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Stem Cell Reports Aug 2023The Human Pluripotent Stem Cell Registry established a database of clinical studies using human pluripotent stem cells (PSCs) as starting material for cell therapies.... (Review)
Review
The Human Pluripotent Stem Cell Registry established a database of clinical studies using human pluripotent stem cells (PSCs) as starting material for cell therapies. Since 2018, we have observed a switch toward human induced pluripotent stem cells (iPSCs) from human embryonic stem cells. However, rather than using iPSCs for personalized medicines, allogeneic approaches dominate. Most treatments target ophthalmopathies, and genetically modified iPSCs are used to generate tailored cells. We observe a lack of standardization and transparency about the PSCs lines used, characterization of the PSC-derived cells, and the preclinical models and assays applied to show efficacy and safety.
Topics: Humans; Induced Pluripotent Stem Cells; Cell Differentiation; Pluripotent Stem Cells; Human Embryonic Stem Cells; Cell- and Tissue-Based Therapy
PubMed: 37028422
DOI: 10.1016/j.stemcr.2023.03.005 -
Biophysical Journal Aug 2013Somatic cell reprogramming to pluripotency requires an immediate increase in cell proliferation and reduction in cell size. It is unknown whether proliferation and...
Somatic cell reprogramming to pluripotency requires an immediate increase in cell proliferation and reduction in cell size. It is unknown whether proliferation and biomass controls are similarly coordinated with early events during the differentiation of pluripotent stem cells (PSCs). This impasse exists because PSCs grow in tight clusters or colonies, precluding most quantifying approaches. Here, we investigate live cell interferometry as an approach to quantify the biomass and growth of HSF1 human PSC colonies before and during retinoic acid-induced differentiation. We also provide an approach for measuring the rate and coordination of intracolony mass redistribution in HSF1 clusters using live cell interferometry images. We show that HSF1 cells grow at a consistent, exponential rate regardless of colony size and display coordinated intracolony movement that ceases with the onset of differentiation. By contrast, growth and proliferation rates show a decrease of only ∼15% decrease during early differentiation despite global changes in gene expression and previously reported changes in energy metabolism. Overall, these results suggest that cell biomass and proliferation are regulated independent of pluripotency during early differentiation, which is distinct from what occurs with successful reprogramming.
Topics: Biomass; Cell Differentiation; Cell Movement; Cell Proliferation; Embryoid Bodies; Embryonic Stem Cells; Humans; Interferometry; Pluripotent Stem Cells
PubMed: 23931307
DOI: 10.1016/j.bpj.2013.06.041 -
Cold Spring Harbor Perspectives in... Nov 2013Understanding the molecular basis of many cardiac diseases has been hampered by the lack of appropriate in vitro cell culture models that accurately reflect the human... (Review)
Review
Understanding the molecular basis of many cardiac diseases has been hampered by the lack of appropriate in vitro cell culture models that accurately reflect the human disease phenotypes. In the past few years, remarkable advances in stem cell biology have made possible this long-standing ambition-the generation of human and even patient-specific cellular models of diseases. Combined with other novel technologies in the fields of human genetics, tissue engineering, and gene-targeted manipulation, disease modeling with pluripotent stem cells has the promise to influence modern cardiovascular medicine on several fronts: molecular understanding of pathological mechanisms, early diagnosis, drug development, and effective treatment.
Topics: Cell Differentiation; Epithelial Cells; Forecasting; Heart Diseases; Humans; Models, Biological; Muscle, Smooth, Vascular; Myocytes, Cardiac; Pluripotent Stem Cells; Precision Medicine; Tissue Engineering
PubMed: 24186488
DOI: 10.1101/cshperspect.a014027 -
Journal of Biosciences 2020Pluripotency in stem cells is regulated by a complex network between the transcription factors, signaling molecules, mRNAs, and epigenetic regulators like non-coding...
Pluripotency in stem cells is regulated by a complex network between the transcription factors, signaling molecules, mRNAs, and epigenetic regulators like non-coding RNAs. Different pluripotent stem cell (PSC) lines were isolated and characterized to study the regulatory network topology to understand the mechanism that control developmental potential of pluripotent cells. PSCRIdb is a manually curated database of regulatory interactions including protein-protein, protein-DNA, gene-gene, and miRNA-mRNA interactions in mouse and human pluripotent stem cells including embryonic stem cells and embryonic carcinoma cells. At present, 22 different mouse and human pluripotent stem-cell-line-specific regulatory interactions are compiled in the database. Detailed information of the four types of interaction data are presented in tabular format and graphical network view in Cytoscape layout. The database is available at http://bicresources.jcbose.ac.in/ ssaha4/pscridb. The database contains 3037 entries of experimentally validated molecular interactions that can be useful for systematic study of pluripotency integrating multi-omics data. In summary, the database can be a useful resource for identification of regulatory networks present in different pluripotent stem cell lines.
Topics: Animals; Cell Line; Computational Biology; Databases, Factual; Embryonic Stem Cells; Epigenesis, Genetic; Gene Expression Regulation, Developmental; Gene Regulatory Networks; Humans; Induced Pluripotent Stem Cells; Mice; MicroRNAs; Pluripotent Stem Cells; Protein Interaction Mapping; RNA, Messenger; Transcription Factors
PubMed: 32345779
DOI: No ID Found -
Stem Cell Reports Aug 2018The human pluripotent stem cell (hPSC) research landscape is rapidly evolving. To assess possible novel trends in hPSC usage, we analyzed experimental hPSC research... (Review)
Review
The human pluripotent stem cell (hPSC) research landscape is rapidly evolving. To assess possible novel trends in hPSC usage, we analyzed experimental hPSC research published from 2014 to 2016 and compared our data with those of earlier periods. The number of papers describing experimental work involving hPSCs increased further with clear differences in the scientific impact of publications from different countries. Our results confirm the leading position of US-based hPSC research, although to a lesser degree than observed previously. Our data reveal that research into human induced pluripotent stem cells alone surpassed human embryonic stem cell (hESC) research by 2015 and rapidly grew after that. We also report on continuing and even slightly growing research activities in the hESC field as well as on a generally declining rate of the generation of new hESC lines. An increasing portion of new hESC lines represents disease-specific and clinical-grade cell lines. The previously noted usage of only a few early established hESC lines in the vast majority of scientific work is sustained. We also provide a comprehensive overview on clinical trials on the basis of hPSCs. We find that the vast majority of those trials are based on hESC-derived cell products that were generated from an only limited number of relatively old cell lines.
Topics: Cell Line; Clinical Trials as Topic; Embryonic Stem Cells; Humans; Induced Pluripotent Stem Cells; Pluripotent Stem Cells; Publications; Stem Cell Research
PubMed: 30033087
DOI: 10.1016/j.stemcr.2018.06.012 -
Brain Research May 2016With the technology of reprogramming somatic cells by introducing defined transcription factors that enables the generation of "induced pluripotent stem cells (iPSCs)"... (Review)
Review
With the technology of reprogramming somatic cells by introducing defined transcription factors that enables the generation of "induced pluripotent stem cells (iPSCs)" with pluripotency comparable to that of embryonic stem cells (ESCs), it has become possible to use this technology to produce various cells and tissues that have been difficult to obtain from living bodies. This advancement is bringing forth rapid progress in iPSC-based disease modeling, drug screening, and regenerative medicine. More and more studies have demonstrated that phenotypes of adult-onset neurodegenerative disorders could be rather faithfully recapitulated in iPSC-derived neural cell cultures. Moreover, despite the adult-onset nature of the diseases, pathogenic phenotypes and cellular abnormalities often exist in early developmental stages, providing new "windows of opportunity" for understanding mechanisms underlying neurodegenerative disorders and for discovering new medicines. The cell reprogramming technology enables a reverse engineering approach for modeling the cellular degenerative phenotypes of a wide range of human disorders. An excellent example is the study of the human neurodegenerative disease amyotrophic lateral sclerosis (ALS) using iPSCs. ALS is a progressive neurodegenerative disease characterized by the loss of upper and lower motor neurons (MNs), culminating in muscle wasting and death from respiratory failure. The iPSC approach provides innovative cell culture platforms to serve as ALS patient-derived model systems. Researchers have converted iPSCs derived from ALS patients into MNs and various types of glial cells, all of which are involved in ALS, to study the disease. The iPSC technology could be used to determine the role of specific genetic factors to track down what's wrong in the neurodegenerative disease process in the "disease-in-a-dish" model. Meanwhile, parallel experiments of targeting the same specific genes in human ESCs could also be performed to control and to complement the iPSC-based approach for ALS disease modeling studies. Much knowledge has been generated from the study of both ALS iPSCs and ESCs. As these methods have advantages and disadvantages that should be balanced on experimental design in order for them to complement one another, combining the diverse methods would help build an expanded knowledge of ALS pathophysiology. The goals are to reverse engineer the human disease using ESCs and iPSCs, generate lineage reporter lines and in vitro disease models, target disease related genes, in order to better understand the molecular and cellular mechanisms of differentiation regulation along neural (neuronal versus glial) lineages, to unravel the pathogenesis of the neurodegenerative disease, and to provide appropriate cell sources for replacement therapy. This article is part of a Special Issue entitled SI: PSC and the brain.
Topics: Amyotrophic Lateral Sclerosis; Animals; Cellular Reprogramming; Humans; Induced Pluripotent Stem Cells; Motor Neurons; Neurodegenerative Diseases; Pluripotent Stem Cells; Stem Cell Transplantation
PubMed: 26423934
DOI: 10.1016/j.brainres.2015.09.023 -
Journal of Biomedicine & Biotechnology 2011Although there are a number of weaknesses for clinical use, pluripotent stem cells are valuable sources for patient-specific cell therapies against various diseases.... (Review)
Review
Although there are a number of weaknesses for clinical use, pluripotent stem cells are valuable sources for patient-specific cell therapies against various diseases. Backed-up by a huge number of basic researches, neuronal differentiation mechanism is well established and pluripotent stem cell therapies against neurological disorders are getting closer to clinical application. However, there are increasing needs for standardization of the sourcing pluripotent stem cells by establishing stem cell registries and banking. Global harmonization will accelerate practical use of personalized therapies using pluripotent stem cells.
Topics: Cell Differentiation; Cell- and Tissue-Based Therapy; Embryonic Stem Cells; Humans; Induced Pluripotent Stem Cells; Nervous System Diseases; Pluripotent Stem Cells; Stem Cell Transplantation
PubMed: 22203784
DOI: 10.1155/2011/520816 -
Cytotherapy Apr 2021Induced pluripotent stem cells (iPSCs) have the capacity to generate β cells in vitro, but the differentiation is incomplete and generates a variable percentage of...
BACKGROUND AIMS
Induced pluripotent stem cells (iPSCs) have the capacity to generate β cells in vitro, but the differentiation is incomplete and generates a variable percentage of off-target cells. Single-cell RNA sequencing offers the possibility of characterizing the transcriptional dynamics throughout differentiation and determining the identity of the final differentiation product.
METHODS
Single-cell transcriptomics data were obtained from four stages across differentiation of iPSCs into β cells and from human donor islets.
RESULTS
Clustering analysis revealed that iPSCs undertake a full endoderm commitment, and the obtained endocrine pancreatic cells have high homology with mature islets. The iPSC-derived β cells were devoid of pluripotent residual cells, and the differentiation was pancreas-specific, as it did not generate ectodermal or mesodermal cells. Pseudotime trajectory identified a dichotomic endocrine/non-endocrine cell fate and distinct subgroups in the endocrine branch.
CONCLUSIONS
Future efforts to produce β cells from iPSCs must aim not only to improve the resulting endocrine cell but also to avoid differentiation into non-pancreatic endoderm cells.
Topics: Cell Differentiation; Endoderm; Humans; Induced Pluripotent Stem Cells; Islets of Langerhans; Pluripotent Stem Cells
PubMed: 33246884
DOI: 10.1016/j.jcyt.2020.10.004 -
Biotechnology Advances 2021Research in stem cells paved the way to an enormous amount of knowledge, increasing expectations on cardio regenerative therapeutic approaches in clinic. While the first... (Review)
Review
Research in stem cells paved the way to an enormous amount of knowledge, increasing expectations on cardio regenerative therapeutic approaches in clinic. While the first generation of clinical trials using cell-based therapies in the heart were performed with bone marrow and adipose tissue derived mesenchymal stem cells, second generation cell therapies moved towards the use of cardiac-committed cell populations, including cardiac progenitor cells and pluripotent stem cell derived cardiomyocytes. Despite all these progresses, translating the aptitudes of R&D and pre-clinical data into effective clinical treatments is still highly challenging, partially due to the demanding regulatory and safety concerns but also because of the lack of knowledge on the regenerative mechanisms of action of these therapeutic products. Thus, the need of analytical methodologies that enable a complete characterization of such complex products and a deep understanding of their therapeutic effects, at the cell and molecular level, is imperative to overcome the hurdles of these advanced therapies. Omics technologies, such as proteomics and glyco(proteo)mics workflows based on state of the art mass-spectrometry, have prompted some major breakthroughs, providing novel data on cell biology and a detailed assessment of cell based-products applied in cardiac regeneration strategies. These advanced 'omics approaches, focused on the profiling of protein and glycan signatures are excelling the identification and characterization of cell populations under study, namely unveiling pluripotency and differentiation markers, as well as paracrine mechanisms and signaling cascades involved in cardiac repair. The leading knowledge generated is supporting a more rational therapy design and the rethinking of challenges in Advanced Therapy Medicinal Products development. Herein, we review the most recent methodologies used in the fields of proteomics, glycoproteomics and glycomics and discuss their impact on the study of cardiac progenitor cells and pluripotent stem cell derived cardiomyocytes biology. How these discoveries will impact the speed up of novel therapies for cardiovascular diseases is also addressed.
Topics: Cell Differentiation; Cell- and Tissue-Based Therapy; Induced Pluripotent Stem Cells; Mesenchymal Stem Cells; Myocytes, Cardiac; Pluripotent Stem Cells; Proteomics
PubMed: 33895330
DOI: 10.1016/j.biotechadv.2021.107755 -
Cells Apr 2024The human respiratory system is susceptible to a variety of diseases, ranging from chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis to acute... (Review)
Review
The human respiratory system is susceptible to a variety of diseases, ranging from chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis to acute respiratory distress syndrome (ARDS). Today, lung diseases represent one of the major challenges to the health care sector and represent one of the leading causes of death worldwide. Current treatment options often focus on managing symptoms rather than addressing the underlying cause of the disease. The limitations of conventional therapies highlight the urgent clinical need for innovative solutions capable of repairing damaged lung tissue at a fundamental level. Pluripotent stem cell technologies have now reached clinical maturity and hold immense potential to revolutionize the landscape of lung repair and regenerative medicine. Meanwhile, human embryonic (HESCs) and human-induced pluripotent stem cells (hiPSCs) can be coaxed to differentiate into lung-specific cell types such as bronchial and alveolar epithelial cells, or pulmonary endothelial cells. This holds the promise of regenerating damaged lung tissue and restoring normal respiratory function. While methods for targeted genetic engineering of hPSCs and lung cell differentiation have substantially advanced, the required GMP-grade clinical-scale production technologies as well as the development of suitable preclinical animal models and cell application strategies are less advanced. This review provides an overview of current perspectives on PSC-based therapies for lung repair, explores key advances, and envisions future directions in this dynamic field.
Topics: Animals; Humans; Endothelial Cells; Pluripotent Stem Cells; Induced Pluripotent Stem Cells; Lung; Pulmonary Fibrosis
PubMed: 38607074
DOI: 10.3390/cells13070635