Tfap2b specifies an embryonic melanocyte stem cell that retains adult multifate potential.

Melanocytes, the pigment-producing cells, are replenished from multiple stem cell niches in adult tissue. Although pigmentation traits are known risk factors for melanoma, we know little about melanocyte stem cell (McSC) populations other than hair follicle McSCs and lack key lineage markers with which to identify McSCs and study their function. Here we find that Tfap2b and a select set of target genes specify an McSC population at the dorsal root ganglia in zebrafish. Functionally, Tfap2b is required for only a few late-stage embryonic melanocytes, and is essential for McSC-dependent melanocyte regeneration. Fate mapping data reveal that tfap2b+ McSCs have multifate potential, and are the cells of origin for large patches of adult melanocytes, two other pigment cell types (iridophores and xanthophores), and nerve-associated cells. Hence, Tfap2b confers McSC identity in early development, distinguishing McSCs from other neural crest and pigment cell lineages, and retains multifate potential in the adult zebrafish.

Airway basal stem cells generate distinct subpopulations of PNECs.

Pulmonary neuroendocrine cells (PNECs) have crucial roles in airway physiology and immunity by producing bioactive amines and neuropeptides (NPs). A variety of human diseases exhibit PNEC hyperplasia. Given accumulated evidence that PNECs represent a heterogenous population of cells, we investigate how PNECs differ, whether the heterogeneity is similarly present in mouse and human cells, and whether specific disease involves discrete PNECs. Herein, we identify three distinct types of PNECs in human and mouse airways based on single and double positivity for TUBB3 and the established NP markers. We show that the three PNEC types exhibit significant differences in NP expression, homeostatic turnover, and response to injury and disease. We provide evidence that these differences parallel their distinct cell of origin from basal stem cells (BSCs) or other airway epithelial progenitors.

Regenerative Stem Cell Therapy for Neurodegenerative Diseases: An Overview.

Neurodegenerative diseases resulting from the progressive loss of structure and/or function of neurons contribute to different paralysis degrees and loss of cognition and sensation. The lack of successful curative therapies for neurodegenerative disorders leads to a considerable burden on society and a high economic impact. Over the past 20 years, regenerative cell therapy, also known as stem cell therapy, has provided an excellent opportunity to investigate potentially powerful innovative strategies for treating neurodegenerative diseases. This is due to stem cells' capability to repair injured neuronal tissue by replacing the damaged or lost cells with differentiated cells, providing a conducive environment that is in favor of regeneration, or protecting the existing healthy neurons and glial cells from further damage. Thus, in this review, the various types of stem cells, the current knowledge of stem-cell-based therapies in neurodegenerative diseases, and the recent advances in this field are summarized. Indeed, a better understanding and further studies of stem cell technologies cause progress into realistic and efficacious treatments of neurodegenerative disorders.

Will stem cells from fat and growth factors from blood bring new hope to female patients with reproductive disorders?

Female reproductive system disorders (FRSD) with or without infertility are prevalent women's health problems with a variety of treatment approaches including surgery and hormone therapy. It currently considering to sub-branch of regenerative medicine including stem cells or growth factors injection-based delivery treatment might be improved female reproductive health life. The most common products used for these patients treatment are autologous cell or platelet-based products from patients, including platelet-rich plasma, plasma rich in growth factor, platelet-rich fibrin, and stromal vascular fraction. In this review, we discuss each of the above products used in treatment of FRSD and critically evaluate the clinical outcome.

A single-cell atlas of the mouse and human prostate reveals heterogeneity and conservation of epithelial progenitors.

Understanding the cellular constituents of the prostate is essential for identifying the cell of origin for prostate adenocarcinoma. Here, we describe a comprehensive single-cell atlas of the adult mouse prostate epithelium, which displays extensive heterogeneity. We observe distal lobe-specific luminal epithelial populations (LumA, LumD, LumL, and LumV), a proximally enriched luminal population (LumP) that is not lobe-specific, and a periurethral population (PrU) that shares both basal and luminal features. Functional analyses suggest that LumP and PrU cells have multipotent progenitor activity in organoid formation and tissue reconstitution assays. Furthermore, we show that mouse distal and proximal luminal cells are most similar to human acinar and ductal populations, that a PrU-like population is conserved between species, and that the mouse lateral prostate is most similar to the human peripheral zone. Our findings elucidate new prostate epithelial progenitors, and help resolve long-standing questions about anatomical relationships between the mouse and human prostate.

Umbilical cord stem cells: Background, processing and applications.

Stem cells have currently gained attention in the field of medicine not only due to their ability to repair dysfunctional or damaged cells, but also they could be used as drug delivery system after being engineered to do so. Human umbilical cord is attractive source for autologous and allogenic stem cells that are currently amenable to treatment of various diseases. Human umbilical cord stem cells are -in contrast to embryonic and fetal stem cells- ethically noncontroversial, inexpensive and readily available source of cells. Umbilical cord, umbilical cord vein, amnion/placenta and Wharton's jelly are all rich of many types of multipotent stem cell populations capable of forming many different cell types. This review will focus on umbilical cord stem cells processing and current application in medicine.

Stem cells in tissues, organoids, and cancers.

Stem cells give rise to all cells and build the tissue structures in our body, and heterogeneity and plasticity are the hallmarks of stem cells. Epigenetic modification, which is associated with niche signals, determines stem cell differentiation and somatic cell reprogramming. Stem cells play a critical role in the development of tumors and are capable of generating 3D organoids. Understanding the properties of stem cells will improve our capacity to maintain tissue homeostasis. Dissecting epigenetic regulation could be helpful for achieving efficient cell reprograming and for developing new drugs for cancer treatment. Stem cell-derived organoids open up new avenues for modeling human diseases and for regenerative medicine. Nevertheless, in addition to the achievements in stem cell research, many challenges still need to be overcome for stem cells to have versatile application in clinics.

Stem Cells as a Resource for Treatment of Infertility-related Diseases.

Worldwide, infertility affects 8-12% of couples of reproductive age and has become a common problem. There are many ways to treat infertility, including medication, intrauterine insemination, and in vitro fertilization. In recent years, stem-cell therapy has raised new hope in the field of reproductive disability management. Stem cells are self-renewing, self-replicating undifferentiated cells that are capable of producing specialized cells under appropriate conditions. They exist throughout a human's embryo, fetal, and adult stages and can proliferate into different cells. While many issues remain to be addressed concerning stem cells, stem cells have undeniably opened up new ways to treat infertility. In this review, we describe past, present, and future strategies for the use of stem cells in reproductive medicine.

Stem cell therapy for Parkinson's disease using non-human primate models.

Stem cell therapy (SCT) for Parkinson's disease (PD) has received considerable attention in recent years. Non-human primate (NHP) models of PD have played an instrumental role in the safety and efficacy of emerging PD therapies and facilitated the translation of initiatives for human patients. NHP models of PD include primates with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism, who are responsive to dopamine replacement therapies, similar to human PD patients. Extensive research in SCT has been conducted to better treat the progressive dopaminergic neurodegeneration that underlies PD. For effective application of SCT in PD, however, a number of basic parameters still need to be tested and optimized in NHP models, including preparation and storage of cells for engraftment, methods of transplantation, choice of target sites, and timelines for recovery. In this review, we discuss the current status of NHP models of PD in stem cell research. We also analyze the advances and remaining challenges for successful clinical translation of SCT for this persistent disease.

Towards a classification of stem cells.

The characteristic properties of stem cells - notably their ability to self-renew and to differentiate - have meant that they have traditionally been viewed as distinct from most other types of cells. However, recent research has blurred the line between stem cells and other cells by showing that the former display a range of behaviors in different tissues and at different stages of development. Here, we use the tools of metaphysics to describe a classification scheme for stem cells, and to highlight what their inherent diversity means for cancer treatment.

Rapid and selective mobilization of specific stem cell types after consumption of a polyphenol-rich extract from sea buckthorn berries (Hippophae) in healthy human subjects.

PURPOSE: The aim of this study was to evaluate the effects of a proanthocyanidin-rich extract of sea buckthorn berry (SBB-PE) on the numbers of various types of adult stem cells in the blood circulation of healthy human subjects. STUDY DESIGN AND METHODS: A randomized, double-blind, placebo-controlled, cross-over trial was conducted in 12 healthy subjects. Blood samples were taken immediately before and at 1 and 2 hours after consuming either placebo or 500 mg SBB-PE. Whole blood was used for immunophenotyping and flow cytometry to quantify the numbers of CD45dim CD34+ CD309+ and CD45dim CD34+ CD309- stem cells, CD45- CD31+ CD309+ endothelial stem cells, and CD45- CD90+ mesenchymal stem cells. RESULTS: Consumption of SBB-PE was associated with a rapid and highly selective mobilization of CD45dim CD34+ CD309- progenitor stem cells, CD45- CD31+ CD309+ endothelial stem cells, and CD45- CD90+ lymphocytoid mesenchymal stem cells. In contrast, only minor effects were seen for CD45dim CD34+ CD309+ pluripotential stem cells. CONCLUSION: Consumption of SBB-PE resulted in selective mobilization of stem cell types involved in regenerative and reparative functions. These data may contribute to the understanding of the traditional uses of SBB for preventive health, regenerative health, and postponing the aging process.

Stem cells: past, present, and future.

In recent years, stem cell therapy has become a very promising and advanced scientific research topic. The development of treatment methods has evoked great expectations. This paper is a review focused on the discovery of different stem cells and the potential therapies based on these cells. The genesis of stem cells is followed by laboratory steps of controlled stem cell culturing and derivation. Quality control and teratoma formation assays are important procedures in assessing the properties of the stem cells tested. Derivation methods and the utilization of culturing media are crucial to set proper environmental conditions for controlled differentiation. Among many types of stem tissue applications, the use of graphene scaffolds and the potential of extracellular vesicle-based therapies require attention due to their versatility. The review is summarized by challenges that stem cell therapy must overcome to be accepted worldwide. A wide variety of possibilities makes this cutting edge therapy a turning point in modern medicine, providing hope for untreatable diseases.

Stem cells in animal models of Huntington disease: A systematic review.

Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder encoding a mutant form of the huntingtin protein (HTT). HD is pathologically characterized by loss of neurons in the striatum and cortex, which leads to progressive motor dysfunction, cognitive decline and behavioral symptoms. Stem cell-based therapy has emerged as a feasible therapeutic approach for the treatment of neurodegenerative diseases and may be effective in alleviating and/or halting the pathophysiological mechanisms underlying HD. Several pre-clinical studies have used stem cells in animal models of HD. Here, we performed a systematic review of preclinical studies to estimate the treatment efficacy of stem cells in animal models of HD. Based on our systematic review, treatment with stem cells significantly improves neurological and behavioral outcomes in animal models of HD. Although promising results were found, the design of animal studies, the types of transplanted cells and the route of administration are poorly standardized and this greatly complicates comparative analysis.

Stem cell therapies for Alzheimer's disease: is it time?

PURPOSE OF REVIEW: Stem cell therapy has the potential to modify the disease of Alzheimer's disease. This article aims to describe the mechanisms of action, preclinical animal studies, human clinical trials, and challenges for the future direction of stem cell therapy for Alzheimer's disease. RECENT FINDINGS: Stem cells of diverse origins (embryonic, placental or umbilical cord blood, and induced pluripotent stem cells) and cell types (neural and mesenchymal stem cells) are widely studied in both animals and humans. SUMMARY: In terms of mechanism of actions, recent research focused on the interplay between amyloid-beta Aß (and tau), neurons, and glia. Stem cells can induce direct regeneration of neurons and synapses. They can also prevent activation of pro-inflammatory microglia, promote activation of anti-inflammatory microglia, inhibit astrogliosis, and promote nonreactive astrocytes. These effects in return may increase amyloid-beta (Aß) degradation, decrease the risk of the Aß cascade, repair injured neurons, and enhance synaptogenesis. Two completed and nine ongoing clinical trials using diverse stem cells and administration methods (intravenous, subcutaneous, and intra-cranial) were found for the treatment of Alzheimer's disease. Although stem cell therapy shows great potential to become a prospective treatment for Alzheimer's disease in the future, these studies are still in their early stages and more studies showing safety and efficacy are needed.

Cancer Stem Cells or Tumor Survival Cells?

Research endeavors originally generated stem cell definitions for the purpose of describing normally sustainable developmental and tissue turnover processes in various species, including humans. The notion of investigating cells that possess a vague capacity of "stamm (phylum)" can be traced back to the late 19th century, mainly concentrating on cells that could produce the germline or the entire blood system. Lately, such undertakings have been recapitulated for oncogenesis, tumor growth, and cancer cell resistance to oncolytic therapies. However, due to the complexity and basic life-origin mechanisms comprising the genetic and epigenetic repertoire of the stemness in every developing or growing cell, presently there are ongoing debates regarding the biological essentials of the stem cell-like tumor initiation cells (ie, cancer stem cells; CSCs). This conceptual analysis focuses on the potential pitfalls of extrapolating that CSCs bear major traits of stemness. We propose a novel nomenclature of Tumor Survival Cells (TSCs) to further define tumor cells behaving like CSCs, based on the ruthless and detrimental features of Cancer Cell Survivology that appears fundamentally different from stem cell biology. Hence, precise academic separation of TSCs from all the stem cell-related labels applied to these unique tumor cells may help to improve scientific reasoning and strategies to decode the desperado-like survival behaviors of TSCs to eventually overcome cancer.

Stem Cell Therapy for Hypoplastic Left Heart Syndrome: Mechanism, Clinical Application, and Future Directions.

Hypoplastic left heart syndrome is a type of congenital heart disease characterized by underdevelopment of the left ventricle, outflow tract, and aorta. The condition is fatal if aggressive palliative operations are not undertaken, but even after the complete 3-staged surgical palliation, there is significant morbidity because of progressive and ultimately intractable right ventricular failure. For this reason, there is interest in developing novel therapies for the management of right ventricular dysfunction in patients with hypoplastic left heart syndrome. Stem cell therapy may represent one such innovative approach. The field has identified numerous stem cell populations from different tissues (cardiac or bone marrow or umbilical cord blood), different age groups (adult versus neonate-derived), and different donors (autologous versus allogeneic), with preclinical and clinical experience demonstrating the potential utility of each cell type. Preclinical trials in small and large animal models have elucidated several mechanisms by which stem cells affect the injured myocardium. Our current understanding of stem cell activity is undergoing a shift from a paradigm based on cellular engraftment and differentiation to one recognizing a primarily paracrine effect. Recent studies have comprehensively evaluated the individual components of the stem cells' secretomes, shedding new light on the intracellular and extracellular pathways at the center of their therapeutic effects. This research has laid the groundwork for clinical application, and there are now several trials of stem cell therapies in pediatric populations that will provide important insights into the value of this therapeutic strategy in the management of hypoplastic left heart syndrome and other forms of congenital heart disease. This article reviews the many stem cell types applied to congenital heart disease, their preclinical investigation and the mechanisms by which they might affect right ventricular dysfunction in patients with hypoplastic left heart syndrome, and finally, the completed and ongoing clinical trials of stem cell therapy in patients with congenital heart disease.

CD271+, CXCR7+, CXCR4+, and CD133+ Stem/Progenitor Cells and Clinical Characteristics of Acute Ischemic Stroke Patients.

Ischemic stroke causes mobilization of various groups of progenitor cells from bone marrow to bloodstream and this correlates with the neurological status of stroke patients. The goal of our study was to identify the activity of chosen progenitor/stem cells in the peripheral blood of acute ischemic stroke patients in the first 7 days after the incident, through associations between the levels of the cells and clinical features of the patients. Thirty-three acute ischemic stroke patients and 15 non-stroke control subjects had their venous blood collected repeatedly in order to assess the levels of the CD45-CD34 + CD271+, the CD45-CD34 + CXCR4+, the CD45-CD34 + CXCR7+, and the CD45-CD34 + CD133+ stem/progenitor cells by means of flow cytometry. The patients underwent repeated neurological and clinical assessments, pulse wave velocity (PWV) assessment on day 5, and MRI on day 1 and 5 ± 2. The levels of the CD45-CD34 + CXCR7+ and the CD45-CD34 + CD271+ cells were lower in the stroke patients compared with the control subjects. Only the CD45-CD34 + CD271+ cells correlated positively with lesion volume in the second MRI. The levels of the CD45-CD34 + CD133+ cells on day 2 correlated negatively with PWV and NIHSS score on day 9. The patients whose PWV was above 10 m/s had significantly higher levels of the CD45-CD34 + CXCR4+ and the CD45-CD34 + CXCR7+ cells on day 1 than those with PWV below 10 m/s. This study discovers possible activity of the CD45-CD34 + CD271+ progenitor/stem cells during the first 7 days after ischemic stroke, suggests associations of the CD45-CD34 + CD133+ cells with the neurological status of stroke patients, and some activity of the CD45-CD34 + CD133+, the CD45-CD34 + CXCR4+, and the CD45-CD34 + CXCR7+ progenitor/stem cells in the process of arterial remodeling.

The differentiation potential of adipose tissue-derived mesenchymal stem cells into cell lineage related to male germ cells / Potencial de diferenciação de células-tronco mesenquimais derivadas do tecido adiposo em células da linhagem germinativa masculina

The adipose tissue is a reliable source of Mesenchymal stem cells (MSCs) showing a higher plasticity and transdifferentiation potential into multilineage cells. In the present study, adipose tissue-derived mesenchymal stem cells (AT-MSCs) were isolated from mice omentum and epididymis fat depots. The AT-MSCs were initially compared based on stem cell surface markers and on the mesodermal trilineage differentiation potential. Additionally, AT-MSCs, from both sources, were cultured with differentiation media containing retinoic acid (RA) and/or testicular cell-conditioned medium (TCC). The AT-MSCs expressed mesenchymal surface markers and differentiated into adipogenic, chondrogenic and osteogenic lineages. Only omentum-derived AT-MSCs expressed one important gene marker related to male germ cell lineages, after the differentiation treatment with RA. These findings reaffirm the importance of adipose tissue as a source of multipotent stromal-stem cells, as well as, MSCs source regarding differentiation purpose.(AU)

O tecido adiposo é uma fonte apropriada de células-tronco mesenquimais (MSCs), as quais demonstram ampla plasticidade com capacidade de transdiferenciar em diversas linhagens. No presente estudo, as células-tronco mesenquimais derivadas do tecido adiposo (AT-MSC) foram isoladas de tecido adiposo localizado nas regiões próximas ao omento e testículos de camundongos. Primeiramente, as AT-MSCs foram comparadas com base na expressão de marcadores antigênicos de superfície e no potencial de diferenciação nas três linhagens mesodérmicas. Além disso, AT-MSC, de ambas as fontes, foram cultivadas com meio de diferenciação contendo ácido retinóico (RA) e / ou meio condicionado testicular (TCC). As AT-MSCs expressaram marcadores de superfície mesenquimais e diferenciaram nas linhagens adipogênica, condrogênica e osteogênica. Após o tratamento com RA, somente as AT-MSCs isoladas do tecido adiposo depositado na região do omento expressaram um único importante marcador relacionado às células da linhagem germinativa masculina. Estes resultados reafirmam a importância do tecido adiposo como fonte de células-tronco estromais-multipotentes, bem como, uma fonte de MSCs para estudos de diferenciação.(AU)