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The term 'stem cell' most commonly refers to embryonic stem cells, particularly in the lay media; however, it also describes other cell types. A stem cell represents a cell of multi-lineage potential with the ability for self-renewal. It is now clear that the plasticity and immortality of a given stem cell will depend on what type of stem cell it is, whether an embryonic stem cell, a fetal-placental stem cell or an adult stem cell. Stem cells offer great promise as cell-based therapies for the future. With evolving technology, much of the socio-political debate regarding stem cells can now be avoided. [ABSTRACT FROM AUTHOR]

Background: The transdifferentiation of skin‐derived stem cells (SDSCs) into primordial germ cell‐like cells (PGCLCs) is one of the major breakthroughs in the field of stem cells research in recent years. This technology provides a new theoretical basis for the treatment of human infertility. However, the transdifferentiation efficiency of SDSCs to PGCLCs is very low, and scientists are still exploring ways to improve this efficiency or promote the proliferation of PGCLCs. This study aims to investigate the molecular mechanism of luteinising hormone (LH) to enhance porcine PGCLCs (pPGCLCs) proliferation. Results: In this study, we dissected the proliferation regulatory network of pPGCLCs by whole transcriptome sequencing, and the results showed that the pituitary‐secreted reproductive hormone LH significantly promoted the proliferation of pPGCLCs. We combined whole transcriptome sequencing and related validation experiments to explore the mechanism of LH on the proliferation of pPGCLCs, and found that LH could affect the expression of Hippo signalling pathway‐related mRNAs, miRNAs and lncRNAs in pPGCLCs. Conclusions: For the first time, we found that LH promotes pPGCLCs proliferation through the competing endogenous RNA (ceRNA) regulatory networks and Hippo signalling pathway. This finding may help to elucidate the molecular mechanism by which LH promotes pPGCLCs proliferation. [ABSTRACT FROM AUTHOR]

Abstract: Aim: There have been increased interests in the use of stems cells in the research of osteoarthritis (OA). The present study aimed to investigate the global status and trends in this field. Method: Publications related to stem cells search in OA from 1994 to 2017 were retrieved from the Science Citation Index‐Expanded Web of Science. The source data were studied and indexed using a bibliometric methodology. For visualized study, VOS viewer software was used to conduct bibliographic coupling, co‐authorship, co‐citation and co‐occurrence analysis and to analyze the publication trends in stem cells for OA research. Result: A total of 1933 articles were included. The relative research interests and number of publications were globally increasing per year. The USA made the highest contributions to the global research with the most citations and the highest H‐index. The journal Osteoarthritis and Cartilage had the highest publication number. The Tokyo Medical and Dental University, University of Pittsburgh and Shanghai Jiaotong University were the most contributive institutions. Studies could be divided into four clusters: mechanism study, animal study, clinical trials and tissue engineering. The clinical studies were predicted to be the next popular topic in this field. Conclusion: The number of publications about stem cells for OA would be increasing based on the current global trends. The USA was the largest contributor in this field. Most efforts could be put into clinical studies involving mesenchymal stem cells for OA, which may be the next hot spots in OA and stem cells research. [ABSTRACT FROM AUTHOR]

Stem cell therapy has recently progressed from the preclinical to the early clinical trial arena for a variety of diseases. Moreover, the medical students lack the deep and full understanding of its significance and potential as the promising future cure for diverse diseases worldwide. This study aims at evaluating the knowledge, awareness, and perception of medical students as far as stem cells applications are related in the medical field. A cross‐sectional survey was carried out using online questionnaires, which were distributed via e‐mail to cover all medical faculties in Jordan. The data show that medical students are supportive of using stem cells and their therapeutic applications, and most of them are willing and enthusiastically want to improve their knowledge about stem cells; however, due to the tight schedule and the lack of an elective course about stem cells in the curriculum, many of them are not ready to undergo further training in regenerative medicine unless it becomes part of the assigned training and part of the learning objectives for medical students. These findings indicated the need to update the medical school curriculum with new hits in medicine and expand the range of courses offered for medical students so they can be up‐to‐date with the quick advances in different medical disciplines. [ABSTRACT FROM AUTHOR]

Abstract: The focus of the present review on regenerative medicine is limited; first, on a few human clinical trials carried out thus far in the urology field, and second, on more basic but important biological progress that regenerative medicine has brought us. Clinical trials for the bladder, urethra and urethral sphincter have been carried out thus far. Reconstruction with autologous cell‐seeded biomaterial failed in patients in need of bladder augmentation. The strategy succeeded for urethral reconstruction in patients who might not have required this approach. Sphincter function improvement was attained by cell therapy, but did not equal the conventional standard therapy – the artificial sphincter. The radical progress in regenerative medicine is reported in more basic stem cell technology. The strategy to induce therapeutic cells from inducible pluripotent stem cells has shed novel light on developmental biology. In vitro creation of novel kidney tissue from inducible pluripotent stem cells has been attained. Other kinds of therapeutic cells could also be induced from the inducible pluripotent stem cells. Research should be encouraged to fill the gap between patient needs and what current regenerative medicine can attain. [ABSTRACT FROM AUTHOR]

Loss of functional beta cells is the central event of all forms of diabetes. Conventional therapies for type 2 diabetes (T2D) fail to preserve beta cells, leading to worsening glycemia as beta cell function progressively declines. While immunotherapies for type 1 diabetes (T1D) have been unsuccessful, emerging evidence suggests that therapies to revitalize beta cells are essential to reverse T1D. Islet transplantation represents a promising beta cell replacement therapy. However, its widespread application is limited by the scarcity of available islets and post-transplant islet graft loss. Hence, preserving beta cells is fundamental for managing all types of diabetes. Several key beta cell regulators, including pancreatic and duodenal homeobox 1 (PDX1), v-Maf musculoaponeurotic fibrosarcoma oncogene family protein A (MAFA), and paired box 6 (PAX6), are crucial for beta cell function, with their dysregulation tightly linked to beta cell dysfunction. In this commentary, we summarize the roles of PDX1, MAFA, and PAX6 in determining beta cell function and diabetes development. We also explore the potential of gene therapy that delivers these beta cell regulators as therapeutic interventions to rescue beta cell function in diabetes and discuss the strategies of combining gene therapy with cell therapy to enhance islet transplant efficacy. In this Comment, Wing Yan So and Weiping Han discuss the recent achievements and therapeutic potential of gene therapy targeting beta cell regulators for the treatment of diabetes. [ABSTRACT FROM AUTHOR]

At present, the existence of a variety of dental derived stem cells has been documented. These cells displayed promising clinical application potential not only for teeth and its surrounding tissue regeneration, but also for other tissues, such as nerve and bone regeneration. Proteomics is an unbiased, global informatics tool that provides information on all protein expression levels as well as post-translational modification in cells or tissues and is applicable to dental derived stem cells research. Over the last decade, considerable progress has been made to study the global proteome, secrotome, and membrane proteome of dental derived stem cells. Here, we present an overview of the proteomics studies in the context of stem cell research. Particular attention is given to dental derived stem cell types as well as current challenges and opportunities. J. Cell. Physiol. 232: 1602-1610, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background: Fourier Transform Infrared (FTIR) spectroscopy has emerged as a powerful analytical tool in medical research, offering non‐invasive and precise examination of the molecular composition of biological samples. The primary objective of this review is to underscore the benefits of FTIR spectroscopy in medicinal research, emphasizing its ability to delineate molecular fingerprints and assist in the identification of biochemical structures and key peaks in biological samples. Methods: This review comprehensively explores the diverse applications of FTIR spectroscopy in medical investigations, with a specific focus on its utility in analyzing tissue, cells, and hair samples. Various sources, including Google Scholar, PubMed, WorledCat and Scopus, were utilized to conduct this comprehensive literature review. Results: Recent advancements showcase the versatility of FTIR spectroscopy in elucidating cellular and molecular processes, facilitating disease diagnostics, and enabling treatment monitoring. Notably, FTIR spectroscopy has found significant utility in clinical assessment, particularly in screening counterfeit medicines, owing to its user‐friendly operation and minimal sample preparation requirements. Furthermore, customs officials can leverage this technique for preliminary analysis of suspicious samples. Conclusion: This review aims to bridge a gap in the literature and serve as a valuable resource for future research endeavors in FTIR spectroscopy within the medical domain. Additionally, it presents fundamental concepts of FTIR spectroscopy and spectral data interpretation, highlighting its utility as a tool for molecular analysis using Mid‐Infrared (MIR) radiation. [ABSTRACT FROM AUTHOR]

Over the past few years, several proposals aimed at procuring human pluripotent (embryonic-like) stem cells without involving the destruction of a human embryo have been proposed and widely discussed. This article focuses on a basic aspect of the debate, namely the plausibility of one or more of these new proposals being able to meet the ethical requirements that those who regard the human embryo as sacred have tried to impose on stem cells research in the last ten years. The thesis of the article is that focusing the discussion only on the sources of stem cells has prevented a full understanding of the foundation, meaning and scope of these ethical requirements. To substantiate this thesis, the article takes into consideration two issues: the first has to do with the potential of the cells obtained through some of the new approaches (iPS included), the second (and decisive) with the argument of the 'indirect complicity', applied to the use of 'contaminated' knowledge. [ABSTRACT FROM AUTHOR]

In spite of the attention given to the study of mesenchymal stem cells (MSCs) derived from the bone marrow (BM) of humans and other species, there is a lack of information about murine MSCs. We describe the establishment of conditions for the in vitro expansion of plastic-adherent cells from murine BM for over 50 passages, and provide their characterization regarding morphology, surface marker profile and growth kinetics. These cells were shown to differentiate along osteogenic and adipogenic pathways, and to support the growth and differentiation of haematopoietic stem cells, and were thus operationally defined as murine mesenchymal stem cells (mMSCs). mMSCs were positive for the surface markers CD44, CD49e, CD29 and Sca-1, and exhibited a homogeneous, distinctive morphology. Their frequency in the BM of adult BALB/c and C57Bl/6 mice, normal or knockout for the α-L-iduronidase ( IDUA) gene, was preliminarily estimated to be 1 per 11 300–27 000 nucleated cells. The emergence of a defined methodology for the culture of mMSCs, as well as a comprehensive understanding of their biology, will make the development of cellular and genetic therapy protocols in murine models possible, and provide new perspectives in the field of adult stem cells research. [ABSTRACT FROM AUTHOR]

Exosomes are membrane‐bound vesicles that are released by most cells. They carry nucleic acids, cytokines, growth factors, proteins, lipids, and metabolites. They are responsible for inter‐ and intracellular communications and their role in drug delivery is well defined. Exosomes have great potential for therapeutic applications, but the clinical use is restricted because of limitations in standardized procedures for isolation, purification, and drug delivery. Bioengineering of exosomes could be one approach to achieve standardization and reproducible isolation for clinical use. Exosomes are important transporters for targeted drug delivery because of their small size, stable structure, non‐immunogenicity, and non‐toxic nature, as well as their ability to carry a wide variety of compounds. These features of exosomes can be enhanced further by bioengineering. In this review, possible exosome bioengineering approaches, their biomedical applications, and targeted drug delivery are discussed. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular diseases are prevalent in autistic patients. As exercise is useful in the treatment of medical conditions, this study aimed to identify the effect of low-intensity endurance exercise (LIEE) and moderate-intensity endurance exercise (MIEE) on cardiovascular events in autistic rats. Methods: Valproic acid (VPA) was administrated once on gestational day 12.5 to pregnant rats to produce autism-like symptoms in offspring. Thirtyday-old offspring were divided into 12 groups: Male-CTL, Male-VPA, Male-CTL + LIEE, Male-CTL + MIEE, Male-VPA + LIEE, Male-VPA + MIEE, Female-CTL, Female-VPA, Female-CTL + LIEE, Female-CTL + MIEE, Female-VPA + LIEE, and Female-VPA + MIEE. LIEE and MIEE were performed 5 days a week for 30 days. Twenty-four hours after the last exercise session, electrocardiogram and hemodynamic and cardiac function indices were recorded. Results: The results indicated that +dp/dt max and contractility index (CI) decreased in the Female-VPA group compared to the Female-CTL group. LIEE increased these parameters in the Female-VPA + LIEE group. However, MIEE normalized CI in the Male-VPA + MIEE compared to the Male-VPA group. Tau increased in the Female-VPA group compared to the Female-CTL group and it decreased in the Female-VPA + MIEE group compared to the Female-VPA group. LIEE and MIEE recovered the reduction of heart rate and the increase in P, R, and T amplitudes in Male-VPA group. LIEE and MIEE increased heart rate variability in the Male-VPA and Female-VPA groups. Conclusions: The findings showed that LIEE and MIEE alleviated cardiac dysfunction and disturbances in heart rhythm in the autistic offspring. Exercise may be recommended as a routine program for autistic patients to prevent and treat the harmful cardiovascular consequences of autism. [ABSTRACT FROM AUTHOR]

Regeneration is a complex process affected by many elements independent or combined, including inflammation, proliferation, and tissue remodeling. Stem cells is a class of primitive cells with the potentiality of differentiation, regenerate with self‐replication, multidirectional differentiation, and immunomodulatory functions. Stem cells and their cytokines not only inextricably linked to the regeneration of ectodermal and skin tissues, but also can be used for the treatment of a variety of chronic wounds. Stem cells can produce exosomes in a paracrine manner. Stem cell exosomes play an important role in tissue regeneration, repair, and accelerated wound healing, the biological properties of which are similar with stem cells, while stem cell exosomes are safer and more effective. Skin and bone tissues are critical organs in the body, which are essential for sustaining life activities. The weak repairing ability leads a pronounced impact on the quality of life of patients, which could be alleviated by stem cell exosomes treatment. However, there are obstacles that stem cells and stem cells exosomes trough skin for improved bioavailability. This paper summarizes the applications and mechanisms of stem cells and stem cells exosomes for skin and bone healing. We also propose new ways of utilizing stem cells and their exosomes through different nanoformulations, liposomes and nanoliposomes, polymer micelles, microspheres, hydrogels, and scaffold microneedles, to improve their use in tissue healing and regeneration. [ABSTRACT FROM AUTHOR]

Aplastic anemia (AA) is a disease of bone marrow hematopoietic failure, and the main clinical manifestation is pancytopenia. Its pathogenesis is still unclear. In recent years, more research has been done on its immune abnormalities to explain its pathogenesis and less on the hematopoietic microenvironment, but there are still some advances. This article summarizes the research on the hematopoietic microenvironment of AA in recent years to provide new ideas for the clinical treatment of AA. [ABSTRACT FROM AUTHOR]

Background: Cancer stem cells (CSCs) are responsible for drug resistance, cancer relapse, and metastasis. Here, we report the first analysis of Palladin expression and its impacts on stem cell‐like properties in lung cancer. Methods: Tissue microarrays were used to investigate Palladin expression and its association with prognosis. Immunofluorescence (IF), flow fluorescence assay, and Western blot were performed to detect Palladin expression in 6 NSCLC cell lines. Cell phenotypes and drug resistance were evaluated. Xenograft models were constructed to confirm the role of Palladin in vivo. Results: By using the tissue microarrays, Palladin was identified to be highly expressed in the cytoplasm, specifically in the cytomembrane of NSCLC, and its high expression is associated with poor prognosis. Palladin is widely expressed and enriched in the sphere cells. The in vitro and in vivo studies showed that Palladin promoted stem cell‐like properties, including cell viability, invasion, migration, self‐renewal abilities, taxol resistance, and tumorigenicity. Western blot revealed that Palladin promoted the accumulation of β‐catenin and activated Wnt/β‐catenin signaling. Tissue microarrays analysis further confirmed the positive correlation between Palladin and β‐catenin. Wnt/β‐catenin pathway inhibitor blocked the Palladin‐induced enhancement of sphere‐forming. Conclusions: Palladin might act as an oncogene by promoting CSCs‐like properties and tumorigenicity of NSCLC cells via the Wnt/β‐catenin signaling pathway. Besides, Palladin was identified to have the potential as a cell surface marker for LCSCs identification. These findings provide a possible target for developing putative agents targeted to LCSCs. [ABSTRACT FROM AUTHOR]

Porcine embryonic fibroblasts (PEFs) can be directly reprogrammed into porcine induced pluripotent stem cells (piPSCs). However, the reprogramming process is generally lengthy and inefficient. Here, we established a fast and efficient induction system of piPSCs from porcine Sertoli cells (SCs) via forced expression of pig Yamanaka factors. The alkaline phosphatase (AP)‐positive colonies from SCs developed on Day 3 after lentivirus infection, and were expanded and then picked up on Day 7, whereas reprogramming process from PEFs did not show any colonies in the same period. The picked piPSCs strongly expressed pluripotent genes, had the differentiation capacity to three germ layers, and could be also induced into primordial germ cell‐like cells. Screening for transcription factor combinations showed that POU class 5 homeobox 1 (OCT4) is the core factor for AP‐positive colony formation, and two factors (OCT4 and c‐MYC) could successfully reprogram SCs into piPSCs. We then compared the RNA‐sequencing data of piPSCs derived from SCs and PEFs, and found that the most significant difference was the activation of Transforming Growth Factor β signaling pathway. We also compared the RNA levels of SCs and PEFs, and found that SCs exhibited higher Wnt signaling activity and Bone Morphogenetic Protein 4 expression than PEFs, which might be correlated with higher cell proliferation rate and reprogramming efficiency. In summary, the data demonstrated that starting cell sources of piPSCs significantly affect reprogramming dynamics and SCs could serve as cell sources for efficient reprogramming. [ABSTRACT FROM AUTHOR]

This article is the lead piece in a special report that presents the results of a bioethical investigation into chimeric research, which involves the insertion of human cells into nonhuman animals and nonhuman animal embryos, including into their brains. Rapid scientific developments in this field may advance knowledge and could lead to new therapies for humans. They also reveal the conceptual, ethical, and procedural limitations of existing ethics guidance for human‐nonhuman chimeric research. Led by bioethics researchers working closely with an interdisciplinary work group, the investigation focused on generating conceptual clarity and identifying improvements to governance approaches, with the goal of helping scholars, funders, scientists, institutional leaders, and oversight bodies (embryonic stem cell research oversight [ESCRO] committees and institutional animal care and use committees [IACUCs]) deliver principled and trustworthy oversight of this area of science. The article, which focuses on human‐nonhuman animal chimeric research that is stem cell based, identifies key ethical issues in and offers ten recommendations regarding the ethics and oversight of this research. Turning from bioethics' previous focus on human‐centered questions about the ethics of "humanization" and this research's potential impact on concepts like human dignity, this article emphasizes the importance of nonhuman animal welfare concerns in chimeric research and argues for less‐siloed governance and oversight and more‐comprehensive public communication. [ABSTRACT FROM AUTHOR]

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Cellular 3D structures, for example, organoids, are an excellent model for studying and developing treatments for various diseases, including hereditary ones. Therefore, they are increasingly being used in biomedical research. From the point of view of safety and efficacy, recombinant adeno‐associated viral (rAAV) vectors are currently most in demand for the delivery of various transgenes for gene replacement therapy or other applications. The delivery of transgenes using rAAV vectors to various types of organoids is an urgent task, however, it is associated with a number of problems that are discussed in this review. Cellular heterogeneity and specifics of cultivation of 3D structures determine the complexity of rAAV delivery and are sometimes associated with low transduction efficiency. This review surveys the main ways to solve emerging problems and increase the efficiency of transgene delivery using rAAVs to organoids. A clear understanding of the stage of development of the organoid, its cellular composition and the presence of surface receptors will allow obtaining high levels of organoid transduction with existing rAAV vectors. [ABSTRACT FROM AUTHOR]

Advancing age is associated with several diseases and disorders due to multiorgan atrophy. The increasing proportion of elderly humans demands the identification of means to counteract aging and age‐associated disorders. There is an increased depletion of stem cells in the aged organs, resulting in their inability to repair the damage and hence organ degeneration. Stem cell therapy has been implicated in counteracting aging and shown promise. However, the use of stem cells encounters several side effects and complications such as handling and storage of the cells for transplantation purpose. Stem cells secretome has proven to be of significant importance in a variety of disorders. In this study, we have shown that secretome derived from dental pulp stem cells (DPSCs) can reverse the age‐associated degeneration induced by chronic exposure to d‐galactose in a rat model. The secretome was able to increase muscle grip strength and animal activity. Secretome also improved the kidney function and hepatic biochemistry similar to healthy controls as evaluated by renal function test and Fourier‐transform infrared spectroscopy. We also showed that secretome reduced the levels of monoamine oxidase and acetylcholinesterase in the brain and liver, indicating aging reversal. Finally, proteomic profiling of DPSCs secretome revealed the presence of 13 proteins which have antiaging functions. Thus, our study provides first proof of concept that DPSCs secretome can render protection against d‐galactose induced accelerated aging. Significance statement: With the ever increasing number of geriatric population, the problems associated with the increased age resulting in multiorgan degeneration and dysfunction demand appropriate antiaging therapies to improve the overall living conditions. Although mesenchymal stem cells have shown remarkable tissue reparative properties, their use if often limited in the clinics due to several safety issues. We have provided concrete evidence that cell‐free extract (i.e., secretome) from dental pulp stem cells (DPSCs) can be used to treat age‐associated deterioration of the tissues by improving the overall metabolic health and physiological status of the organism. Proteomic profiling of DPSCs secretome revealed the presence of several antiaging proteins which can be explored further to develop cell‐free therapeutics for age‐related disorders. [ABSTRACT FROM AUTHOR]

Aim: Chemotherapy with cyclophosphamide can damage ovaries and cause infertility in girls and women. Sesamol is a phenolic antioxidant that can protect various organs from damage. The purpose of this study was to evaluate the effects of sesamol on protecting the function and structure of rat ovaries against the side effects of a chemotherapy model with cyclophosphamide. Methods: Twenty‐four adult female Wistar rats were randomly divided into three groups: (1) normal group, without any treatment, (2) control group, immediately after receiving cyclophosphamide, 0.5% dimethyl sulfoxide (DMSO) as the solvent of sesamol was intraperitoneally injected for 14 consecutive days, (3) sesamol group, immediately after receiving cyclophosphamide, 50 mg/kg sesamol was intraperitoneally injected for 14 consecutive days. Four weeks after the last injection, superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels in the ovary, anti‐Mullerian hormone (AMH) levels in the serum, number of ovarian follicles in different stages, and expression of proteins growth differentiation factor‐9 (GDF‐9), Bcl‐2, and Bax in the ovary were evaluated. Results: The results of SOD activity and MDA levels in the ovary, AMH levels in the serum, number of ovarian follicles in different stages, and expression of proteins GDF9, Bcl‐2, and Bax in the ovary were significantly more favorable in the sesamol group than the control group. Conclusions: The results suggest that sesamol may protect function and structure in the rat ovaries against side effects of the chemotherapy model with cyclophosphamide by decreasing oxidative stress and apoptosis in the ovary. [ABSTRACT FROM AUTHOR]

Amniotic fluid surrounding the developing fetus is a complex biological fluid rich in metabolically active bio‐factors. The presence of extracellular vesicles (EVs) in amniotic fluid has been mainly related to foetal urine. We here characterized EVs from term amniotic fluid in terms of surface marker expression using different orthogonal techniques. EVs appeared to be a heterogeneous population expressing markers of renal, placental, epithelial and stem cells. Moreover, we compared amniotic fluid EVs from normal pregnancies with those of preeclampsia, a hypertensive disorder affecting up to 8% of pregnancies worldwide. An increase of CD105 (endoglin) expressing EVs was observed in preeclamptic amniotic fluid by bead‐based cytofluorimetric analysis, and further confirmed using a chip‐based analysis. HLA‐G, a typical placental marker, was not co‐expressed by the majority of CD105+ EVs, in analogy with amniotic fluid stromal cell derived‐EVs. At a functional level, preeclampsia‐derived EVs, but not normal pregnancy EVs, showed an antiangiogenic effect, possibly due to the decoy effect of endoglin. Our results provide a characterization of term amniotic fluid‐EVs, supporting their origin from foetal and placental cells. In preeclampsia, the observed antiangiogenic characteristics of amniotic fluid‐EVs may reflect the hypoxic and antiangiogenic microenvironment and could possibly impact on the developing fetus or on the surrounding foetal membranes. [ABSTRACT FROM AUTHOR]

Stem cells have been proposed as a wonder solution for tissue repair in many situations and have attracted much attention in the media for both their therapeutic potential and ethical implications. In addition to the excitement generated by embryonic stem cells, research has now identified a number of stem cells within adult tissues which pose much more realistic targets for therapeutic interventions. Myoblast transfer therapy (MTT) has long been viewed as a potential therapy for the debilitating muscle-wasting disorder Duchenne Muscular Dystrophy. This technique relies on the transplantation of committed muscle precursor cells directly into the muscle fibres but has had little success in clinical trials. The recent discovery of a population of cells within adult muscle with stem cell-like characteristics has interesting implications for the future of such putative cell transplantation therapies. This review focuses on the characterization and application of these potential muscle-derived stem cells (MDSC) to MTT. IUBMB Life , 57: 731–736, 2005 [ABSTRACT FROM AUTHOR]

Background and Objective: Neuropathic pain arises as a direct consequence of a lesion or disease affecting the somatosensory system. A number of preclinical studies have provided evidence for the involvement of cytokines, predominantly secreted by a variety of immune cells and by glial cells from the nervous system, in neuropathic pain conditions. Clinical trials and the use of anti‐cytokine drugs in different neuropathic aetiologies support the relevance of cytokines as treatment targets. However, the use of such drugs, in particularly biotherapies, can provoke notable adverse effects. Moreover, it is challenging to select one given cytokine as a target, among the various neuropathic pain conditions. It could thus be of interest to target other proteins, such as growth factors, in order to act more widely on the neuroinflammation network. Thus, platelet‐rich plasma (PRP), an autologous blood concentrate, is known to contain a natural concentration of growth factors and immune system messengers and is widely used in the clinical setting for tissue regeneration and repair. Database and Data Treatment: In the present review, we critically assess the current knowledge on cytokines in neuropathic pain by taking into consideration both human studies and animal models. Results: This analysis of the literature highlights the pathophysiological importance of cytokines. We particularly highlight the concept of time‐ and tissue‐dependent cytokine activation during neuropathic pain conditions. Conclusion: Thus, direct or indirect cytokines modulation with biotherapies or growth factors appears relevant. In addition, we discuss the therapeutic potential of localized injection of PRP as neuropathic pain treatment by pointing out the possible link between cytokines and the action of PRP. Significance: Preclinical and clinical studies highlight the idea of a cytokine imbalance in the development and maintenance of neuropathic pain. Clinical trials with anticytokine drugs are encouraging but are limited by a 'cytokine candidate approach' and adverse effect of biotherapies. PRP, containing various growth factors, is a new therapeutic used in regenerative medicine. Growth factors can be also considered as modulators of cytokine balance. Here, we emphasize a potential therapeutic effect of PRP on cytokine imbalance in neuropathic pain. We also underline the clinical interest of the use of PRP, not only for its therapeutic effect but also for its safety of use. [ABSTRACT FROM AUTHOR]

Mesenchymal stromal cells (MSCs) isolated from fetal adnexa namely amniotic membrane/epithelium, amniotic fluid and umbilical cord have hogged the limelight in recent times, as a proposed alternative to MSCs from conventional sources. These cells which are identified as being in a developmentally primitive state have many advantages, the most important being the non‐invasive nature of their isolation procedures, absence of ethical concerns, proliferation potential, differentiation abilities and low immunogenicity. In the present review, we are focusing on the potential preclinical and clinical applications of different cell types of fetal adnexa, in wound healing therapy. We also discuss the isolation‐culture methods, cell surface marker expression, multi‐lineage differentiation abilities, immune‐modulatory capabilities and their homing property. Different mechanisms involved in the wound healing process and the role of stromal cells in therapeutic wound healing are highlighted. Further, we summarize the findings of the cell delivery systems in skin lesion models and paracrine functions of their secretome in the wound healing process. Overall, this holistic review outlines the research findings of fetal adnexa derived MSCs, their usefulness in wound healing therapy in human as well as in veterinary medicine. [ABSTRACT FROM AUTHOR]

The aim of this study was to synthesize Hydroxyapatite (HA) from carp bone waste by calcination treatment. The effects of calcination temperature and time on crystallite size, crystallinity%, powder size and morphology, formed phases, and Ca/P ratio were analyzed. The XRD analyses indicated that for 1 h calcination time, HA was the only phase produced at all temperatures. However, for 5 h calcination time, temperatures other than 700ºC resulted in formation of TCP+HA. The HA obtained at 700ºC at both times had less crystallinity compared to other temperatures. Crystallite size increased by increase in temperature at 1 h calcination time. The smallest and largest particulate sizes were obtained at 800ºC for 1 h and 900ºC for 5 h, respectively. The Ca/P ratio close to theoretical value (1.67) was obtained for 5 h calcination time. Finally, the results showed the usefulness of the methodology used in natural HA production that can be used in orthopedics and dentistry. [ABSTRACT FROM AUTHOR]

Breast cancer is a heterogeneous disease manifesting diversity at the molecular, histological and clinical level. The development of breast cancer classification was centered on informing clinical decisions. The current approach to the classification of breast cancer, which categorizes this disease into clinical subtypes based on the detection of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and proliferation marker Ki67, is not ideal. This is manifested as a heterogeneity of therapeutic responses and outcomes within the clinical subtypes. The newer classification model, based on gene expression profiling (intrinsic subtyping) informs about transcriptional responses downstream from IHC single markers, revealing deeper appreciation for the disease heterogeneity and capturing tumor biology in a more comprehensive way than an expression of a single protein or gene alone. While accumulating evidences suggest that intrinsic subtypes provide clinically relevant information beyond clinical surrogates, it is imperative to establish whether the current conventional immunohistochemistry‐based clinical subtyping approach could be improved by gene expression profiling and if this approach has a potential to translate into clinical practice. [ABSTRACT FROM AUTHOR]

Background Information: Wnt/β‐catenin signalling, in the microenvironment of pluripotent stem cells (PSCs), plays a critical role in their differentiation and proliferation. Contradictory reports on the role of Wnt/β‐catenin signalling in PSCs self‐renewal and differentiation, however, render these mechanisms largely unclear. Results: Wnt/β‐catenin signalling pathway in human‐induced pluripotent stem cells (hiPSCs) was activated by inhibiting glycogen synthase kinase 3 (GSK3), driving the cells into a mesodermal/mesenchymal state, exhibiting proliferative, invasive and anchorage‐independent growth properties, where over 70% of cell population became CD 44 (+)/CD133 (+). Wnt/β‐catenin signalling activation also altered the metabolic state of hiPSCs from aerobic glycolysis to oxidative metabolism and changed their drug and oxidative stress sensitivities. These effects of GSK3 inhibition were suppressed in HIF1α‐stabilised cells. Conclusions: Persistent activation of Wnt/β‐catenin signalling endows hiPSCs with proliferative/invasive 'teratoma‐like' states, shifting their metabolic dependence and allowing HIF1α‐stabilisation to inhibit their proliferative/invasive properties. Significance: The hiPSC potential to differentiate into 'teratoma‐like' cells suggest that stem cells may exist in two states with differential metabolic and drug dependency. [ABSTRACT FROM AUTHOR]

Nanomaterials are excellent drug delivery systems, yet, they must be functionalized in a manner compatible with the biological environment. Regarding delivery of the payloads, it is critical to monitor the nanocarrier's biocompatibility and the ability to control its drug encapsulation and release, as well as targeting. The current challenges include avoiding negative host immune responses, optimizing stability in biological environments, and achieving precise interactions with the targets. Contemporary advances in structural DNA nanotechnology, DNA origami, and supramolecular DNA assembly make it possible to produce complex multi‐functional DNA nanostructures, wherein precise control of the size, geometry, and appearance of the ligands is feasible. DNA nanostructures offer ease of synthesis and conjugation of functional moieties to target the release of cargo or to analyze important biomarkers for diagnostics. Furthermore, the biocompatibility, programmability, responsiveness to biomolecules, cell‐surfaces, and organisms make such DNA nanomaterials highly suitable for potential translational applications. This overview summarizes the recent developments in functionalizing, stabilizing, and applying DNA nanostructures for potential biomedical applications. [ABSTRACT FROM AUTHOR]

The article presents abstracts on stem cells research topics which include the ranking of values as a basis for ethical decision making in ethical controversies: the case of stem cell research, the import of embryonic stem cell lines, and ethics and legislations on stem cell research examples on European legislations on stem cell research.

Drug resistance represents an obstacle in colorectal cancer (CRC) treatment because of its association with poor prognosis. rBC2LCN is a lectin isolated from Burkholderia that binds cell surface glycans that have fucose moieties. Because fucosylation is enhanced in many types of cancers, this lectin could be an efficient drug carrier if CRC cells specifically present such glycans. Therefore, we examined the therapeutic efficacy and toxicity of lectin drug conjugate therapy in CRC mouse xenograft models. The affinity of rBC2LCN for human CRC cell lines HT‐29, LoVo, LS174T, and DLD‐1 was assessed in vitro. The cytocidal efficacy of a lectin drug conjugate, rBC2LCN‐38 kDa domain of pseudomonas exotoxin A (PE38) was evaluated by MTT assay. The therapeutic effects and toxicity for each CRC cell line‐derived mouse xenograft model were compared between the intervention and control groups. LS174T and DLD‐1 cell lines showed a strong affinity for rBC2LCN. In the xenograft model, the tumor volume in the rBC2LCN‐PE38 group was significantly reduced compared with that using control treatment alone. However, the HT‐29 cell line showed weak affinity and poor therapeutic efficacy. No significant toxicities or adverse responses were observed. In conclusion, we demonstrated that rBC2LCN lectin binds CRC cells and that rBC2LCN‐PE38 significantly suppresses tumor growth in vivo. In addition, the efficacy of the drug conjugate correlated with its binding affinity for each CRC cell line. These results suggest that lectin drug conjugate therapy has potential as a novel targeted therapy for CRC cell surface glycans. [ABSTRACT FROM AUTHOR]

Umbilical cord‐derived mesenchymal stem cells (UCDMSC) are attractive candidates for cell‐based regenerative medicine. However, they are susceptible to replicative senescence during repetitive passaging for in‐vitro expansion and induced senescence in an oxidative, inflammatory microenvironment in vivo. Aim of this study is to investigate if honey‐incorporated matrices can be employed to reduce senescence of UCDMSC. Matrices were prepared by electrospinning solutions of honey with poly‐vinyl alcohol (PVA). PVA:honey matrices exhibited free radical scavenging activity. Culture of UCDMSC on PVA:honey matrices showed improvement in cell proliferation compared to pure PVA nanofibres. Expression of vimentin indicated that mesenchymal phenotype is preserved after culturing on these matrices. Further, UCDMSC were serially subcultured and cells of two passages (P2 and P6) were evaluated for reactive oxygen species (ROS) load and senescence parameters. P6 cells showed a higher ROS load and β‐galactosidase (β‐gal) positive senescent cells compared to P2. However, culturing on PVA:honey substrates significantly reduced both ROS and β‐gal markers compared to cells on PVA substrates. Honey contains several antioxidant and anti‐inflammatory components, which can reduce the ROS‐related senescence. Thus, it is concluded that honey containing nanofibres can be effective substrates for stem cell‐based wound healing and regenerative medicine. [ABSTRACT FROM AUTHOR]

In this study we designed high‐throughput 3D bioprinting of corneal equivalents which may address the need for in vitro models. In our digital 3D cornea model, average dimensions of adult cornea were converted to 3D shapes, then to G‐code files which were printed by BIOX printer (CELLINK). To maintain the curvature of cornea, a support scaffold was designed using stereolithographic printer. The support scaffold could facilitate the printing of 6–12 corneas at a time thus enabling high‐throughput printing. Human corneal keratocytes (HCKs) were incorporated in the optimized bio‐ink, and cell‐laden corneal stromal equivalents were printed. Printed structures were cross‐linked by calcium chloride 100 mM, washed with Hanks' Balanced Salt Solution and incubated at 37°C in fibroblast media. Printed corneas were analyzed for live dead assay, Alamar assay, and expression of fibronectin and actin green markers. Printed corneas were able to maintain their structure, integrity, and clarity. Live dead assay and Alamar assay demonstrated that HCKs maintained high viability (>95%) for 2 weeks. HCKs in the printed corneas showed expression for fibronectin and actin green. In conclusion, high‐throughput fabrication of 3D printed corneal stromal equivalents using a combination of stereolithography printing, extrusion based printing, and micro‐transfer molding techniques was achieved. [ABSTRACT FROM AUTHOR]

Three‐dimensional (3D) culture provides a biomimicry of the naive microenvironment that can support cell proliferation, differentiation, and regeneration. Some growth factors, such as epidermal growth factor (EGF), facilitate normal meiosis during oocyte maturation in vivo. In this study, a scaffold‐based 3D coculture system using purified alginate was applied to induce oocyte differentiation from mouse embryonic stem cells (mESCs). mESCs were induced to differentiate into oocyte‐like cells using embryoid body protocol in the two‐dimensional or 3D microenvironment in vitro. To increase the efficiency of the oocyte‐like cell differentiation from mESCs, we employed a coculture system using ovarian granulosa cells in the presence or absence of epidermal growth factor (+EGF or −EGF) for 14 days and then the cells were assessed for germ cell differentiation, meiotic progression, and oocyte maturation markers. The cultures exposed to EGF in the alginate‐based 3D microenvironment showed the highest level of premeiotic (Oct4 and Mvh), meiotic (Scp1, Scp3, Stra8, and Rec8), and oocyte maturation (Gdf9, Cx37, and Zp2) marker genes (p <.05) in comparison to other groups. According to the gene‐expression patterns, we can conclude that alginate‐based 3D coculture system provided a highly efficient protocol for oocyte‐like cell differentiation from mESCs. The data showed that this culture system along with EGF improved the rate of in vitro oocyte‐like cell differentiation. [ABSTRACT FROM AUTHOR]

Although considerable efforts have been conducted to diagnose, improve, and treat cancer in the past few decades, existing therapeutic options are insufficient, as mortality and morbidity rates remain high. Perhaps the best hope for substantial improvement lies in early detection. Recent advances in nanotechnology are expected to increase the current understanding of tumor biology, and will allow nanomaterials to be used for targeting and imaging both in vitro and in vivo experimental models. Owing to their intrinsic physicochemical characteristics, nanostructures (NSs) are valuable tools that have received much attention in nanoimaging. Consequently, rationally designed NSs have been successfully employed in cancer imaging for targeting cancer‐specific or cancer‐associated molecules and pathways. This review categorizes imaging and targeting approaches according to cancer type, and also highlights some new safe approaches involving membrane‐coated nanoparticles, tumor cell‐derived extracellular vesicles, circulating tumor cells, cell‐free DNAs, and cancer stem cells in the hope of developing more precise targeting and multifunctional nanotechnology‐based imaging probes in the future. [ABSTRACT FROM AUTHOR]

The prognosis of patients with progressive prostate cancers that are hormone refractory and/or have bone metastasis is poor. Multiple therapeutic targets to improve prostate cancer patient survival have been investigated, including orphan GPCRs. In our study, we identified G Protein‐Coupled Receptor Class C Group 5 Member A (GPRC5A) as a candidate therapeutic molecule using integrative gene expression analyses of registered data sets for prostate cancer cell lines. Kaplan–Meier analysis of TCGA data sets revealed that patients who have high GPRC5A expression had significantly shorter overall survival. PC3 prostate cancer cells with CRISPR/Cas9‐mediated GPRC5A knockout exhibited significantly reduced cell proliferation both in vitro and in vivo. RNA‐seq revealed that GPRC5A KO PC3 cells had dysregulated expression of cell cycle‐related genes, leading to cell cycle arrest at the G2/M phase. Furthermore, the registered gene expression profile data set showed that the expression level of GPRC5A in original lesions of prostate cancer patients with bone metastasis was higher than that without bone metastasis. In fact, GPRC5A KO PC3 cells failed to establish bone metastasis in xenograft mice models. In addition, our clinical study revealed that GPRC5A expression levels in prostate cancer patient samples were significantly correlated with bone metastasis as well as the patient's Gleason score (GS). Combined assessment with the immunoreactivity of GPRC5A and GS displayed higher specificity for predicting the occurrence of bone metastasis. Together, our findings indicate that GPRC5A can be a possible therapeutic target and prognostic marker molecule for progressive prostate cancer. What's new? Although androgen deprivation is effective in most prostate cancer patients, cellular pathways outside androgen receptor signaling are being explored to treat castration‐resistant cancer forms. Here the authors focus on GPRC5A, an orphan G protein‐coupled receptor, they find is overexpressed in prostate cancer cell lines. Knockout of GPRC5A decreased proliferation of a prostate cancer cell line and prevented bone metastasis in a xenograft model. In patients, GPRC5A expression correlated with shorter overall survival and bone metastasis, underscoring its clinical potential as a therapeutic or prognostic target. [ABSTRACT FROM AUTHOR]

The native microenvironment of mesenchymal stem cells (hMSCs)—the extracellular matrix (ECM), is a complex and heterogenous environment structured at different scales. The present study aims at mimicking the hierarchical microorganization of proteins or growth factors within the ECM using the photolithography technique. Polyethylene terephthalate substrates were used as a model material to geometrically defined regions of RGD + BMP‐2 or RDG + OGP mimetic peptides. These ECM‐derived ligands are under research for regulation of mesenchymal stem cells osteogenic differentiation in a synergic manner. The hMSCs osteogenic differentiation was significantly affected by the spatial distribution of dually grafted peptides on surfaces, and hMSCs cells reacted differently according to the shape and size of peptide micropatterns. Our study demonstrates the presence of a strong interplay between peptide geometric cues and stem cell differentiation toward the osteoblastic lineage. These tethered surfaces provide valuable tools to investigate stem cell fate mechanisms regulated by multiple ECM cues, thereby contributing to the design of new biomaterials and improving hMSCs differentiation cues. [ABSTRACT FROM AUTHOR]

Comments on the conclusions of Geron's Ethics Advisory Board on the benefits of stem cells research. Failure of the Geron's report to elaborate the issues associated with the moral status of human stem cells; Distinction between stem cell research that involves cells derived from blastocysts and research that involves cells from fetal tissue obtained from aborted fetuses.

Enhancing differentiation of mesenchymal stem cells (MSCs) to endothelial cells may improve their ability to vascularize tissue and promote wound healing. This study describes a novel role for nitric oxide (NO) in reprogramming MSCs towards an endothelial lineage and highlights the role of Wnt signaling and epigenetic modification by NO. Rat MSCs were transduced with lentiviral vectors expressing endothelial nitric oxide synthase (pLV‐eNOS) and a mutated caveolin gene (pLV‐CAV‐1F92A) to enhance NO generation resulting in increased in vitro capillary tubule formation and endothelial marker gene expression. An exogenous source of NO could also stimulate CD31 expression in MSCs. NO was associated with an arterial‐specific endothelial gene expression profile of Notch1, Dll4, and Hey2 and significantly reduced expression of venous markers. Wnt signaling associated with NO was evident through increased gene expression of Wnt3a and β‐catenin protein, and expression of the endothelial marker Pecam‐1 could be significantly reduced by treatment with the Wnt signaling inhibitor Dkk‐1. The role of NO as an epigenetic modifier was evident with reduced gene expression of the methyltransferase, DNMT1, and bisulfite sequencing of the endothelial Flt1 promoter region in NO‐producing MSCs showed significant demethylation compared to control cells. Finally, subcutaneous implantation of NO‐producing MSCs seeded in a biomaterial scaffold (NovoSorb®) resulted in survival of transplanted cells and the formation of blood vessels. In summary, this study describes, NO as a potent endothelial programming factor which acts as an epigenetic modifier in MSCs and may provide a novel platform for vascular regenerative therapy. [ABSTRACT FROM AUTHOR]

New types of devices made using thin‐film‐transistor (TFT) technology were used in this article for dielectrophoresis purpose with microbeads, yeast cells, and HepG2 cells. That technology allows obtaining centimeter size transparent substrates covered with a large and dense array of 100 µm microelectrodes individually controllable. The purpose of these devices is the development of platforms for various applications on cells and cells culture, like manipulation, sensing, monitoring, or stimulation on the same device. Dielectrophoresis is one of the applications and is a key target for precise patterning and 2D displacement of cells on the device. In this article, 2D results of dielectrophoresis with microbeads and yeast cells and device programming are described. Then, application to mammal HepG2 liver cells shows the possibility of cells patterning with such devices. © 2019 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc. [ABSTRACT FROM AUTHOR]