18 June 2020
Stem cells from development to the clinic
Advances in technologies that help to characterize stem cells, including genetic and epigenetic properties and lineage trajectories, have increased our knowledge about their physiological roles and contributions to development, ageing, regeneration and disease. Stem cells, and cells differentiated from them, are now used in vitro and in vivo in a variety of applications, such as disease modelling, drug screening and for transplantations.
Hans Clevers discusses the value of organoids as an experimental platform for understanding the biology of novel viruses.
Genetic engineering prevents immune rejection of allogeneic cell transplants derived from iPSCs.
Expression of ETV2 in human cortical organoids induces the formation of vascular-like networks, which reduces cell death within organoids and increases their functional maturation.
Skin organoids generated in vitro from human pluripotent stem cells form complex, multilayered skin tissue with hair follicles, sebaceous glands and neural circuitry, and integrate with endogenous skin when grafted onto immunocompromised mice.
A set of five small molecules can induce the transformation of fibroblasts into rod photoreceptor-like cells, which can partially restore pupil reflex and visual function when transplanted into a rod degeneration mouse model.
‘Tubuloids’ grown from human kidney tissue and urine aid the study of BK virus infection, Wilms tumors and cystic fibrosis.
Pig embryos with a human endothelium are generated through blastocyst complementation using human induced pluripotent stem cells.
Nair et al. report the generation of human ESC-derived mature and functional β cells in vitro with a culture system including a step to induce clustering of immature β-like cells.
Gopika G. Nair,
Wang, Yu, Zhou, Song et al. profile cardiomyocytes and neighbouring cells from healthy adults and patients with heart failure and in recovery, and delineate their cellular compositions and interaction networks.
Boretto et al. demonstrate that organoids derived from patients with various types of endometrial pathologies can model disease traits and diversity, and can be used as a drug-screening tool.
Cardiac organoids incorporating an oxygen-diffusion gradient and stimulated with the neurotransmitter noradrenaline can model the structure and function of the human heart after myocardial infarction.
Dylan J. Richards,
iPSC-derived motor neurons and skeletal muscle cells are co-cultured to establish a model of the human neuromuscular junction (NMJ) within a microfluidic device, which facilitates assessment of axonal outgrowth, NMJ formation and muscle maturation.
hPSCs in culture acquire a more naïve pluripotent state upon tankyrase inhibition. Here, the authors show that tankyrase inhibitor-regulated naïve hiPSCs from diabetic donors generate more vascular progenitors and more efficient engraftment into mouse retina than conventional PSCs.
Tea Soon Park,
Single cell transcriptomics identifies stem cell-derived graft composition in a model of Parkinson’s disease
What happens to cells on engrafting into the brain in animal models to treat Parkinson’s disease is unclear. Here, the authors use scRNA-seq to examine ventral midbrain (VM)-patterned human embryonic stem cells after functional maturation in a pre-clinical rat model for Parkinson’s disease and identify perivascular-like cells.
A Wnt-mediated transformation of the bone marrow stromal cell identity orchestrates skeletal regeneration
Bone marrow stromal cells (BMSCs) lining sinusoidal blood vessels are mesenchymal cells whose function is critical for the skeleton. Here the authors show that quiescent CXCL12-expressing BMSCs can convert into a skeletal stem cell-like state, and differentiate into cortical bone osteoblasts only in response to injury.
Dual stem cell therapy synergistically improves cardiac function and vascular regeneration following myocardial infarction
Myocardial infarction causes damage to the myocardium and vasculature. Here the authors show in a rat model of myocardial infarction that cardiomyocytes derived from human induced pluripotent stem cells combined with a human mesenchymal stem cell-loaded patch lead to improved cardiac function and promote vessel formation.
Integrin-specific hydrogels modulate transplanted human bone marrow-derived mesenchymal stem cell survival, engraftment, and reparative activities
Mesenchymal stromal cells enhance bone and cartilage repair, but are limited by poor survival and retention after transplantation. Here, the authors show that synthetic hydrogels presenting integrin-specific peptides enhance the survival and persistence of human mesenchymal stromal cells after transplant, as well as bone repair.
Amy Y. Clark,
Next-generation stem cells — ushering in a new era of cell-based therapies
Primary stem cells have long been used therapeutically for applications such as bone marrow transplantation. This Review discusses how cell-engineering approaches are enabling the development of next-generation stem cell therapies with improved function, specificity and responsiveness, thereby expanding their applications into areas such as delivering drugs and oncolytic viruses to tumours and promoting tissue repair in various diseases.
Erin A. Kimbrel &
Single-cell technologies in hepatology: new insights into liver biology and disease pathogenesis
Single-cell transcriptomic technologies are transforming our understanding of cellular diversity and function in health and disease. This Review discusses how these technologies have been applied in hepatology, advancing our understanding of cellular heterogeneity and providing novel insights into liver biology such as metabolic zonation and the mechanisms underpinning liver regeneration.
Organoid models of gastrointestinal cancers in basic and translational research
Organoid technology has emerged as a powerful method for studying gastrointestinal cancers. This Review describes organoid models of gastrointestinal cancers, such as colorectal and liver cancer, and discusses how they can be used in basic and translational research in fields such as drug discovery and personalized medicine.
Harry Cheuk Hay Lau,
Gene regulatory programmes of tissue regeneration
The capacity to regenerate tissue varies across different species and tissue types. The poor regenerative capacity of organs such as the heart and nervous system contributes to the aetiology of a number of serious diseases, including heart failure and Alzheimer disease. In this Review, Goldman and Poss discuss how genetic programmes of regeneration are regulated and how the control mechanisms might be adapted to treat human disease.
Joseph A. Goldman &