scholarly journals Human artificial oocytes from patients’ somatic cells: past, present and future

2021 ◽  
Vol 2 (1) ◽  
pp. H1-H8
Author(s):  
Jan Tesarik ◽  
Carmen Mendoza ◽  
Raquel Mendoza-Tesarik
Keyword(s):  
Somatic Cell ◽  
Cell Types ◽  
Ips Cells ◽  
Cell Nuclei ◽  
Human Oocytes ◽  
Age Related ◽  
Human Ips Cells ◽  
Ovarian Diseases ◽  
Induced Pluripotent ◽  
The One

The first attempts at generating functional human oocytes by using the transfer of patients’ somatic cell nuclei, as DNA source, into donor enucleated oocytes date back to the early 2000s. After initial attempts, that gave rather encouraging results, the technique was abandoned because of adverse results with this technique in the mouse model. Priority was then given to the use of induced pluripotent stem (iPS) cells, based on excellent results in the mouse, where mature oocytes and live healthy offspring were achieved. However, these results could not be reproduced in humans, and oogenesis with human iPS cells did not continue beyond the stage of oogonium. These data suggest that the use of enucleated donor oocytes will be necessary to achieve fertilizable human oocytes with somatic cell-derived DNA. The main problem of all these techniques is that they have to meet with two, sometimes contradictory, requirements: the haploidization of somatic cell-derived DNA, on the one hand, and the remodeling/reprogramming of DNA of somatic cell origin, so as to be capable of supporting all stages of preimplantation and postimplantation development and to give rise to all cell types of the future organism. Further research is needed to determine the optimal strategy to cope with these two requirements. Lay summary The recourse to artificial oocytes, generated by using the patient’s own DNA derived from cells of somatic origin, represents the ultimate opportunity for women who lack healthy oocytes of their own but yearn for genetically related offspring. Many different pathologies, such as ovarian cancer, premature ovarian failure, other ovarian diseases and natural, age-related ovarian decay can cause the absence of available oocytes. The demand for artificial oocytes is increasing continuously, mainly because of the tendency to postpone maternity to still more advanced ages, when the quantity and quality of oocytes is low. This minireview focuses on the generation of artificial oocytes using different strategies and scenarios, based on the accumulated experience in humans and experimental animals.

Cell-cycle-dependent Ca2+ transients in human induced pluripotent stem cells revealed by a simultaneous imaging of cell nuclei and intracellular Ca2+ level

2016 ◽  
Vol 8 (9) ◽  
pp. 985-990
Author(s):  
Kenta Shimba ◽  
Shoko Iida ◽  
Kiyoshi Kotani ◽  
Yasuhiko Jimbo
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Ips Cells ◽  
Cell Nuclei ◽  
Simultaneous Imaging ◽  
Human Ips Cells ◽  
Intracellular Ca ◽  
Induced Pluripotent ◽  
Cycle Dependent

Simultaneous imaging of cell nuclei and intracellular Ca2+ level revealed that human iPS cells exhibited cell cycle-dependent Ca2+ transients.

scholarly journals Bone Morphogenetic Protein 4 (BMP4) Enhances the Differentiation of Human Induced Pluripotent Stem Cells into Limbal Progenitor Cells

2021 ◽  
Vol 43 (3) ◽  
pp. 2124-2134
Author(s):  
Hyun Soo Lee ◽  
Jeewon Mok ◽  
Choun-Ki Joo
Keyword(s):  
Progenitor Cells ◽  
Dermal Fibroblast ◽  
Ips Cells ◽  
Human Dermal Fibroblast ◽  
Corneal Epithelial ◽  
Specific Medium ◽  
Morphogenetic Protein ◽  
Human Ips Cells ◽  
Limbal Stem Cell ◽  
Induced Pluripotent

Corneal epithelium maintains visual acuity and is regenerated by the proliferation and differentiation of limbal progenitor cells. Transplantation of human limbal progenitor cells could restore the integrity and functionality of the corneal surface in patients with limbal stem cell deficiency. However, multiple protocols are employed to differentiate human induced pluripotent stem (iPS) cells into corneal epithelium or limbal progenitor cells. The aim of this study was to optimize a protocol that uses bone morphogenetic protein 4 (BMP4) and limbal cell-specific medium. Human dermal fibroblast-derived iPS cells were differentiated into limbal progenitor cells using limbal cell-specific (PI) medium and varying doses (1, 10, and 50 ng/mL) and durations (1, 3, and 10 days) of BMP4 treatment. Differentiated human iPS cells were analyzed by real-time polymerase chain reaction (RT-PCR), Western blotting, and immunocytochemical studies at 2 or 4 weeks after BMP4 treatment. Culturing human dermal fibroblast-derived iPS cells in limbal cell-specific medium and BMP4 gave rise to limbal progenitor and corneal epithelial-like cells. The optimal protocol of 10 ng/mL and three days of BMP4 treatment elicited significantly higher limbal progenitor marker (ABCG2, ∆Np63α) expression and less corneal epithelial cell marker (CK3, CK12) expression than the other combinations of BMP4 dose and duration. In conclusion, this study identified a successful reprogramming strategy to induce limbal progenitor cells from human iPS cells using limbal cell-specific medium and BMP4. Additionally, our experiments indicate that the optimal BMP4 dose and duration favor limbal progenitor cell differentiation over corneal epithelial cells and maintain the phenotype of limbal stem cells. These findings contribute to the development of therapies for limbal stem cell deficiency disorders.

Developmental potential of human oocytes reconstructed by transferring somatic cell nuclei into polyspermic zygote cytoplasm

2009 ◽  
Vol 382 (1) ◽  
pp. 119-123 ◽  
Author(s):  
Yong Fan ◽  
Xinjie Chen ◽  
Yumei Luo ◽  
Xiaolin Chen ◽  
Shaoying Li ◽  
...  
Keyword(s):  
Somatic Cell ◽  
Cell Nuclei ◽  
Developmental Potential ◽  
Human Oocytes

scholarly journals Potential and Limitation of HLA-Based Banking of Human Pluripotent Stem Cells for Cell Therapy

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Casimir de Rham ◽  
Jean Villard
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Ethical Issues ◽  
Human Leukocyte ◽  
Ips Cells ◽  
Abo Blood Group ◽  
Leukocyte Antigen ◽  
Induced Pluripotent ◽  
The One ◽  
Standard Medication

Great hopes have been placed on human pluripotent stem (hPS) cells for therapy. Tissues or organs derived from hPS cells could be the best solution to cure many different human diseases, especially those who do not respond to standard medication or drugs, such as neurodegenerative diseases, heart failure, or diabetes. The origin of hPS is critical and the idea of creating a bank of well-characterized hPS cells has emerged, like the one that already exists for cord blood. However, the main obstacle in transplantation is the rejection of tissues or organ by the receiver, due to the three main immunological barriers: the human leukocyte antigen (HLA), the ABO blood group, and minor antigens. The problem could be circumvented by using autologous stem cells, like induced pluripotent stem (iPS) cells, derived directly from the patient. But iPS cells have limitations, especially regarding the disease of the recipient and possible difficulties to handle or prepare autologous iPS cells. Finally, reaching standards of good clinical or manufacturing practices could be challenging. That is why well-characterized and universal hPS cells could be a better solution. In this review, we will discuss the interest and the feasibility to establish hPS cells bank, as well as some economics and ethical issues.

Human induced pluripotent stem cells are capable of B-cell lymphopoiesis

Blood ◽  
2011 ◽  
Vol 117 (15) ◽  
pp. 4008-4011 ◽  
Author(s):  
Lee Carpenter ◽  
Ram Malladi ◽  
Cheng-Tao Yang ◽  
Anna French ◽  
Katherine J. Pilkington ◽  
...  
Keyword(s):  
Stem Cells ◽  
B Cell ◽  
Embryonic Stem ◽  
Ips Cells ◽  
Ips Cell ◽  
Lymphoid Lineage ◽  
Human Ips Cells ◽  
Induced Pluripotent ◽  
First Time ◽  
Unique Potential

Abstract Induced pluripotent stem (iPS) cells offer a unique potential for understanding the molecular basis of disease and development. Here we have generated several human iPS cell lines, and we describe their pluripotent phenotype and ability to differentiate into erythroid cells, monocytes, and endothelial cells. More significantly, however, when these iPS cells were differentiated under conditions that promote lympho-hematopoiesis from human embryonic stem cells, we observed the formation of pre-B cells. These cells were CD45+CD19+CD10+ and were positive for transcripts Pax5, IL7αR, λ-like, and VpreB receptor. Although they were negative for surface IgM and CD5 expression, iPS-derived CD45+CD19+ cells also exhibited multiple genomic D-JH rearrangements, which supports a pre–B-cell identity. We therefore have been able to demonstrate, for the first time, that human iPS cells are able to undergo hematopoiesis that contributes to the B-cell lymphoid lineage.

scholarly journals NAMPT/SIRT2-mediated inhibition of the p53-p21 signaling pathway is indispensable for maintenance and hematopoietic differentiation of human iPS cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yun Xu ◽  
Masoud Nasri ◽  
Benjamin Dannenmann ◽  
Perihan Mir ◽  
Azadeh Zahabi ◽  
...  
Keyword(s):  
Embryoid Body ◽  
P53 Protein ◽  
Ips Cells ◽  
Hematopoietic Differentiation ◽  
Cellular Functions ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Signaling Axis ◽  
Human Ips Cells ◽  
Induced Pluripotent

Abstract Background Nicotinamide phosphoribosyltransferase (NAMPT) regulates cellular functions through the protein deacetylation activity of nicotinamide adenine dinucleotide (NAD+)-dependent sirtuins (SIRTs). SIRTs regulate functions of histones and none-histone proteins. The role of NAMPT/SIRT pathway in the regulation of maintenance and differentiation of human-induced pluripotent stem (iPS) cells is not fully elucidated. Methods We evaluated the effects of specific inhibitors of NAMPT or SIRT2 on the pluripotency, proliferation, survival, and hematopoietic differentiation of human iPS cells. We also studied the molecular mechanism downstream of NAMPT/SIRTs in iPS cells. Results We demonstrated that NAMPT is indispensable for the maintenance, survival, and hematopoietic differentiation of iPS cells. We found that inhibition of NAMPT or SIRT2 in iPS cells induces p53 protein by promoting its lysine acetylation. This leads to activation of the p53 target, p21, with subsequent cell cycle arrest and induction of apoptosis in iPS cells. NAMPT and SIRT2 inhibition also affect hematopoietic differentiation of iPS cells in an embryoid body (EB)-based cell culture system. Conclusions Our data demonstrate the essential role of the NAMPT/SIRT2/p53/p21 signaling axis in the maintenance and hematopoietic differentiation of iPS cells.

scholarly journals Modeling SARS-CoV-2 infection and its individual differences with ACE2-expressing human iPS cells

2021 ◽  
Author(s):  
Emi Sano ◽  
Ayaka Sakamoto ◽  
Natsumi Mimura ◽  
Ai Hirabayashi ◽  
Yukiko Muramoto ◽  
...  
Keyword(s):  
Individual Differences ◽  
Es Cells ◽  
Membrane Vesicles ◽  
Ips Cells ◽  
Genetic Differences ◽  
Progeny Virus ◽  
Double Membrane ◽  
Human Ips Cells ◽  
Induced Pluripotent

AbstractGenetic differences are a primary reason for differences in the susceptibility and severity of coronavirus disease 2019 (COVID-19). Because induced pluripotent stem (iPS) cells maintain the genetic information of the donor, they can be used to model individual differences in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in vitro. Notably, undifferentiated human iPS cells themselves cannot be infected bySARS-CoV-2. Using adenovirus vectors, here we found that human iPS cells expressing the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) (ACE2-iPS cells) can be infected with SARS-CoV-2. In infected ACE2-iPS cells, the expression of SARS-CoV-2 nucleocapsid protein, the budding of viral particles, the production of progeny virus, double membrane spherules, and double-membrane vesicles were confirmed. We also evaluated COVID-19 therapeutic drugs in ACE2-iPS cells and confirmed the strong antiviral effects of Remdesivir, EIDD-2801, and interferon-beta. In addition, we performed SARS-CoV-2 infection experiments on ACE2-iPS/ES cells from 8 individuals. Male iPS/ES cells were more capable of producing the virus as compared with female iPS/ES cells. These findings suggest that ACE2-iPS cells can not only reproduce individual differences in SARS-CoV-2 infection in vitro, but they are also a useful resource to clarify the causes of individual differences in COVID-19 due to genetic differences.Graphical Abstract

scholarly journals Human ES and iPS Cells Display Less Drug Resistance Than Differentiated Cells, and Naïve-State Induction Further Decreases Drug Resistance

2020 ◽  
Author(s):  
Yulia Panina ◽  
Junko Yamane ◽  
Kenta Kobayashi ◽  
Hideko Sone ◽  
Wataru Fujibuchi
Keyword(s):  
Drug Resistance ◽  
Drug Exposure ◽  
Es Cells ◽  
Embryonic Stem ◽  
Cell Types ◽  
Ips Cells ◽  
Toxicity Assessment ◽  
Research Knowledge ◽  
Differentiated Cells ◽  
Induced Pluripotent

AbstractPluripotent stem cells (PSCs) possess unique characteristics that distinguish them from other cell types. Human embryonic stem (ES) cells are recently gaining attention as a powerful tool for human toxicity assessment without the use of experimental animals, and an embryonic stem cell test (EST) was introduced for this purpose. However, human PSCs have not been thoroughly investigated in terms of drug resistance or compared with other cell types or cell states, such as naïve state, to date. Aiming to close this gap in research knowledge, we assessed and compared several human PSC lines for their resistance to drug exposure. Firstly, we report that RIKEN-2A human induced pluripotent stem (iPS) cells possessed approximately the same sensitivity to selected drugs as KhES-3 human ES cells. Secondly, both ES and iPS cells were several times less resistant to drug exposure than other non-pluripotent cell types. Finally, we showed that iPS cells subjected to naïve-state induction procedures exhibited a sharp increase in drug sensitivity. Upon passage of these naïve-like cells in non-naïve PSC culture medium, their sensitivity to drug exposure decreased. We thus revealed differences in sensitivity to drug exposure among different types or states of PSCs and, importantly, indicated that naïve-state induction could increase this sensitivity.

scholarly journals Beyond the limitation of randomized controlled trials (RCTs)-current drug repositioning by using human induced pluripotent stem (iPS) cells technology-

2017 ◽  
Author(s):  
M.D. Midori Okabe
Keyword(s):  
Randomized Controlled Trials ◽  
Drug Repositioning ◽  
Ips Cells ◽  
Medical Intervention ◽  
Controlled Trials ◽  
Clinical Value ◽  
Weak Point ◽  
Randomized Controlled ◽  
Human Ips Cells ◽  
Induced Pluripotent

AbstractTo ensure the clinical value of medical interventions, randomized controlled trials (RCTs) are necessary. However, the results of conventional RCTs cannot show individual therapeutic efficacy and safety for medical intervention to a targeted patient. It is the most important weak point of conventional RCTs. Here I show that the new clinical research method by using human induced pluripotent stem (iPS) cells technology will be able to complement the most important weak point of conventional RCTs.As the representative examples, I show the new clinical values of statins (inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase) found by using human iPS cells technology in achondroplasia or hanatophoric dysplasia (type 1) case and hepatitis C virus (HCV) infection case. Furthermore, they are also important examples for drug repositioning.Therefore, my article would be valuable as a scientific communication for physicians and/or scientists.

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