![]() Caicedo, “Stemness in cancer: Stem cells, cancer stem cells, and their microenvironment,” Stem Cells Int, 2017:1-17, 2017. Zakrzewski et al., “Stem cells: past, present, and future,” Stem Cell Res Ther, 10:1-22, 2019. For example, scientists study patient-derived iPSCs in vitro to investigate the effects of mutations linked to disease risk that are identified in genome-wide association studies (GWAS). In addition, patient-specific pluripotent stem cells provide a promising platform for drug discovery and cell therapy in vitro. Scientists use disease-specific iPSCs to investigate possible degenerative disorder treatments with stem cell transplants. Regenerative medicine aims to restore the function of specific tissues for patients with severe injuries or chronic disease conditions. Regenerative Medicine and Drug Discovery with Patient-Specific Pluripotent Stem Cells Scientists also apply pluripotent stem cells in disease modeling with organoids, 3D structures derived from stem cells, progenitor cells, and/or differentiated cells that self-organize to recapitulate aspects of the native tissue structure and function in vitro. For example, iPSC-derived disease-specific stem cells are useful in the study of degenerative disorders, and to gain insight into diseases that lack suitable preclinical models. Thus, researchers use pluripotent stem cells to model diseases with the aim of developing therapies. Scientists generate a variety of disease-relevant cell types with human ESCs and iPSCs using differentiation protocols that mimic in vivo organogenesis. 3,4ĭisease Modeling with Pluripotent Stem Cells This finding advanced researchers’ understanding of epigenetic mechanisms that commit specialized cells to their differentiated states during development. ![]() Additionally, the discovery of iPSCs demonstrated that scientists can change cell fate artificially by activating only a few transcription factors. During development, cells mature through a continuum of pluripotent states with unique properties that researchers can capture in vitro with stable pluripotent stem cell types. Pluripotent stem cell features evolve as development proceeds through embryogenesis, and different stages of this process are marked by distinct cellular transcriptional and epigenetic signatures. Scientists culture pluripotent stems cells to understand how they may be employed in regenerative medicine, disease modeling, and drug discovery. These cell lines are also a source of unspecialized cells with therapeutic potential. Because of this, researchers use pluripotent stem cell lines to study early development. Pluripotent stem cells can self-renew indefinitely while maintaining the ability to differentiate into all cell types in vitro and in vivo. How Do Researchers Use Pluripotent Stem Cells? 1,3 Conversely, the stem cell environment and specific stem cell factors can promote the dedifferentiation of specialized cells and return them to a primitive state of development or stemness. These cells proliferate to form the next generation of stem cells and differentiate into specialized cells under specific physiological conditions. After embryogenesis, pluripotent stem cells also exist as undifferentiated cells throughout the organism. These layers produce differentiated cells and tissues. During embryogenesis, ESCs differentiate into one of three germ layers: ectoderm, mesoderm, or endoderm. This means that they can develop into all cells of the adult body, but do not form extraembryonic structures such as the placenta. Human pluripotent stem cells give rise to all three primary germ layers during embryonic development. As the totipotent zygote divides into more specialized cells, it forms a blastocyst that contains pluripotent cells in the inner cell mass, including embryonic stem cells (ESCs). An example of a totipotent cell is a zygote that develops after a sperm fertilizes an egg. Unlike pluripotent stem cells, totipotent stem cells can divide and differentiate into every cell that makes a whole organism, including both embryonic and extraembryonic structures. Totipotent stem cells have the highest differentiation potential. The developmental potential, or potency, of a stem cell varies based on its specialization. For example, a unipotent stem cell cannot differentiate into as many cell types as a pluripotent stem cell. Stem cells exist both in embryos and adult tissue, and their developmental potential decreases as they become more specialized. They cannot survive outside of their environment without specific factors and cytokines. Stem cells are unspecialized cells capable of self-renewal that can differentiate into other types of cells.
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