This review article examines how stem cell therapies can cure various diseases and injuries while also discussing the difficulties and moral conundrums that come with their application. The article focuses on the revolutionary developments in stem cell research, especially the introduction of gene editing tools like CRISPR-Cas9, which can potentially improve the safety and effectiveness of stem cell-based treatments. To guarantee the responsible use of stem cells in clinical applications, it is also argued that standardizing clinical procedures and fortifying ethical and regulatory frameworks are essential first steps. The assessment also highlights the substantial obstacles that still need to be addressed, such as the moral dilemmas raised by the use of embryonic stem cells, the dangers of unlicensed stem cell clinics, and the difficulties in obtaining and paying for care for patients. The study emphasizes how critical it is to address these problems to stop exploitation, guarantee patient safety, and increase the accessibility of stem cell therapy. The review also addresses the significance of thorough clinical trials, public education, and policy development to guarantee that stem cell research may fulfill its full potential. The review concludes by describing stem cell research as a promising but complicated topic that necessitates a thorough evaluation of both the hazards and the benefits. To overcome the ethical, legal, and accessibility obstacles and eventually guarantee that stem cell treatments may be safely and fairly included in conventional healthcare, it urges cooperation between the scientific community, legislators, and the general public.

Neurological disorders, ranging from common conditions like Alzheimer's disease that is a progressive neurodegenerative disorder and remains the most common cause of dementia worldwide to rare disorders such as Angelman syndrome, impose a significant global health burden. Altered facial expressions are a common symptom across these disorders, potentially serving as a diagnostic indicator. Deep learning algorithms, especially convolutional neural networks (CNNs), have shown promise in detecting these facial expression changes, aiding in diagnosing and monitoring neurological conditions.

Acute kidney injury (AKI) has a high morbidity and mortality rate but can only be treated with supportive therapy in most cases. The diagnosis of AKI is mainly based on serum creatinine level and urine volume, which cannot detect kidney injury sensitive and timely. Therefore, new diagnostic and therapeutic molecules of AKI are being actively explored. Extracellular vesicles (EVs), secreted by almost all cells, can originate from different parts of the kidney and mediate intercellular communication between various cell types of nephrons. At present, numerous successful EV-based biomarker discoveries and treatments for AKI have been made, such as the confirmed diagnostic role of urine-derived EVs in AKI and the established therapeutic role of mesenchymal stem cell-derived EVs in AKI have been confirmed; however, these related studies lack a full discussion. In this review, we summarize the latest progression in the profound understanding of the functional role of EVs in AKI caused by various etiologies in recent years and provide new insights into EVs as viable biomarkers and therapeutic molecules for AKI patients. Furthermore, the current challenges and prospects of this research area are briefly discussed, presenting a comprehensive overview of the growing foregrounds of EVs in AKI.

With the discovery of intercellular mitochondrial transfer, the intricate mitochondrial regulatory networks on stem cell fate have aroused intense academic interest. Apart from capturing freely released mitochondria from donor cells, stem cells are able to receive mitochondria through tunneling nanotubes (TNTs), gap junctional channels (GJCs) and extracellular vesicles (EVs), especially when undergoing stressful conditions such as inflammation, hypoxia, chemotherapy drug exposure, and irradiation. Stem cells that are potentiated by exogenous mitochondria show enhanced potential for proliferation, differentiation, and immunomodulation. The well-tolerated nature of either autogenous or allogenous mitochondria when locally injected in the human ischemic heart has validated the safety and therapeutic potential of mitochondrial transplantation. In children diagnosed with mitochondrial DNA deletion syndrome, functional improvements have been observed when empowering their hematopoietic stem cells with maternally derived mitochondria. Apart from the widely investigated applications of mitochondrial transfer in ischemia-reperfusion injury, neurodegenerative diseases and mitochondrial diseases etc., therapeutic potentials of mitochondrial transfer in tissue repair and regeneration are equally noteworthy, though there has been no systematic summary in this regard.This review analyzed the research and development trends of mitochondrial transfer in stem cells and regenerative medicine over the past decade from a bibliometric perspective, introduced the concept and associated mechanisms of mitochondrial transfer, summarized the regulations of intercellular mitochondrial transfer on stem cell fate. Finally, the therapeutic application of mitochondrial transplantation in diseases and tissue regeneration has been reviewed, including recent clinical studies related to mitochondrial transplantation.Mitochondrial transfer shows promise in modifying and reshaping the cellular properties of stem cells, making them more conducive to regeneration. Mesenchymal stem cells (MSCs)-derived mitochondria have shown multifaceted potential in promoting the revitalization and regeneration of cardiac, cutaneous, muscular, neuronal tissue. This review integrates novel research findings on mitochondrial transfer in stem cell biology and regenerative medicine, emphasizing the crucial translational value of mitochondrial transfer in regeneration. It serves to underscore the significant impact of mitochondrial transfer and provides a valuable reference for further exploration in this field.

The niche microenvironment plays a crucial role in regulating the fate of normal skin stem cells (SSCs) and cancer stem cells (CSCs). Therapeutically targeting the CSC niche holds promise as an effective strategy; however, the dual effects of shared SSC niche signaling in CSCs have contributed to the aggressive characteristics of tumors and poor survival rates in skin cancer patients. The lack of a clear underlying mechanism has significantly hindered drug development for effective treatment. This article explores recent advances in understanding how niche factors regulate cell fate determination between skin stem cells and skin CSCs, along with their clinical implications. The dual roles of key components of the adhesive niche, including the dermo-epidermal junction and adherens junction, various cell types-especially immune cells and fibroblasts-as well as major signaling pathways such as Sonic hedgehog (Shh), Wingless-related integration site (Wnt)/β-catenin, YAP (Yes-associated protein)/TAZ (transcriptional coactivator with PDZ-binding motif), and Notch, are highlighted. Additionally, recent advances in clinical trials and drug development targeting these pathways are discussed. Overall, this review provides valuable insights into the complex interactions between skin cancer stem cells and their microenvironment, laying the groundwork for future research and clinical strategies.

Freezing sperm for artificial insemination (AI) has been common for decades, but this method causes damage to sperm, which affects its viability and fertility. Various strategies have been used to treat sperm cryopreservation complications, but their results are still not satisfactory. The latest approach in this field is using extracellular vesicles (EVs). The role of EVs in reproduction, such as spermatogenesis, sperm capacitation, and fertility has been proven. EVs can deliver proteins, lipids, nucleic acids, and other molecules to the sperm for repair. The EVs carry proteins, lipids, nucleic acids, and other molecules, which could be involved in sperm quality, functionality or fertility. The application of EV derived from animal and human cell sources for cryoinjury treatment indicates the improvement of sperm quality after freeze-thawing. In addition, different EV engineering methods regarding various EV cargos could be more influential for cryopreserved sperm treatment because they could provide EV customized content for delivering to cryoinjured sperm, according to their unique needs to enhance viability and fertility. In this review, first, we reminded the sperm cryopreservation complications, and next explained the conventional and modern strategies for overcoming them. Then, we have pointed out the role of EV in sperm development and the following mentioned the study results of using EV from different cell sources in sperm cryoinjuries repair. Also, we suggested several predisposing molecules (including microRNAs and proteins) for EV engineering to treat sperm cryopreservation complications by indirect engineering procedure, including genetic manipulation and incubation with therapeutic molecules, and direct engineering procedure, including electroporation, sonication, incubation, saponin permeabilization, extrusion, CaCl2-heat shock, and freeze/thawing. Finally, we discussed the limitations of EV application and ethical considerations in this context. In the meantime, despite these limitations, we pointed out the promising potential of the EV engineering strategies to reduce infertility rates by helping to overcome sperm cryopreservation challenges.

The role of embryology in metazoan evolution is rooted deeply in the history of science. Viewing Neoplasia as an evolutionary engine provides a scientific basis for reexamining the disease cancer. Once the embryo is understood as a benign tumor with a pivotal role in the evolution of all animal forms, there will be an immediate paradigm shift in the search for cancer cure, potentially revealing insights that may be buried within the great developmental transitions of metazoans. This article discusses one of the unifying principles between embryology and oncology, namely cancer stem cells. Some considerations are also provided on the central role of physics and biomechanics in the assembly of the first embryo, which can be regarded as a differentiated benign tumor. Mechanical impregnation of the nucleus of a stem cell, culminating in a totipotent/multipotent cell, was a major event safeguarding the success of embryogenesis throughout evolution. Germ cells in the earliest ctenophore embryos underwent delayed differentiation, subsequent to the mechanical assembly of the embryo. Finally, a discussion is presented on the concept that cancer and embryogenesis (cancer and healthy stem cells) are two sides of the same coin, that is, of the same process. The only difference is that cancer stem cells reveal themselves in inappropriate contexts. Neoplasia is a free force, whereas cancer is a force contained by animal organization.

The development of enamel relies on the precise regulation of ameloblast differentiation, enamel matrix secretion, and mineralization. The formation of enamel is crucial for the normal function of dental tissues, and promoting enamel remineralization is of significant importance for the treatment of dental caries. Understanding the underlying mechanisms of enamel development is essential for oral therapy and provides a bridge to tooth regeneration. Among various growth factors, the insulin-like growth factor (IGF) family, including IGF-1 and IGF-2, has been shown to play a key role in enamel formation by activating signaling pathways such as PI3K/AKT and MAPK. This review summarizes the role of the IGF family in tooth development and enamel formation and sheds light on key parts of the research for future treatment improvements.

Parkinson's disease (PD) is a systemic neurodegenerative disorder that is characterized by motor and non-motor symptoms. Although aging is the primary risk factor, environmental and genetic factors also contribute to risk, and identifying genetic risks may aid in preventive strategies. The present perspective outlines the two main genetic research strategies: research into familial PD using known causative gene screening and next-generation sequencing, and the analysis of sporadic PD using genome-wide association studies (GWAS). Recent advances in next-generation sequencing have improved gene screening, allowing researchers to quickly and inexpensively identify novel rare variants. However, challenges remain, such as accurately analyzing repetitive sequences and structural variants. The role of neurologists in gathering clinical and genomic data ─ especially from familial cases ─ is crucial. International collaborations, such as the Global Parkinson's Genetic Program, address issues such as population diversity and missing heritability in GWAS. Contributions from Juntendo University include the discovery of PD-related genes and the implementation of validation studies in Japanese populations. We also aim to develop molecular targeted therapies using induced pluripotent stem cells. To elucidate the unknown causes of PD and advance treatment approaches, it is important to continuously conduct genetic research.

Mitochondria are traditionally known as the cells' powerhouses; however, their roles go far beyond energy suppliers. They are involved in intracellular signaling and thus play a crucial role in shaping cells' destiny and functionality, including immune cells. Mitochondria can be actively exchanged between immune and non-immune cells via mechanisms such as nanotubes and extracellular vesicles. The mitochondria transfer from immune cells to different cells is associated with physiological and pathological processes, including inflammatory disorders, cardiovascular diseases, diabetes, and cancer. On the other hand, mitochondrial transfer from mesenchymal stem cells, bone marrow-derived stem cells, and adipocytes to immune cells significantly affects their functions. Mitochondrial transfer can prevent exhaustion/senescence in immune cells through intracellular signaling pathways and metabolic reprogramming. Thus, it is emerging as a promising therapeutic strategy for immune system diseases, especially those involving inflammation and autoimmune components. Transferring healthy mitochondria into damaged or dysfunctional cells can restore mitochondrial function, which is crucial for cellular energy production, immune regulation, and inflammation control. Also, mitochondrial transfer may enhance the potential of current therapeutic immune cell-based therapies such as CAR-T cell therapy.

Notch signaling is a widely preserved communication pathway that supports essential cellular functions by allowing adjacent cells to interact. The Notch signaling pathway consists of Notch ligands (DSL proteins), Notch receptors, DNA-binding proteins, and downstream target genes. Hepatocellular carcinoma (HCC) represents the predominant cause of cancer-related deaths globally and poses a significant threat to human health. For highly malignant HCC, current treatment options, including chemotherapy, radiotherapy, immunotherapy, targeted therapies, and surgical procedures, often have poor prognoses. Therefore, there is a need to explore additional therapeutic strategies. Many studies have found that abnormal activation of the Notch signaling pathway contributes to tumor initiation and progression by promoting HCC proliferation, metastasis, stem cell-like properties, and drug resistance. In this research, we reveal the composition and activation mechanisms of the Notch signaling pathway, as well as the molecular mechanism underlying its aberrant activation in HCC. Furthermore, we summarize recent advances in targeting Notch signaling for the treatment of HCC. This review aims to highlight the promising potential of investigating the Notch pathway as a therapeutic target in HCC.

The metal-based devices may corrode, degrade, or release metal ions and fragments after being implanted in the body, exhibiting their own consequences on hosting organs/tissues. The biocompatibility of metal implants has been investigated in various studies using a number of cell types. Mesenchymal stem cells (MSCs) are more relevant cells than others for evaluating the cytocompatibility of metal-based orthopedic implants because they are essential cells for bone regeneration and a promising cell population in regenerative medicine. In this regard, stemness preservation of MSCs is a key property in both body's own repair process and success of renewing/compensating approaches. In general, MSCs adhesion, viability, and function at the cell-metal interface is directly dependent on the metal alloys composing elements, which, along with consideration of compatibility, could guarantee the success of implants. This review scrutinizes the effects of orthopedic metal materials on the biocompatibility and stemness of MSCs at metal interface. Additionally, in vivo, host responses to metal implants are investigated.

Cells membrane-coated nanoparticles (CMs-NPs) represent a highly promising platform in cancer treatment. Due to the various types of cell sources employed and the broad designs of NPs, CM-NPs have emerged as versatile and multifunctional platforms with wide applicability in medicine. This literature review showcases the applications of CMs-NPs in cancer therapy, highlighting significant advancements in tumor-targeted delivery, phototherapy, and immunotherapy. Different cell types employed as CMs sources are reviewed, including cancer cells, red blood cells, platelets, white blood cells, stem cells, fibroblasts, and bacterium. Hybrid CMs-coatings and the technology to produce them are also included. Additionally, the state of the art in methodologies is critically examined, noting that while effective methods for coating and isolation of CMs exist, further optimization is still required. The latest reports and research findings in this regard are also presented, emphasizing the continuous need for innovation to overcome substantial challenges related to this promising nanotechnology. The aim of this review is to provide an in-depth overview of the evolving landscape in the development of effective and targeted cancer treatments, underscoring the transformative potential of CMs-NPs in revolutionizing cancer care and improving patient outcomes.

Cardiovascular diseases are the main cause of death and disability in the clinical setting. Among several pathological conditions, myocardial infarction (MI) is a common clinical finding and happens due to the reduction or complete interruption of blood support. Stem cells and progenitors are valid cell sources with significant potential to alleviate several tissue injuries. Differentiation to mature and functional cells and the release of various growth factors, and cytokines are the main reparative mechanisms by which stem cells mediate their reparative tasks. Exosomes (Exos), a subset of extracellular vesicles (EVs), exhibit great theranostic potential in biomedicine. Along with whole-cell-based therapies, the pre-clinical and clinical application of Exos has been extended in animals and humans with ischemic heart diseases (IHD). Here, in this review article, we aimed to highlight the importance of Exos in IHD and address the mechanism of action by focusing on their regenerative potential.

Engineered cells provide versatile tools for precise, tunable drug delivery, especially when synthetic stimulus-responsive gene circuits are incorporated. In many complex disease conditions, endogenous pathologic signals such as inflammation can vary dynamically over different time scales. For example, in autoimmune conditions such as rheumatoid arthritis or juvenile idiopathic arthritis, local (joint) and systemic inflammatory signals fluctuate daily, peaking in the early morning, but can also persist over long periods of time, triggering flare-ups that can last weeks to months. However, treatment with disease-modifying anti-rheumatic drugs is typically provided at continuous high doses, regardless of disease activity and without consideration for levels of inflammatory signals. In previous studies, we have developed cell-based drug delivery systems that can automatically address the different scales of flares using either chronogenetic circuits (i.e., clock gene-responsive elements) that can be tuned for optimal drug delivery to dampen circadian variations in inflammatory levels or inflammation-responsive circuits (i.e., NF-κB-sensitive elements) that can respond to sustained arthritis flares on demand with proportional synthesis of drug. The goal of this study was to develop a novel dual-responsive synthetic gene circuit that responds to both circadian and inflammatory inputs using OR-gate logic for both daily timed therapeutic output and enhanced therapeutic output during chronic inflammatory conditions.

Glucagon-like peptide-1 is an enteric proinsulin hormone secreted by intestinal L-cells that orchestrates insulin secretion in a glucose-dependent manner. Renowned for preserving pancreatic β-cell mass, glucagon-like peptide-1 facilitates β-cell proliferation and inhibits apoptosis, while concurrently suppressing glucagon secretion from pancreatic α-cells, thereby exerting hypoglycemic effects.Recent in vitro and in vivo studies have clarified the benefits of combination therapy with glucagon-like peptide-1 and stem cells in Type 2 diabetes mellitus. Glucagon-like peptide-1 enhances the repair of type 2 diabetes mellitus-afflicted tissues and organs by modulating sourced mesenchymal stem cell differentiation, proliferation, apoptosis, and migration. Importantly, glucagon-like peptide-1 overcomes the detrimental effects of the diabetic microenvironment on transplanted mesenchymal stem cells by increasing the number of localized cells in stem cell therapy and the unstable efficacy of stem cell therapy.This review elucidates the molecular and cellular mechanisms through which glucagon-like peptide-1 regulates mesenchymal stem cells in the type 2 diabetes mellitus context and discuss its therapeutic prospects for type 2 diabetes mellitus and its associated complications, proposing a novel and comprehensive treatment paradigm.

Diabetes mellitus (DM) is a grave autoimmune disorder because of no insulin self-generation. Currently, mainly clinical methods exist, serious adverse effects leading to stem cell therapy are considered. The mesenchymal stem cells (MSCs), require high differentiation capacity and are judged as crucial in DM treatment. The meta-analysis aimed to systemically analyze the particular types of MSCs which play a more important role in DM and which DM is treated more effectively.

Adult hippocampal neurogenesis, while occurring throughout life, decreases with age and in some neurodegenerative diseases. As decreased hippocampal neurogenesis is correlated with cognitive decline, efforts have been made to increase levels of neurogenesis, either through natural compounds, environmental interventions or novel pharmacological compounds. Nutraceuticals are food products with medical benefits such as antioxidation, anti-inflammation or neuroprotection. There has been increasing interest in these "functional foods" and their active compounds in recent years, providing natural alternatives to de novo pharmaceuticals. This review highlights key nutraceuticals that promote neurogenesis and/or improve cognitive outcomes. By outlining the effects of these compounds in the animal models employed and in clinical populations, we also suggest further investigations. We examine common targets and pathways through which these nutraceuticals are believed to exert pro-neurogenic effects. Most nutraceutical preparations contain multiple components, any of which may exert effects on neurogenesis. Identifying key active compounds in nutraceuticals may enable researchers to better understand their effects and standardize doses across studies. The less stringent regulatory requirements for nutraceuticals can be a double-edged sword. While allowing easier access to the beneficial effects, higher doses of these compounds may have detrimental effects. Hence, research in this field should not only aim to identify the benefits of these compounds but also to identify efficacious and safe dosages for them. Our aims are to provide understanding of nutraceuticals, provide evidence for their benefits on neurogenesis and neurogenesis-related behaviors and finally to summarize potential mechanisms and help guide future work.

Facial symptoms of systemic sclerosis (SSc)-such as reduced skin elasticity, fibrosis and microstomy-significantly impact quality of life. In recent years, autologous fat grafting has emerged as a promising treatment for these issues, but determining the optimal timing and techniques for fat injection remains a challenge for surgeons. Our study aimed to perform a systematic review of the available literature to establish a standardised protocol for this procedure. We reviewed all relevant studies published up to 18 August 2023, focusing specifically on diffuse facial scleroderma. In addition to clinical reports, we included articles discussing the pathophysiological mechanisms behind the effects of adipose stem cells. A total of 18 articles were analysed, revealing a range of methods and timelines for the procedure. The volume of fat injected varied from 6 cc for perioral treatment to 72 cc for a full-face approach, with treatment intervals ranging from one session per year to one every 3 months. On average, around 50% of the fat was reabsorbed within 6 months. Adipose stem cells were identified as a key factor in both tissue regeneration and fat resorption rates. This review supports the effectiveness of autologous fat grafting for facial scleroderma, emphasising the role of adipose stem cells. For optimal results, two procedures spaced 3-6 months apart, followed by annual maintenance, are recommended. Consistent fat volumes in different facial areas are essential to achieve longer-lasting outcomes and minimise resorption.

Cancer constitutes a significant public health concern, and addressing the challenge of cancer holds paramount importance and requires immediate attention. Epigenetic alterations, encompassing DNA methylation, have emerged as pivotal contributors to the development of diverse cancer types. These modifications exert their influence by modulating chromatin structure, gene expression patterns and other nuclear processes, thereby influencing cancer pathogenesis. Over the last two decades, an increasing body of evidence has established the involvement of DNA methyltransferase 1 (DNMT1) in various aspects of cancer development, including tumorigenesis, aggressiveness and treatment response. Furthermore, non-coding RNAs (ncRNAs), such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are increasingly recognised as significant modulators in diverse biological processes, encompassing metastasis, apoptosis, cell proliferation and differentiation. Several recent studies have elucidated the intricate relationship between epigenetic machinery, specifically DNMT1, and the expression of ncRNAs in the context of cancer. In this review, we provide a comprehensive overview of the interaction between DNMT1 and ncRNAs in cancer pathogenesis. Furthermore, we discuss the important role of the ncRNAs-DNMT1 axis in cancer stem cells and cancer therapy resistance as critical issues in cancer therapy. Finally, we demonstrate that herbal medicine and synthetic RNA molecules regulate DNMT1 activity and hold great promise in cancer treatment.