recent application of these MSC therapies to treating emerging and severe coronavirus disease 2019 (COVID-19) infections, and, given that skeletal stem cell ageing is one proposed driver for haematopoietic ageing, the potential contributions of these stem cells to haematopoiesis in healthy bone marrow and the benefits and challenges of using this knowledge for rejuvenating the age-compromised bone marrow haematopoietic niches and restoring haematopoiesis.

    Shuqin Cao, Quan Yuan
    2022, 3(1):  55-64.  doi:10.12336/biomatertransl.2022.01.006
    Three different types of nanotopographic structures and their fabrication are discussed, namely, static patterned surface, dynamic patterned surface, and roughness surface. The application of these nanotopographical features in modulating stem cell fate are illustrated, furthermore, their future perspective in fundamental research and clinical application are also discussed.
    Abstract ( 115 )   HTML ( 14)   PDF (399KB) ( 257 )  
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    Stem cells have been one of the ideal sources for tissue regeneration owing to their capability of self-renewal and differentiation. In vivo, the extracellular microenvironment plays a vital role in modulating stem cell fate. When developing biomaterials for regenerative medicine, incorporating biochemical and biophysical cues to mimic extracellular matrix can enhance stem cell lineage differentiation. More specifically, modulating the stem cell fate can be achieved by controlling the nanotopographic features on synthetic surfaces. Optimization of nanotopographical features leads to desirable stem cell functions, which can maximize the effectiveness of regenerative treatment. In this review, nanotopographical surfaces, including static patterned surface, dynamic patterned surface, and roughness are summarized, and their fabrication, as well as the impact on stem cell behaviour, are discussed. Later, the recent progress of applying nanotopographical featured biomaterials for altering different types of stem cells is presented, which directs the design and fabrication of functional biomaterial. Last, the perspective in fundamental research and for clinical application in this field is discussed.

    Emma Steijvers, Armaan Ghei, Zhidao Xia
    2022, 3(1):  65-80.  doi:10.12336/biomatertransl.2022.01.007
    Potential manufacture of artificial bone grafts in two steps: (1) Engineering biodegradable synthetic bone-like scaffolds using allogenic human osteogenic stem cells in vitro. (2) Removing living cells to form the end product substantially equivalent to bone allograft.
    Abstract ( 157 )   HTML ( 25)   PDF (1261KB) ( 434 )  
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    Bone grafts have traditionally come from four sources: the patients’ own tissue (autograft), tissue from a living or cadaveric human donor (allograft), animal donors (xenograft) and synthetic artificial biomaterials (ceramics, cement, polymers, and metal). However, all of these have advantages and drawbacks. The most commercially successful bone grafts so far are allografts, which hold 57% of the current bone graft market; however, disease transmission and scarcity are still significant drawbacks limiting their use. Tissue-engineered grafts have great potential, in which human stem cells and synthetical biomaterials are combined to produce bone-like tissue in vitro, but this is yet to be approved for widespread clinical practice. It is hypothesised that artificial bone allografts can be mass-manufactured to replace conventional bone allografts through refined bone tissue engineering prior to decellularisation. This review article aims to review current literature on (1) conventional bone allograft preparation; (2) bone tissue engineering including the use of synthetic biomaterials as bone graft substitute scaffolds, combined with osteogenic stem cells in vitro; (3) potential artificial allograft manufacturing processes, including mass production of engineered bone tissue, osteogenic enhancement, decellularisation, sterilisation and safety assurance for regulatory approval. From these assessments, a practical route map for mass production of artificial allografts for clinical use is proposed.

    Ke Hu, Yuxuan Li, Zunxiang Ke, Hongjun Yang, Chanjun Lu, Yiqing Li, Yi Guo, Weici Wang
    2022, 3(1):  81-98.  doi:10.12336/biomatertransl.2022.01.008
    During the development of artificial blood vessels, various materials and manufacturing methods have been continuously explored, and modifications can be made to improve the causes of failure. Through in vitro and in vivo evaluation, we will eventually select the ideal artificial blood vessel.
    Abstract ( 456 )   HTML ( 64)   PDF (2405KB) ( 872 )  
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    Cardiovascular disease serves as the leading cause of death worldwide, with stenosis, occlusion, or severe dysfunction of blood vessels being its pathophysiological mechanism. Vascular replacement is the preferred surgical option for treating obstructed vascular structures. Due to the limited availability of healthy autologous vessels as well as the incidence of postoperative complications, there is an increasing demand for artificial blood vessels. From synthetic to natural, or a mixture of these components, numerous materials have been used to prepare artificial vascular grafts. Although synthetic grafts are more appropriate for use in medium to large-diameter vessels, they fail when replacing small-diameter vessels. Tissue-engineered vascular grafts are very likely to be an ideal alternative to autologous grafts in small-diameter vessels and are worthy of further investigation. However, a multitude of problems remain that must be resolved before they can be used in biomedical applications. Accordingly, this review attempts to describe these problems and provide a discussion of the generation of artificial blood vessels. In addition, we deliberate on current state-of-the-art technologies for creating artificial blood vessels, including advances in materials, fabrication techniques, various methods of surface modification, as well as preclinical and clinical applications. Furthermore, the evaluation of grafts both in vivo and in vitro, mechanical properties, challenges, and directions for further research are also discussed.