The human intestinal epithelial barrier comprises diverse proliferative, secretory and absorptive cell types that facilitate nutrient digestion and absorption and protect against harmful environmental agents. The barrier and its function can vary between individuals due to genetic differences thus impact processes such as digestion, drug metabolism, and drug sensitivity. Our guests today investigated the effect of diverse culture conditions on the cell type composition, gene expression profil...
The blood-brain barrier (BBB), formed by brain endothelial cells, pericytes, and astrocytes, is organized into a neurovascular unit that regulates the exchange of proteins between blood circulation and brain parenchyma. Human stem-cell-based models using brain endothelial cells are a powerful tool to investigate how disease-related conditions might affect the blood-brain barrier integrity. However, the cell type composition is critical to faithfully model transcytosis across the blood-brain b...
Hematopoietic stem cells (HSCs) normally reside in the bone marrow niche but can traffic across the bone marrow endothelium into the bloodstream to populate different niches. This process of HSC mobilization from the bone marrow to the blood, is an increasingly favored procedure to obtain HSCs for hematopoietic cell transplantation therapy. Though mobilization is robust in many donors due to years of refined protocols and drug combinations, the process remains difficult or contraindicated amo...
The role of neuronal influences on cancer pathogenesis and progression is increasingly appreciated in the nervous system. Neurons have been shown to enhance the proliferation and migration of gliomas, a glial-derived tumor of the CNS, via diffusible paracrine factors or synaptic inputs onto tumor cells. In glioblastomas, a highly aggressive glioma, mostly glutamatergic inputs have been identified. While the potential for glioblastomas to receive projections from neurons of other neurotransmit...
Skeletal muscle is one of the most abundant tissues in the human body, representing approximately 40% of body weight. Under certain circumstances, skeletal muscle can be regenerated through satellite cells, a reservoir of quiescent muscle stem cells, that can be activated with injury or in certain diseases and give rise to newly formed multi-nucleated myotubes and myofibers. However, the regenerative potential of muscle is diminished or is completely absent in the course of normal aging, cert...
The potential of pluripotent stem cells and the ability to scale and differentiate them to generate large numbers of enriched cell populations has created new opportunities and approaches to treat human disease. Preclinical proof-of-principle data demonstrates that stem cell-derived neural grafts can be used to reverse symptoms of multiple neurological conditions, including Parkinson’s Disease. Cell grafts enriched with dopaminergic neurons, can structurally and functionally integrate in the ...
Parent-specific epigenetic marks (imprints) leading to parent-specific gene expression are crucial for normal growth and development, yet their mechanisms of establishment and maintenance are not fully understood. In humans, approximately 200 imprinted genes have been discovered, and improper imprinting can manifest in growth restriction, obesity, intellectual disabilities, behavioral abnormalities, and an increased risk of certain cancers. While the use of pluripotent stem cells, especially ...
The mature lung in both humans and mice is highly vascularized, with approximately 30% of all cells being endothelial cells (ECs). The blood vessels have a physiological role in gas exchange within the tissue, but the vascular cells have additional role(s) beyond supplying oxygen and nutrients to the tissue. For example, the adult lung endothelium responds to injury by activating pathways for alveolar re epithelialization and during embryonic development, disrupting vascularization ex v...
In this special edition of the podcast, we will talk with the new Editor-in-Chief Janet Rossant and hear about her vision for the journal, its promising future, and what she sees as some of the exciting prospects over the horizon for stem cell research. We will also talk with Yvonne Fisher, the journal’s Managing Editor, and Jack Mosher of the ISSCR, about the evolution of the journal and its role in the Society. Guests Janet Rossant is the new Editor-in-Chief of Stem Cell Reports. She hold...
During the last decade, advances in genome editing and pluripotent stem cell (PSC) culture have let researchers generate edited PSC lines to study a wide variety of biological questions. However, abnormalities in cell lines such as aneuploidy, mutations, on-target and off-target editing errors, and microbial contamination can arise during PSC culture or due to undesired editing outcomes. To ensure valid experimental results and the safety of PSC-derived therapeutics, it is important to detect...
The ability of human pluripotent and somatic stem cells to differentiate into multiple cell types of the human body makes them uniquely useful to model human development and disease. As a result, these cells are shared, edited, and differentiated by laboratories across the world for basic research, clinical translation, and commercial applications. Large and genotypically diverse collections of pluripotent stem cells are being generated to support large cohort-scale research into conditions s...
Pluripotent stem cells are defined, in part, by their potential to generate cell types from all three embryonic germ layers. However, it is well known within the field that there is variability in developmental potential between cell lines. This phenomenon, sometimes referred to as lineage bias, is manifest in a variable response of individual cell lines to induction of differentiation into a specific germ layer lineage. Although lineage bias in pluripotent stem cells has been reported for so...
Epigenetic clocks based on tissue DNA methylation analysis have emerged as robust and powerful biomarkers of aging. This technology has allowed scientists to investigate how diseases affect the aging process, to evaluate the effectiveness of therapeutic aging interventions, and to correlate age with overall health among the general public. Today you can even purchase test kits online that enable you to measure your own biological age. However, despite the growing use of epigenetic...
Those who study neurological diseases and their underlying cellular and molecular mechanisms have a number of scientific models at their disposal. In vivo animal models, particularly those bearing targeted genetic modifications, remain the gold standard, especially when it comes to assessment of behavioral readouts and neurobiological disease mechanisms in vivo. Historically, animal models have been widely used for preclinical validation of drug efficacy and safety. Increasingly there...
This episode of The Stem Cell Report will discuss the process of directing stem cells to acquire the proper identity, an essential step in the development of effective and durable cell replacement therapies. Specifically, we will talk about the process of directing cells into a ventral mesencephalic dopaminergic fate for treating Parkinson’s disease. Guests Agnete Kirkeby is an Associate Professor in the Department of Neuroscience at the University of Copenhagen, a Principal Investigato...
Myelination is one of the last events during mammalian brain development and is thought to continue into young adulthood in humans. Even in adulthood, ongoing low-level myelination is essential for neural homeostasis, and for dynamic processes such as learning and memory. Deficits in myelination resulting in abnormal white matter and disruption of neuronal function are observed in a wide variety of disorders of the CNS. One strategy for alleviating these deficits is to enhance the genesis of ...
Biomedical researchers have long sought ways to repair spinal cord damage with the holy grail of the pursuit being the reconstitution of lost function. In the mid 1990’s with the successful culture of human embryonic stem cells, and about a decade later induced pluripotent stem cells (iPSCs), the field was energized with a potential new approach to replace the lost neurons and glia cells and restoring neural connections. In the decades since that discovery some progress has been made, h...
Collectively, retinal degenerative disorders are a major cause of blindness worldwide. For example, one of the most common disorders is age related macular degeneration, which alone affects nearly 200 million globally. In humans, and other mammals, the loss of the retinal cells is an irreversible process. However, in some non-mammalian vertebrates like frogs and fish, retinal neurons can regenerate. This process is dependent upon Müller glia, which can re-enter the cell cycle and reprog...
Since the 1930’s research using human fetal tissue has been used in numerous scientific and medical advances that have saved millions of lives, including the development of vaccines and treatments for diseases. Despite its substantial contribution to medicine and science, significant public debate and misinformation persists surrounding the ethical use of human fetal tissue in biomedical research. The ISSCR, led by its Public Policy Committee, have been tireless champions and advocate...
This November marks the 25th anniversary of the successful isolation and culture of human embryonic stem cells by Jamie Thompson. This breakthrough was a turning point in biomedical research. This discovery provided scientists with a limitless source of human cells to understand human biology and model disease. The discovery also provided a novel pathway to develop tissues and cells that could potentially be used to provide curative diseases like diabetes and Parkinson’s, among others. ...