scholarly journals Induction of functional hypothalamus and pituitary tissues from pluripotent stem cells for regenerative medicine

2020 ◽  
Author(s):  
Mayuko Kano ◽  
Hidetaka Suga ◽  
Hiroshi Arima
Keyword(s):  
Stem Cells ◽  
Regenerative Medicine ◽  
Pluripotent Stem Cells ◽  
Hormone Replacement ◽  
Three Dimensional ◽  
Embryonic Stem ◽  
Hormone Deficiency ◽  
Adrenal Crisis ◽  
Mouse Escs

Abstract The hypothalamus and pituitary have been identified to play essential roles in maintaining homeostasis. Various diseases can disrupt the functions of these systems, which can often result in serious lifelong symptoms. The current treatment for hypopituitarism involves hormone replacement therapy. However, exogenous drug administration cannot mimic the physiological changes that are a result of hormone requirements. Therefore, patients are at a high risk of severe hormone deficiency, including adrenal crisis. Pluripotent stem cells (PSCs) self-proliferate and differentiate into all types of cells. The generation of endocrine tissues from PSCs has been considered as another new treatment for hypopituitarism. Our colleagues established a three-dimensional culture method for embryonic stem cells (ESCs). In this culture, the ESC-derived aggregates exhibit self-organization and spontaneous formation of highly ordered patterning. Recent results have shown that strict removal of exogenous patterning factors during early differentiation efficiently induces rostral hypothalamic progenitors from mouse ESCs. These hypothalamic progenitors generate vasopressinergic neurons, which release neuropeptides upon exogenous stimulation. Subsequently, we reported adenohypophysis tissue self-formation in three-dimensional cultures of mouse ESCs. The ESCs were found to differentiate into both non-neural oral ectoderm and hypothalamic neuroectoderm in adjacent layers. Interactions between the two tissues appear to be critically important for in vitro induction of a Rathke's pouch-like developing embryo. Various endocrine cells were differentiated from non-neural ectoderm. The induced corticotrophs efficiently secreted adrenocorticotropic hormone when engrafted in vivo, which rescued hypopituitary hosts. For future regenerative medicine, generation of hypothalamic and pituitary tissues from human PSCs is necessary. We and other groups succeeded in establishing a differentiation method with the use of human PSCs. Researchers could use these methods for models of human diseases to elucidate disease pathology or screen potential therapeutics.

scholarly journals Formative pluripotent stem cells show features of epiblast cells poised for gastrulation

Cell Research ◽  
2021 ◽  
Author(s):  
Xiaoxiao Wang ◽  
Yunlong Xiang ◽  
Yang Yu ◽  
Ran Wang ◽  
Yu Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Germ Cells ◽  
Pluripotent Stem Cells ◽  
Primordial Germ Cells ◽  
Embryonic Stem ◽  
Large Set ◽  
Mouse Escs ◽  
Epiblast Stem Cells ◽  
Early Gastrula

AbstractThe pluripotency of mammalian early and late epiblast could be recapitulated by naïve embryonic stem cells (ESCs) and primed epiblast stem cells (EpiSCs), respectively. However, these two states of pluripotency may not be sufficient to reflect the full complexity and developmental potency of the epiblast during mammalian early development. Here we report the establishment of self-renewing formative pluripotent stem cells (fPSCs) which manifest features of epiblast cells poised for gastrulation. fPSCs can be established from different mouse ESCs, pre-/early-gastrula epiblasts and induced PSCs. Similar to pre-/early-gastrula epiblasts, fPSCs show the transcriptomic features of formative pluripotency, which are distinct from naïve ESCs and primed EpiSCs. fPSCs show the unique epigenetic states of E6.5 epiblast, including the super-bivalency of a large set of developmental genes. Just like epiblast cells immediately before gastrulation, fPSCs can efficiently differentiate into three germ layers and primordial germ cells (PGCs) in vitro. Thus, fPSCs highlight the feasibility of using PSCs to explore the development of mammalian epiblast.

Hepatic differentiation of pluripotent stem cells

2009 ◽  
Vol 390 (10) ◽  
Author(s):  
Komal Loya ◽  
Reto Eggenschwiler ◽  
Kinarm Ko ◽  
Malte Sgodda ◽  
Francoise André ◽  
...  
Keyword(s):  
Stem Cells ◽  
Regenerative Medicine ◽  
Pluripotent Stem Cells ◽  
Ethical Issues ◽  
Es Cells ◽  
Embryonic Stem ◽  
Hepatic Differentiation ◽  
Alternative Source ◽  
Organ Specific

Abstract In regenerative medicine pluripotent stem cells are considered to be a valuable self-renewing source for therapeutic cell transplantations, given that a functional organ-specific phenotype can be acquired by in vitro differentiation protocols. Furthermore, derivatives of pluripotent stem cells that mimic fetal progenitor stages could serve as an important tool to analyze organ development with in vitro approaches. Because of ethical issues regarding the generation of human embryonic stem (ES) cells, other sources for pluripotent stem cells are intensively studied. Like in less developed vertebrates, pluripotent stem cells can be generated from the female germline even in mammals, via parthenogenetic activation of oocytes. Recently, testis-derived pluripotent stem cells were derived from the male germline. Therefore, we compared two different hepatic differentiation approaches and analyzed the generation of definitive endoderm progenitor cells and their further maturation into a hepatic phenotype using murine parthenogenetic ES cells, germline-derived pluripotent stem cells, and ES cells. Applying quantitative RT-PCR, both germline-derived pluripotent cell lines show similar differentiation capabilities as normal murine ES cells and can be considered an alternative source for pluripotent stem cells in regenerative medicine.

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.

scholarly journals Resetting Human Naïve Pluripotency

2016 ◽  
Vol 8 ◽  
pp. GEG.S38093 ◽  
Author(s):  
Jifang Xiao ◽  
Daniel H. Mai ◽  
Liangqi Xie
Keyword(s):  
Stem Cells ◽  
Regenerative Medicine ◽  
Pluripotent Stem Cells ◽  
Inner Cell Mass ◽  
Cell Mass ◽  
Embryonic Stem ◽  
Human Escs ◽  
Pluripotent State ◽  
Primed State

The rodent naive pluripotent state is believed to represent the preimplantation inner cell mass state of the developing blastocyst and can derive self-renewing pluripotent embryonic stem cells (ESCs) in vitro. Nevertheless, human ESCs exhibit epigenetic, metabolic, and transcriptomic characteristics more akin to primed pluripotent stem cells (PSCs) derived from the postimplantation epiblast. Understanding the genetic and epigenetic mechanisms that constrain human ESCs in the primed state is crucial for the human naive pluripotent state resetting and numerous applications in regenerative medicine. In this review, we begin by defining the naive and primed states in the murine model and compare the epigenetic characteristics of those states to the human PSCs. We also examine the various reprogramming schemes to derive the human naive pluripotent state. Finally, we discuss future perspectives of studying and deriving the human naive PSCs in the context of cellular engineering and regenerative medicine.

Prospects for the use of the achievements of regenerative medicine in otorhinolaryngology

2017 ◽  
Vol 6 (1) ◽  
pp. 1-7
Author(s):  
Andrzej K. Ciechanowicz
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Regenerative Medicine ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Bone Marrow Cells ◽  
Embryonic Stem ◽  
Promising Alternative ◽  
Induced Pluripotent

Regenerative medicine is focusing on searching for stem cells, which can be efficiently and safely used for regeneration of damaged tissues and organs. Pluripotent stem cells would be ideal for this purpose. It is because they have the ability to differentiate into cells of all three germ layers (ecto-, meso- and endoderm). One of the sources of their isolation are embryos. For many years, they are made unsuccessful attempts to use of very controversial embryonic stem cells that are isolated from embryos. So strong ethical controversy forced scientists to look for other, undoubted ethically, sources of pluripotent stem cells. Induced pluripotent stem cells are proposed, as a more promising alternative to cells isolated from embryos. Unfortunately, both embryonic stem cells and induced pluripotent stem cells tend to genetic instability leading to the formation of teratomas. In parallel studies scientists try to use of stem cells isolated from adult tissues (e.g. bone marrow cells or adipose tissue) in the regeneration of parenchymal organs. Unfortunately, there is no convincing evidence for most of these cells that can regenerate damaged parenchymal organs. Regenerative medicine more frequently is employed in the otorhinolaryngological therapies. More and more researchers’ efforts are put into the development of an effective method of stimulation (in vitro) of pluripotent stem cells isolated from adult tissue for differentiation of the renewable progenitor stem cells which can keep their potential after transplantation into the recipient (e.g. in the treatment of imbalances or hearing loss). Moreover, there are promising methods for employing of the stem cells potential in tissue engineering as they are more effectively introduced as a clinical therapies.

scholarly journals Directed Differentiation of Pluripotent Stem Cells into Kidney

2015 ◽  
Vol 10s1 ◽  
pp. BMI.S20055 ◽  
Author(s):  
Ryuji Morizane ◽  
Albert Q. Lam
Keyword(s):  
Stem Cells ◽  
Progenitor Cells ◽  
Pluripotent Stem Cells ◽  
Kidney Development ◽  
Three Dimensional ◽  
Embryonic Stem ◽  
Directed Differentiation ◽  
Metanephric Mesenchyme ◽  
Nephron Progenitor

Pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), represent an ideal substrate for regenerating kidney cells and tissue lost through injury and disease. Recent studies have demonstrated the ability to differentiate PSCs into populations of nephron progenitor cells that can organize into kidney epithelial structures in three-dimensional contexts. While these findings are highly encouraging, further studies need to be performed to improve the efficiency and specificity of kidney differentiation. The identification of specific markers of the differentiation process is critical to the development of protocols that effectively recapitulate nephrogenesis in vitro. In this review, we summarize the current studies describing the differentiation of ESCs and iPSCs into cells of the kidney lineage. We also present an analysis of the markers relevant to the stages of kidney development and differentiation and propose a new roadmap for the directed differentiation of PSCs into nephron progenitor cells of the metanephric mesenchyme.

scholarly journals Induced Tissue-Specific Stem Cells (iTSCs): Their Generation and Possible Use in Regenerative Medicine

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 780
Author(s):  
Issei Saitoh ◽  
Masahiro Sato ◽  
Yuki Kiyokawa ◽  
Emi Inada ◽  
Yoko Iwase ◽  
...  
Keyword(s):  
Stem Cells ◽  
Regenerative Medicine ◽  
Pluripotent Stem Cells ◽  
Somatic Cells ◽  
Embryonic Stem ◽  
Additional Treatment ◽  
Tissue Specific ◽  
Immunocompromised Mice ◽  
Tissue Specific Stem Cells

Induced tissue-specific stem cells (iTSCs) are partially reprogrammed cells which have an intermediate state, such as progenitors or stem cells. They originate from the de-differentiation of differentiated somatic cells into pluripotent stem cells, such as induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs), or from the differentiation of undifferentiated cells. They show a limited capacity to differentiate and a morphology similar to that of somatic cell stem cells present in tissues, but distinct from that of iPSCs and ESCs. iTSCs can be generally obtained 7 to 10 days after reprogramming of somatic cells with Yamanaka’s factors, and their fibroblast-like morphology remains unaltered. iTSCs can also be obtained directly from iPSCs cultured under conditions allowing cellular differentiation. In this case, to effectively induce iTSCs, additional treatment is required, as exemplified by the conversion of iPSCs into naïve iPSCs. iTSCs can proliferate continuously in vitro, but when transplanted into immunocompromised mice, they fail to generate solid tumors (teratomas), implying loss of tumorigenic potential. The low tendency of iTSCs to elicit tumors is beneficial, especially considering applications for regenerative medicine in humans. Several iTSC types have been identified, including iTS-L, iTS-P, and iTS-D, obtained by reprogramming hepatocytes, pancreatic cells, and deciduous tooth-derived dental pulp cells, respectively. This review provides a brief overview of iPSCs and discusses recent advances in the establishment of iTSCs and their possible applications in regenerative medicine.

Mini Review; Differentiation of Human Pluripotent Stem Cells into Oocytes

2020 ◽  
Vol 15 (4) ◽  
pp. 301-307 ◽  
Author(s):  
Gaifang Wang ◽  
Maryam Farzaneh
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Human Pluripotent Stem Cells ◽  
Human Oocyte ◽  
Differentiation Potential ◽  
Cell Lineages ◽  
Cell Based Therapy ◽  
Induced Pluripotent

Primary Ovarian Insufficiency (POI) is one of the main diseases causing female infertility that occurs in about 1% of women between 30-40 years of age. There are few effective methods for the treatment of women with POI. In the past few years, stem cell-based therapy as one of the most highly investigated new therapies has emerged as a promising strategy for the treatment of POI. Human pluripotent stem cells (hPSCs) can self-renew indefinitely and differentiate into any type of cell. Human Embryonic Stem Cells (hESCs) as a type of pluripotent stem cells are the most powerful candidate for the treatment of POI. Human-induced Pluripotent Stem Cells (hiPSCs) are derived from adult somatic cells by the treatment with exogenous defined factors to create an embryonic-like pluripotent state. Both hiPSCs and hESCs can proliferate and give rise to ectodermal, mesodermal, endodermal, and germ cell lineages. After ovarian stimulation, the number of available oocytes is limited and the yield of total oocytes with high quality is low. Therefore, a robust and reproducible in-vitro culture system that supports the differentiation of human oocytes from PSCs is necessary. Very few studies have focused on the derivation of oocyte-like cells from hiPSCs and the details of hPSCs differentiation into oocytes have not been fully investigated. Therefore, in this review, we focus on the differentiation potential of hPSCs into human oocyte-like cells.

scholarly journals Establishing a deeper understanding of the osteogenic differentiation of monolayer cultured human pluripotent stem cells using novel and detailed analyses

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ping Zhou ◽  
Jia-Min Shi ◽  
Jing-E Song ◽  
Yu Han ◽  
Hong-Jiao Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Osteogenic Differentiation ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Telomerase Activity ◽  
Human Pluripotent Stem Cells ◽  
Cell Counting ◽  
Cell Type ◽  
Alizarin Red

Abstract Background Derivation of osteoblast-like cells from human pluripotent stem cells (hPSCs) is a popular topic in bone tissue engineering. Although many improvements have been achieved, the low induction efficiency because of spontaneous differentiation hampers their applications. To solve this problem, a detailed understanding of the osteogenic differentiation process of hPSCs is urgently needed. Methods Monolayer cultured human embryonic stem cells and human-induced pluripotent stem cells were differentiated in commonly applied serum-containing osteogenic medium for 35 days. In addition to traditional assays such as cell viability detection, reverse transcription-polymerase chain reaction, immunofluorescence, and alizarin red staining, we also applied studies of cell counting, cell telomerase activity, and flow cytometry as essential indicators to analyse the cell type changes in each week. Results The population of differentiated cells was quite heterogeneous throughout the 35 days of induction. Then, cell telomerase activity and cell cycle analyses have value in evaluating the cell type and tumourigenicity of the obtained cells. Finally, a dynamic map was made to integrate the analysis of these results during osteogenic differentiation of hPSCs, and the cell types at defined stages were concluded. Conclusions Our results lay the foundation to improve the in vitro osteogenic differentiation efficiency of hPSCs by supplementing with functional compounds at the desired stage, and then establishing a stepwise induction system in the future.

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