Cancer stem cells are a subset of cells within the tumor that possess the ability to self-renew as well as differentiate into different cancer cell lineages. The exact mechanisms by which cancer stem cells arise is still not completely understood. However, current research suggests that cancer stem cells may originate from normal stem cells that have undergone genetic mutations or epigenetic changes. A more recent discovery is the dedifferentiation of cancer cells to stem-like cells. These stem-like cells have been found to express and even upregulate induced pluripotent stem cell markers known as Yamanaka factors. Here we discuss developments in how cancer stem cells arise and consider how environmental factors, such as hypoxia, plays a key role in promoting the progression of cancer stem cells and metastasis. Understanding the mechanisms that give rise to these cells could have important implications for the development of new strategies in cancer treatments and therapies.

Induced pluripotent stem cells (iPSCs) are produced by resetting the epigenetic and transcriptional landscapes of somatic cells to express the endogenous pluripotency network and revert them back to an undifferentiated state. The reduced ethical concerns associated with iPSCs and their capacity for extensive self-renewal and differentiation make them an unparalleled resource for drug discovery, disease modeling, and novel therapies. Canines (c) share many human diseases and environmental exposures, making them a superior translational model for drug screening and investigating human pathologies compared to other mammals. However, well-defined protocols for legitimate ciPSC production are lacking. Problems during canine somatic cell reprogramming (SCR) yield putative ciPSCs with incomplete pluripotency, at very low efficiencies. Despite the value of ciPSCs, the molecular mechanisms underlying their unsuccessful production and how these may be addressed have not been fully elucidated. Factors, including cost, safety, and feasibility, may also limit the widespread clinical adoption of ciPSCs for treating canine disease. The purpose of this narrative review is to identify barriers to canine SCR on molecular and cellular levels, using comparative research to inform potential solutions to their use in both research and clinical contexts. Current research is opening new doors for the application of ciPSCs in regenerative medicine for the mutual benefit of veterinary and human medicine.

Oligodendrocytes are a type of glial cells that produce a lipid-rich membrane called myelin. Myelin assembles into a sheath and lines neuronal axons in the brain and spinal cord to insulate them. This not only increases the speed and efficiency of nerve signal transduction but also protects the axons from damage and degradation, which could trigger neuronal cell death. Demyelination, which is caused by a loss of myelin and oligodendrocytes, is a prominent feature of many neurological conditions, including Multiple sclerosis (MS), spinal cord injuries (SCI), and leukodystrophies. Demyelination is followed by a time of remyelination mediated by the recruitment of endogenous oligodendrocyte precursor cells, their migration to the injury site, and differentiation into myelin-producing oligodendrocytes. Unfortunately, endogenous remyelination is not sufficient to overcome demyelination, which explains why there are to date no regenerative-based treatments for MS, SCI, or leukodystrophies. To better understand the role of oligodendrocytes and develop cell-based remyelination therapies, human oligodendrocytes have been derived from somatic cells using cell reprogramming. This review will detail the different cell reprogramming methods that have been developed to generate human oligodendrocytes and their applications to disease modeling and cell-based remyelination therapies. Recent developments in the field have seen the derivation of brain organoids from pluripotent stem cells, and protocols have been devised to incorporate oligodendrocytes within the organoids, which will also be reviewed.

UNASSIGNED: Cardiovascular diseases have been the leading cause of death globally for decades. Pharmacological advances targeting the sympathetic nervous system, renin-angiotensin-aldosterone system, and fibrosis slow the progression of diverse cardiovascular diseases. However, ongoing cardiomyocyte loss is inevitable in divergent cardiovascular diseases, eventually leading to heart failure as the end stage. In this review, we focused on the key biomedical findings and underlying principles of cardiomyocyte regeneration.
UNASSIGNED: Literature regarding the key findings in cardiomyocyte regeneration research, including controversies on the origins of newly formed cardiomyocytes, potential barriers and strategies to heart regeneration, and the key animals, models, and methods applied in the study of heart regeneration, were broadly researched using the PubMed and Web of Science databases.
UNASSIGNED: In the mammalian heart, cardiomyocytes proliferate during the embryonic and early postnatal stages, while the capability of proliferation disappears in the adult stage. An increasing amount of evidence suggests that cardiomyocytes self-renew at a very limited level and that most newly formed cardiomyocytes originate from pre-existing cardiomyocytes and not cardiac progenitor cells (CPCs). Several potential barriers to heart regeneration have been addressed, including metabolic switch, a large increase in multinucleated and polyploid cardiomyocytes, and alteration in the epigenome and transcriptome. In addition, immune system evolution is also associated with the loss of regenerative capacity. However, the activation of resident cardiomyocytes, somatic cell reprogramming, and direct reprogramming, in addition to the promotion of neovascularization and immune modulation, constitute the new insights into those strategies that can boost cardiac regeneration.
UNASSIGNED: Heart regeneration is one of the most popular fields in cardiovascular research and represents a promising avenue of therapeutics for mending a broken heart. Despite the controversies and challenges, a clearer picture of adult mammalian cardiac regeneration is emerging.

The inability of damaged neurons to regenerate within the mature central nervous system (CNS) is a significant neuroscientific challenge. Astrocytes are an essential component of the CNS and participate in many physiological processes including blood-brain barrier formation, axon growth regulation, neuronal support, and higher cognitive functions such as memory. Recent reprogramming studies have confirmed that astrocytes in the mature CNS can be transformed into functional neurons. Building on in vitro work, many studies have demonstrated that astrocytes can be transformed into neurons in different disease models to replace damaged or lost cells. However, many findings in this field are controversial, as the source of new neurons has been questioned. This review summarizes progress in reprogramming astrocytes into neurons in vivo in animal models of spinal cord injury, brain injury, Huntington\'s disease, Parkinson\'s disease, Alzheimer\'s disease, and other neurodegenerative conditions.

Cardiovascular disease (CVD) remains the number one cause of death worldwide. Ischemic heart disease contributes to heart failure and has considerable morbidity and mortality. Therefore, alternative therapeutic strategies are urgently needed. One class of epigenetic regulators known as pioneer factors has emerged as an important tool for the development of regenerative therapies for the treatment of CVD. Pioneer factors bind closed chromatin and remodel it to drive lineage specification. Here, we review pioneer factors within the cardiovascular lineage, particularly during development and reprogramming and highlight the implications this field of research has for the future development of cardiac specific regenerative therapies.

Uterine fibroids are benign monoclonal neoplasms of the myometrium, representing the most common tumors in women worldwide. To date, no long-term or noninvasive treatment option exists for hormone-dependent uterine fibroids, due to the limited knowledge about the molecular mechanisms underlying the initiation and development of uterine fibroids. This paper comprehensively summarizes the recent research advances on uterine fibroids, focusing on risk factors, development origin, pathogenetic mechanisms, and treatment options. Additionally, we describe the current treatment interventions for uterine fibroids. Finally, future perspectives on uterine fibroids studies are summarized. Deeper mechanistic insights into tumor etiology and the complexity of uterine fibroids can contribute to the progress of newer targeted therapies.

Brain 4 (Brn4) is a transcription factor belonging to the POU3 family, and it is important for the embryonic development of the neural tube, inner ear and pancreas. In addition, it serves a crucial role in neural stem cell differentiation and reprogramming. The present review aimed to summarize the chromosomal location, species homology, protein molecular structure and tissue distribution of Brn4, in addition to its biological processes, with the aim of providing a reference of its structure and function for further studies, and its potential use as a gene therapy target.

The study and treatment of neurological disorders have been hampered by a lack of access to live, healthy, or disease-affected human neurons. The recent advances in the field of cell reprogramming offer exciting new possibilities for disease modeling, drug development, and cell-based therapies. Since the derivation of human embryonic stem cells (hESCs) and their differentiation into neurons, cell reprogramming technologies have built on these protocols to generate mature human neurons of disease-associated phenotypes from somatic cells. Mechanistic knowledge of neural patterning and neurogenesis has been essential for the establishment of reprogramming strategies that employ a combination of transcription factors and small molecules selected due to their critical role in brain development. The generation of reprogrammed human neurons has the potential to further enhance our knowledge of pathways underlying the developmental process of the human brain, the current knowledge of which has predominantly come from animal studies, postmortem tissue, and most recently hESCs. Somatic cell reprogramming began in 2006 with the first report of induced pluripotent stem cell (iPSC) derivation from mouse fibroblasts. This has now expanded to direct-to-induced neuron and direct-to-induced neural stem or precursor reprogramming using a variety of viral and nonviral delivery methods. Most recently, iPSC technology has been extended to the development of three-dimensional brain structures referred to as brain spheroids or organoids. This review will discuss the reprogramming strategies that have been formulated to generate cortical neurons that are associated with many diseases, including autism spectrum disorders and schizophrenia.

Stem and non-stem cell behavior is heavily influenced by the surrounding microenvironment, which includes other cells, matrix, and potentially biomaterials. Researchers have been successful in developing scaffolds and encapsulation techniques to provide stem cells with mechanical, topographical, and chemical cues to selectively direct them toward a desired differentiation pathway. However, most of these systems fail to present truly physiological replications of the in vivo microenvironments that stem cells are typically exposed to in tissues. Thus, cell mimicking microparticles (CMMPs) have been developed to more accurately recapitulate the properties of surrounding cells while still offering ways to tailor what stimuli are presented. This nascent field holds the promise of reducing, or even eliminating, the need for live cells in select, regenerative medicine therapies, and diagnostic applications. Recent, CMMP-based studies show great promise for the technology, yet only reproduce a small subset of cellular characteristics from among those possible: size, morphology, topography, mechanical properties, surface molecules, and tailored chemical release to name the most prominent. This Review summarizes the strengths, weaknesses, and ideal applications of micro/nanoparticle fabrication and customization methods relevant to cell mimicking and provides an outlook on the future of this technology. Moving forward, researchers should seek to combine multiple techniques to yield CMMPs that replicate as many cellular characteristics as possible, with an emphasis on those that most strongly influence the desired therapeutic effects. The level of flexibility in customizing CMMP properties allows them to substitute for cells in a variety of regenerative medicine, drug delivery, and diagnostic systems. Stem Cells Translational Medicine 2018;7:232-240.