scholarly journals In Vitro Generation of Oocyte Like Cells and Their In Vivo Efficacy: How Far We have been Succeeded

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 557 ◽  
Author(s):  
Dinesh Bharti ◽  
Si-Jung Jang ◽  
Sang-Yun Lee ◽  
Sung-Lim Lee ◽  
Gyu-Jin Rho
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem ◽  
In Vivo Studies ◽  
Special Focus ◽  
Morphological Alterations ◽  
Cell Sources ◽  
Induced Pluripotent

In the last few decades, stem cell therapy has grown as a boon for many pathological complications including female reproductive disorders. In this review, a brief description of available strategies that are related to stem cell-based in vitro oocyte-like cell (OLC) development are given. We have tried to cover all the aspects and latest updates of the in vitro OLC developmental methodologies, marker profiling, available disease models, and in vivo efficacies, with a special focus on mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), and embryonic stem cells (ESCs) usage. The differentiation abilities of both the ovarian and non-ovarian stem cell sources under various induction conditions have shown different effects on morphological alterations, proliferation- and size-associated developments, hormonal secretions under gonadotropic stimulations, and their neo-oogenesis or folliculogenesis abilities after in vivo transplantations. The attainment of characters like oocyte-like morphology, size expansion, and meiosis initiation have been found to be major obstacles during in vitro oogenesis. A number of reports have either lacked in vivo studies or have shown their functional incapability to produce viable and healthy offspring. Though researchers have gained many valuable insights regarding in vitro gametogenesis, still there are many things to do to make stem cell-derived OLCs fully functional.

scholarly journals Induced Pluripotent Stem Cells (iPSCs) in Vascular Research: from Two- to Three-Dimensional Organoids

2021 ◽  
Author(s):  
Anja Trillhaase ◽  
Marlon Maertens ◽  
Zouhair Aherrahrou ◽  
Jeanette Erdmann
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Induced Pluripotent Stem Cells ◽  
Stem Cell Research ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Cell Types ◽  
3D Models ◽  
Induced Pluripotent

AbstractStem cell technology has been around for almost 30 years and in that time has grown into an enormous field. The stem cell technique progressed from the first successful isolation of mammalian embryonic stem cells (ESCs) in the 1990s, to the production of human induced-pluripotent stem cells (iPSCs) in the early 2000s, to finally culminate in the differentiation of pluripotent cells into highly specialized cell types, such as neurons, endothelial cells (ECs), cardiomyocytes, fibroblasts, and lung and intestinal cells, in the last decades. In recent times, we have attained a new height in stem cell research whereby we can produce 3D organoids derived from stem cells that more accurately mimic the in vivo environment. This review summarizes the development of stem cell research in the context of vascular research ranging from differentiation techniques of ECs and smooth muscle cells (SMCs) to the generation of vascularized 3D organoids. Furthermore, the different techniques are critically reviewed, and future applications of current 3D models are reported. Graphical abstract

Accept or Reject: The Role of Immune Tolerance in the Development of Stem Cell Therapies and Possible Future Approaches

2020 ◽  
pp. 019262332091824
Author(s):  
Richard Haworth ◽  
Michaela Sharpe
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem ◽  
Immune Recognition ◽  
Cell Of Origin ◽  
In Vivo Models ◽  
Cell Product ◽  
A Cell

In 2011, Goldring and colleagues published a review article describing the potential safety issues of novel stem cell-derived treatments. Immunogenicity and immunotoxicity of the administered cell product were considered risks in the light of clinical experience of transplantation. The relative immunogenicity of mesenchymal stem cells, embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs) was being addressed through in vitro and in vivo models. But the question arose as to whether the implanted cells needed to be identical to the recipient in every respect, including epigenetically, to evade immune recognition? If so, this set a high bar which may preclude use of many cells derived from iPSCs which have vestiges of a fetal phenotype and epigenetic memory of their cell of origin. However, for autologous iPSCs, the immunogenicity reduces once the surface antigen expression profile becomes close to that of the parent somatic cells. Therefore, a cell product containing incompletely differentiated cells could be more immunogenic. The properties of the administered cells, the immune privilege of the administration site, and the host immune status influence graft success or failure. In addition, the various approaches available to characterize potential immunogenicity of a cell therapy will be discussed.

scholarly journals Mammalian genes induce partially reprogrammed pluripotent stem cells in non-mammalian vertebrate and invertebrate species

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Ricardo Antonio Rosselló ◽  
Chun-Chun Chen ◽  
Rui Dai ◽  
Jason T Howard ◽  
Ute Hochgeschwender ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Pluripotent Stem Cells ◽  
Mammalian Species ◽  
Embryonic Stem ◽  
Model Organisms ◽  
Differentiated Cells ◽  
Transcription Factor Genes ◽  
Induced Pluripotent

Cells are fundamental units of life, but little is known about evolution of cell states. Induced pluripotent stem cells (iPSCs) are once differentiated cells that have been re-programmed to an embryonic stem cell-like state, providing a powerful platform for biology and medicine. However, they have been limited to a few mammalian species. Here we found that a set of four mammalian transcription factor genes used to generate iPSCs in mouse and humans can induce a partially reprogrammed pluripotent stem cell (PRPSCs) state in vertebrate and invertebrate model organisms, in mammals, birds, fish, and fly, which span 550 million years from a common ancestor. These findings are one of the first to show cross-lineage stem cell-like induction, and to generate pluripotent-like cells for several of these species with in vivo chimeras. We suggest that the stem-cell state may be highly conserved across a wide phylogenetic range.

Reversine: A Synthetic Purine with a Dual Activity as a Cell Dedifferentiating Agent and a Selective Anticancer Drug

2020 ◽  
Vol 27 (21) ◽  
pp. 3448-3462
Author(s):  
Marco Piccoli ◽  
Andrea Ghiroldi ◽  
Michelle M. Monasky ◽  
Federica Cirillo ◽  
Giuseppe Ciconte ◽  
...  
Keyword(s):  
Stem Cells ◽  
Current Knowledge ◽  
Embryonic Stem ◽  
Cell Types ◽  
Cancer Drug ◽  
Anti Cancer ◽  
Adult Cell ◽  
Induced Pluripotent

The development of new therapeutic applications for adult and embryonic stem cells has dominated regenerative medicine and tissue engineering for several decades. However, since 2006, induced Pluripotent Stem Cells (iPSCs) have taken center stage in the field, as they promised to overcome several limitations of the other stem cell types. Nonetheless, other promising approaches for adult cell reprogramming have been attempted over the years, even before the generation of iPSCs. In particular, two years before the discovery of iPSCs, the possibility of synthesizing libraries of large organic compounds, as well as the development of high-throughput screenings to quickly test their biological activity, enabled the identification of a 2,6-disubstituted purine, named reversine, which was shown to be able to reprogram adult cells to a progenitor-like state. Since its discovery, the effect of reversine has been confirmed on different cell types, and several studies on its mechanism of action have revealed its central role in inhibitory activity on several kinases implicated in cell cycle regulation and cytokinesis. These key features, together with its chemical nature, suggested a possible use of the molecule as an anti-cancer drug. Remarkably, reversine exhibited potent cytotoxic activity against several tumor cell lines in vitro and a significant effect in decreasing tumor progression and metastatization in vivo. Thus, 15 years since its discovery, this review aims at critically summarizing the current knowledge to clarify the dual role of reversine as a dedifferentiating agent and anti-cancer drug.

The Emerging Role of Stem Cells in Regenerative Dentistry

2020 ◽  
Vol 20 (4) ◽  
pp. 259-268 ◽  
Author(s):  
Paolo Capparè ◽  
Giulia Tetè ◽  
Maria Teresa Sberna ◽  
Paola Panina-Bordignon
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Biology ◽  
Specific Cell ◽  
Cell Plasticity ◽  
Regenerative Dentistry ◽  
Cell Sources ◽  
Induced Pluripotent

Progress of modern dentistry is accelerating at a spectacular speed in the scientific, technological and clinical areas. Practical examples are the advancement in the digital field, which has guaranteed an average level of prosthetic practices for all patients, as well as other scientific developments, including research on stem cell biology. Given their plasticity, defined as the ability to differentiate into specific cell lineages with a capacity of almost unlimited self-renewal and release of trophic/immunomodulatory factors, stem cells have gained significant scientific and commercial interest in the last 15 years. Stem cells that can be isolated from various tissues of the oral cavity have emerged as attractive sources for bone and dental regeneration, mainly due to their ease of accessibility. This review will present the current understanding of emerging conceptual and technological issues of the use of stem cells to treat bone and dental loss defects. In particular, we will focus on the clinical application of stem cells, either directly isolated from oral sources or in vitro reprogrammed from somatic cells (induced pluripotent stem cells). Research aimed at further unraveling stem cell plasticity will allow to identify optimal stem cell sources and characteristics, to develop novel regenerative tools in dentistry.

scholarly journals Experimental Limitations Using Reprogrammed Cells for Hematopoietic Differentiation

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Katharina Seiler ◽  
Motokazu Tsuneto ◽  
Fritz Melchers
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Pluripotent Stem Cells ◽  
Somatic Cells ◽  
Embryonic Stem ◽  
Clinical Settings ◽  
Hematopoietic Differentiation ◽  
Hematopoietic Stem ◽  
Induced Pluripotent

We review here our experiences with thein vitroreprogramming of somatic cells to induced pluripotent stem cells (iPSC) and subsequentin vitrodevelopment of hematopoietic cells from these iPSC and from embryonic stem cells (ESC). While, in principle, thein vitroreprogramming and subsequent differentiation can generate hematopoietic cell from any somatic cells, it is evident that many of the steps in this process need to be significantly improved before it can be applied to human cells and used in clinical settings of hematopoietic stem cell (HSC) transplantations.

Abstract P482: Elucidating And Characterizing The Molecular Mechanistic Role Of Phospholamban L39 Stop In The Pathophysiology Of Cardiomyopathy Using Patient-derived Human Induced Pluripotent Stem Cells And Humanized Knock-in Mouse Model Systems

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Anichavezhi Devendran ◽  
Rasheed Bailey ◽  
Sumanta Kar ◽  
Francesca Stillitano ◽  
Irene Turnbull ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mouse Model ◽  
Mononuclear Cells ◽  
Embryonic Stem ◽  
Model Systems ◽  
Patient Specific ◽  
Induced Pluripotent

Background: Heart failure (HF) is a complex clinical condition associated with substantial morbidity and mortality worldwide. The contractile dysfunction and arrhythmogenesis related to HF has been linked to the remodelling of calcium (Ca ++ ) handling. Phospholamban (PLN) has emerged as a key regulator of intracellular Ca ++ concentration. Of the PLN mutations, L39X is intriguing as it has not been fully characterized. This mutation is believed to be functionally equivalent to PLN null (KO) but contrary to PLN KO mice, L39X carriers develop a lethal cardiomyopathy (CMP). Our study aims at using induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) from homozygous L39X carriers to elucidate the role of L39X in human pathophysiology. Our plan also involves the characterization of humanized L39X knock-in mice (KM), which we hypothesize will develop a CMP from mis-localization of PLN and disruption of Ca ++ signalling. Methodology and Results: Mononuclear cells from Hom L39X carriers were obtained to generate 11 integration-free patient-specific iPSC clones. The iPSC-CMs were derived using established protocols. Compared to the WT iPSC-CMs, the Hom L39X derived-CMs PLN had an abnormal cytoplasmic distribution and formed intracellular aggregates, with the loss of perinuclear localization. There was also a 70% and 50% reduction of mRNA and protein expression of PLN respectively in L39X compared to WT iPSC-CMs. These findings indicated that L39X PLN is both under-expressed and mis-localized within the cell. To validate this observation in-vivo, we genetically modified FVB mice to harbour the human L39X. Following electroporation, positively transfected mouse embryonic stem cells were injected into host blastocysts to make humanized KM that were subsequently used to generate either a protamine-Cre (endogenous PLN driven expression) or a cardiac TNT mouse (i.e., CMP specific). Conclusion: Our data confirm an abnormal intracellular distribution of PLN, with the loss of perinuclear accumulation and mis-localization, suggestive of ineffective targeting to or retention of L39X. The mouse model will be critically important to validate the in-vitro observations and provides an ideal platform for future studies centred on the development of novel therapeutic strategies including virally delivered CRISPR/Cas9 for in-vivo gene editing and testing of biochemical signalling pathways.

scholarly journals Hypoxia as a Driving Force of Pluripotent Stem Cell Reprogramming and Differentiation to Endothelial Cells

Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1614
Author(s):  
Paulina Podkalicka ◽  
Jacek Stępniewski ◽  
Olga Mucha ◽  
Neli Kachamakova-Trojanowska ◽  
Józef Dulak ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Disease Modeling ◽  
Embryonic Stem ◽  
Hypoxic Conditions ◽  
Vascular Structures ◽  
Induced Pluripotent

Inadequate supply of oxygen (O2) is a hallmark of many diseases, in particular those related to the cardiovascular system. On the other hand, tissue hypoxia is an important factor regulating (normal) embryogenesis and differentiation of stem cells at the early stages of embryonic development. In culture, hypoxic conditions may facilitate the derivation of embryonic stem cells (ESCs) and the generation of induced pluripotent stem cells (iPSCs), which may serve as a valuable tool for disease modeling. Endothelial cells (ECs), multifunctional components of vascular structures, may be obtained from iPSCs and subsequently used in various (hypoxia-related) disease models to investigate vascular dysfunctions. Although iPSC-ECs demonstrated functionality in vitro and in vivo, ongoing studies are conducted to increase the efficiency of differentiation and to establish the most productive protocols for the application of patient-derived cells in clinics. In this review, we highlight recent discoveries on the role of hypoxia in the derivation of ESCs and the generation of iPSCs. We also summarize the existing protocols of hypoxia-driven differentiation of iPSCs toward ECs and discuss their possible applications in disease modeling and treatment of hypoxia-related disorders.

scholarly journals Organoids in domestic animals: with which stem cells?

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Bertrand Pain
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Research ◽  
Pluripotent Stem Cells ◽  
Animal Species ◽  
Three Dimensional ◽  
Embryonic Stem ◽  
Domestic Animals ◽  
Induced Pluripotent

AbstractOrganoids are three-dimensional structures that are derived from the self-organization of stem cells as they differentiate in vitro. The plasticity of stem cells is one of the major criteria for generating organoids most similar to the tissue structures they intend to mimic. Stem cells are cells with unique properties of self-renewal and differentiation. Depending on their origin, a distinction is made between pluripotent (embryonic) stem cells (PSCs), adult (or tissue) stem cells (ASCs), and those obtained by somatic reprogramming, so-called induced pluripotent stem cells (iPSCs). While most data since the 1980s have been acquired in the mouse model, and then from the late 1990s in humans, the process of somatic reprogammation has revolutionized the field of stem cell research. For domestic animals, numerous attempts have been made to obtain PSCs and iPSCs, an approach that makes it possible to omit the use of embryos to derive the cells. Even if the plasticity of the cells obtained is not always optimal, the recent progress in obtaining reprogrammed cells is encouraging. Along with PSCs and iPSCs, many organoid derivations in animal species are currently obtained from ASCs. In this study, we present state-of-the-art stem cell research according to their origins in the various animal models developed.

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