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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.
  • 841
  • 10 Apr 2023
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. 
  • 839
  • 27 May 2022
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.
  • 836
  • 24 May 2021
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.
  • 834
  • 09 Jul 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.
  • 832
  • 27 Jun 2023
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.
  • 824
  • 08 Apr 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.
  • 821
  • 11 Nov 2021
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. 
  • 821
  • 01 Jun 2022
Topic Review
Tumour Microenvironment in Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers worldwide. Currently, treatments available for advanced HCC provide dismal chances of survival, thus there is an urgent need to develop more effective therapeutic strategies. While much of the focus of recent decades has been on targeting malignant cells, promising results have emerged from targeting the tumour microenvironment (TME). The extracellular matrix (ECM) is the main non-cellular component of the TME and it profoundly changes during tumorigenesis to promote the growth and survival of malignant cells.
  • 819
  • 26 Nov 2021
Topic Review
Applications of Magnetic Nanoparticles, Materials and Fields
Magnetic materials and magnetic stimulation have gained increasing attention in tissue engineering (TE), particularly for bone and nervous tissue reconstruction. Magnetism is utilized to modulate the cell response to environmental factors and lineage specifications, which involve complex mechanisms of action. Magnetic fields and nanoparticles (MNPs) may trigger focal adhesion changes, which are further translated into the reorganization of the cytoskeleton architecture and have an impact on nuclear morphology and positioning through the activation of mechanotransduction pathways. Mechanical stress induced by magnetic stimuli translates into an elongation of cytoskeleton fibers, the activation of linker in the nucleoskeleton and cytoskeleton (LINC) complex, and nuclear envelope deformation, and finally leads to the mechanical regulation of chromatin conformational changes. As such, the internalization of MNPs with further magnetic stimulation promotes the evolution of stem cells and neurogenic differentiation, triggering significant changes in global gene expression that are mediated by histone deacetylases (e.g., HDAC 5/11), and the upregulation of noncoding RNAs (e.g., miR-106b~25). Additionally, exposure to a magnetic environment had a positive influence on neurodifferentiation through the modulation of calcium channels’ activity and cyclic AMP response element-binding protein (CREB) phosphorylation.
  • 819
  • 06 Feb 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.
  • 818
  • 06 May 2022
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.
  • 817
  • 21 Aug 2023
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. 
  • 815
  • 29 May 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.
  • 813
  • 14 Mar 2022
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. 
  • 811
  • 26 Oct 2021
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. 
  • 811
  • 04 May 2023
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.
  • 806
  • 30 Jan 2023
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. 
  • 805
  • 29 Mar 2022
Topic Review
Bone Cell Function and Importance
The main functions of bone tissue include: structural support; protection of internal organs and soft tissues from damage; locomotion; mineral storage; production of blood cells; endocrine regulation.
  • 805
  • 22 Jan 2024
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.
  • 802
  • 12 Apr 2022
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