The progressive nature of neurodegenerative diseases (NDs), such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis, presents substantial problems because current treatments are still obscure. Stem cell-based treatments are emerging as a viable solution to address the significant gaps in treating these severe diseases. This study provides a comprehensive analysis of the latest advancements in stem cell research, focusing on the treatment of NDs. Various types of stem cells, such as adult, induced pluripotent, and embryonic stem cells, and their potential applications in immunomodulation, neurotrophic factor release, and neuronal development are also discussed. Recent clinical studies reveal outcomes, challenges, and solutions, with advancements in disease-specific neural cell production, gene editing, and improved stem cell transplantation transport strategies. The review discussed future perspectives on developing more effective stem cell-based interventions. Biomaterials are being used for cell distribution and personalized medicine techniques to improve treatment outcomes, while exploring stem cell treatments for NDs and identifying areas for further research.

Oral squamous cell carcinoma (OSCC) remains a major cause of morbidity and mortality worldwide with high recurrence rates and resistance to conventional therapies. Recent studies have highlighted the pivotal role of oral cancer stem cells (OCSCs) in driving treatment resistance and tumor recurrence. OCSCs possess unique properties, including self-renewal, differentiation potential, and resistance to chemotherapy and radiotherapy, which contribute to their ability to survive treatment and initiate tumor relapse. Several signaling pathways, such as Wnt/β-catenin, Hedgehog, Notch, and PI3K/Akt/mTOR, have been implicated in maintaining OCSC properties, promoting survival, and conferring resistance. Additionally, mechanisms such as drug efflux, enhanced DNA repair, epithelial-mesenchymal transition (EMT), and resistance to apoptosis further contribute to resilience. Targeting these pathways offers promising therapeutic strategies for eliminating OCSCs and improving treatment outcomes. Approaches such as immunotherapy, nanotechnology-based drug delivery, and targeting of the tumor microenvironment are emerging as potential solutions to overcome OCSC-mediated resistance. However, further research is needed to fully understand the molecular mechanisms governing OCSCs and develop effective therapies to prevent tumor recurrence. This review discusses the role of OCSCs in treatment resistance and recurrence and highlights the current and future directions for targeting these cells in OSCC.

The use of stem cell therapy is a rapidly evolving and progressing frontier of science that has been used to treat illnesses such as malignancies, immunodeficiencies, and metabolic syndromes. This review aims to give an overview of the use of stem cell therapy in the treatment of pain caused by diabetic neuropathy, osteoarthritis, and other spinal cord pathologies.

Pain is defined as a generalized or localized feeling of distress related to a physical or emotional stimulus and can be caused by a multitude of pathologies. The field of pain management has explored many strategies such as gene therapies, neuromodulation, platelet-rich plasma, and numerous pharmacotherapies. The approach to the delivery of these strategies has varied, with the method of stem cell therapy delivery being the focus of this present investigation. In addition, we combined several different studies to analyze the effects of stem cell therapies and improvement in pain scores quantified by the visual analog scale (VAS). The overall results showed a mean difference of -2.58, suggesting that the stem cell treatment group had a lower VAS score at 6 months compared to the control group. The use of different types of stem cells, such as pluripotent and mesenchymal stem cells, play a critical role in the care of cases suffering from pain. Effective delivery methods are evolving and can transform treatment options in the future, for which large cohort studies are warranted.

Stem cell-based therapies are emerging as significant approaches in tissue engineering and regenerative medicine, applicable to both fundamental scientific research and clinical practice. Despite remarkable results in clinical studies, challenges such as poor standardization of graft tissues, limited sources, and reduced functionality have hindered the effectiveness of these therapies. In this review, we summarize the engineering approaches involved in fabricating stem cell assisted patches and the substantial strategies for designing stem cell-laden engineered patches (SCP) to complement the existing stem cell-based therapies. We then outline the potential applications of SCP in advancing tissue regeneration and regenerative medicine. By combining living stem cells with engineered patches, SCP can enhance the functions of both components, particularly for tissue engineering applications. Finally, we addressed current challenges, such as ethical considerations, high costs, and regulatory hurdles and proposed future research directions to overcome these barriers.

Exosomes and exosome mimetics are used as alternatives to cell therapy. They have shown potential in treating skin disorders by fortifying the skin barrier, mediating angiogenesis, and regulating the immune response while minimizing side effects. Currently, numerous studies have applied exosome therapy to treat atopic dermatitis (AD) caused by a weakened skin barrier and chronic inflammation. Research on exosomes and exosome mimetics represents a promising avenue for tissue regeneration, potentially paving the way for new therapeutic options. However, the efficacy of the therapy remains poorly understood. Also, the potential of exosome mimetics as alternatives to exosomes in skin therapy remains underexplored.

Here, we reviewed the pathological features and current therapies of AD. Next, we reviewed the application of exosomes and exosome mimetics in regenerative medicine. Finally, we highlighted the therapeutic effects of exosomes based on their cell source and assessed whether exosome mimetics are viable alternatives.

Exosome therapy may treat AD due to its skin regenerative properties, and exosome mimetics may offer an equally effective yet more efficient alternative. Research on exosomes and exosome mimetics represents a promising avenue for tissue regeneration, potentially paving the way for new therapeutic options.

To function and survive cells need to be able to sense and respond to their local environment through mechanotransduction. Crucially, mechanical and biochemical perturbations initiate cell signalling cascades, which can induce responses such as growth, apoptosis, proliferation and differentiation. At the heart of this process are actomyosin stress fibres (SFs), which form part of the cell cytoskeleton, and focal adhesions (FAs), which bind this cytoskeleton to the extra-cellular matrix (ECM). The formation and maturation of these structures (connected by a positive feedback loop) is pivotal in non-motile cells, where SFs are generally of ventral type, interconnecting FAs and producing isometric tension. In this study we formulate a one-dimensional bio-chemo-mechanical continuum model to describe the coupled formation and maturation of ventral SFs and FAs. We use a set of reaction-diffusion-advection equations to describe three sets of biochemical events: the polymerisation of actin and subsequent bundling into activated SFs; the formation and maturation of cell-substrate adhesions; and the activation of signalling proteins in response to FA and SF formation. The evolution of these key proteins is coupled to a Kelvin-Voigt viscoelastic description of the cell cytoplasm and the ECM. We employ this model to understand how cells respond to external and intracellular cues in vitro and are able to reproduce experimentally observed phenomena including non-uniform cell striation and cells forming weaker SFs and FAs on softer substrates.

The incidence of diabetes mellitus (DM) is dramatically increasing worldwide, and it is expected to affect 700 million cases by 2045. Diabetes influences health care economics, human quality of life, morbidity, and mortality, which were primarily seen extensively in developing countries. Uncontrolled DM, which results in consistent hyperglycemia, may lead to severe life-threatening complications such as nephropathy, retinopathy, neuropathy, and cardiovascular complications.

In addition to traditional therapies with insulin and oral anti-diabetics, researchers have developed new approaches for treatment, including stem cell (SC) therapy, which exhibits promising outcomes. Besides its significant role in treating type one DM (T1DM) and type two DM (T2DM), it can also attenuate diabetic complications. Furthermore, the development of insulin- producing cells can be achieved by using the different types of SCs, such as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and multiple types of adult stem cells, such as pancreatic, hepatic, and mesenchymal stem cells (MSC). All these types have been extensively studied and proved their ability to develop insulin-producing cells, but every type has limitations.

This review aims to enlighten researchers about recent advances in stem cell research and their potential benefits in DM and diabetic complications.

Single-cell technology (SCT), which enables the examination of the fundamental units comprising biological organs, tissues, and cells, has emerged as a powerful tool, particularly in the field of biology, with a profound impact on stem cell research. This innovative technology opens new pathways for acquiring cell-specific data and gaining insights into the molecular pathways governing organ function and biology. SCT is not only frequently used to explore rare and diverse cell types, including stem cells, but it also unveils the intricacies of cellular diversity and dynamics. This perspective, crucial for advancing stem cell research, facilitates non-invasive analyses of molecular dynamics and cellular functions over time. Despite numerous investigations into potential stem cell therapies for genetic disorders, degenerative conditions, and severe injuries, the number of approved stem cell-based treatments remains limited. This limitation is attributed to the various heterogeneities present among stem cell sources, hindering their widespread clinical utilization. Furthermore, stem cell research is intimately connected with cutting-edge technologies, such as microfluidic organoids, CRISPR technology, and cell/tissue engineering. Each strategy developed to overcome the constraints of stem cell research has the potential to significantly impact advanced stem cell therapies. Drawing on the advantages and progress achieved through SCT-based approaches, this study aims to provide an overview of the advancements and concepts associated with the utilization of SCT in stem cell research and its related fields.

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder characterized by loss of the neurons, excessive accumulation of misfolded Aβ and Tau proteins, and degeneration of neural synapses, primarily occurring in the neocortex and the hippocampus regions of the brain. AD Progression is marked by cognitive deterioration, memory decline, disorientation, and loss of problem-solving skills, as well as language. Due to limited comprehension of the factors contributing to AD and its severity due to neuronal loss, even today, the medications approved by the U.S. Food and Drug Administration (FDA) are not precisely efficient and curative. Stem cells possess great potential in aiding AD due to their self-renewal, proliferation, and differentiation properties. Stem cell therapy can aid by replacing the lost neurons, enhancing neurogenesis, and providing an enriched environment to the pre-existing neural cells. Stem cell therapy has provided us with promising results in regard to the animal AD models, and even pre-clinical studies have shown rather positive results. Cell replacement therapies are potential curative means to treat AD, and there are a number of undergoing human clinical trials to make Stem Cell therapy accessible for AD patients. In this review, we aim to discuss the AD pathophysiology and varied stem cell types and their application.

The use of alternative treatment modalities for erectile dysfunction (ED) beyond phosphodiesterase inhibitors continues to grow within the practice of Urology. Utilizing U.S. Google trends as a novel epidemiological tool for geographically associating patient search intent, our study aims to capture trends relating to interest in stem cell therapy (SCT) as a potential treatment for ED.

An online search was conducted to identify centers in the United States offering stem cell therapy (SCT) for erectile dysfunction (ED), using specific keywords such as "ED treatment," "stem cells for ED," and "sexual health stem cell." The geographic distribution of these centers was mapped, and their publicly available information was evaluated based on strict inclusion criteria, including direct claims of SCT efficacy for ED and oversight by a licensed urologist. The public interest in SCT treatment was quantified using Google Trends data from July 2018 to July 2023, utilizing search terms related to SCT and comparing them to terms associated with alternative regenerative therapies like platelet-rich plasma and shockwave treatments, to extract the direction and magnitude of national interest over the preceding 5 years. The PubMed, Cochrane Library, and EMBASE databases were then searched from inception to May 2024 regarding evidence for the use of SCT to treat ED.

Despite insufficient evidence, public search interest demonstrates an upward trajectory of this treatment when compared to alternative regenerative therapies for ED. This increased interest in SCT as a potential treatment option for ED may be linked to the marketing efforts of commercial entities. Throughout the qualitative analysis of advertisement sources, only two websites (Stem Cells Transplant Institute, and Ambrose Cell Therapy) summarized the collective results of a directed clinical trial investigating the utility of SCT in ED patients.

Our study demonstrates the public prevalence of patients seeking SCT as a treatment modality for ED is increasing. In addition, varied sources nationwide promote SCT despite limited scientific evidence and consensus. This disparity calls for additional prospective research on the viability, efficacy, and long-term safety of SCT in the context of ED.

Wound management is a major global health problem. With the rising incidence of diabetic wounds, accidents, and other injuries, the demand for prompt wound treatment has become increasingly critical. Millions of people suffer from serious, large wounds resulting from major accidents, surgeries, and wars. These wounds require considerable time to heal and are susceptible to infection. Furthermore, chronic wounds, particularly in elderly and diabetic patients, often require frequent medical interventions to prevent complications. Consequently, wound management imposes a significant economic burden worldwide. The complications arising from wound infections can vary from localized issues to systemic effects. The most severe local complication of wound infection is the non-healing, which results from the disruption of the wound-healing process. This often leads to significant pain, discomfort, and psychological trauma for the patient. Systemic complications may include cellulitis, osteomyelitis, and septicemia. Mesenchymal stem cells are characterized by their high capacity for division, making them suitable candidates for the treatment of tissue damage. Additionally, they produce antimicrobial peptides and various cytokines, which enhance their antimicrobial activity. Evidence shows that phages are effective in treating wound-related infections, and phage therapy has proven to be highly effective for patients when administered correctly. The purpose of this article is to explore the use of bacteriophages and mesenchymal stem cells in wound healing and infection management.

Nanotechnology in stem cell medicine is an interdisciplinary field which has gained a lot of interest recently. This domain addresses key challenges associated with stem cell medicine such as cell isolation, targeted delivery, and tracking. Nanotechnology-based approaches, including magnetic cell sorting, fluorescent tagging, and drug or biomolecule conjugation for delivery, have enhanced precision in stem cell isolation and guided cell migration, increasing the therapeutic potential. Recent studies have focused on using nanomaterials and scaffolds to drive stem cell differentiation by activating specific molecular pathways, achieved through embedding biomolecules within the scaffold or through the scaffold's material composition and structure alone. These innovations hold promise in therapeutic applications across various diseases, including cancer stem cell targeting, neurodegenerative disorders, pre-eclampsia, cardiovascular conditions, and organoid development. This review examines recent advancements in the field, explores potential applications like biosensors and nanochips, and highlights the challenges and research gaps.

Breast cancer is a major health problem, accounting for one third of all cancers in women. There is no definitive treatment for breast cancer and its incidence is increasing worldwide every year. Furthermore, breast cancer stem cells cause resistance to radiation and chemotherapy. Telomerase is an enzyme that protects telomeres and is activated in 90% of cancer cells, and telomerase activation is a hallmark of cancer. In this review, we examine telomerase activation in breast cancer and breast cancer stem cells and the therapeutic effects of telomerase inhibition in these cells. In this review, we aim to highlight the importance and impact of telomerase inhibition in the treatment of breast cancer and the lack of studies specifically in breast cancer stem cells.

Spontaneous chronic corneal epithelial defects (SCCEDs) are characterized by nonadherent corneal epithelium leading to poor attachment to the corneal stroma. The objective of this study was to characterize corneal outcomes concurrently with the quantification of tumor necrosis factor-alpha (TNF-α) and vascular endothelial growth factor-A (VEGF-A) in tear fluid after the subconjunctival injection of canine adipose-derived mesenchymal stem cells (cAD-MSCs) in canine SCCEDs. Ten eyes with SCCEDs, which were nonresponsive to two rounds of diamond burr debridement, were included in this study. All eyes received a single subconjunctival injection of 1 × 106 cAD-MSCs. Ophthalmic examinations were performed before treatment and on day 7, 14, and 21 after treatment. Tear samples were collected for the quantification of TNF-α and VEGF-A concentrations by a canine multiplex immunoassay. Nine out of ten eyes revealed complete healing by day 21. The mean healing time was 10.89 ± 1.7 days. All eyes showed a decreased degree of ocular discomfort, in accordance with the degree of corneal characteristics. The concentrations of VEGF-A significantly reduced from pre-treatment (4334.91 ± 1275.92 pg/mL) to day 21 post-treatment (3064.61 ± 1028.66 pg/mL). No significant difference in TNF-α concentration was observed before/after treatment. In conclusion, the single use of a subconjunctival injection of cAD-MSCs could be used as an alternative treatment for canine SCCEDs.

Spinal cord injury (SCI) is damage to the spinal cord that permanently or temporarily disrupts its function, causing considerable autonomic, sensory, and motor disorders, and involves between 10 and 83 cases per million yearly. Traumatic SCI happens following primary acute mechanical damage, leading to injury to the spinal cord tissue and worsening clinical outcomes. The present therapeutic strategies for this complex disease fundamentally rely on surgical approaches and conservative remedies. However, these modalities are not effective enough for neurological recovery. Therefore, it is necessary to discover more efficient methods to treat patients with SCI. Today, considerable attention has been drawn to bioactive compounds-based remedies and stem cell therapy for curing various ailments and disorders, such as neurological diseases. Some researchers have recommended that harnessing curcumin, a polyphenol obtained from turmeric, in combination with stem cells, like mesenchymal stem cells, neural stem cells, and ependymal stem cells, can remarkably improve neurological recovery-related parameters more effective than the treatment with these two methods separately in experimental models. Hereby, this literature review delves into the functionality of curcumin combined with stem cells in treating SCI with a focus on cellular and molecular mechanisms.

Traditional treatment strategies for recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF) often result in limited success, placing significant emotional and financial burdens on couples. However, novel approaches such as diagnostic gene profiling, cell therapy, stem cell-derived exosome therapy, and pharmacogenomics offer promising, personalized treatments. Combining traditional treatments with precision and regenerative medicine may enhance the efficacy of these approaches and improve pregnancy outcomes. This review explores how integrating these strategies can potentially transform the lives of couples experiencing repeated pregnancy loss or implantation failure, providing hope for improved treatment success. Precision and regenerative medicine represent a new frontier for managing RPL and RIF, offering promising solutions.

Sjögren's syndrome (SS) is a chronic autoimmune disease caused by immune system disorders. The main clinical manifestations of SS are dry mouth and eyes caused by the destruction of exocrine glands, such as the salivary and lacrimal glands, and systemic manifestations, such as interstitial pneumonia, interstitial nephritis and vasculitis. The pathogenesis of this condition is complex. However, this has not been fully elucidated. Treatment mainly consists of glucocorticoids, disease-modifying antirheumatic drugs and biological agents, which can only control inflammation but not repair the tissue. Therefore, identifying methods to regulate immune disorders and repair damaged tissues is imperative. Cell therapy involves the transplantation of autologous or allogeneic normal or bioengineered cells into the body of a patient to replace damaged cells or achieve a stronger immunomodulatory capacity to cure diseases, mainly including stem cell therapy and immune cell therapy. Cell therapy can reduce inflammation, relieve symptoms and promote tissue repair and regeneration of exocrine glands such as the salivary glands. It has broad application prospects and may become a new treatment strategy for patients with SS. However, there are various challenges in cell preparation, culture, storage and transportation. This article reviews the research status and prospects of cell therapies for SS.

This comprehensive review explores the complex terrain of stem cell therapies as a potential therapeutic frontier in the healing of complicated burn wounds. Serious tissue damage, impaired healing processes, and possible long-term consequences make burn wounds a complex problem. An in-depth review is required since, despite medical progress, existing methods for treating severe burn wounds have significant limitations. Burn wounds are difficult to heal because they cause extensive tissue damage. The challenges of burn injury-induced tissue regeneration and functional recovery are also the subject of this review. Although there is a lot of promise in current stem cell treatments, there are also some limitations with scalability, finding the best way to transport the cells, and finding consistent results across different types of patients. To shed light on how to improve stem cell interventions to heal severe burn wounds, this review covers various stem cell applications in burn wounds and examines these obstacles. To overcome these obstacles, one solution is to enhance methods of stem cell distribution, modify therapies according to the severity of the burn, and conduct more studies on how stem cell therapy affects individual patients. Novel solutions may also be possible through the combination of cutting-edge technologies like nanotechnology and biotechnology. This review seeks to increase stem cell interventions by analyzing present challenges and suggesting strategic improvements. The goal is to provide a more effective and tailored way to repair serious burn wounds.

Regenerative medicine shows significant potential in treating kidney diseases through the application of various types of stem and progenitor cells, including mesenchymal stem cells (MSCs), renal stem/progenitor cells, embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs). Stem cells possess the unique ability to repair injured organs and improve impaired functions, making them a key element in the research of therapies for kidney tissue repair and organ regeneration. In kidney transplantation, reperfusion injury can cause tissue destruction, leading to an initially low glomerular filtration rate and long-term impact on function by creating irreversible interstitial fibrosis. MSCs have proven useful in repairing early tissue injury in animal models of kidney, lung, heart, and intestine transplantation. The use of stem cell therapies in solid organ transplantation raises the question of whether autologous or allogeneic cells should be preferred. Adipose-derived stem cells (ASCs), characterized by the lack of HLA Class II molecules and low expression of HLA Class I and co-stimulatory signals, are considered immune-privileged. However, the actual risk of graft rejection associated with allogeneic ASCs remains unclear. It has been demonstrated that donor-derived ASCs can promote the development of Treg cells in vitro, and some degree of tolerance induction has been observed in vivo. Nevertheless, a study comparing the efficacy of autologous and allogeneic ASCs in a rat model with a total MHC mismatch for kidney transplantation showed that donor-derived administration of ASCs did not improve the grafts' survival and was associated with increased mortality through an immunologically mediated mechanism. Given the lack of data, autologous ASCs appear to be a safer option in this research context. The aim of this review was to examine the differences between autologous and allogeneic ASCs in the context of their application in kidney transplantation therapies, considering potential immune reactions and therapeutic efficacy. Some have argued that ASCs harvested from end-stage renal disease (ESRD) patients may have lower regenerative potential due to the toxic effects of uremia, potentially limiting their use in transplantation settings. However, evidence suggests that the beneficial properties of ASCs are not affected by uremia or dialysis. Indeed, some investigators have demonstrated that ASCs harvested from chronic kidney disease (CKD) patients exhibit normal characteristics and function, maintaining consistent proliferative capacity and genetic stability over time, even after prolonged exposure to uremic serum Furthermore, no differences were observed in the response of ASCs to immune activation or their inhibitory effect on the proliferation of alloantigen-activated peripheral blood mononuclear cells between patients with normal or impaired renal function. This review presents the current achievements in stem cell research aimed at treating kidney diseases, highlighting significant progress and ongoing efforts in the development of stem cell-based therapies. Despite the encouraging results, further research is needed to overcome the current limitations and fully realize the potential of these innovative treatments. Advances in this field are crucial for developing effective therapies that can address the complex challenges associated with kidney damage and failure.

Osteoarthritis is a prevalent joint disease affecting both humans and animals. It is characterized by articular cartilage degeneration and joint surface eburnation. Currently, no effective pharmacological treatment is available to restore the original function and structure of defective cartilage.

This study explores the potential of stem cell-based therapy in treating joint diseases involving cartilage degeneration, offering a promising avenue for future research and treatment. The primary aim was to compare the characteristics and, more importantly, the chondrogenic differentiation potential of human and rat adipose-derived mesenchymal stem cells (AD-MSCs).

Rat adipose tissue was collected from Sprague Dawley rats, while human adipose tissue was obtained in the form of lipoaspirate. The mesenchymal stem cells (MSCs) were then harvested using collagenase enzyme and subcultured. We meticulously evaluated and compared the cell morphology, percentage of cell viability, population doubling time, metabolic proliferation, and chondrogenic differentiation potential of MSCs harvested from both sources. Chondrogenic differentiation was induced at passage 3 using the 3D pellet culture method and assessed through histological and molecular analysis.

The findings revealed that human and rat AD-MSCs were phenotypically identical, and an insignificant difference was found in cell morphology, percentage of cell viability, metabolic proliferation, and population doubling time. However, the chondrogenic differentiation potential of human AD-MSCs was evaluated as significantly higher than that of rat AD-MSCs.

The current study suggests that research regarding chondrogenic differentiation of rat AD-MSCs can be effectively translated to humans. This discovery is a significant contribution to the field of regenerative medicine and has the potential to advance our understanding of stem cell-based therapy for joint diseases.

Advances in stem cell technology offer new possibilities for patients with untreated diseases and disorders. Stem cell-based therapy, which includes multipotent mesenchymal stem cells (MSCs), has recently become important in regenerative therapies. MSCs are multipotent progenitor cells that possess the ability to undergo in vitro self-renewal and differentiate into various mesenchymal lineages. MSCs have demonstrated promise in several areas, such as tissue regeneration, immunological modulation, anti-inflammatory qualities, and wound healing. Additionally, the development of specific guidelines and quality control methods that ultimately result in the therapeutic application of MSCs has been made easier by recent advancements in the study of MSC biology. This review discusses the latest clinical uses of MSCs obtained from the umbilical cord (UC), bone marrow (BM), or adipose tissue (AT) in treating various human diseases such as pulmonary dysfunctions, neurological disorders, endocrine/metabolic diseases, skin burns, cardiovascular conditions, and reproductive disorders. Additionally, this review offers comprehensive information regarding the clinical application of targeted therapies utilizing MSCs. It also presents and examines the concept of MSC tissue origin and its potential impact on the function of MSCs in downstream applications. The ultimate aim of this research is to facilitate translational research into clinical applications in regenerative therapies.

Neural diseases are challenging to treat and are regarded as one of the major causes of disability and morbidity in the world. Stem cells can provide a solution, by offering a mechanism to replace damaged circuitry. However, obtaining sufficient cell sources for neural regeneration remains a significant challenge. In recent years, waste-derived stem(-like) cells (WDS-lCs) extracted from both prenatal and adult clinical waste tissues/products, have gained increasing attention for application in neural tissue repair and remodeling. This often-overlooked pool of cells possesses favorable characteristics; including self-renewal, neural differentiation, secretion of neurogenic factors, cost-effectiveness, and low ethical concerns. Here, we offer a perspective regarding the biological properties, extraction protocols, and preclinical and clinical treatments where prenatal and adult WDS-lCs have been utilized for cell replacement therapy in neural applications, and the challenges involved in optimizing these approaches toward patient led therapies.

Finding novel treatments for cardiovascular diseases (CVDs) is a hot topic in medicine; cell-based therapies have reported promising news for controlling dangerous complications of heart disease such as myocardial infarction (MI) and heart failure (HF). Various progenitor/stem cells were tested in various in-vivo, in-vitro, and clinical studies for regeneration or repairing the injured tissue in the myocardial to accelerate the healing. Fetal, adult, embryonic, and induced pluripotent stem cells (iPSC) have revealed the proper potency for cardiac tissue repair. As an essential communicator among cells, exosomes with specific contacts (proteins, lncRNAs, and miRNAs) greatly promote cardiac rehabilitation. Interestingly, stem cell-derived exosomes have more efficiency than stem cell transplantation. Therefore, stem cells induced pluripotent stem cells (iPSCs), embryonic stem cells (ESCs), cardiac stem cells (CDC), and skeletal myoblasts) and their-derived exosomes will probably be considered an alternative therapy for CVDs remedy. In addition, stem cell-derived exosomes have been used in the diagnosis/prognosis of heart diseases. In this review, we explained the advances of stem cells/exosome-based treatment, their beneficial effects, and underlying mechanisms, which will present new insights in the clinical field in the future.

Nowadays, biological therapies are booming and more of these formulations are coming to the market. Platelet-rich plasma, or PRP, is one of the most widely used biological therapies due to its ease of obtention and autologous character. Most of the techniques to obtain PRP are focusing on new processes and methods of optimization. However, not enough consideration is being given to modify the molecular components of PRP to generate more effective formulations with the aim of improving PRP treatments. Therefore, this review covers different novel PRP-obtaining methods that attempt to modify the molecular composition of the plasma.

In tissue engineering, the interaction among three primary elements, namely cells, material scaffolds, and stimuli, plays a pivotal role in determining the fate of cells and the formation of new tissue. Understanding the characteristics of these components and their interplay through various methodologies can significantly enhance the efficiency of the designed tissue engineering system. In silico methods, such as molecular dynamics (MD) simulation, use mathematical calculations to investigate molecular properties and can overcome the limitations of laboratory methods in delivering adequate molecular-level information.

The studies that used molecular dynamics simulation, either alone or in combination with other techniques, have been reviewed in this paper.

The review explores the use of molecular dynamics simulations in studying substrate formation mechanism and its optimization. It highlights MD simulations' role in predicting biomolecule binding strength, understanding substrate properties' impact on biological activity, and factors influencing cell attachment and proliferation. Despite limited studies, MD simulations are considered a reliable tool for identifying ideal substrates for cell proliferation. The review also touches on MD simulations' contribution to cell differentiation studies, emphasizing their role in designing engineered extracellular matrix for desired cell fates.

Molecular dynamics simulation as a non-laboratory tool has many capabilities in providing basic and practical information about the behavior of the molecular components of the cell as well as the interaction of the cell and its components with the surrounding environment. Using this information along with other information obtained from laboratory tools can ultimately lead to the advancement of tissue engineering through the development of more appropriate and efficient methods.

The aim of this study was to identify related scientific outputs and emerging topics of stem cells in neonatal hypoxic-ischemic encephalopathy (NHIE) and cerebral palsy (CP) through bibliometrics and literature review. All relevant publications on stem cell therapy for NHIE and CP were screened from websites and analyzed research trends. VOSviewer and CiteSpace were applied to visualize and quantitatively analyze the published literature to provide objective presentation and prediction. In addition, the clinical trials, published articles, and projects of the National Natural Science Foundation of China associated with stem cell therapy for NHIE and CP were summarized. A total of 294 publications were associated with stem cell therapy for NHIE and CP. Most publications and citations came from the USA and China. Monash University and University Medical Center Utrecht produced the most publications. Pediatric research published the most studies on stem cell therapy for NHIE and CP. Heijnen C and Kavelaars A published the most articles. Cluster analyses show that current research trend is more inclined toward the repair mechanism and clinical translation of stem cell therapy for NHIE and CP. By summarizing various studies of stem cells in NHIE and CP, it is indicated that this research direction is a hot topic at present. Furthermore, organoid transplantation, as an emerging and new therapeutic approach, brings new hope for the treatment of NHIE and CP. This study comprehensively summarized and analyzed the research trend of global stem cell therapy for NHIE and CP. It has shown a marked increase in stem cell therapy for NHIE and CP research. In the future, more efforts will be made on exploring stem cell or organoid therapy for NHIE and CP and more valuable related mechanisms of action to achieve clinical translation as soon as possible.

Fibrosis is a pathological process, that could result in permanent scarring and impairment of the physiological function of the affected organ; this condition which is categorized under the term organ failure could affect various organs in different situations. The involvement of the major organs, such as the lungs, liver, kidney, heart, and skin, is associated with a high rate of morbidity and mortality across the world. Fibrotic disorders encompass a broad range of complications and could be traced to various illnesses and impairments; these could range from simple skin scars with beauty issues to severe rheumatologic or inflammatory disorders such as systemic sclerosis as well as idiopathic pulmonary fibrosis. Besides, the overactivation of immune responses during any inflammatory condition causing tissue damage could contribute to the pathogenic fibrotic events accompanying the healing response; for instance, the inflammation resulting from tissue engraftment could cause the formation of fibrotic scars in the grafted tissue, even in cases where the immune system deals with hard to clear infections, fibrotic scars could follow and cause severe adverse effects. A good example of such a complication is post-Covid19 lung fibrosis which could impair the life of the affected individuals with extensive lung involvement. However, effective therapies that halt or slow down the progression of fibrosis are missing in the current clinical settings. Considering the immunomodulatory and regenerative potential of distinct stem cell types, their application as an anti-fibrotic agent, capable of attenuating tissue fibrosis has been investigated by many researchers. Although the majority of the studies addressing the anti-fibrotic effects of stem cells indicated their potent capabilities, the underlying mechanisms, and pathways by which these cells could impact fibrotic processes remain poorly understood. Here, we first, review the properties of various stem cell types utilized so far as anti-fibrotic treatments and discuss the challenges and limitations associated with their applications in clinical settings; then, we will summarize the general and organ-specific mechanisms and pathways contributing to tissue fibrosis; finally, we will describe the mechanisms and pathways considered to be employed by distinct stem cell types for exerting anti-fibrotic events.

Current chemical treatments for cerebrovascular disease and neurological disorders have limited efficacy in tissue repair and functional restoration. Induced pluripotent stem cells (iPSCs) present a promising avenue in regenerative medicine for addressing neurological conditions. iPSCs, which are capable of reprogramming adult cells to regain pluripotency, offer the potential for patient-specific, personalized therapies. The modulation of molecular mechanisms through specific growth factor inhibition and signaling pathways can direct iPSCs' differentiation into neural stem cells (NSCs). These include employing bone morphogenetic protein-4 (BMP-4), transforming growth factor-beta (TGFβ), and Sma-and Mad-related protein (SMAD) signaling. iPSC-derived NSCs can subsequently differentiate into various neuron types, each performing distinct functions. Cell transplantation underscores the potential of iPSC-derived NSCs to treat neurodegenerative diseases such as Parkinson's disease and points to future research directions for optimizing differentiation protocols and enhancing clinical applications.

With the increase in the aging population, the occurrence of neurological disorders is rising. Recently, stem cell therapy has garnered attention due to its convenient sourcing, minimal invasiveness, and capacity for directed differentiation. However, there are some disadvantages, such as poor quality control, safety assessments, and ethical and logistical issues. Consequently, scientists have started to shift their attention from stem cells to extracellular vesicles due to their similar structures and properties. Beyond these parallels, extracellular vesicles can enhance biocompatibility, facilitate easy traversal of barriers, and minimize side effects. Furthermore, stem cell-derived extracellular vesicles can be engineered to load drugs and modify surfaces to enhance treatment outcomes. In this review, we summarize the functions of native stem cell-derived extracellular vesicles, subsequently review the strategies for the engineering of stem cell-derived extracellular vesicles and their applications in Alzheimer's disease, Parkinson's disease, and stroke, and discuss the challenges and solutions associated with the clinical translation of stem cell-derived extracellular vesicles.

Hyperbaric Oxygen Therapy (HBOT) utilizes 100% oxygen at high atmospheric pressure for clinical applications. HBOT has proven to be an effective supplementary treatment for a variety of clinical and pathological disorders. HBOT's therapeutic results are based on the physiological effects of increased tissue oxygenation, or improved oxygen bioavailability. HBOT's current indications in illnesses like as wound healing, thermal or radiation burns, and tissue necrosis point to its function in facilitating the regeneration process. Various research has revealed that HBOT plays a function in vascularization, angiogenesis, and collagen production augmentation. Individual regeneration capacity is influenced by both environmental and genetic factors. Furthermore, the regenerating ability of different types of tissues varies, and this ability declines with age. HBOT affects physiological processes at the genetic level by altering gene expression, delaying cell senescence, and assisting in telomere length enhancement. The positive results in a variety of indications, ranging from tissue regeneration to better cognitive function, indicate that it has enormous potential in regenerative and anti-aging therapy.

Over the recent decades, stem cell-based therapies have been considered as a beneficial approach for the treatment of various diseases. In these types of therapies, the stem cells and their products are used as treating agents. Despite the helpful efficacy of stem cell-based therapies, there may be challenges. Oxidative stress (OS) is one of these challenges that can affect the therapeutic properties of stem cells. Therefore, it seems that employing strategies for the reduction of OS in combination with stem cell therapy can lead to better results of these therapies. Based on the available evidence, antioxidant therapy and photobiomodulation (PBM) are strategies that can regulate the OS in the cells. Antioxidant therapy is a method in which various antioxidants are used in the therapeutic processes. PBM is also the clinical application of light that gained importance in medicine. Antioxidants and PBM can regulate OS by the effect on mitochondria as an important source of OS in the cells. Considering the importance of OS in pathologic pathways and its effect on the treatment outcomes of stem cells, in the present review first the stem cell therapy and effects of OS on this type of therapy are summarized. Then, antioxidant therapy and PBM as approaches for reducing OS with a focus on mitochondrial function are discussed. Also, a novel combination treatment with the hope of achieving better and more stable outcomes in the treatment process of diseases is proposed.

This study investigated how adipose tissue-derived mesenchymal stem cells (AT-MSCs) respond to chondrogenic induction using droplet-based single-cell RNA sequencing (scRNA-seq). We analyzed 37,219 high-quality transcripts from control cells and cells induced for 1 week (1W) and 2 weeks (2W). Four distinct cell clusters (0-3), undetectable by bulk analysis, exhibited varying proportions. Cluster 1 dominated in control and 1W cells, whereas clusters (3, 2, and 0) exclusively dominated in control, 1W, and 2W cells, respectively. Furthermore, heterogeneous chondrogenic markers expression within clusters emerged. Gene ontology (GO) enrichment analysis of differentially expressed genes unveiled cluster-specific variations in key biological processes (BP): (1) Cluster 1 exhibited up-regulation of GO-BP terms related to ribosome biogenesis and translational control, crucial for maintaining stem cell properties and homeostasis; (2) Additionally, cluster 1 showed up-regulation of GO-BP terms associated with mitochondrial oxidative metabolism; (3) Cluster 3 displayed up-regulation of GO-BP terms related to cell proliferation; (4) Clusters 0 and 2 demonstrated similar up-regulation of GO-BP terms linked to collagen fibril organization and supramolecular fiber organization. However, only cluster 0 showed a significant decrease in GO-BP terms related to ribosome production, implying a potential correlation between ribosome regulation and the differentiation stages of AT-MSCs. Overall, our findings highlight heterogeneous cell clusters with varying balances between proliferation and differentiation before, and after, chondrogenic stimulation. This provides enhanced insights into the single-cell dynamics of AT-MSCs during chondrogenic differentiation. [BMB Reports 2024; 57(5): 232-237].

This manuscript summarizes novel clinical and interventional approaches in the management of chronic, nociceptive, and neuropathic pain.

Pain can be defined as a feeling of physical or emotional distress caused by an external stimulus. Pain can be grouped into distinct types according to characteristics including neuropathic pain, which is a pain caused by disease or lesion in the sensory nervous system; nociceptive pain, which is pain that can be sharp, aching, or throbbing and is caused by injury to bodily tissues; and chronic pain, which is long lasting or persisting beyond 6 months. With improved understanding of different signaling systems for pain in recent years, there has been an upscale of methods of analgesia to counteract these pathological processes. Novel treatment methods such as use of cannabinoids, stem cells, gene therapy, nanoparticles, monoclonal antibodies, and platelet-rich plasma have played a significant role in improved strategies for therapeutic interventions. Although many management options appear to be promising, extensive additional clinical research is warranted to determine best practice strategies in the future for clinicians.

Neuroinflammation refers to a highly complicated reaction of the central nervous system (CNS) to certain stimuli such as trauma, infection, and neurodegenerative diseases. This is a cellular immune response whereby glial cells are activated, inflammatory mediators are liberated and reactive oxygen and nitrogen species are synthesized. Neuroinflammation is a key process that helps protect the brain from pathogens, but inappropriate, or protracted inflammation yields pathological states such as Parkinson's disease, Alzheimer's, Multiple Sclerosis, and other neurodegenerative disorders that showcase various pathways of neurodegeneration distributed in various parts of the CNS. This review reveals the major neuroinflammatory signaling pathways associated with neurodegeneration. Additionally, it explores promising therapeutic avenues, such as stem cell therapy, genetic intervention, and nanoparticles, aiming to regulate neuroinflammation and potentially impede or decelerate the advancement of these conditions. A comprehensive understanding of the intricate connection between neuroinflammation and these diseases is pivotal for the development of future treatment strategies that can alleviate the burden imposed by these devastating disorders.

Although stem cell research and therapeutic applications hold great promise for medical advancements, and have rapidly progressed globally, there remains a lack of genuine public awareness of the status of this subject in Saudi Arabia. Successful integration of stem cell therapy into healthcare relies on public awareness, understanding, and trust. Therefore, we aimed in this cross-sectional study to assess the public's knowledge, awareness, trust, support, participation, and confidence in stem cell treatments and centers involved in it.

A voluntary questionnaire of 20 questions was distributed randomly via social media outlets.

Three thousand five hundred eighty four individuals participated in the survey, with approximately half of them falling within the age range of 35-50 years (46.71%). Majority of the participants, 90.71%, would like to know more about stem cell therapy and more than half of the participants (56.94%) were unfamiliar with the idea, and a comparable proportion (50.41%) expressed concerns about the safety of stem cell therapy. A lower level of awareness, indicated by a score of 5, was evenly distributed across all age groups and genders. However, regardless of gender, older participants-especially those 50 years of age or older-tended to report higher levels of confidence, trust, and support than participants in other age groups. Moreover, trust, support, participation, and confidence score for those attained high school or less was statistically significantly lower than those attained master's or PhD degree. Of the participants, 33.57% had either received stem cell therapy themselves or known someone who had; about 24.07% of them reported that it was a cosmetic type of treatment.

The study emphasizes the persistent need for awareness and educational initiatives to minimize the lack of public awareness and understanding of approved stem cell treatments in Saudi Arabia. It advocates for increased education, transparency, and communication to bridge knowledge gaps and enhance public trust to ensure the understanding of successful treatment.

Mesenchymal stem cell (MSC) therapy has been actively applied in veterinary regenerative medicine to treat various canine and feline diseases. With increasing emphasis on safe cell-based therapies, evaluations of their tumorigenic potential are in great demand. However, a direct confirmation of whether tumors originate from stem cells or host cells is not easily achievable. Additionally, previous studies evaluating injections of high doses of MSCs into nude mice did not demonstrate tumor formation. Recent research focused on optimizing MSC-based therapies for veterinary patients, such as MSC-derived extracellular vesicles in treating different diseases. This progress also signifies a broader shift towards personalized veterinary medicine, where treatments can be tailored to individual pets based on their unique genetic profiles. These findings related to different treatments using MSCs emphasize their future potential for veterinary clinical applications. In summary, because of lower tumor-associated risk of MSCs as compared to embryonic and induced pluripotent stem cells, MSCs are considered a suitable source for treating various canine and feline diseases.

Current pharmacological and surgical therapies for the central nervous system (CNS) show a limited capacity to reduce the damage progression; that together with the intrinsic limited capability of the CNS to regenerate greatly reduces the hopes of recovery. Among all the therapies proposed, the tissue engineering strategies supplemented with therapeutic stem cells remain the most promising. Neural tissue engineering strategies are based on the development of devices presenting optimal physical, chemical, and mechanical properties which, once inserted in the injured site, can support therapeutic cells, limiting the effect of a hostile environment and supporting regenerative processes. Thus, this review focuses on the employment of hydrogel and nanofibrous scaffolds supplemented with stem cells as promising therapeutic tools for the central and peripheral nervous systems in preclinical and clinical applications.

Mitochondria serve as essential organelles that play a key role in regulating stem cell fate. Mitochondrial dysfunction and stem cell exhaustion are two of the nine distinct hallmarks of aging. Emerging research suggests that epigenetic modification of mitochondria-encoded genes and the regulation of epigenetics by mitochondrial metabolites have an impact on stem cell aging or differentiation. Here, we review how key mitochondrial metabolites and behaviors regulate stem cell fate through an epigenetic approach. Gaining insight into how mitochondria regulate stem cell fate will help us manufacture and preserve clinical-grade stem cells under strict quality control standards, contributing to the development of aging-associated organ dysfunction and disease.

Neurodegenerative disorders pose significant challenges in the realm of healthcare, as these conditions manifest in complex, multifaceted ways, often attributed to genetic anomalies. With the emergence of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) technology, a new frontier has been unveiled in the quest for targeted, precise genetic manipulation. This abstract explores the recent advancements and potential applications of CRISPR-based therapies in addressing genetic components contributing to various neurodegenerative disorders. The review delves into the foundational principles of CRISPR technology, highlighting its unparalleled ability to edit genetic sequences with unprecedented precision. In addition, it talks about the latest progress in using CRISPR to target specific genetic mutations linked to neurodegenerative diseases like Huntington's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and Parkinson's disease. It talks about the most important studies and trials that show how well and safely CRISPR-based therapies work. This shows how this technology can change genetic variants that cause diseases. Notably, the discussion emphasizes the challenges and ethical considerations associated with the implementation of CRISPR in clinical settings, including off-target effects, delivery methods, and long-term implications. Furthermore, the article explores the prospects and potential hurdles in the widespread application of CRISPR technology for treating neurodegenerative disorders. It touches upon the need for continued research, improved delivery mechanisms, and ethical frameworks to ensure responsible and equitable access to these groundbreaking therapies.

Schizophrenia is a severe psychological disorder in which reality is interpreted abnormally by the patient. The symptoms of the disease include delusions and hallucinations, associated with extremely disordered behavior and thinking, which may affect the daily lives of the patients. Advancements in technology have led to understanding the dynamics of the disease and the identification of the underlying causes. Multiple investigations prove that it is regulated genetically, and epigenetically, and is affected by environmental factors. The molecular and neural pathways linked to the regulation of schizophrenia have been extensively studied. Over 180 Schizophrenic risk loci have now been recognized due to several genome-wide association studies (GWAS). It has been observed that multiple transcription factors (TF) binding-disrupting single nucleotide polymorphisms (SNPs) have been related to gene expression responsible for the disease in cerebral complexes. Copy number variation, SNP defects, and epigenetic changes in chromosomes may cause overexpression or underexpression of certain genes responsible for the disease. Nowadays, gene therapy is being implemented for its treatment as several of these genetic defects have been identified. Scientists are trying to use viral vectors, miRNA, siRNA, and CRISPR technology. In addition, nanotechnology is also being applied to target such genes. The primary aim of such targeting was to either delete or silence such hyperactive genes or induce certain genes that inhibit the expression of these genes. There are challenges in delivering the gene/DNA to the site of action in the brain, and scientists are working to resolve the same. The present article describes the basics regarding the disease, its causes and factors responsible, and the gene therapy solutions available to treat this disease.

Multiple sclerosis (MS) is a chronic inflammatory, autoimmune, and neurodegenerative disease of the central nervous system (CNS), characterized by demyelination and axonal loss. It is induced by attack of autoreactive lymphocytes on the myelin sheath and endogenous remyelination failure, eventually leading to accumulation of neurological disability. Disease-modifying agents can successfully address inflammatory relapses, but have low efficacy in progressive forms of MS, and cannot stop the progressive neurodegenerative process. Thus, the stem cell replacement therapy approach, which aims to overcome CNS cell loss and remyelination failure, is considered a promising alternative treatment. Although the mechanisms behind the beneficial effects of stem cell transplantation are not yet fully understood, neurotrophic support, immunomodulation, and cell replacement appear to play an important role, leading to a multifaceted fight against the pathology of the disease. The present systematic review is focusing on the efficacy of stem cells to migrate at the lesion sites of the CNS and develop functional oligodendrocytes remyelinating axons. While most studies confirm the improvement of neurological deficits after the administration of different stem cell types, many critical issues need to be clarified before they can be efficiently introduced into clinical practice.

Neural cells are the most important components of the nervous system and have the duty of electrical signal transmission. Damage to these cells can lead to neurological disorders. Scientists have discovered different methods, such as stem cell therapy, to heal or regenerate damaged neural cells. Dental stem cells are among the different cells used in this method. This review attempts to evaluate the effect of biomaterials mentioned in the cited papers on differentiation of human dental pulp stem cells (hDPSCs) into neural cells for use in stem cell therapy of neurological disorders. We searched international databases for articles about the effect of biomaterials on neuronal differentiation of hDPSCs. The relevant articles were screened by title, abstract, and full text, followed by selection and data extraction. Totally, we identified 731 articles and chose 18 for inclusion in the study. A total of four studies employed polymeric scaffolds, four assessed chitosan scaffolds (CS), two utilised hydrogel scaffolds, one investigation utilised decellularised extracellular matrix (ECM), and six studies applied the floating sphere technique. hDPSCs could heal nerve damage in regenerative medicine. In the third iteration of nerve conduits, scaffolds, stem cells, regulated growth factor release, and ECM proteins restore major nerve damage. hDPSCs must differentiate into neural cells or neuron-like cells to regenerate nerves. Plastic-adherent cultures, floating dentosphere cultures, CS, polymeric scaffolds, hydrogels, and ECM mimics have been used to differentiate hDPSCs. According to our findings, the floating dentosphere technique and 3D-PLAS are currently the two best techniques since they result in neuroprogenitor cells, which are the starting point of differentiation and they can turn into any desired neural cell.