In recent years, the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative medicine. Considering the non-regenerative nature of the mature central nervous system, the concept that "blank" cells could be reprogrammed and functionally integrated into host neural networks remained intriguing. Previous work has also demonstrated the ability of such cells to stimulate intrinsic growth programs in post-mitotic cells, such as neurons. While embryonic stem cells demonstrated great potential in treating central nervous system pathologies, ethical and technical concerns remained. These barriers, along with the clear necessity for this type of treatment, ultimately prompted the advent of induced pluripotent stem cells. The advantage of pluripotent cells in central nervous system regeneration is multifaceted, permitting differentiation into neural stem cells, neural progenitor cells, glia, and various neuronal subpopulations. The precise spatiotemporal application of extrinsic growth factors in vitro, in addition to microenvironmental signaling in vivo, influences the efficiency of this directed differentiation. While the pluri- or multipotency of these cells is appealing, it also poses the risk of unregulated differentiation and teratoma formation. Cells of the neuroectodermal lineage, such as neuronal subpopulations and glia, have been explored with varying degrees of success. Although the risk of cancer or teratoma formation is greatly reduced, each subpopulation varies in effectiveness and is influenced by a myriad of factors, such as the timing of the transplant, pathology type, and the ratio of accompanying progenitor cells. Furthermore, successful transplantation requires innovative approaches to develop delivery vectors that can mitigate cell death and support integration. Lastly, host immune responses to allogeneic grafts must be thoroughly characterized and further developed to reduce the need for immunosuppression. Translation to a clinical setting will involve careful consideration when assessing both physiologic and functional outcomes. This review will highlight both successes and challenges faced when using human induced pluripotent stem cell-derived cell transplantation therapies to promote endogenous regeneration.

Stem cell-based therapies offer promising treatment for spinal cord injury (SCI) by reducing inflammation, restoring plasticity, and supporting neuroprotection and nerve regeneration. Brain-derived neurotrophic factor (BDNF) is crucial in SCI pathophysiology. This study reviews the impact of stem cells on BDNF expression in preclinical SCI models. A thorough search was performed in PubMed, Scopus, and Web of Science until June 2023, identifying studies on the effects of stem cells on BDNF in SCI. Two researchers reviewed and extracted data from relevant studies. This review is registered in the Prospective Register of Systematic Reviews (PROSPERO) with the registration number [CRD42023441466]. Out of 923 records, 51 studies met the inclusion criteria, involving rats (46 studies) and mice (5 studies). The contusion or compression model was used in 40 studies, and the transection model in 11. The most common stem cell types were bone marrow mesenchymal stem cells (BM-MSCs), neural stem cells (NSCs), and adipose-derived stem cells (ADSCs). BM-MSCs increased BDNF expression in 16 studies, NSCs in 9 studies, and ADSCs in only one study. This review highlights that BM-MSCs and NSCs are effective in enhancing BDNF expression in preclinical SCI models, while other stem cell types may not significantly affect BDNF levels. These findings suggest variability in the effectiveness of different stem cell therapies in modulating BDNF production for SCI treatment.

The acquisition of suitable stem cell sources is a significant issue in regenerative medicine. There has been considerable interest in utilizing mesenchymal stem cells (MSCs) derived from endometrial and menstrual blood as a promising resource of MSCs, owing to their unique biochemical properties and prospective use in clinical therapies. This population of stem cells has distinct characteristics in terms of immunophenotype, proliferation rate, and differentiation capacity. A notable characteristic of these stem cells is their capacity to develop into mesodermal lineages, highlighting their regenerative capability. Moreover, the presence of certain surface markers facilitates the augmentation of clonogenic endometrial MSCs. Their distinctive characteristics, along with their swift multiplication ability, underscore their significant promise for therapeutic applicability in regenerative medicine and cell-based treatments. Current investigations are examining possible usage of diverse stem cell resources in the treatment of inflammatory diseases and perhaps intractable illnesses like Parkinson's disease, utilizing their immunomodulatory properties. This review aims to analyze stem cell-related research that has utilized endometrial and menstrual blood-derived MSCs (enMSCs and MenSCs) with a special focus on their clinical application. We will explore the existing evidence about the therapeutic potential for these stem cells across many medical diseases and address the obstacles and prospective trajectories in this domain. Additionally, we will study the unique properties of enMSCs and MenSCs that make them promising candidates for regenerative medicine.

We explore the interaction between corneal immunity and mesenchymal stem/stromal cells (MSCs) and their potential in treating corneal and ocular surface disorders. We outline the cornea's immune privilege mechanisms and the immunomodulatory substances involved. In this realm, MSCs are characterized by their immunomodulatory properties and regenerative potential, making them promising for therapeutic application. Therefore, we focus on the role of MSCs in immune-mediated corneal diseases such as dry eye disease, corneal transplantation rejection, limbal stem cell deficiency, and ocular graft-versus-host disease. Preclinical and clinical studies demonstrate MSCs' efficacy in promoting corneal healing and reducing inflammation in these conditions. Overall, we emphasize the potential of MSCs as innovative therapies in ophthalmology, offering promising solutions for managing various ocular surface pathologies.

With the significant challenges in using human embryonic stem cells (ESCs) for research and clinical applications, there is a growing impetus to seek alternative pluripotent cell sources. Embryonic stem-like (ES-like) cells emerge as a promising avenue in this pursuit. Our research demonstrates the potential for deriving ES-like cells from spermatogonial stem cells (SSCs) in a time-dependent manner under defined culture conditions. To better understand this process, we investigated the gene expression dynamics and underlying pathways associated with ES-like cell generation from SSCs. A deeper understanding of the signaling pathways underlying this biological process can lead us to refine protocols for ES-like cell generation, which could catalyze the development of more efficient and expedited methodologies inspired by the derivation pathway for future research in regenerative medicine. To identify differentially expressed genes (DEGs), we analyzed publicly available microarray data from murine cells obtained from the Gene Expression Omnibus (GEO). This analysis enabled the prediction of protein-protein interactions (PPIs), which were subsequently used for pathway enrichment analysis to identify biologically relevant pathways. Complementing these computational findings, we conducted in vitro experiments, including Fluidigm qPCR and immunostaining. These experiments serve as validation for our microarray data and the DEGs identified, providing reassurance about the reliability of our research. Among the identified enriched pathways in our investigation are the Toll-like receptor (TLR), GDNF/RET, interleukins (ILs), FGF/FGFR, and SMAD signaling pathway, along with the activation of NIMA kinases. Additionally, miR-410-3p, miRNA let-7e, Miat, and Xist are among some of the predicted non-coding RNAs.

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.

Myocardial infarction, commonly known as a heart attack, or ischemic heart disease (IHD), remains one of the most fatal health conditions worldwide due to the limited regenerative capacity of the heart muscle after infarction. Conventional medical treatments primarily focus on symptom control and tissue preservation but fail to address the loss of cardiomyocytes, the cells responsible for heart contraction. This systematic review explores the hypothesis that stem cell therapies can enhance cardiac regeneration by replacing or repairing damaged myocardium, with a focus on mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), and embryonic stem cells (ESCs). The review was restricted to literature published between 2015 and 2024, sourced from PubMed, Web of Science, and Google Scholar. This timeframe reflects advances in stem cell research and regenerative therapies. Findings from trials such as Bone Marrow-Derived Mononuclear Cell Therapy in Acute Myocardial Infarction (BAMI) and Cardiopoietic Stem Cell Therapy in Heart Failure (C-CURE) suggest that stem cell therapies may improve left ventricular ejection fraction (LVEF) and reduce infarct size. However, the heterogeneity of trials, small sample sizes, and short follow-up durations limit the generalizability of these results. Long-term benefits, including improved survival rates and reduced hospital readmissions, remain inconclusive. Ethical concerns, particularly the use of ESCs, pose additional challenges, including controversies over embryonic sources and varying regulatory landscapes. Key areas for advancement include optimizing stem cell survival and differentiation, with genetic engineering to enhance tissue repair capabilities considered the most critical for improving clinical outcomes. The integration of regenerative treatments such as extracellular vesicle therapy, derived from stem cells to modulate repair, also shows promise. Imaging techniques, such as MRI and PET, provide real-time monitoring of stem cell effects, offering insights into therapeutic efficacy and safety. Despite promising results from preclinical models and early-phase trials, the full therapeutic potential of stem cell therapy for IHD remains unrealized. Effective treatment protocols, addressing patient-specific factors, ethical considerations, and long-term outcome evaluations, are essential. This review emphasizes the need for ongoing research and clinical development to maximize the potential of stem cell-based approaches in cardiac repair.

Endocrine-disrupting chemicals (EDCs) are compounds, either natural or man-made, that interfere with the normal functioning of the endocrine system. There is increasing evidence that exposure to EDCs can have profound adverse effects on reproduction, metabolic disorders, neurological alterations, and increased risk of hormone-dependent cancer. Stem cells (SCs) are integral to these pathological processes, and it is therefore crucial to understand how EDCs may influence SC functionality. This review examines the literature on different types of EDCs and their effects on various types of SCs, including embryonic, adult, and cancer SCs. Possible molecular mechanisms through which EDCs may influence the phenotype of SCs are also evaluated. Finally, the possible implications of these effects on human health are discussed. The available literature demonstrates that EDCs can influence the biology of SCs in a variety of ways, including by altering hormonal pathways, DNA damage, epigenetic changes, reactive oxygen species production and alterations in the gene expression patterns. These disruptions may lead to a variety of cell fates and diseases later in adulthood including increased risk of endocrine disorders, obesity, infertility, reproductive abnormalities, and cancer. Therefore, the review emphasizes the importance of raising broader awareness regarding the intricate impact of EDCs on human health.

Loss and functional failure of pancreatic β-cells results in disruption of glucose homeostasis and progression of diabetes. Although whole pancreas or pancreatic islet transplantation serves as a promising approach for β-cell replenishment and diabetes therapy, the severe scarcity of donor islets makes it unattainable for most diabetic patients. Stem cells, particularly induced pluripotent stem cells (iPSCs), are promising for the treatment of diabetes owing to their self-renewal capacity and ability to differentiate into functional β-cells. In this review, we first introduce the development of functional β-cells and their heterogeneity and then turn to highlight recent advances in the generation of β-cells from stem cells and their potential applications in disease modeling, drug discovery and clinical therapy. Finally, we have discussed the current challenges in developing stem cell-based therapeutic strategies for improving the treatment of diabetes. Although some significant technical hurdles remain, stem cells offer great hope for patients with diabetes and will certainly transform future clinical practice.

Regenerative medicine refers to medical research focusing on repairing, replacing, or regenerating damaged or diseased tissues or organs. Cardiovascular disease (CVDs) is a significant health issue globally and is the leading cause of death in many countries. According to the Centers for Disease Control and Prevention (CDC), one person dies every 34 seconds in the United States from cardiovascular diseases, and according to a World Health Organization (WHO) report, cardiovascular diseases are the leading cause of death globally, taking an estimated 17.9 million lives each year. Many conventional treatments are available using different drugs for cardiovascular diseases, but these treatments are inadequate. Stem cells and nanotechnology are promising research areas for regenerative medicine treating CVDs. Regenerative medicines are a revolutionary strategy for advancing and successfully treating various diseases, intending to control cardiovascular disorders. This review is a comprehensive study of different treatment methods for cardiovascular diseases using different types of biomaterials as regenerative medicines, the importance of different stem cells in therapeutics, the expanded role of nanotechnology in treatment, the administration of several types of stem cells, their tracking, imaging, and the final observation of clinical trials on many different levels as well as it aims to keep readers up to pace on emerging therapeutic applications of some specific organs and disorders that may improve from regenerative medicine shortly.

Stem cell-based therapies have emerged as a promising approach for treating various neurological disorders by harnessing the regenerative potential of stem cells to restore damaged neural tissue and circuitry. This comprehensive review provides an in-depth analysis of the current state of stem cell applications in primary neurological conditions, including Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), stroke, spinal cord injury (SCI), and other related disorders. The review begins with a detailed introduction to stem cell biology, discussing the types, sources, and mechanisms of action of stem cells in neurological therapies. It then critically examines the preclinical evidence from animal models and early human trials investigating the safety, feasibility, and efficacy of different stem cell types, such as embryonic stem cells (ESCs), mesenchymal stem cells (MSCs), neural stem cells (NSCs), and induced pluripotent stem cells (iPSCs). While ESCs have been studied extensively in preclinical models, clinical trials have primarily focused on adult stem cells such as MSCs and NSCs, as well as iPSCs and their derivatives. We critically assess the current state of research for each cell type, highlighting their potential applications and limitations in different neurological conditions. The review synthesizes key findings from recent, high-quality studies for each neurological condition, discussing cell manufacturing, delivery methods, and therapeutic outcomes. While the potential of stem cells to replace lost neurons and directly reconstruct neural circuits is highlighted, the review emphasizes the critical role of paracrine and immunomodulatory mechanisms in mediating the therapeutic effects of stem cells in most neurological disorders. The article also explores the challenges and limitations associated with translating stem cell therapies into clinical practice, including issues related to cell sourcing, scalability, safety, and regulatory considerations. Furthermore, it discusses future directions and opportunities for advancing stem cell-based treatments, such as gene editing, biomaterials, personalized iPSC-derived therapies, and novel delivery strategies. The review concludes by emphasizing the transformative potential of stem cell therapies in revolutionizing the treatment of neurological disorders while acknowledging the need for rigorous clinical trials, standardized protocols, and multidisciplinary collaboration to realize their full therapeutic promise.

Capitalizing on breakthroughs in reproductive genetics, the utilization of in vitro embryo culture and stem cell technologies heralds a transformative era in addressing global challenges posed by rare genetic diseases. These cutting-edge practices illuminate the intricacies of early human development, elucidate the mechanisms behind rare diseases, and guide the development of potential therapies. Balancing this remarkable innovation with necessary ethical considerations, these technologies have the potential to revolutionize the trajectory of rare genetic disorders, transforming the landscape of diagnosis, treatment, and genetic counseling while offering renewed hope for affected individuals and families worldwide.

Stem cells have been widely applied in regenerative and therapeutic medicine for their unique regenerative properties. Although much research has shown their potential, it remains tricky in directing stem cell differentiation. The advancement of genetic and therapeutic technologies, however, has facilitated this issue through development of design molecules. These molecules are designed to overcome the drawbacks previously faced, such as unexpected differentiation outcomes and insufficient migration of endogenous or exogenous MSCs. Here, we introduced aptamer, bacteriophage, and biological vectors as design molecules and described their characteristics. The methods of designing/developing discussed include various Systematic Evolution of Ligands by Exponential Enrichment (SELEX) procedures, in silico approaches, and non-SELEX methods for aptamers, and genetic engineering methods such as homologous recombination, Bacteriophage Recombineering of Electroporated DNA (BRED), Bacteriophage Recombineering with Infectious Particles (BRIP), and genome rebooting for bacteriophage. For biological vectors, methods such as alternate splicing, multiple promoters, internal ribosomal entry site, CRISPR-Cas9 system and Cre recombinase mediated recombination were used to design viral vectors, while non-viral vectors like exosomes are generated through parental cell-based direct engineering. Besides that, we also discussed the pros and cons, and applications of each design molecule in directing stem cell differentiation to illustrate their great potential in stem cells research. Finally, we highlighted some safety and efficacy concerns to be considered for future studies.

Acute liver failure (ALF) results from severe liver damage or end-stage liver disease. It is extremely fatal and causes serious health and economic burdens worldwide. Once ALF occurs, liver transplantation (LT) is the only definitive and recommended treatment; however, LT is limited by the scarcity of liver grafts. Consequently, the clinical use of bioartificial liver (BAL) has been proposed as a treatment strategy for ALF. Human primary hepatocytes are an ideal cell source for these methods. However, their high demand and superior viability prevent their widespread use. Hence, finding alternatives that meet the seed cell quality and quantity requirements is imperative. Stem cells with self-renewing, immunogenic, and differentiative capacities are potential cell sources. MSCs and its secretomes encompass a spectrum of beneficial properties, such as anti-inflammatory, immunomodulatory, anti-ROS (reactive oxygen species), anti-apoptotic, pro-metabolomic, anti-fibrogenesis, and pro-regenerative attributes. This review focused on the recent status and future directions of stem cell-based strategies in BAL for ALF. Additionally, we discussed the opportunities and challenges associated with promoting such strategies for clinical applications.

Completely synthetic cell cultivation materials for human pluripotent stem cells (hPSCs) are important for the future clinical use of hPSC-derived cells. Currently, cell culture materials conjugated with extracellular matrix (ECM)-derived peptides are being prepared using only one specific integrin-targeting peptide. We designed dual peptide-conjugated hydrogels, for which each peptide was selected from different ECM sites: the laminin β4 chain and fibronectin or vitronectin, which can target α6β1 and α2β1 or αVβ5. hPSCs cultured on dual peptide-conjugated hydrogels, especially on hydrogels conjugated with peptides obtained from the laminin β4 chain and vitronectin with a low peptide concentration of 200 μg/mL, showed high proliferation ability over the long term and differentiated into cells originating from 3 germ layers in vivo as well as a specific lineage of cardiac cells. The design of grafting peptides was also important, for which a joint segment and positive amino acids were added into the designed peptide. Because of the designed peptides on the hydrogels, only 200 μg/mL peptide solution was sufficient for grafting on the hydrogels, and the hydrogels supported hPSC cultures long-term; in contrast, in previous studies, greater than 1000 μg/mL peptide solution was needed for the grafting of peptides on cell culture materials.

Dental pulp stem cells from humans possess self-renewal and versatile differentiation abilities. These cells, known as DPSC, are promising for tissue engineering due to their outstanding biological characteristics and ease of access without significant donor site trauma. Existing methods for isolating DPSC mainly include enzyme digestion and explant techniques. Compared with the enzymatic digestion technique, the outgrowth method is less prone to cell damage and loss during the operation, which is essential for DPSC with fewer tissue sources.

In order to maximize the amount of stem cells harvested while reducing the cost of DPSC culture, the feasibility of the optimized explant technique was evaluated in this experiment. Cell morphology, minimum cell emergence time, the total amount of cells harvested, cell survival, and proliferative and differentiation capacity of DPSC obtained with different numbers of explant attachments (A1-A5) were evaluated.

There was a reduction in the survival rate of the cells in groups A2-A5, and the amount of harvested DPSC decreased in A3-A5 groups, but the DPSC harvested in groups A1-A4 had similar proliferative and differentiation abilities. However, starting from group A5, the survival rate, proliferation and differentiation ability of DPSC decreased significantly, and the adipogenic trend of the cells became more apparent, indicating that the cells had begun to enter the senescence state.

The results of our study demonstrated that the DPSC obtained by the optimized explant method up to 4 times had reliable biological properties and is available for tissue engineering.

This review comprehensively explores the versatile potential of mesenchymal stem cells (MSCs) with a specific focus on adipose-derived MSCs. Ophthalmic and oculoplastic surgery, encompassing diverse procedures for ocular and periocular enhancement, demands advanced solutions for tissue restoration, functional and aesthetic refinement, and aging. Investigating immunomodulatory, regenerative, and healing capacities of MSCs, this review underscores the potential use of adipose-derived MSCs as a cost-effective alternative from bench to bedside, addressing common unmet needs in the field of reconstructive and regenerative surgery.

Regenerative medicine (RM) has emerged as a promising and revolutionary solution to address a range of unmet needs in healthcare, including ophthalmology. Moreover, RM takes advantage of the body's innate ability to repair and replace pathologically affected tissues. On the other hand, despite its immense promise, RM faces challenges such as ethical concerns, host-related immune responses, and the need for additional scientific validation, among others. The primary aim of this review is to present a high-level overview of current strategies in the domain of RM (cell therapy, exosomes, scaffolds, in vivo reprogramming, organoids, and interspecies chimerism), centering around the field of ophthalmology. A search conducted on clinicaltrials.gov unveiled a total of at least 209 interventional trials related to RM within the ophthalmological field. Among these trials, there were numerous early-phase studies, including phase I, I/II, II, II/III, and III trials. Many of these studies demonstrate potential in addressing previously challenging and degenerative eye conditions, spanning from posterior segment pathologies like Age-related Macular Degeneration and Retinitis Pigmentosa to anterior structure diseases such as Dry Eye Disease and Limbal Stem Cell Deficiency. Notably, these therapeutic approaches offer tailored solutions specific to the underlying causes of each pathology, thus allowing for the hopeful possibility of bringing forth a treatment for ocular diseases that previously seemed incurable and significantly enhancing patients' quality of life. As advancements in research and technology continue to unfold, future objectives should focus on ensuring the safety and prolonged viability of transplanted cells, devising efficient delivery techniques, etc.

An overview of various cell engineering techniques being developed for modern conservative and reconstructive periodontology is presented. The accelerated development of cellular engineering technologies poses to medicine and, in particular, periodontics, the task of early implementation of the results of such experiments into patient management protocols. The main groups of promising techniques that are closest to practical healthcare are: isolation and use of stem cells; synthesis of biologically active (inductive) signaling molecules; development of scaffolds that ensure three-dimensional tissue growth.

There are many gynecological diseases, among which breast cancer (BC), cervical cancer (CC), endometriosis (EMs), and polycystic ovary syndrome (PCOS) are common and difficult to cure. Stem cells (SCs) are a focus of regenerative medicine. They are commonly used to treat organ damage and difficult diseases because of their potential for self-renewal and multidirectional differentiation. SCs are also commonly used for difficult-to-treat gynecological diseases because of their strong directional differentiation ability with unlimited possibilities, their tendency to adhere to the diseased tissue site, and their use as carriers for drug delivery. SCs can produce exosomes in a paracrine manner. Exosomes can be produced in large quantities and have the advantage of easy storage. Their safety and efficacy are superior to those of SCs, which have considerable potential in gynecological treatment, such as inhibiting endometrial senescence, promoting vascular reconstruction, and improving anti-inflammatory and immune functions. In this paper, we review the mechanisms of the regenerative and anti-inflammatory capacity of SCs and exosomes in incurable gynecological diseases and the current progress in their application in genetic engineering to provide a foundation for further research.

Premature ovarian insufficiency (POI) is a complex disorder that can result in varying degrees of infertility. Recently, mesenchymal stem cell (MSC) therapy and its derivatives, such as exosomes, have been introduced as novel strategies for the treatment of POI. This review discusses the features, limitations, and challenges of MSC and exosome therapy in the treatment of POI and provides readers with new insights for comparing and selecting chemical agents, optimizing doses, and other factors involved in study design and treatment strategies. MSC therapy has been shown to improve ovarian function in some animals with POI, but it can also have side effects such as high cost, time-consuming processes, limited lifespan and cell sources, loss of original characteristics during in vitro proliferation, dependence on specific culture environments, potential immune reactions, unknown therapeutic mechanisms, etc. However, exosome therapy is a newer therapy that has not been studied as extensively as MSC therapy, but that it has shown some promise in animal studies. The evidence for the effectiveness of MSC and exosome therapy is still limited, and more research is needed to determine whether these therapies are effective and safe for women with POI. This study presents a new perspective for researchers to advance their research in the fields of cell-based and cell-free therapies.

Advanced Therapy Medicinal Products (ATMPs) are innovative clinical treatments exploiting the pharmacological, immunological, or metabolic properties of cells and/or gene(s) with the aim to restore, correct, or modify a biological function in the recipient. ATMPs are heterogeneous medicinal products, developed mainly as individualized and patient-specific treatments, and represent new opportunities for diseases characterized by a high-unmet medical need, including rare, genetic and neurodegenerative disorders, haematological malignancies, cancer, autoimmune, inflammatory and orthopaedic conditions. Into the European Union (EU) market, the first ATMP has been launched in 2009 and, to date, a total of 24 ATMPs have been approved. This review aims at reporting on current evidence of cell-based therapies authorized in the EU, including Somatic Cell Therapies, Tissue Engineering Products, and Cell-based Gene Therapy Products as Chimeric Antigen Receptor (CAR) T-cells, focusing on the evaluation of efficacy and safety in clinical trials and real-world settings. Despite cell-based therapy representing a substantial promise for patients with very limited treatment options, some limitations for its widespread use in the clinical setting remain, including restricted indications, highly complex manufacturing processes, elevated production costs, the lability of cellular products over time, and the potential safety concerns related to the intrinsic characteristics of living cells, including the risk of severe or life-threatening toxicities, such as CAR-T induced neurotoxicity and cytokine release syndrome (CRS). Although encouraging findings support the clinical use of ATMPs, additional data, comparative studies with a long-term follow-up, and wider real-world evidences are needed to provide further insights into their efficacy and safety profiles.

According to estimations, approximately about 15% of couples worldwide suffer from infertility, in which individuals with azoospermia or oocyte abnormalities cannot be treated with assisted reproductive technology. The skin-derived stem cells (SDSCs) differentiation into primordial germ cell-like cells (PGCLCs) is one of the major breakthroughs in the field of stem cells intervention for infertility treatment in recent years. However, the cellular origin of SDSCs and their dynamic changes in transcription profile during differentiation into PGCLCs in vitro remain largely undissected. Here, the results of single-cell RNA sequencing indicated that porcine SDSCs are mainly derived from multipotent dermal fibroblast progenitors (MDFPs), which are regulated by growth factors (EGF/bFGF). Importantly, porcine SDSCs exhibit pluripotency for differentiating into three germ layers and can effectively differentiate into PGCLCs through complex transcriptional regulation involving histone modification. Moreover, this study also highlights that porcine SDSC-derived PGCLCs specification exhibit conservation with the human primordial germ cells lineage and that its proliferation is mediated by the MAPK signaling pathway. Our findings provide substantial novel insights into the field of regenerative medicine in which stem cells differentiate into germ cells in vitro, as well as potential therapeutic effects in individuals with azoospermia and/or defective oocytes.

The placenta and the extraembryonic tissues represent a valuable source of cells for regenerative medicine. In particular, the amniotic membrane possesses cells with stem cells characteristics that have attracted research attention. Human amniotic epithelial cells (hAECs) have unique and desirable features that position them over other stem cells, not only because of the unlimited potential supplied of, the easy access to placental tissues, and the minimal ethical and legal barriers associated, but also due to the embryonic stem cells markers expression and their ability to differentiate into the three germ layers. In addition, they are non-tumorigenic and have immunomodulatory and anti-inflammatory properties. Hepatic failure is one of the major causes of morbidity and mortality worldwide. Organ transplantation is the best way to treat acute and chronic liver failure, but there are several associated obstacles. Stem cells have been highlighted as alternative hepatocytes source because of their potential for hepatogenic differentiation. HAECs, in particular, have some properties that make them suitable for hepatocyte differentiation. In this work, we review the general characteristics of the epithelial stem cells isolated from human amniotic membrane as well as their ability to differentiate to hepatic cells. We also revise their regenerative properties, with the focus on their potential application in the liver disease treatment.

Osteoarthritis is a common disease resulting in significant disability without approved disease-modifying treatment (other than total joint replacement). Stem cell-based therapy is being actively explored for the repair of cartilage lesions in the treatment and prevention of osteoarthritis. Embryonic stem cells are a very attractive source as they address many of the limitations inherent in autologous stem cells, such as variability in function and limited expansion. Over the past 20 years, there has been widespread interest in differentiating ESC into mesenchymal stem cells and chondroprogenitors with successful in vitro, ex vivo, and early animal studies. However, to date, none have progressed to clinical trials. In this review, we compare and contrast the various approaches to differentiating ESC; and discuss the benefits and drawbacks of each approach. Approaches relying on spontaneous differentiation are simpler but not as efficient as more targeted approaches. Methods replicating developmental biology are more efficient and reproducible but involve many steps in a complicated process. The small-molecule approach, arguably, combines the advantages of the above two methods because of the relative efficiency, reproducibility, and simplicity. To better understand the reasons for lack of progression to clinical applications, we explore technical, scientific, clinical, and regulatory challenges that remain to be overcome to achieve success in clinical applications.

Currently, there are no specific and efficient vaccines or drugs for COVID-19, particularly in severe cases. A wide range of variations in the clinical symptoms of different patients attributed to genomic differences. Therefore, personalized treatments seem to play a critical role in improving these symptoms and even similar conditions. Prompted by the uncertainties in the area of COVID-19 therapies, we reviewed the published papers and concepts to gather and provide useful information to clinicians and researchers interested in personalized medicine and cell-based therapy. One novel aspect of this study focuses on the potential application of personalized medicine in treating severe cases of COVID-19. However, it is theoretical, as any real-world examples of the use of genuinely personalized medicine have not existed yet. Nevertheless, we know that stem cells, especially MSCs, have immune-modulatory effects and can be stored for future personalized medicine applications. This theory has been conjugated with some evidence that we review in the present study. Besides, we discuss the importance of personalized medicine and its possible aspects in COVID-19 treatment, then review the cell-based therapy studies for COVID-19 with a particular focus on stem cell-based therapies as a primary personalized tool medicine. However, the idea of cell-based therapy has not been accepted by several scientific communities due to some concerns of lack of satisfactory clinical studies; still, the MSCs and their clinical outcomes have been revealed the safety and potency of this therapeutic approach in several diseases, especially in the immune-mediated inflammatory diseases and some incurable diseases. Promising outcomes have resulted in that clinical studies are going to continue.