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Topic Review
Multifunctionality in Microbial Adhesins
Microbial adhesins have multiple functions, and these activities are all evolved and selected. Adhesins can act as enzymes, as assembly scaffolds and components of complex nano-machines. Sometimes, these activities are called secondary because they were discovered secondarily. For instance, microbial type IV pili were first called adhesive. In contrast, phosphoglycerate kinase has its well-known enzymatic activity, but in fungi it also moonlights as an extracellular adhesin.
  • 802
  • 16 Jun 2023
Topic Review
Spheroid-Based Cell Therapies for Degenerative Disc Disease
Degenerative disc disease, a painful pathology of the intervertebral disc (IVD), often causes disability and reduces quality of life. A long-lasting episode of low back pain (LBP) affects 80% of people at least once in their lifetime. The major cause of LBP is degenerative disc disease (DDD), an age-related pathology of the intervertebral disc (IVD). IVD contains distinct anatomical regions, namely the nucleus pulposus (NP), annulus fibrosus (AF), and cartilaginous endplates, which are all substantially different and unique structurally, mechanically, and biochemically, and present challenges for IVD tissue engineering. Ideally, an engineered construct should closely resemble the ECM architecture of the target tissue and rapidly integrate within a defect. Spheroids are three-dimensional multicellular aggregates with architecture that enables the cells to differentiate and synthesize endogenous ECM, promotes cell-ECM interactions, enhances adhesion, and protects cells from harsh conditions. Spheroids could be applied in the IVD both in scaffold-free and scaffold-based configurations, possibly providing advantages over cell suspensions.
  • 801
  • 14 Mar 2022
Topic Review
Growth Factors for Bone
Growth factors are bio-factors that target reparatory cells during bone regeneration. These growth factors are needed in complicated conditions of bone and joint damage to enhance tissue repair. The delivery of these growth factors is key to ensuring the effectiveness of regenerative therapy. Therapeutic growth factors are needed to enhance bone or cartilage repair in some conditions where healing is complicated or delayed. Traumatic bone healing could be complicated in up to 15% of the cases. Several other pathological conditions, such as osteonecrosis and arthritis, are accompanied by degenerative bone lesions. 
  • 801
  • 27 May 2022
Topic Review
Energy Sources for Exosome Communication in Cancer Microenvironment
Exosomes are crucial extracellular vesicles (EVs) with a diameter of approximately 30–200 nm. They are released by most cell types in their extracellular milieu and carry various biomolecules, including proteins and nucleic acids. Exosomes are increasingly studied in various diseases, including cancer, due to their role in local and distant cell–cell communication in which they can promote tumor growth, cancer progression, and metastasis. Interestingly, a tremendous number of exosomes is released by malignant cancer cells, and these are then taken up by autologous and heterologous recipient stromal cells such as immune cells, cancer stem cells, and endothelial cells. All these events demand an enormous amount of energy and require that exosomes remain stable while having the capacity to reach distant sites and cross physical barriers. Nevertheless, there is a dearth of research pertaining to the energy sources of exosomes, and questions remain about how they maintain their motility in the tumor microenvironment (TME) and beyond. Moreover, exosomes can produce adenosine triphosphate (ATP), an important energy molecule required by all cells, and mitochondria have been identified as one of the exosomal cargoes. These findings strengthen the prospect of exosomal communication via transfer of mitochondria and the bioenergetics of target recipient cells. In the TME, the accumulation of ATP and lactate may facilitate the entry of exosomes into cancer cells to promote metastasis, as well as help to target cancer cells at the tumor site.
  • 800
  • 08 Apr 2022
Topic Review
Lymphatic Tissue Bioengineering based on Stem Cells
Lymphedema is characterized by progressive and chronic tissue swelling and inflammation from local accumulation of interstitial fluid due to lymphatic injury or dysfunction. It is a debilitating condition that significantly impacts a patient’s quality of life, and has limited treatment options. With better understanding of the molecular mechanisms and pathophysiology of lymphedema and advances in tissue engineering technologies, lymphatic tissue bioengineering and regeneration have emerged as a potential therapeutic option for postsurgical lymphedema. Various strategies involving stem cells, lymphangiogenic factors, bioengineered matrices and mechanical stimuli allow more precisely controlled regeneration of lymphatic tissue at the site of lymphedema without subjecting patients to complications or iatrogenic injuries associated with surgeries. 
  • 800
  • 01 Jun 2022
Topic Review
Prostate Cancer Applying Upconversion Nanoparticles
Upconversion nanoparticles (UCNPs) are nanoscale crystals equipped, for instance, with rare earth ions that have the ability to absorb two or even more low energy photons and therefore are able to emit fluorescence at a shorter wavelength than the excitation wavelength. 
  • 799
  • 31 May 2021
Topic Review
TMDC Nanozymes: Application Perspective
Applications of TMDC NZs in different fields—starting from biosensing to different treatment fields like antibacterial, anti-inflammation activity and cancer therapy—are discussed in more details. 
  • 795
  • 29 Mar 2022
Topic Review
Mesenchymal Stem Cell-Based Therapy in Acute Kidney Injury
Acute kidney injury (AKI) causes a lot of harm to human health but is treated by only supportive therapy in most cases. Recent evidence shows that mesenchymal stem cells (MSCs) benefit kidney regeneration through releasing paracrine factors and extracellular vesicles (EVs) to the recipient kidney cells and are considered to be promising cellular therapy for AKI. To develop more efficient, precise therapies for AKI, we review the therapeutic mechanism of MSCs and MSC-derived EVs in AKI and look for a better understanding of molecular signaling and cellular communication between donor MSCs and recipient kidney cells. We also review recent clinical trials of MSC-EVs in AKI. This review summarizes the molecular mechanisms of MSCs’ therapeutic effects on kidney regeneration, expecting to comprehensively facilitate future clinical application for treating AKI.
  • 792
  • 11 Nov 2021
Topic Review
Bone Mineral Phase and Localized Ionic Microenvironment
Calcium phosphates (CaPs) based on inorganic biomaterials are one of the most extensively studied types for bone grafting. They are composed of calcium ions and phosphate groups, which are omnipresent in the bloodstream or fixed in the bone mineral phase. Considering the abundance of ions in the bone environment and the current knowledge of their modulatory roles in maintaining the bone remodeling balance, it is expected that a deeper understanding of ions in the bone environment would provide new insights to guide the future design of inorganic biomaterials for bone tissue engineering.
  • 788
  • 20 Feb 2023
Topic Review
Cardiac Regeneration
Cardiac regeneration is a critical endeavor in the treatment of heart diseases, aimed at repairing and enhancing the structure and function of damaged myocardium. Stem cell-based therapies, which involve the utilization of adult stem cells and pluripotent stem cells hold immense potential for replenishing lost cardiomyocytes and facilitating cardiac tissue repair and regeneration. Tissue engineering also plays a prominent role employing synthetic or natural biomaterials, engineering cardiac patches and grafts with suitable properties, and fabricating upscale bioreactors to create functional constructs for cardiac recovery. These constructs can be transplanted into the heart to provide mechanical support and facilitate tissue healing. Additionally, the production of organoids and chips that accurately replicate the structure and function of the whole organ is an area of extensive research. 
  • 777
  • 24 Aug 2023
Topic Review
Mesenchymal Stem Cells in Gastric Cancer
Bone marrow-derived mesenchymal stem cells (MSCs) naturally present in the stomach have been reported to carry a malignancy risk, but their effect in gastric cancer (GC) is still being researched. The pro- and antiangiogenic effects of MSCs derived from various sources complement their role in immune regulation and tissue regeneration and provide further understanding into the heterogeneous biology of GC, the aberrant morphology of tumor vasculature and the mechanisms of resistance to antiangiogenic drugs.
  • 775
  • 19 Apr 2023
Topic Review
Ageing and Inflammation in Periodontium
Periodontitis is a ubiquitous chronic inflammatory disease characterized by the gradual destruction of the periodontal ligament and alveolar bone, leading to periodontal pocket formation and gingival recession. Ageing is a primary risk factor for the development of periodontitis, exacerbating alveolar bone loss and leading to tooth loss in the geriatric population.
  • 774
  • 24 Nov 2023
Topic Review
Secretome Derived from SHED in Tissue Regeneration
Stem cells from human exfoliated deciduous teeth (SHED) have emerged as an alternative stem cell source for cell therapy and regenerative medicine because they are readily available, pose fewer ethical concerns, and have low immunogenicity and tumourigenicity. SHED offer a number of advantages over other dental stem cells, including a high proliferation rate with the potential to differentiate into multiple developmental lineages. The therapeutic effects of SHED are mediated by multiple mechanisms, including immunomodulation, angiogenesis, neurogenesis, osteogenesis, and adipogenesis. Since SHED are more potentially useful source of stem cells than BM-MSCs and DPSCs in cell therapy, therefore it could be suggested that the secretome derived from SHED could enhance tissue regeneration and repair and hence, considered as a suitable candidate for a cell-free approach in regenerative medicine and dentistry.
  • 771
  • 21 Aug 2023
Topic Review
Direct Cardiac Reprogramming
Coronary artery disease is the most common form of cardiovascular diseases, resulting in the loss of cardiomyocytes (CM) at the site of ischemic injury. To compensate for the loss of CMs, cardiac fibroblasts quickly respond to injury and initiate cardiac remodeling in an injured heart. In the remodeling process, cardiac fibroblasts proliferate and differentiate into myofibroblasts, which secrete extracellular matrix to support the intact structure of the heart, and eventually differentiate into matrifibrocytes to form chronic scar tissue. Discovery of direct cardiac reprogramming offers a promising therapeutic strategy to prevent/attenuate this pathologic remodeling and replace the cardiac fibrotic scar with myocardium in situ. Since the first discovery in 2010, many progresses have been made to improve the efficiency and efficacy of reprogramming by understanding the mechanisms and signaling pathways that are activated during direct cardiac reprogramming.
  • 764
  • 06 May 2022
Topic Review
Challenges in Adoptive T Cell Therapy for AML
Despite exhaustive studies, researchers have made little progress in the field of adoptive cellular therapies for relapsed-refractory acute myeloid leukemia (AML), unlike the notable uptake for B cell malignancies. Various single antigen targeting chimeric antigen receptor (CAR) T cell Phase I trials have been established worldwide and have recruited approximately 100 patients. The high heterogeneity at the genetic and molecular levels within and between AML patients resembles a black hole: a great gravitational field that sucks in everything, considering only around 30% of patients show a response but with consequential off-tumor effects. It is obvious that a new point of view is needed to achieve more promising results. Below information first introduces the unique therapeutic challenges of not only CAR T cells but also other adoptive cellular therapies in AML. 
  • 764
  • 29 May 2023
Topic Review Peer Reviewed
Primary Progenitor Tenocytes: Cytotherapeutics and Cell-Free Derivatives
Primary progenitor tenocytes are diploid cells that may be cultured in vitro and therapeutically used for allogeneic musculoskeletal regenerative medicine. Firstly, technical aspects of cell banking, biotechnological manufacturing, and extensive preclinical characterization data have confirmed that FE002-Ten primary progenitor tenocytes may be safely considered for human cytotherapeutic use (e.g., in tissue engineering products, standardized transplants). Parallelly, lyophilized progenitor tenocyte extracts (e.g., stabilized cells or cell-free derivatives) were shown to optimally act as potent hyaluronan-based hydrogel functionalizing agents, useful for stability enhancement against oxidative product degradation. Therefore, primary progenitor tenocytes (e.g., FE002-Ten cell source) may potentially be used in diverse clinical presentations of tendon-related pathologies, ranging from volumetric tissue replacement (i.e., for the promotion of enhanced graft bio-integration) to local management of tissular inflammation and pain (i.e., ancillary action of the cellular extracts for the functional enhancement of injectable hyaluronan-based preparations). Overall, the primary progenitor tenocytes investigated under the Swiss progenitor cell transplantation program were shown to represent highly standardized biotechnological materials with a versatility of potential therapeutic uses after formulation into an array of cytotherapeutic preparations or cell-free devices.
  • 756
  • 29 Mar 2023
Topic Review
Evolution of Skin-on-a-Chip Platforms
The increased demand for physiologically relevant in vitro human skin models for testing pharmaceutical drugs has led to significant advancements in skin engineering. One of the most promising approaches is the use of in vitro microfluidic systems to generate advanced skin models, commonly known as skin-on-a-chip (SoC) devices. These devices allow the simulation of key mechanical, functional and structural features of the human skin, better mimicking the native microenvironment. Importantly, contrary to conventional cell culture techniques, SoC devices can perfuse the skin tissue, either by the inclusion of perfusable lumens or by the use of microfluidic channels acting as engineered vasculature.
  • 754
  • 12 Apr 2022
Topic Review
Extracellular Matrix in Chronic Inflammation
Bidirectional communication between cells and their microenvironment has a key function in normal tissue homeostasis and for disease initiation, progression and patient’s prognosis at least. The extracellular matrix (ECM), as an element of all tissues and cellular microenvironment, is a frequently overlooked component in implication in pathogenesis and progression of several diseases. In inflammatory microenvironment (IME) different alterations affect ECM resulting from remodeling processes which progressively induce cancer initiation and the passage toward a tumor microenvironment (TME). Indeed, it is demonstrated that altered ECM components interact with a variety of surface receptors triggering intracellular signaling that, in turn, affect cellular pathways. Supporting this concept, new studies have offered exciting clues about the function of decellularized ECM (dECM) and its components, as active participants in cancer and inflammation diseases evolution, once matched it with other cellular elements. Research results support the notion that the ECM, rather than acting as a passive element, is an active participant in promotion of chronic inflammatory and cancer initiation. Particularly it highlights the different effects of ECM components alterations in both disease and the correlation between chronic inflammation and cancer initiation. In conclusion, it soughts to explore the employment of dECM models as a tool to prevent cancer initiation. Indeed, reporting some of the data obtained in cancer research, it reflects about the employment of dECM models to investigate the short-circuits contributing to create distinct IME, representing, thus, a potential tool to avoid the progression toward a malignant lesion.
  • 753
  • 30 Jan 2023
Topic Review
Current Applications of MSC-Derived Extracellular Vesicles
Extensive research has shown that unmodified MSC-EVs have various therapeutic roles including immune regulation, anti-inflammatory effects and tissue regeneration. Nevertheless, improvements are still needed in what concerns their targeting and payload potency, and thus bioengineering strategies have been widely employed to potentiate the benefits of MSC-EVs. 
  • 752
  • 04 May 2023
Topic Review
MSCs in Cell and Cell-Free Therapies
The progressive loss of the regenerative potential of tissues is one of the most obvious consequences of aging, driven by altered intercellular communication, cell senescence and niche-specific stem cell exhaustion, among other drivers. Mesenchymal tissues, such as bone, cartilage and fat, which originate from mesenchymal stem cell (MSC) differentiation, are especially affected by aging. Senescent MSCs show limited proliferative capacity and impairment in key defining features: their multipotent differentiation and secretory abilities, leading to diminished function and deleterious consequences for tissue homeostasis. 
  • 751
  • 26 Oct 2021
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