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Topic Review
Sex Hormone-Specific Neuroanatomy of Takotsubo Syndrome
TTS(Takotsubo syndrome) was first officially reported in 1991 as a reversible cardiomyopathy that appeared to be precipitated by acute emotional stress. The majority of TTS patients were postmenopausal females and usually developed symptoms similar to those of an acute coronary syndrome. A strong emotional stressor was thought to cause a transient abnormality of LV wall motion in the apical and mid-ventricular portion without obstructive coronary artery disease with ECG changes. TTS was initially called “Takotsubo cardiomyopathy”. Although most TTS cases were described as having been caused by negative emotions, there are cases in which positive emotions, such as joy, triggered TTS. In addition, 10% of TTS patients are male.
  • 860
  • 21 Jan 2022
Topic Review
Oral Diseases and Related Biomaterials
Oral diseases such as gingivitis, periodontitis, and oral cancer affect millions of people worldwide. Much research has been conducted to understand the pathogenetic mechanisms of these diseases and translate this knowledge into therapeutics. 
  • 860
  • 24 May 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. 
  • 853
  • 27 May 2022
Topic Review
Recent Advances in Cardiac Organoids
Cardiac organoids are in vitro self-organizing and three-dimensional structures composed of multiple cardiac cells (i.e., cardiomyocytes, endothelial cells, cardiac fibroblasts, etc.) with or without biological scaffolds. Since cardiac organoids recapitulate structural and functional characteristics of the native heart to a higher degree compared to the conventional two-dimensional culture systems, their applications, in combination with pluripotent stem cell technologies, are being widely expanded for the investigation of cardiogenesis, cardiac disease modeling, drug screening and development, and regenerative medicine.
  • 851
  • 10 Apr 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.
  • 849
  • 06 May 2022
Topic Review
CAR T Cell Therapy in Hematological Malignancies
Chimeric antigen receptor (CAR) T cell therapy has ushered in a new era in cancer treatment. Remarkable outcomes have been demonstrated in patients with previously untreatable relapsed/refractory hematological malignancies. However, optimizing efficacy and reducing the risk of toxicities have posed major challenges, limiting the success of this therapy. The tumor microenvironment (TME) plays an important role in CAR T cell therapy’s effectiveness and the risk of toxicities. Increasing research studies have also identified various biomarkers that can predict its effectiveness and risk of toxicities.
  • 849
  • 09 Jul 2022
Topic Review
Definite Biogel Composed of Collagen and Fibronectin
In vitro culture of endothelial cells to form capillary-like networks is essential in tissue engineering. Vascular endothelial growth factor (VEGF) is one of the primary signal proteins stimulating blood vessel formation. This growth factor can be soluble in the medium or protein-bound to the substrate. However, less attention has been paid to distinguishing the specific stimulations by soluble and bound VEGF. We conducted a series of experiments to explore the respective effects of these two VEGF forms. An in-house synthesized biogel comprising a definite concentration of collagen and fibronectin was designed to cultivate human umbilical vein endothelial cells to form the capillary-like network. Collagen served as the primary substrate for cell attachment. Fibronectin provided the surface to bind soluble VEGF in the culture medium to create the bound VEGF. The experiment of adding VEGF-blocking-peptide was conducted to prevent the formation of VEGF bound to the fibronectin domains, to distinguish the respective effects of the soluble and bound VEGF. With the in-house biogel of definite components, we were able to clarify the different roles of soluble and bound VEGF. The results indicated that the soluble VEGF promptly induced the cells to change from round to elongated shape, which contributed to forming network cords. Simultaneously, the bound VEGF provided long-term stimulation, causing the cells to migrate and differentiate into the final capillary-like network. 
  • 846
  • 20 Oct 2021
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.
  • 844
  • 21 Aug 2023
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.
  • 842
  • 11 Nov 2021
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.
  • 841
  • 30 Jan 2023
Topic Review
PKD1 in UCB-MSC
Polycystic Kidney Disease (PKD) is a disorder that affects the kidneys and other organs, and its major forms are encoded by polycystin-1 (PC1) and polycystin-2 (PC2), as PKD1 and PKD2. It is located sandwiched inside and outside cell membranes and interacts with other cells. This protein is most active in kidney cells before birth, and PC1 and PC2 work together to help regulate cell proliferation, cell migration, and interactions with other cells. The molecular relationship and the function between PKD1 and cancer is well known, such as increased or decreased cell proliferation and promoting or suppressing cell migration depending on the cancer cell type specifically.
  • 840
  • 24 May 2021
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. 
  • 838
  • 26 Oct 2021
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.
  • 837
  • 12 Apr 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.
  • 836
  • 08 Apr 2022
Topic Review
Epicardial Adipose Tissue Extracellular Vesicles in Cardiovascular Diseases
Epicardial adipose tissue (EAT) is a specialized fat depot that surrounds the heart, in direct contact with the myocardium. EAT is found between the visceral pericardium and the myocardium, with which it shares a bloodstream, EAT being circulation-dependent on the branches of the coronary arteries. The localization of EAT in the heart is distributed between the right ventricle, the anterior wall of the left ventricle, the atrioventricular groove, and the great coronary vessels, reaching the main thickness at the anterior and lateral walls of the right atrium. In physiological conditions, the EAT abundance depends on genetic, epigenetic, and environmental factors, such as pollution, aging, microbiota, and excessive caloric intake. The EAT mass can comprise up to 80% of the heart surface, contributing 20% to its whole mass.
  • 836
  • 27 Jun 2023
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. 
  • 834
  • 01 Jun 2022
Topic Review
Modelling Ischaemic Stroke In Vitro
Most of the knowledge on the pathophysiological mechanisms of an ischaemic stroke is derived from animal-based in vitro and in vivo models. Over the past decades, different animal models of stroke have been developed, induced by emboli, intraluminal suture, photothrombosis or endothelin-1, typically in rodents. The rat is one of the most commonly used species in stroke research, among other reasons, due to the similarity of the cerebral vasculature and physiology with that of humans. Moreover, mice are often used, since they are helpful in unravelling the function of certain genes in the pathophysiology of stroke by means of the creation of transgenic mice. Animal stroke models have been an indispensable tool, as they can model different aspects of the complex pathophysiology of ischaemic stroke that cannot be modelled (yet) in simple in vitro models lacking intact blood vessels and blood flow. However, simplified, highly controlled in vitro systems are required and preferred when investigating specific basic mechanisms and cell type-specific responses under ischaemia-like conditions. Besides, in the context of testing potential neuroprotective compounds, working in vitro allows high-throughput screenings, even on a human-based background.
  • 833
  • 19 Jul 2022
Topic Review
Heterotypic Multicellular Spheroids as Models of Sprouting Angiogenesis
Sprouting angiogenesis is the common response of live tissues to physiological and pathological angiogenic stimuli. Its accurate evaluation is of utmost importance for basic research and practical medicine and pharmacology and requires adequate experimental models. A variety of assays for angiogenesis were developed, none of them perfect. In vitro approaches are generally less physiologically relevant due to the omission of essential components regulating the process. However, only in vitro models can be entirely non-xenogeneic. The limitations of the in vitro angiogenesis assays can be partially overcome using 3D models mimicking tissue O2 and nutrient gradients, the influence of the extracellular matrix (ECM), and enabling cell-cell interactions.
  • 832
  • 25 Jan 2022
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.
  • 828
  • 14 Mar 2022
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. 
  • 828
  • 04 May 2023
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