scholarly journals The Stability of the Induced Epigenetic Programs

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Maria J. Barrero
Keyword(s):  
Stem Cells ◽  
Somatic Cells ◽  
Cell Types ◽  
Specific Cell ◽  
Cell Type ◽  
Pluripotent Cells ◽  
Potential Applications ◽  
The Stability

For many years scientists have been attracted to the possibility of changing cell identity. In the last decades seminal discoveries have shown that it is possible to reprogram somatic cells into pluripotent cells and even to transdifferentiate one cell type into another. In view of the potential applications that generating specific cell types in the laboratory can offer for cell-based therapies, the next important questions relate to the quality of the induced cell types. Importantly, epigenetic aberrations in reprogrammed cells have been correlated with defects in differentiation. Therefore, a look at the epigenome and understanding how different regulators can shape it appear fundamental to anticipate potential therapeutic pitfalls. This paper covers these epigenetic aspects in stem cells, differentiation, and reprogramming and discusses their importance for the safety of in vitro engineered cell types.

scholarly journals Gold-coated plant virus as computed tomography imaging contrast agent

2019 ◽  
Vol 10 ◽  
pp. 1983-1993 ◽  
Author(s):  
Alaa A A Aljabali ◽  
Mazhar S Al Zoubi ◽  
Khalid M Al-Batanyeh ◽  
Ali Al-Radaideh ◽  
Mohammad A Obeid ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Contrast Agent ◽  
Low Cost ◽  
Cell Types ◽  
Specific Cell ◽  
Scan Time ◽  
Ct Contrast Agent ◽  
Potential Applications ◽  
Resolution Imaging

Chemical modification of the surface of viruses, both the interior and the exterior, imparts new functionalities, that have potential applications in nanomedicine. In this study, we developed novel virus-based nanomaterials as a contrast agent for computed tomography (CT) imaging in vitro. The gold-coated cowpea mosaic virus (Au-CPMV) particles were generated by the electrostatic adsorption of positively charged electrolyte on the virus capsid with the subsequent incubation and reduction of anionic gold complexes. Au-CPMV particles as a CT contrast agent offer a fast scan time (less than 2 min), low cost, and biocompatibility and allow for high-resolution imaging with ca. 150 Hounsfield units (HU). The Au-CPMV surface was further modified allowing for the incorporation of targeting molecules of specific cell types.

Effects of Aging and TGF-Beta 3 on Chondrocyte and Mesenchymal Stem Cell Matrix Formation

2010 ◽  
Author(s):  
Isaac E. Erickson ◽  
Steven C. van Veen ◽  
Swarnali Sengupta ◽  
Sydney R. Kestle ◽  
Jason A. Burdick ◽  
...  
Keyword(s):  
Stem Cells ◽  
Articular Chondrocytes ◽  
Cell Types ◽  
Matrix Proteins ◽  
Cell Type ◽  
Cell Matrix ◽  
Age Related ◽  
Cartilage Restoration ◽  
Effects Of Aging

Articular cartilage pathology is common in the aged population. Numerous studies have shown that aged chondrocytes (CHs) are inferior to juvenile CHs in their ability to proliferate and produce cartilage-specific extracellular matrix proteins, potentially limiting their use in tissue engineering applications for cartilage restoration [1,2]. Mesenchymal stem cells (MSCs) are an alternative cell type that can be expanded in vitro while maintaining their ability to differentiate into cell types comparable to articular chondrocytes. However, organismal aging also influences human MSC proliferation [3,4] and multi-potential differentiation [5], though for chondrogenesis these findings are mixed, with some suggesting that aged progenitor cells retain their chondrogenic capacity [6]. The objective of this study was to assess age related differences in donor-matched CH and MSC potential for chondrogenic repair. In addition, the effects of the chondrogenic growth factor TGF-β3 on CHs and MSCs were evaluated.

scholarly journals Human Organoids for Predictive Toxicology Research and Drug Development

2021 ◽  
Vol 12 ◽  
Author(s):  
Toshikatsu Matsui ◽  
Tadahiro Shinozawa
Keyword(s):  
Stem Cells ◽  
Drug Development ◽  
Disease Modeling ◽  
Cell Types ◽  
Underlying Disease ◽  
Future Research ◽  
Specific Cell ◽  
Predictive Toxicology

Organoids are three-dimensional structures fabricated in vitro from pluripotent stem cells or adult tissue stem cells via a process of self-organization that results in the formation of organ-specific cell types. Human organoids are expected to mimic complex microenvironments and many of the in vivo physiological functions of relevant tissues, thus filling the translational gap between animals and humans and increasing our understanding of the mechanisms underlying disease and developmental processes. In the last decade, organoid research has attracted increasing attention in areas such as disease modeling, drug development, regenerative medicine, toxicology research, and personalized medicine. In particular, in the field of toxicology, where there are various traditional models, human organoids are expected to blaze a new path in future research by overcoming the current limitations, such as those related to differences in drug responses among species. Here, we discuss the potential usefulness, limitations, and future prospects of human liver, heart, kidney, gut, and brain organoids from the viewpoints of predictive toxicology research and drug development, providing cutting edge information on their fabrication methods and functional characteristics.

57 NUCLEAR TRANSFER WITH RABBIT EMBRYONIC STEM CELLS: SERUM-STARVATION IMPROVES THE QUALITY OF CLONED EMBRYOS

2009 ◽  
Vol 21 (1) ◽  
pp. 129
Author(s):  
V. Zakhartchenko ◽  
F. Flisikovska ◽  
R. Hao ◽  
S. Li ◽  
A. Kind ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Nuclear Transfer ◽  
Somatic Cells ◽  
Embryonic Stem ◽  
Serum Starvation ◽  
Chromosomal Dna ◽  
Culture Dish

Rabbit cloning by NT with somatic cells is so far a rather inefficient process. However, this technology is urgently required to generate rabbits with a humanized immune system as a source of human polyclonal antibodies. Embryonic stem cells (ESCs) have a number of advantages over somatic cells as tools for cell-mediated transgenesis including long periods of proliferation in vitro, higher frequency of homologous recombination between exogenous and chromosomal DNA, and less requirements for reprogramming (Rideout et al. 2000 Nat. Genet. 24, 109–110). To improve rabbit cloning we have derived and characterized 19 putative rabbit ESC lines and tested cells from 6 lines as donors for NT. First, we assessed in vitro development of NT embryos. Blastocyst rates varied in the range of 6–68% depending on the particular cell line and passage number, but the quality of the resultant embryos was worse compared to NT embryos derived from adult fibroblasts [hatched blastocysts: 13/214 (6%) v. 36/86 (42%), respectively]. Transfer of NT embryos derived from the ESC line showing the highest development to blastocysts into recipients resulted only in implantations (70%, 7/10) but not in offspring. Assuming that poor quality of NT embryos derived from ESCs could be due to the incompatibility between cell cycles of donor and recipient cells we used serum starvation to make ESCs more suitable for nuclear transfer. Serum starvation of one of the ESC lines (0.5% FCS for 3 days) greatly improved the quality of cloned embryos compared to those derived from non-starved cells of the same ESC line as indicated by the high proportions of hatched [38/151 (25%) v. 4/153 (3%)] and attached [25/151 (17%) v. 0%] to the surface of a culture dish blastocysts. Moreover, some of these blastocysts grew in vitro for 14–25 days. Our study provides evidence that the quality of NT embryos derived from ESCs can be significantly improved using serum starvation of donor cells suggesting possible effect of this treatment on the cell cycle synchronization. We are currently testing whether serum starvation of ESCs would also improve post-implantation development of rabbit NT embryos. This work is supported by Roche Diagnostic GmbH.

Partial Reprogramming As An Emerging Strategy for Safe Induced Cell Generation and Rejuvenation

2019 ◽  
Vol 19 (4) ◽  
pp. 248-254
Author(s):  
Marianne Lehmann ◽  
Martina Canatelli-Mallat ◽  
Priscila Chiavellini ◽  
Gloria M. Cónsole ◽  
Maria D. Gallardo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Somatic Cell ◽  
Fluorescent Protein ◽  
Somatic Cells ◽  
Cell Types ◽  
Cell Reprogramming ◽  
Green Fluorescent ◽  
Original Cell

Background: Conventional cell reprogramming involves converting a somatic cell line into induced pluripotent stem cells (iPSC), which subsequently can be re-differentiated to specific somatic cell types. Alternatively, partial cell reprogramming converts somatic cells into other somatic cell types by transient expression of pluripotency genes thus generating intermediates that retain their original cell identity, but are responsive to appropriate cocktails of specific differentiation factors. Additionally, biological rejuvenation by partial cell reprogramming is an emerging avenue of research. Objective: Here, we will briefly review the emerging information pointing to partial reprogramming as a suitable strategy to achieve cell reprogramming and rejuvenation, bypassing cell dedifferentiation. Methods: In this context, regulatable pluripotency gene expression systems are the most widely used at present to implement partial cell reprogramming. For instance, we have constructed a regulatable bidirectional adenovector expressing Green Fluorescent Protein and oct4, sox2, klf4 and c-myc genes (known as the Yamanaka genes or OSKM). Results: Partial cell reprogramming has been used to reprogram fibroblasts to cardiomyocytes, neural progenitors and neural stem cells. Rejuvenation by cyclic partial reprogramming has been achieved both in vivo and in cell culture using transgenic mice and cells expressing the OSKM genes, respectively, controlled by a regulatable promoter. Conclusion: Partial reprogramming emerges as a powerful tool for the genesis of iPSC-free induced somatic cells of therapeutic value and for the implementation of in vitro and in vivo rejuvenation keeping cell type identity unchanged.

scholarly journals Differentiation of trophoblast cells from human embryonic stem cells: to be or not to be?

Reproduction ◽  
2014 ◽  
Vol 147 (5) ◽  
pp. D1-D12 ◽  
Author(s):  
R Michael Roberts ◽  
Kyle M Loh ◽  
Mitsuyoshi Amita ◽  
Andreia S Bernardo ◽  
Katsuyuki Adachi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Full Range ◽  
Embryonic Stem ◽  
Cell Types ◽  
Embryonic Cells ◽  
Cell Type ◽  
Differentiated Cells ◽  
Developmental Hierarchy

It is imperative to unveil the full range of differentiated cell types into which human pluripotent stem cells (hPSCs) can develop. The need is twofold: it will delimit the therapeutic utility of these stem cells and is necessary to place their position accurately in the developmental hierarchy of lineage potential. Accumulated evidence suggested that hPSC could develop in vitro into an extraembryonic lineage (trophoblast (TB)) that is typically inaccessible to pluripotent embryonic cells during embryogenesis. However, whether these differentiated cells are truly authentic TB has been challenged. In this debate, we present a case for and a case against TB differentiation from hPSCs. By analogy to other differentiation systems, our debate is broadly applicable, as it articulates higher and more challenging standards for judging whether a given cell type has been genuinely produced from hPSC differentiation.

scholarly journals Epigenetic Manipulation Facilitates the Generation of Skeletal Muscle Cells from Pluripotent Stem Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Tomohiko Akiyama ◽  
Shunichi Wakabayashi ◽  
Atsumi Soma ◽  
Saeko Sato ◽  
Yuhki Nakatake ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Myogenic Differentiation ◽  
Ectopic Expression ◽  
Cell Types ◽  
Culture Conditions ◽  
The Body ◽  
Specific Cell ◽  
Modifying Factors

Human pluripotent stem cells (hPSCs) have the capacity to differentiate into essentially all cell types in the body. Such differentiation can be directed to specific cell types by appropriate cell culture conditions or overexpressing lineage-defining transcription factors (TFs). Especially, for the activation of myogenic program, early studies have shown the effectiveness of enforced expression of TFs associated with myogenic differentiation, such as PAX7 and MYOD1. However, the efficiency of direct differentiation was rather low, most likely due to chromatin features unique to hPSCs, which hinder the access of TFs to genes involved in muscle differentiation. Indeed, recent studies have demonstrated that ectopic expression of epigenetic-modifying factors such as a histone demethylase and an ATP-dependent remodeling factor significantly enhances myogenic differentiation from hPSCs. In this article, we review the recent progress for in vitro generation of skeletal muscles from hPSCs through forced epigenetic and transcriptional manipulation.

Cell contact induces multiple types of electrical excitability from ascidian two-cell embryos that are cleavage arrested and contain all cell fate determinants

2007 ◽  
Vol 293 (5) ◽  
pp. R1976-R1996
Author(s):  
Motoko Tanaka-Kunishima ◽  
Kunitaro Takahashi ◽  
Fumiyuki Watanabe
Keyword(s):  
Stem Cells ◽  
Cell Fate ◽  
Single Cells ◽  
Muscle Cells ◽  
Cell Types ◽  
Specific Cell ◽  
Cell Type ◽  
Cell Pair ◽  
Fate Determinants ◽  
Cell Fate Determinants

Ascidian early embryonic cells undergo cell differentiation without cell cleavage, thus enabling mixture of cell fate determinants in single cells, which will not be possible in mammalian systems. Either cell in a two-cell embryo (2C cell) has multiple fates and develops into any cell types in a tadpole. To find the condition for controlled induction of a specific cell type, cleavage-arrested cell triplets were prepared in various combinations. They were 2C cells in contact with a pair of anterior neuroectoderm cells from eight-cell embryos (2C-aa triplet), with a pair of presumptive notochordal neural cells (2C-AA triplet), with a pair of presumptive posterior epidermal cells (2C-bb triplet), and with a pair of presumptive muscle cells (2C-BB triplet). The fate of the 2C cell was electrophysiologically identified. When two-cell embryos had been fertilized 3 h later than eight-cell embryos and triplets were formed, the 2C cells became either anterior-neuronal, posterior-neuronal or muscle cells, depending on the cell type of the contacting cell pair. When two-cell embryos had been fertilized earlier than eight-cell embryos, most 2C cells became epidermal. When two- and eight-cell embryos had been simultaneously fertilized, the 2C cells became any one of three cell types described above or the epidermal cell type. Differentiation of the ascidian 2C cell into major cell types was reproducibly induced by selecting the type of contacting cell pair and the developmental time difference between the contacting cell pair and 2C cell. We discuss similarities between cleavage-arrested 2C cells and vertebrate embryonic stem cells and propose the ascidian 2C cell as a simple model for toti-potent stem cells.

In vitro development of nuclear transfer embryos derived from porcine embryonic germ cells and their descendent neural precursor cells

Zygote ◽  
2011 ◽  
Vol 20 (1) ◽  
pp. 9-15 ◽  
Author(s):  
Susa Shin ◽  
Kwang Sung Ahn ◽  
Seong-Jun Choi ◽  
Soon Young Heo ◽  
Hosup Shim
Keyword(s):  
Stem Cells ◽  
Germ Cells ◽  
Nuclear Transfer ◽  
Primordial Germ Cells ◽  
Somatic Cells ◽  
Cell Types ◽  
Neural Precursor ◽  
Blastocyst Development ◽  
Donor Cells

SummaryUndifferentiated stem cells may support a greater development of cloned embryos compared with differentiated cell types due to their ease of reprogramming during the nuclear transfer (NT) process. Hence, stem cells may be more suitable as nuclear donor cells for NT procedures than are somatic cells. Embryonic germ (EG) cells are undifferentiated stem cells that are isolated from cultured primordial germ cells (PGC) and can differentiate into several cell types. In this study, the in vitro development of NT embryos using porcine EG cells and their derivative neural precursor (NP) cells was investigated, thus eliminating any variation in genetic differences. The rates of fusion did not differ between NT embryos from EG and NP cells; however, the rate of cleavage in NT embryos derived from EG cells was significantly higher (p < 0.05) than that from NP cells (141/247 [57.1%] vs. 105/228 [46.1%]). Similarly, the rate of blastocyst development was significantly higher (P < 0.05) in NT using EG cells than the rate using NP cells (43/247 [17.4%] vs. 18/228 [7.9%]). The results obtained from the present study in pigs demonstrate a reduced capability for nuclear donor cells to be reprogrammed following the differentiation of porcine EG cells. Undifferentiated EG cells may be more amenable to reprogramming after reconstruction compared with differentiated somatic cells.

scholarly journals Adult Human Multipotent Neural Cells Could Be Distinguished from Other Cell Types by Proangiogenic Paracrine Effects via MCP-1 and GRO

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Sung Soo Kim ◽  
Hee-Jang Pyeon ◽  
Yoon Kyung Bae ◽  
Hyun Nam ◽  
Chung Kwon Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Types ◽  
Neural Cells ◽  
Cell Type ◽  
Paracrine Factors ◽  
Adult Human ◽  
Cell Type Specific ◽  
Functional Features

Adult human multipotent neural cells (ahMNCs) are unique cells derived from adult human temporal lobes. They show multipotent differentiation potentials into neurons and astrocytes. In addition, they possess proangiogenic capacities. The objective of this study was to characterize ahMNCs in terms of expression of cell type-specific markers, in vitro differentiation potentials, and paracrine factors compared with several other cell types including fetal neural stem cells (fNSCs) to provide detailed molecular and functional features of ahMNCs. Interestingly, the expression of cell type-specific markers of ahMNCs could not be differentiated from those of pericytes, mesenchymal stem cells (MSCs), or fNSCs. In contrast, differentiation potentials of ahMNCs and fNSCs into neural cells were higher than those of other cell types. Compared with MSCs, ahMNCs showed lower differentiation capacities into osteogenic and adipogenic cells. Moreover, ahMNCs uniquely expressed higher levels of MCP-1 and GRO family paracrine factors than fNSCs and MSCs. These high levels of MCP-1 and GRO family mediated in vivo proangiogenic effects of ahMNCs. These results indicate that ahMNCs have their own distinct characteristics that could distinguish ahMNCs from other cell types. Characteristics of ahMNCs could be utilized further in the preclinical and clinical development of ahMNCs for regenerative medicine. They could also be used as experimental references for other cell types including fNSCs.

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