Current Stem Cell Reports

PURPOSE OF REVIEW: This article gives a broad overview of quantitative modelling approaches in biology and provides guidance on how to employ them to boost stem cell research, by helping to answer biological questions and to predict the outcome of biological processes. RECENT FINDINGS: The twenty-first century has seen a steady increase in the proportion of cell biology publications employing mathematical modelling to aid experimental research. However, quantitative modelling is often used as a rather decorative element to confirm experimental findings, an approach which often yields only marginal added value, and is in many cases scientifically questionable...

PURPOSE OF REVIEW: To explore the advances and future research directions in image analysis and computational modelling of human stem cells (hSCs) for ophthalmological applications. RECENT FINDINGS: hSCs hold great potential in ocular regenerative medicine due to their application in cell-based therapies and in disease modelling and drug discovery using state-of-the-art 2D and 3D organoid models. However, a deeper characterisation of their complex, multi-scale properties is required to optimise their translation to clinical practice...

Purpose of Review: Organoids are an emerging technology utilizing three-dimensional (3D), multi-cellular in vitro models to represent the function and physiological responses of tissues and organs. By using physiologically relevant models, more accurate tissue responses to viral infection can be observed, and effective treatments and preventive strategies can be identified. Animals and two-dimensional (2D) cell culture models occasionally result in inaccurate disease modeling outcomes...

PURPOSE OF REVIEW: Malicious or accidental radiation exposure increases risk for the hematopoietic acute radiation syndrome (H-ARS) and the delayed effects of acute radiation exposure (DEARE). Radiation medical countermeasure (MCM) development relies on robust animal models reflective of all age groups and both sexes. This review details critical considerations in murine H-ARS and DEARE model development including divergent radiation responses dependent on age, sex, and genetic diversity...

Purpose of review: Immunological memory is an important evolutionary adaptation of the immune system. Previously restricted to the adaptive immune system, the concept of memory has recently been broadened to the innate immune system. This review summarizes recent studies that highlight the contribution of the hematopoietic stem cells (HSCs) in supporting immunological memory. Recent findings: Short-lived innate immune cells can build a long-lasting memory of infection to improve their response to secondary challenges...

PURPOSE OF REVIEW: Cell and tissue products do not just reflect their present conditions; they are the culmination of all they have encountered over time. Currently, routine cell culture practices subject cell and tissue products to highly variable and non-physiologic conditions. This article defines five cytocentric principles that place the conditions for cells at the core of what we do for better reproducibility in Regenerative Medicine. RECENT FINDINGS: There is a rising awareness of the cell environment as a neglected, but critical variable...

PURPOSE OF REVIEW: Human pluripotent stem cells have the potential to revolutionize the treatment of inborn and degenerative diseases, including aging and autoimmunity. A major barrier to their wider adoption in cell therapies is immune rejection. Genome editing allows for tinkering of the human genome in stem and progenitor cells and raises the prospect for overcoming the immune barriers to transplantation. RECENT FINDINGS: Initial attempts have focused primarily on the major histocompatibility barrier that is formed by the human leukocyte antigens (HLA)...

Purpose of Review: Cryopreservation and its associated freezing and thawing procedures-short "freeze-thawing"-are among the final steps in economically viable manufacturing and clinical application of diverse cellular therapeutics. Translation from preclinical proof-of-concept studies to larger clinical trials has indicated that these processes may potentially present an Achilles heel to optimal cell product safety and particularly efficacy in clinical trials and routine use. Recent Findings: We review the current state of the literature on how cryopreservation of cellular therapies has evolved and how the application of this technique to different cell types is interlinked with their ability to engraft and function upon transfer in vivo, in particular for hematopoietic stem and progenitor cells (HSPCs), their progeny, and therapeutic cell products derived thereof...

Purpose of Review: How stem cells balance proliferation with differentiation, giving rise to specific daughter cells during development to build an embryo or tissue, remains an open question. Here, we discuss recent evidence that cytokinetic abscission regulation in stem cells, particularly neural stem cells (NSCs), is part of the answer. Abscission is a multi-step process mediated by the midbody, a microtubule-based structure formed in the intercellular bridge between daughter cells after mitosis...

Purpose of Review: The placenta is a transient organ that forms de novo and serves a critical role in supporting fetal growth and development. Placental oxygen, nutrients, and waste are transported through processes that depend on vascular structure and cell type-specific expression and localization of membrane transporters. Understanding how the placenta develops holds great significance for maternal-fetal medicine. The purpose of this review is to examine current information regarding placental progenitor populations...

Purpose of Review: The promise of cell and gene therapy (CGT) products for a multitude of diseases has revitalized investigators to advance novel CGT product candidates to first-in-human trials by pursuing the investigational new drug (IND) mechanism administered by the United States (US) Food and Drug Administration (FDA). This review is intended to familiarize academic investigators with the IND governing regulations set forth by the FDA. Recent Findings: CGT products are extraordinarily complex biologics and, therefore, early-stage evaluation programs must be customized to satisfactorily address their unique developmental challenges...

Purpose of Review: From invertebrates to vertebrates, the ability to sense nutrient availability is critical for survival. Complex organisms have evolved numerous signaling pathways to sense nutrients and dietary fluctuations, which influence many cellular processes. Although both overabundance and extreme depletion of nutrients can lead to deleterious effects, dietary restriction without malnutrition can increase lifespan and promote overall health in many model organisms. In this review, we focus on age-dependent changes in stem cell metabolism and dietary interventions used to modulate stem cell function in aging...

Purpose of Review: Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) have received widespread attention from researchers owing to the remarkable benefits offered by these cells over other stem cells. The primitive nature of WJ-MSCs, ease of isolation, differentiation ability, and immuno-modulatory nature make these cells superior to bone marrow MSCs and ideal to treat various human ailments. This review explores ability of WJ-MSCs to mitigate acute radiation syndrome caused by planned or unplanned radiation exposure...

PURPOSE OF REVIEW: The well-established crosstalk between hematopoietic stem cells (HSC) and bone marrow (BM) microenvironment is critical for the homeostasis and hematopoietic regeneration in response to blood formation emergencies. Past decade has witnessed that the intercellular communication mediated by the transfer of cytoplasmic material and organelles between cells can regenerate and/or repair the damaged cells. Mitochondria have recently emerged as a potential regulator of HSC fate...

Purpose of review: Cancer stem cells (CSCs) are increasingly understood to play a central role in tumor progression. Growing evidence implicates tumor microenvironments as a source of signals that regulate or even impose CSC states on tumor cells. This review explores points of integration for microenvironment-derived signals that are thought to regulate CSCs in carcinomas. Recent findings: CSC states are directly regulated by the mechanical properties and extra cellular matrix (ECM) composition of tumor microenvironments that promote CSC growth and survival, which may explain some modes of therapeutic resistance...

Purpose of Review: Hematopoietic stem cells (HSCs) are formed embryonically during a dynamic developmental process and later reside in adult hematopoietic organs in a quiescent state. In response to their changing environment, HSCs have evolved diverse mechanisms to cope with intrinsic and extrinsic challenges. This review intends to discuss how HSCs and other stem cells co-opted DNA and RNA innate immune pathways to fine-tune developmental processes. Recent Findings: Innate immune receptors for nucleic acids like the RIG-I-like family receptors and members of DNA sensing pathways are expressed in HSCs and other stem cells...

Purpose of Review: Hematopoietic stem cells (HSCs) sit at the top of the hierarchy that meets the daily burden of blood production. HSC maintenance relies on extrinsic cues from the bone marrow (BM) microenvironment to balance stem cell self-renewal and cell fate decisions. In this brief review, we will highlight the studies and model systems that define the centralized role of BM vascular endothelium in modulating HSC activity in health and stress. Recent Findings: The BM microenvironment is composed of a diverse array of intimately associated vascular and perivascular cell types...

Purpose of review: Intestinal stem cells, the most rapidly proliferating adult stem cells, are exquisitely sensitive to extrinsic dietary factors. Uncontrolled regulation of intestinal stem cells is closely linked to colon tumorigenesis. This review focuses on how dietary and microbial derived cues regulate intestinal stem cell functionality and colon tumorigenesis in mouse models by targeting the aryl hydrocarbon receptor (AhR). Recent findings: AhR, a ligand activated transcription factor, can integrate environmental, dietary and microbial cues to modulate intestinal stem cell proliferation, differentiation and their microenvironment, affecting colon cancer risk...

PURPOSE OF REVIEW: RNA epigenetic modifications have been identified as novel, dynamic regulators of gene expression, with important impacts on stem cell fate decisions. Here we examine the functions of RNA modifications, with a focus on N 6 -methyladenosine (m6 A), in hematopoietic stem cells under normal conditions and in malignancy. RECENT FINDINGS: The m6 A RNA modification is a critical regulator of hematopoiesis. Disruption of different elements of the m6 A machinery can skew the balance of self-renewal and differentiation in normal hematopoietic stem cells...

Purpose of Review: Diet has profound impacts on health and longevity. Evidence is emerging to suggest that diet impinges upon the metabolic pathways in tissue-specific stem cells to influence health and disease. Here, we review the similarities and differences in the metabolism of stem cells from several tissues, and highlight the mitochondrial metabolic checkpoint in stem cell maintenance and aging. We discuss how diet engages the nutrient sensing metabolic pathways and impacts stem cell maintenance...