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Objective: Understanding and targeting cancer stem cells (CSC) are areas of active research in oncology and further dissemination of scientific results is urgently needed to accelerate the comprehension of their involvement in tumor heterogeneity, resistance to conventional therapies and metastasis. In the context of open science, open access and data sharing, the aim of this study is to assess the current practices of cancer researchers in terms of publications and dissemination of research data. Method: A bibliometric study was conducted based on a bibliographic search using the Web of Science, and CSC articles with at least one Spanish affiliation were retrieved. A comparative study of the openness criteria of the journals was carried out, as well as an analysis of the associated data attached to the articles as supplementary material or deposited in repositories. Results: 708 documents from 282 journals were retrieved. 303 articles contained associated research data, mostly published in Q1 journals, demonstrating a correlation between impact journals and their commitment to quality improvement. Supplementary material was the preferred method of data sharing, being pdf the most used file type. Only 69 articles mentioned datasets deposited in repositories, mainly from genomic nature. The main cancers studied were digestive and gastrointestinal, neurological, breast, hematological and respiratory, which coincided with the tumor types with the highest incidence and mortality, and in which the presence of CSC has been described. Conclusions: Researchers and publishers have become more aware of open science practices, but there is still a need for data quality according to the FAIR principles. Resumen: Objetivo: La investigación activa en células madre cancerosas (CMC) requiere la difusión de los resultados científicos para acelerar la comprensión de la heterogeneidad tumoral, la resistencia a las terapias convencionales y la metástasis. En el contexto de la ciencia abierta, el acceso abierto y el intercambio de datos, el objetivo de este estudio es evaluar las prácticas actuales de los investigadores del cáncer en términos de publicaciones y difusión de datos de investigación. Método: Se realizó un estudio bibliométrico a partir de una búsqueda bibliográfica utilizando Web of Science y se recuperaron artículos sobre CMC firmados por al menos una institución española. Se realizó un análisis de los criterios de apertura de las revistas, así como de los datos asociados a los artículos. Resultados: Se recuperaron 708 documentos de 282 revistas. De ellos, 303 artículos contenían datos de investigación asociados, mayoritariamente publicados en revistas del primer cuartil, mostrando una correlación entre las revistas de impacto y su calidad. El material suplementario fue el método preferido para compartir datos, siendo el pdf el formato más utilizado. Solo 69 artículos mencionaron conjuntos de datos depositados en repositorios, principalmente de naturaleza genómica. Los cánceres estudiados fueron el digestivo y gastrointestinal, el neurológico, el de mama, el hematológico y el respiratorio, coincidiendo con los tumores con mayor incidencia y mortalidad, y en los que se ha descrito la presencia de CMC. Conclusiones: Los investigadores y los editores se han vuelto más conscientes de las prácticas de ciencia abierta, pero todavía existe la necesidad de implementar la calidad de los datos de acuerdo con los principios FAIR.

Single-Cell Sequencing (SCS) technology plays an important role in the field of Mesenchymal Stem Cells (MSCs) research. This paper comprehensively describes the application of SCS technology in the field of MSCs research, including (1) SCS enables more precise MSCs characterization and biomarker definition. (2) SCS reveals the prevalent gene expression heterogeneity among different subclusters within MSCs, which contributes to a more comprehensive understanding of MSCs function and diversity in developmental, regenerative, and pathological contexts. (3) SCS provides insights into the dynamic transcriptional changes experienced by MSCs during differentiation and the complex web of important signaling pathways and regulatory factors controlling key processes within MSCs, including proliferation, differentiation and regulation, and interactions mechanisms. (4) The analytical methods underpinning SCS data are rapidly evolving and converging with the field of histological research to systematically deconstruct the functions and mechanisms of MSCs. This review provides new perspectives for unraveling the biological properties, heterogeneity, differentiation potential, biological functions, and clinical potential of MSCs at the single-cell level.

Introduction: Stem cells are definite units competent of both self-renewal and differentiation into numerous cells. Embryonic and postnatal tissues are the major sources of stem cells. The aim of the study was to assess the knowledge and level of information about stem cells research and therapeutic potential among Medical and Dental postgraduate students of Sumandeep Vidyapeeth, Vadodara. Materials and Methods: The Medical and Dental postgraduate students of Sumandeep Vidyapeeth, Vadodara, were selected. The questionnaire form was taken to them by the principal investigator personally and explained about the study and asked to fill the questionnaire after obtaining consent. The collected questionnaire was excluded if more than 30% of questions were not filled. Results: A total of 435 medical and dental postgraduate students of Sumandeep Vidyapeeth, Vadodara, were included in the study. 109 dental postgraduates (26.58%), and 301 were medical postgraduates. All participants had a basic knowledge of stem cells (100%), but only a few had specific knowledge (3.90%). Only a few agreed to human embryo research and considered it ethical (0.73%). All agreed to conserve their child's umbilical cord for the child's therapeutic purposes. Conclusion: We can conclude that the knowledge and level of information about stem cells exhibited by most of the participants were minimal. However, all participants expressed a genuine desire to enhance their knowledge regarding stem cells. There is a need for Continuing Medical Education/ Continuing Dental Education (CME/CDE) workshops as well as conferences on this subject to upgrade the knowledge of participants and the community as a whole.

Objective: The importance and potential of the use of stem cells as therapeutic tools is enormous and therefore, health professionals should be expected to have thorough knowledge and a positive attitude towards their utilization in medical practice. Hence this study was carried out to report and assess the knowledge and attitude regarding stem cell in our region. Methodology: The study was conducted amongst the residents employed at the Aga Khan University hospital, Karachi Pakistan from September-October 2022 with a sample size of 57. Results: Amongst our survey participants, 33 (54.2%) responded with a score of 48 and above (i.e., 60% or above); 25 (40.9%) of the study participants scored between 50-60% only 3 (4.9%) had a score 40-50% Conclusion: Our survey shows a reasonable level of knowledge of the generic principles and implications Stem cell therapy amongst the residents Keywords: Stem cell, Head and Neck, Risk, Cell, Tissue, Therapy

The applicability of machine learning-based analysis in the field of biomedical field has been very beneficial in determining the biological mechanism and validation for a wide range of biological scenarios. This approach is also gaining momentum in various stem cells research activities, specifically for stem cells characterization and differentiation pattern. The adoption of similar computational approaches to study and assess biosafety and bioefficacy risks of stem cells for clinical application is the next progression. In particular where tumorigenicity has been one of the major concerns in stem cells therapy. There are many factors influencing tumorigenicity in stem cells which may be difficult to capture under conventional laboratory settings. In addition, given the possible multifactorial etiology of tumorigenicity, defining a one-size-fits-all strategy to test such risk in stem cells might not be feasible and may compromise stem cells safety and effectiveness in therapy. Given the increase in biological datasets (which is no longer limited to genomic data) and the advancement of health informatics powered by state-of-the-art machine learning algorithms, there exists a potential for practical application in biosafety and bioefficacy of stem cells therapy. Here, we identified relevant machine learning approaches and suggested protocols intended for stem cells research focusing on the possibility of its usage for stem cells biosafety and bioefficacy assessment. Ultimately, generating models that may assist healthcare professionals to make a better-informed decision in stem cell therapy.

The human body possesses an endogenous regeneration system based on stem cells, which may be found in practically every tissue type. They are classified as embryonic stem cells (ESCs) or nonembryonic stem cells (NESCs). Despite its enormous promise, the use of ESCs is presently limited because of ethical and scientific issues. Stem cells have the potential to improve healthcare by using and boosting the body's inherent regenerative capabilities. Although the stem cells offer an enormous promise for tissue regeneration and repair, much more about their biology, administration, and safety must be studied before they may be employed therapeutically. Stem cells and their derivatives will have enormous medical promise in the future. Current animal and laboratory investigations are looking into the viability of bringing stem cell therapy into clinical practice for regeneration in muscular dystrophy, intervertebral disc degeneration, cerebral infarctions, and transplantation medicine. This article delves into the many aspects at play, as well as current situation and possible issues with stem cell treatment in patient care and management (Fig. 1, Ref. 86). [ABSTRACT FROM AUTHOR]

Introduction: Stem cells are definite units competent of both self-renewal and differentiation into numerous cells. Embryonic and postnatal tissues are the major sources of stem cells. The aim of the study was to assess the knowledge and level of information about stem cells research and therapeutic potential among Medical and Dental postgraduate students of Sumandeep Vidyapeeth, Vadodara. Materials and Methods: The Medical and Dental postgraduate students of Sumandeep Vidyapeeth, Vadodara, were selected. The questionnaire form was taken to them by the principal investigator personally and explained about the study and asked to fill the questionnaire after obtaining consent. The collected questionnaire was excluded if more than 30% of questions were not filled. Results: A total of 435 medical and dental postgraduate students of Sumandeep Vidyapeeth, Vadodara, were included in the study. 109 dental postgraduates (26.58%), and 301 were medical postgraduates. All participants had a basic knowledge of stem cells (100%), but only a few had specific knowledge (3.90%). Only a few agreed to human embryo research and considered it ethical (0.73%). All agreed to conserve their child's umbilical cord for the child's therapeutic purposes. Conclusion: We can conclude that the knowledge and level of information about stem cells exhibited by most of the participants were minimal. However, all participants expressed a genuine desire to enhance their knowledge regarding stem cells. There is a need for Continuing Medical Education/ Continuing Dental Education (CME/CDE) workshops as well as conferences on this subject to upgrade the knowledge of participants and the community as a whole. [ABSTRACT FROM AUTHOR]

Camels have cultural value in the Arab society and are considered one of the most important animals in the Arabian Peninsula and arid environments, due to the distinct characteristics of their meat and milk. Moreover, there is a great interest in camel racing and beauty shows. Therefore, treatment of elite animals, increasing the number of camels as well as genetic improvement is an essential demand. Because there are unique camels for milk production, meat, or in racing, the need to propagate genetically superior camels is urgent. Recent biotechnological approaches such as stem cells hold great promise for biomedical research, genetic engineering, and as a model for studying early mammalian developmental biology. Establishment of stem cells lines from camels would tremendously facilitate regenerative medicine for genetically superior camels, permit the gene targeting of the camel genome and the generation of genetically modified animal and be a mean for genome conservation for the elite breeds. In this mini-review, we show the current research, future horizons and potential applications for camel stem cells. Keywords: Camel, Cloning, Embryo, Regenerative medicine, Stem cells

As the primary goal in the wound care intervention is the promotion of rapid wound healing, researchers sought to find a remedy. In this progression course, nanocomposite-based hydrogels have attracted the attention. Herein, we used a polyvinyl alcohol (PVA) hydrogel in combination with two forms of clay nanoparticles, namely unmodified montmorillonite (MONT) and modified (OMONT), to fabricate a nanocomposite-based hydrogels and combat the lack of stem cells' adhesion to PVA, followed by seeding of adipose-derived stem cells (ADSCs) on them. To investigate the characteristics of these constructs, corresponding tests were performed. The Young's modulus and elongation at break of PVA/5% OMONT were 3.7 [+ or -] 0.014 and 800 [+ or -] 35, respectively, which were higher than those of PVA/5% MONT (3 [+ or -] 0.03 and 320 [+ or -] 14). In addition, the hardness of the modified group (7.2 [+ or -] 0.07) was lower than the unmodified one (9.8 [+ or -] 0.07). The water vapor transmission rate (WVTR) in the OMONT group was 39 [+ or -] 0.28, which was lower than PVA/5% MONT (46 [+ or -] 4.24). Hence, ADSCs/PVA montmorillonite dressing may improve wound healing and provide a new way to employ stem cells, significantly impacting skin tissue engineering safely. Highlights * Modified montmorillonite had higher stem cell binding. * The lack of stem cells' adhesion to polyvinyl alcohol (PVA) was solved. * Adipose-derived stem cells/PVA montmorillonite dressing may improve wound healing. * It is a novel promising approach for skin tissue engineering. KEYWORDS montmorillonite, nanocomposites, PVA hydrogel, stem cells, 1 | INTRODUCTION As the primary goal in the wound care intervention is the promotion of rapid wound healing, researchers sought to find a remedy. (1) In this progression course, [...]

Continuation of mammalian species requires the formation and development of the sexually dimorphic germ cells. Cultured embryonic stem cells are generally considered pluripotent rather than totipotent because of the failure to detect germline cells under differentiating conditions. Here we show that mouse embryonic stem cells in culture can develop into oogonia that enter meiosis, recruit adjacent cells to form follicle-like structures, and later develop into blastocysts. Oogenesis in culture should contribute to various areas, including nuclear transfer and manipulation of the germ tine, and advance studies on fertility treatment and germ and somatic cell interaction and differentiation., In the early mammalian embryo, the germ line and soma are indistinguishable from each other. In the mouse, germ cell competence is induced at embryonic day 6.5 in proximal epiblast [...]

Lung cancer is the most common cancer worldwide, accounting for 1.8 million new cases and 1.6 million deaths in 2012. Non-small cell lung cancer (NSCLC), which is one of two types of lung cancer, accounts for 85–90% of all lung cancers. Despite advances in therapy, lung cancer still remains a leading cause of death. Cancer relapse and dissemination after treatment indicates the existence of a niche of cancer cells that are not fully eradicated by current therapies. These chemoresistant populations of cancer cells are called cancer stem cells (CSCs) because they possess the self-renewal and differentiation capabilities similar to those of normal stem cells. Targeting the niche of CSCs in combination with chemotherapy might provide a promising strategy to eradicate these cells. Thus, understanding the characteristics of CSCs has become a focus of studies of NSCLC therapies.

Summary: Vascular complications caused by diabetes mellitus contribute a major threat to increased disability and mortality of diabetic patients, which are characterized by damaged endothelial cells and angiogenesis. Human umbilical cord-derived mesenchymal stem cells (hucMSCs) have been demonstrated to alleviate endothelial cell damage and improve angiogenesis. However, these investigations overlooked the pivotal role of vasculogenesis. In this study, we utilized blood vessel organoids (BVOs) to investigate the impact of high glucose on vasculogenesis and subsequent angiogenesis. We found that BVOs in the vascular lineage induction stage were more sensitive to high glucose and more susceptible to affect endothelial cell differentiation and function. Moreover, hucMSCs can alleviate the high glucose-induced inhibition of endothelial cell differentiation and dysfunction through MAPK signaling pathway downregulation, with the MAPK activator dimethyl fumarate further illustrating the results. Thereby, we demonstrated that high glucose can lead to abnormal vasculogenesis and impact subsequent angiogenesis, and hucMSCs can alleviate this effect.

Summary: p53 is the most mutated tumor suppressor gene in human cancers. Besides p53 classical functions inducing cell-cycle arrest and apoptosis in stressed cells, additional p53 non-canonical roles in unstressed cells have emerged over the past years, including the mode of stem cell division regulation. However, the mechanisms by which p53 impacts on this process remain elusive. Here, we show that Drosophila p53 controls asymmetric stem cell division (ASCD), a key process in development, cancer and adult tissue homeostasis, by transcriptionally activating Numb, Brat, and Traf4 ASCD regulators. p53 knockout caused failures in their localization in dividing neural stem cells, as well as a significant decrease in their expression levels. Moreover, p53 directly bound numb, brat, and Traf4 regulatory regions. Remarkably, human and mice genes related to Drosophila brat (TRIM32) and Traf4 (TRAF4) were recently identified in a meta-analysis of transcriptomic and ChIP-seq datasets as predicted conserved p53 targets.

Summary: Obstructive sleep apnea (OSA) leads to chronic intermittent hypoxia (CIH) and is not well addressed by current therapies. The genioglossus (GG) is the largest upper airway dilator controlling OSA pathology, making its repair a potential treatment. This study investigates dental pulp stem cells (DPSCs) in repairing GG injury in a CIH mouse model. We induced DPSCs to myogenic lineage cells (iDPSCs) and transplanted them into GG of CIH mice. DPSCs/iDPSCs grafts improved EMGGG and muscle type transitions while reducing tumor necrosis factor α (TNF-α), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and creatine kinase (CK) levels, improving body weight. Moreover, iDPSCs increased Pax7+/Ki67+ and human-derived STEM121 cells in the GG compared with DPSCs. DPSCs/iDPSCs enhanced Desmin+ myotube formation in myoblasts under hypoxia in vitro, with iDPSCs increased human-derived myogenic markers and nuclei in myotubes. These results indicate that iDPSCs, beyond their paracrine effects like DPSCs, directly participate in myogenic differentiation, supporting the potential use of DPSCs for OSA treatment.

Summary: Pluripotent-stem-cell-derived blastocyst-like structures (blastoids) offer insights into early human embryogenesis (5–10 days post-fertilization). The similarity between blastoids and human blastocysts remains uncertain. To investigate, we evaluated single-cell RNA sequencing (scRNAseq) data from seven blastoid models, comparing them to peri-implantation blastocysts. We quantified cell-type composition, transcriptomic overlap, lineage profiles, and developmental propensities for primary (epiblast, primitive endoderm, trophectoderm) and potential lineages (amnion, extravillous cytotrophoblasts, syncytial trophoblasts). Blastoids from extended pluripotent stem cells (EPSCs) are distinct from those from naive pluripotent stem cells (nPSCs), which cluster closer to natural blastocysts. EPSC-blastoids show a higher composition of primitive endoderm cells and ambiguous cells with notable endoderm signatures. Starting cell lines' scRNAseq analysis reveals higher heterogeneity in nPSCs and prevalent amnionic signatures in EPSCs. These findings suggest gene expression heterogeneity in founding cells influences blastoid lineage differentiation, aiding protocol optimization for better human embryogenesis models.

Summary: Cellular quiescence is a reversible and tightly regulated stem cell function essential for healthy aging. However, the elements that control quiescence during aging remain poorly defined. Using melanocyte stem cells (McSCs), we find that stem cell quiescence is neither passive nor static. For example, gene expression profiling of the transition from proliferating melanoblasts to quiescent melanocyte stem cells reveals tissue-specific regulation of the immune checkpoint protein PD-L1. In vitro, quiescence assays demonstrate that PD-L1 expression is a physiological attribute of quiescence in this cell lineage and reinforces this cell state. In vivo, a subset of quiescent McSCs is marked by PD-L1. While the overall number of McSCs decreases with age, PD-L1+ McSCs appear resistant to depletion. This phenomenon coincides with an aged McSC pool that exhibits a deeper transcriptomic quiescence. We predict that quiescent PD-L1+ stem cells retained with age may serve as cellular targets for reactivation.

Summary: The etiology of inflammatory bowel disease (IBD) is complex, with much room for a greater understanding and development of improved therapies. Therefore, establishing a reliable IBD model is crucial for future advancements. In this study, human induced pluripotent stem (iPS) cell-derived colon organoids (hiPSC-COs) were treated with a combination of tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ), and interleukin (IL)-1β (3 cytokines [3CK]), known to be elevated in the serum of IBD patients. Inflammatory responses in stromal cells and damage to intestinal epithelial cells were observed in the 3CK-treated hiPSC-COs. Comparison of molecular signatures of 3CK-treated hiPSC-COs with those of ulcerative colitis (UC) patient’s colon revealed that 3CK-treated hiPSC-COs resemble UC patient’s colon. Furthermore, the elevated production of inflammatory cytokines observed in 3CK-treated hiPSC-COs was attenuated by treatment with tofacitinib. Our UC model will be an essential tool to understand its pathologic mechanisms and identify effective therapeutic approaches.

Lung cancer is one of the most common tumor, which lacks of effective clinical treatment to lead to desirable prognosis. According to cancer stem cell hypothesis, lung cancer stem cells are considered to be responsible for carcinogenesis, development, metastasis, recurrence, invasion, resistance to chemotherapy and radiotherapy of lung cancer. In recent years, more and more institutes used glycosylated CD133 epitopes to define, isolate, purify lung cancer stem cells. However, along with deeply research, the application of CD133 epitopes in lung cancer stem cell research is questioned. The utilization and limitation of CD133 epitopes in lung cancer stem cells research for the past few years is summaried in this review.

The conventional view is that female mammals lose their ability to generate new germ cells after birth. However, in recent years, researchers have successfully isolated and cultured a type of germ cell from postnatal ovaries in a variety of mammalian species that have the abilities of self-proliferation and differentiation into oocytes, and this finding indicates that putative germline stem cells maybe exist in the postnatal mammalian ovaries. Herein, we review the research history and discovery of putative female germline stem cells, the concept that putative germline stem cells exist in the postnatal mammalian ovary, and the research progress, challenge, and application of putative germline stem cells in recent years.

Stem cell research has appeared as a silver lining of hope over the dark cloud of some untreatable diseases like cancer and certain neurological disorders. Embryonic stem cells, the tabula rasa, holds much promise in this regard owing to its totipotency, howbeit, it has whirled a severe tempest all over the world on the point of humanity. The present review article includes the chronology of stem cell research with special reference to the techniques that were evolved in due course of research, the controversy over the application of embryonic stem cells for therapeutics and present status of stem cell research under Indian context. India is being increasingly alluring the foreign companies to invest in this project since a huge prospect in stem cell marketing business is foreseen in this country. [Vet. World 2011; 4(6.000): 281-286]

In decades, stem cell nanotechnology has become a new promising field for stem cell research and development. So, stem cell nanotechnology has attracted lots of researchers’ attention and made great progress. The unique properties of nanomaterials and nanostructures which applied in the fundamental research of stem cell-based therapies have been recognized. Nanomaterials and nanotechnology have been highlighted as promising candidates for efficient control over proliferation and differentiation of stem cells, revolutionizing the treatment of neurodegenerative disorders, neuroprotection in traumatic brain injury, improving the osteospecific differentiation and function, tissue engineering scaffold, dental implant application, drug delivery, gene therapy and cell imaging or tracking. Here we summarize the main progress in this field, explore the application prospects in injuries, diseases, regenerative medicine, etc. and discuss the methods and challenges with the aim of improving application of nanotechnology in the stem cell research and development.

Extracellular matrix can influence stem cell choices, such as self-renewal, quiescence, migration, proliferation, phenotype maintenance, differentiation, or apoptosis. Three aspects of extracellular matrix were extensively studied during the last decade: physical properties, spatial presentation of adhesive epitopes, and molecular complexity. Over 15 different parameters have been shown to influence stem cell choices. Physical aspects include stiffness (or elasticity), viscoelasticity, pore size, porosity, amplitude and frequency of static and dynamic deformations applied to the matrix. Spatial aspects include scaffold dimensionality (2D or 3D) and thickness; cell polarity; area, shape, and microscale topography of cell adhesion surface; epitope concentration, epitope clustering characteristics (number of epitopes per cluster, spacing between epitopes within cluster, spacing between separate clusters, cluster patterns, and level of disorder in epitope arrangement), and nanotopography. Biochemical characteristics of natural extracellular matrix molecules regard diversity and structural complexity of matrix molecules, affinity and specificity of epitope interaction with cell receptors, role of non-affinity domains, complexity of supramolecular organization, and co-signaling by growth factors or matrix epitopes. Synergy between several matrix aspects enables stem cells to retain their function in vivo and may be a key to generation of long-term, robust, and effective in vitro stem cell culture systems.

Summary: The capability of human pluripotent stem cells (hPSCs) to self-renew and differentiate into any cell type has greatly contributed to the advancement of biomedicine. Reporter lines derived from hPSCs have played a crucial role in elucidating the mechanisms underlying human development and diseases by acting as an alternative reporter system that cannot be used in living humans. To bring hPSCs closer to clinical application in transplantation, scientists have generated reporter lines for isolating the desired cell populations, as well as improving graft quality and treatment outcomes. This review presents an overview of the applications of hPSC reporter lines and the important variables in designing a reporter system, including options for gene delivery and editing tools, design of reporter constructs, and selection of reporter genes. It also provides insights into the prospects of hPSC reporter lines and the challenges that must be overcome to maximize the potential of hPSC reporter lines.

Summary: Stem cell therapies for degenerative cartilage disease are limited by an incomplete understanding of hyaline cartilage formation and maintenance. Human bone marrow stromal cells/skeletal stem cells (hBMSCs/SSCs) produce stable hyaline cartilage when attached to hyaluronic acid-coated fibrin microbeads (HyA-FMBs), yet the mechanism remains unclear. In vitro, hBMSC/SSC/HyA-FMB organoids exhibited reduced BMP signaling early in chondrogenic differentiation, followed by restoration of BMP signaling in chondrogenic IGFBP5+/MGP+ cells. Subsequently, human-induced pluripotent stem cell (hiPSC)-derived sclerotome cells were established (BMP inhibition) and then treated with transforming growth factor β (TGF-β) −/+ BMP2 and growth differentiation factor 5 (GDF5) (BMP signaling activation). TGF-β alone elicited a weak chondrogenic response, but TGF-β/BMP2/GDF5 led to delamination of SOX9+ aggregates (chondrospheroids) with high expression of COL2A1, ACAN, and PRG4 and minimal expression of COL10A1 and ALP in vitro. While transplanted hBMSCs/SSCs/HyA-FMBs did not heal articular cartilage defects in immunocompromised rodents, chondrospheroid-derived cells/HyA-FMBs formed non-hypertrophic cartilage that persisted until at least 5 months in vivo.

Summary: Lineage-specific differentiation of human induced pluripotent stem cells (hiPSCs) relies on complex interactions between biochemical and physical cues. Here we investigated the ability of hiPSCs to undergo lineage commitment in response to inductive signals and assessed how this competence is modulated by substrate stiffness. We showed that Activin A-induced hiPSC differentiation into mesendoderm and its derivative, definitive endoderm, is enhanced on gel-based substrates softer than glass. This correlated with changes in tight junction formation and extensive cytoskeletal remodeling. Further, live imaging and biophysical studies suggested changes in cell motility and interfacial contacts underlie hiPSC layer reshaping on soft substrates. Finally, we repurposed an ultra-soft silicone gel, which may provide a suitable substrate for culturing hiPSCs at physiological stiffnesses. Our results provide mechanistic insight into how epithelial mechanics dictate the hiPSC response to chemical signals and provide a tool for their efficient differentiation in emerging stem cell therapies.

Summary: In response to corneal injury, an activation of corneal epithelial stem cells and their direct progeny the early transit amplifying (eTA) cells to rapidly proliferate is critical for proper re-epithelialization. Thus, it is important to understand how such stem/eTA cell activation is regulated. Angiotensin-converting enzyme 2 (ACE2) is predominantly expressed in the stem/eTA-enriched limbal epithelium but its role in the limbal epithelium was unclear. Single cell RNA sequencing (scRNA-seq) suggested that Ace2 involved the proliferation of the stem/eTA cells. Ace2 was reduced following corneal injury. Such reduction enhanced limbal epithelial proliferation and downregulated LCN2, a negative regulator of proliferation in a variety of tissues, via upregulating TGFA and consequently activating epidermal growth factor receptor (EGFR). Inhibition of EGFR or overexpression of LCN2 reversed the increased proliferation in limbal epithelial cells lacking ACE2. Our findings demonstrate that after corneal injury, ACE2 is downregulated, which activates limbal epithelial cell proliferation via a TGFA/EGFR/LCN2 pathway.

Summary: 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.

Summary: Facial infiltrating lipomatosis (FIL) is a congenital disorder. The pathogenesis of FIL is associated with PIK3CA mutations, but the underlying mechanisms remain undetermined. We found that the adipose tissue in FIL demonstrated adipocytes hypertrophy and increased lipid accumulation. All adipose-derived mesenchymal stem cells from FIL (FIL-ADSCs) harbored PIK3CA mutations. Moreover, FIL-ADSCs exhibited a greater capacity for adipogenesis. Knockdown of PIK3CA resulted in a reduction in the adipogenic potential of FIL-ADSCs. Furthermore, WX390, a dual-target PI3K/mTOR inhibitor, was found to impede PIK3CA-mediated adipogenesis both in vivo and in vitro. RNA sequencing (RNA-seq) revealed that the expression of transient receptor potential vanilloid subtype 1 (TRPV1) was upregulated after PI3K pathway inhibition, and overexpression or activation of TRPV1 both inhibited adipogenesis. Our study showed that PIK3CA mutations promoted adipogenesis in FIL-ADSCs and this effect was achieved by suppressing TPRV1. Pathogenesis experiments suggested that WX390 may serve as an agent for the treatment of FIL.

Summary: Hematopoietic aging is associated with decreased hematopoietic stem cell (HSC) self-renewal capacity and myeloid skewing. We report that culture of bone marrow (BM) HSCs from aged mice with epidermal growth factor (EGF) suppressed myeloid skewing, increased multipotent colony formation, and increased HSC repopulation in primary and secondary transplantation assays. Mice transplanted with aged, EGF-treated HSCs displayed increased donor cell engraftment within BM HSCs and systemic administration of EGF to aged mice increased HSC self-renewal capacity in primary and secondary transplantation assays. Expression of a dominant negative EGFR in Scl/Tal1+ hematopoietic cells caused increased myeloid skewing and depletion of long term-HSCs in 15-month-old mice. EGF treatment decreased DNA damage in aged HSCs and shifted the transcriptome of aged HSCs from genes regulating cell death to genes involved in HSC self-renewal and DNA repair but had no effect on HSC senescence. These data suggest that EGFR signaling regulates the repopulating capacity of aged HSCs.

Summary: Adult stem cells play a critical role in tissue repair and maintenance. In tissues with slow turnover, including skeletal muscle, these cells are maintained in a mitotically quiescent state yet remain poised to re-enter the cell cycle to replenish themselves and regenerate the tissue. Using a panomics approach we show that the PAX7/NEDD4L axis acts against muscle stem cell activation in homeostatic skeletal muscle. Our findings suggest that PAX7 transcriptionally activates the E3 ubiquitin ligase Nedd4L and that the conditional genetic deletion of Nedd4L impairs muscle stem cell quiescence, with an upregulation of cell cycle and myogenic differentiation genes. Loss of Nedd4L in muscle stem cells results in the expression of doublecortin (DCX), which is exclusively expressed during their in vivo activation. Together, these data establish that the ubiquitin proteasome system, mediated by Nedd4L, is a key contributor to the muscle stem cell quiescent state in adult mice.

In practice, stem-cell and embryo research have encountered little resistance in Arab and Islamic countries, and it is already in progress in Egypt, Iran, Turkey, Malaysia, and elsewhere. The Islamic scientific community is largely free of religious inhibitions that jeopardize attempts of scientists in Christian-oriented countries, for example, to engage in embryo and stem-cell research. The reason lies with the nature of Islamic medical ethics. According to this ethical system, obtaining knowledge is a human's duty, and an act of faith. Also, science is revealed by God to humans to serve humankind, and human life must be saved by all possible means. According to Islamic theology, "humanity"/the soul, is inspired into the fetus only at 120 days of pregnancy. Therefore, the use of fetuses younger than 120 days in research, and especially if sick or disabled and with a short life expectancy, if born alive at all, is not prohibited, provided that certain stipulations are followed. The use of superfluous zygotes in research is also encouraged, instead of their simply being destroyed. The principle that guides the ethics is that the public good [maslaha] gained from the fruits of the research outweighs the harm [darar]. The research is welcomed. [ABSTRACT FROM AUTHOR]

BACKGROUND: Meniscus cartilage injury is a most common injury of knee joint. In the past decade, stem cell based therapies have been widely applied, and the related studies have been increased rapidly. Pluripotent stem cells have been shown to exist in the meniscus, which may play a key role in the healing of meniscus. OBJECTIVE: To determine the source and culture conditions of stem cells related to tissue-engineered meniscus, and to understand the current development status of tissue- engineered meniscus. METHODS: PubMed, Embase, EBSCO, Cochrane library, and Clinical library databases were retrieved for relevant articles published between 2009 and 2019. The articles concerning tissue-engineered meniscus and selection of seed cells were selected, and finally 64 eligible articles were included for analysis. RESULTS AND CONCLUSION: Stem cells have been extensively used as seed cells in tissue-engineered meniscus due to its high proliferation ability and multipotent property. These cells can effectively repair the meniscus in animals, but the clinical outcomes still remain unclear. Therefore, there is a certain distance from basic research to clinical application. [ABSTRACT FROM AUTHOR]

Summary: Receptor tyrosine kinases (RTKs) control stem cell maintenance vs. differentiation decisions. Casitas B-lineage lymphoma (CBL) family ubiquitin ligases are negative regulators of RTKs, but their stem cell regulatory roles remain unclear. Here, we show that Lgr5+ intestinal stem cell (ISC)-specific inducible Cbl-knockout (KO) on a Cblb null mouse background (iDKO) induced rapid loss of the Lgr5Hi ISCs with transient expansion of the Lgr5Lo transit-amplifying population. LacZ-based lineage tracing revealed increased ISC commitment toward enterocyte and goblet cell fate at the expense of Paneth cells. Functionally, Cbl/Cblb iDKO impaired the recovery from radiation-induced intestinal epithelial injury. In vitro, Cbl/Cblb iDKO led to inability to maintain intestinal organoids. Single-cell RNA sequencing in organoids identified Akt-mTOR (mammalian target of rapamycin) pathway hyperactivation upon iDKO, and pharmacological Akt-mTOR axis inhibition rescued the iDKO defects. Our results demonstrate a requirement for Cbl/Cblb in the maintenance of ISCs by fine-tuning the Akt-mTOR axis to balance stem cell maintenance vs. commitment to differentiation.

Summary: Stem cell therapy for intrauterine adhesions (IUAs) has been widely used in clinical treatment. However, intravenous injection lacks sufficient targeting capabilities, while in situ injection poses challenges in ensuring the effective survival of stem cells. Furthermore, the mechanism underlying the interaction between stem cells and endometrial cells in vivo remains poorly understood, and there is a lack of suitable in vitro models for studying these problems. Here, we designed an extracellular matrix (ECM)-adhesion mimic hydrogel for intrauterine administration, which was more effective than direct injection in treating IUAs. Additionally, we analyzed the epithelial-mesenchymal transition (EMT) and confirmed that the activation of endometrial epithelial stem cells is pivotal. Our findings demonstrated that umbilical cord mesenchymal stem cells (UC-MSCs) secrete WNT7A to activate endometrial epithelial stem cells, thereby accelerating regeneration of the endometrial epithelium. Concurrently, under transforming growth factor alpha (TGFA) stimulation secreted by the EMT epithelium, UC-MSCs upregulate E-cadherin while partially implanting into the endometrial epithelium.

Summary: Inflammatory bowel disease (IBD) is a chronic disorder with an increasing global prevalence. Managing disease activity relies on various pharmacological options. However, the effectiveness of current therapeutics is limited and not universally applicable to all patients and circumstances. Consequently, developing new management strategies is necessary. Recent advances in endoscopically obtained intestinal biopsy specimens have highlighted the potential of intestinal epithelial organoid transplantation as a novel therapeutic approach. Experimental studies using murine and human organoid transplantations have shown promising outcomes, including tissue regeneration and functional recovery. Human trials with organoid therapy have commenced; thus, this article provides readers with insights into the necessity and potential of intestinal organoid transplantation as a new regenerative therapeutic option in clinical settings and explores its associated challenges.

Summary: Cancer-associated fibroblasts (CAFs) play a major role in reorganizing the physical tumor micro-environment and changing tissue stiffness. Herein, using an engineered three-dimensional (3D) model that mimics the tumor’s native biomechanical environment, we characterized the changes in matrix stiffness caused by six patient-specific colorectal CAF populations. After 21 days of culture, atomic force microscopy (AFM) was performed to precisely measure the local changes in tissue stiffness. Each CAF population exhibited heterogeneity in remodeling capabilities, with some patient-derived cells stiffening the matrix and others softening it. Tissue stiffening was mainly attributed to active contraction of the matrix by the cells, whereas the softening was due to enzymatic activity of matrix-cleaving proteins. This measured heterogeneity was lost when the CAFs were cocultured with colorectal cancer cells, as all samples significantly soften the tissue. The interplay between cancer cells and CAFs was critical as it altered any heterogeneity exhibited by CAFs alone.

Summary: The intestine is vulnerable to chemotherapy-induced damage due to the high rate of intestinal epithelial cell (IEC) proliferation. We have developed a human intestinal organoid-based 3D model system to study the direct effect of chemotherapy-induced IEC damage on T cell behavior. Exposure of intestinal organoids to busulfan, fludarabine, and clofarabine induced damage-related responses affecting both the capacity to regenerate and transcriptional reprogramming. In ex vivo co-culture assays, prior intestinal organoid damage resulted in increased T cell activation, proliferation, and migration. We identified galectin-9 (Gal-9) as a key molecule released by damaged organoids. The use of anti-Gal-9 blocking antibodies or CRISPR/Cas9-mediated Gal-9 knock-out prevented intestinal organoid damage-induced T cell proliferation, interferon-gamma release, and migration. Increased levels of Gal-9 were found early after HSCT chemotherapeutic conditioning in the plasma of patients who later developed acute GVHD. Taken together, chemotherapy-induced intestinal damage can influence T cell behavior in a Gal-9-dependent manner which may provide novel strategies for therapeutic intervention.

Summary: The developing mouse pancreas is surrounded by mesoderm compartments providing signals that induce pancreas formation. Most pancreatic organoid protocols lack this mesoderm niche and only partially capture the pancreatic cell repertoire. This work aims to generate pancreatic aggregates by differentiating mouse embryonic stem cells (mESCs) into mesoderm progenitors (MPs) and pancreas progenitors (PPs), without using Matrigel. First, mESCs were differentiated into epiblast stem cells (EpiSCs) to enhance the PP differentiation rate. Next, PPs and MPs aggregated together giving rise to various pancreatic cell types, including endocrine, acinar, and ductal cells, and to endothelial cells. Single-cell RNA sequencing analysis revealed a larger endocrine population within the PP + MP aggregates, as compared to PPs alone or PPs in Matrigel aggregates. The PP + MP aggregate gene expression signatures and its endocrine population percentage closely resembled those of the endocrine population found in the mouse embryonic pancreas, which holds promise for studying pancreas development.

Summary: Hypertension is a major cause of morbidity and mortality in patients with hypertrophic cardiomyopathy (HCM), suggesting a potential role for mechanics in HCM pathogenesis. Here, we developed an in vitro physiological model to investigate how mechanics acts together with HCM-linked myosin binding protein C (MYBPC3) mutations to trigger disease. Micro-heart muscles (μHM) were engineered from induced pluripotent stem cell (iPSC)-derived cardiomyocytes bearing MYBPC3+/− mutations and challenged to contract against substrates of different elasticity. μHMs that worked against substrates with stiffness at or exceeding the stiffness of healthy adult heart muscle exhibited several hallmarks of HCM, including cellular hypertrophy, impaired contractile energetics, and maladaptive calcium handling. Remarkably, we discovered changes in troponin C and T localization in MYBPC3+/− μHM that were entirely absent in 2D culture. Pharmacologic studies suggested that excessive Ca2+ intake through membrane-embedded channels underlie the observed electrophysiological abnormalities. These results illustrate the power of physiologically relevant engineered tissue models to study inherited disease with iPSC technology.

Summary: Establishing robust models of human myelinating Schwann cells is critical for studying peripheral nerve injury and disease. Stem cell differentiation has emerged as a key human cell model and disease motivating development of Schwann cell differentiation protocols. Human embryonic stem cells (hESCs) are considered the ideal pluripotent cell but ethical concerns regarding their use have propelled the popularity of human induced pluripotent stem cells (hiPSCs). Given that the equivalence of hESCs and hiPSCs remains controversial, we sought to compare the molecular and functional equivalence of hESC- and hiPSC-derived Schwann cells generated with our previously reported protocol. We identified only modest transcriptome differences by RNA sequencing and insignificant proteome differences by antibody array. Additionally, both cell types comparably improved nerve regeneration and function in a chronic denervation and regeneration animal model. Our findings demonstrate that Schwann cells derived from hESCs and hiPSCs with our protocol are molecularly comparable and functionally equivalent.