Embryonic Stem Cells, Derived Either after In Vitro Fertilization or Nuclear Transfer, Prolong Survival of Semiallogeneic Heart Transplants

2011 ◽  
Vol 186 (7) ◽  
pp. 4164-4174 ◽  
Author(s):  
Barbara Imberti ◽  
Federica Casiraghi ◽  
Daniela Cugini ◽  
Nadia Azzollini ◽  
Paola Cassis ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
In Vitro Fertilization ◽  
Nuclear Transfer ◽  
Embryonic Stem ◽  
Heart Transplants ◽  
Vitro Fertilization

scholarly journals Le cellule staminali: dall’applicazione clinica al parere etico Parte I. Le cellule staminali embrionali

2006 ◽  
Vol 55 (4) ◽  
Author(s):  
Jacques Suaudeau
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Nuclear Transfer ◽  
Ethical Issues ◽  
Heart Function ◽  
Embryonic Stem ◽  
Sono State ◽  
Clinical Use ◽  
Vitro Fertilization

Otto anni dopo l'inizio della ricerca sulle cellule staminali umane, sembra essere arrivato il momento di considerare oggettivamente quale possa essere il futuro di tale ricerca, e quali siano i problemi etici collegati. In questo articolo sono considerate le cellule staminali embrionali (ES) a livello tecnico e clinico. L'interesse particolare di tali cellule risiede nella loro capacità di continua proliferazione indifferenziata e di stabile sviluppo potenziale in un’ampia tipologia di cellule, anche dopo una coltura prolungata. Numerosi lavori mostrano, in particolare, che le cellule ES possono essere differenziate in neuroni e glia ed integrarsi nel tessuto neurale in animali riceventi. La differenziazione verso neuroni dopaminergici è stata ottenuta per le cellule staminali embrionali umane (hES) con promesse per il trattamento clinico della malattia di Parkinson. Le cellule ES hanno anche dimostrato la capacità di facilitare il recupero del danno del midollo spinale, nel topo. L'innesto di cellule ES in ratti con infarto miocardico provoca un miglioramento a lungo termine della funzione del cuore ed aumenta la percentuale di sopravvivenza. Tuttavia, ci sono molti ostacoli che devono essere superati prima di pensare ad un uso clinico di tali cellule. Il problema forse più complesso è di poter dirigere in modo efficiente e riproducibile la differenziazione delle cellule ES attraverso percorsi specifici. In secondo luogo, il rischio di difetti o instabilità epigenetiche nelle cellule ES è reale, tenendo conto della loro origine da embrioni ottenuti da fecondazione in vitro e del processo di coltura di tali cellule, una volta individuate. Terzo, le cellule ES allo stato indifferenziato sono cancerogeniche, il che, per un uso clinico, rende necessaria la loro differenziazione e l’attenta eliminazione di cellule ES rimaste indifferenziate. Infine, l'uso clinico delle cellule ES richiede la soluzione del problema immunologico della compatibilità HLA con il ricevente. A tale scopo sono state proposte varie soluzioni, per prima il trasferimento nucleare, detto anche “clonazione terapeutica”. Allo stato attuale essa non è applicabile ai primati ed alla specie umana. Inoltre sarebbe necessaria una quantità enorme ed irrealistica di ovociti umani. Ci si orienta oggi, anche per motivi etici, verso soluzioni "alternative" come il trasferimento nucleare modificato, nel quale si producono embrioni deficitari incapaci di svilupparsi correttamente, la partenogenesi, la raccolta di blastomeri in occasione della diagnosi preimpiantatoria, o la riprogrammazione delle cellule staminali somatiche. Ad oggi, lo studio delle cellule staminali embrionali rappresenta una promettente chiave per futuri progressi in ambito biologico (biologia dello sviluppo, biologia cellulare e biologia molecolare), nella misura in cui permette di capire meglio i processi ed i meccanismi della differenziazione e della rigenerazione dei tessuti. ---------- Eight years after the onset of the investigation on embryonic stem cells (ESCs), it seems that time has come to consider objectively what the future of such research can be, and what are the ethical issues that are involved. In this first part ESCs are considered at the technical and clinical level. The particular interest of such cells resides in their ability for endless undifferentiated proliferation and for potential development in a large array of various types of cells, even after prolonged culture. A large amount of studies show in particular that ESCs can differentiate in neurons and glia and integrate in the neural tissue of recipient animals. The promotion of such differentiation toward dopaminergic neurons has been obtained for human embryonic stem cells (hESCS), which is promising for possible future clinical application to the treatment of Parkinson's disease. The ESCs have also demonstrated their ability to facilitate the recovery of damaged spinal cord in mice. The graft of ESCs in the hearts of rats with myocardial infarction leads to an improvement of heart function and increases survival. Nevertheless, there are many obstacles that must be overcome before thinking to a clinical use of such cells. The problem perhaps more complex is to be able to direct in an efficient and reproducible way the differentiation of the ESCs in culture. Second, the risk of epigenetic defects or instability with ESCs is real, keeping in mind their origin from embryos created by in vitro fertilization, and the fact that they are kept proliferating in culture for a long period of time, once individualized. Third, ESCs in the undifferentiated state generate cancers when injected in tissues, and that makes necessary, for a clinical use, to start their differentiation in vitro and then to eliminate carefully from the end product these ESCs that are still undifferentiated. Finally, the clinical use of ESCs supposes resolved the immunological problem of their HLA compatibility with the patient who will receive them. Various solutions have been proposed for resolving this last problem, with, in first line, nuclear transfer, the so called "therapeutic cloning." Up to now this nuclear transfer has not been successful in primates and humans. Moreover, it would require the availability of unrealistically large amounts of human ovocytes. Today, also for ethical reasons, the tendency is to look after "alternative solutions" such as "altered nuclear transfer", in which are created disabled embryos, unable to develop correctly, parthenogenesis, the harvest of human blastomeres in the course of preimplantation diagnosis or the reprogramming of human somatic stem cells to an "embryonic state". At present time, the study of ESCs represents a promising key to progresses in the knowledge of cellular and molecular aspects of development, healing and tissue regeneration. These progresses may in turn lead to clinical applications, especially in the field of degenerative diseases and for the recovery of damaged tissues and organs.

Derivation and maintenance of human embryonic stem cells from poor-quality in vitro fertilization embryos

2008 ◽  
Vol 3 (5) ◽  
pp. 923-933 ◽  
Author(s):  
Paul H Lerou ◽  
Akiko Yabuuchi ◽  
Hongguang Huo ◽  
Justine D Miller ◽  
Leah F Boyer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
In Vitro Fertilization ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Poor Quality ◽  
Vitro Fertilization

In Vitro Fertilization and the Embryonic Revolution

2009 ◽  
pp. 609-622
Author(s):  
D. Gareth Jones
Keyword(s):  
Stem Cells ◽  
In Vitro Fertilization ◽  
Human Embryo ◽  
Human Life ◽  
Genetic Diagnosis ◽  
Embryonic Stem ◽  
Reproductive Technologies ◽  
Vitro Fertilization ◽  
Human Embryology

The advent of in vitro fertilization (IVF) marked a watershed in the scientific understanding of the human embryo. This, in turn, led to a renaissance of human embryology, accompanied by the ability to manipulate the human embryo in the laboratory. This ability has resulted in yet further developments: refinements of IVF itself, preimplantation genetic diagnosis, the derivation and extraction of embryonic stem cells, and even various forms of cloning. There are immense social and scientific pressures to utilize the artificial reproductive technologies in ways that have little or no connection with overcoming infertility. As the original clinical goals of IVF have undergone transformation ethical concerns have escalated, so much so that they are condemned by some as illustrations of ‘playing God’, while any babies born via some of these procedures are labelled as ‘designer babies’. Both terms reflect the fear and repugnance felt by some at the interference with the earliest stages of human life by the artificial reproductive technologies. It is at these points that bioethical analyses have an important contribution to make.

scholarly journals Ultrastructural comparison of porcine putative embryonic stem cells derived by in vitro fertilization and somatic cell nuclear transfer

2016 ◽  
Vol 62 (2) ◽  
pp. 177-185 ◽  
Author(s):  
Hyunju YOO ◽  
Eunhye KIM ◽  
Seon-Ung HWANG ◽  
Junchul David YOON ◽  
Yubyeol JEON ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Somatic Cell ◽  
Somatic Cell Nuclear Transfer ◽  
Nuclear Transfer ◽  
Embryonic Stem

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.

Why Scientific Details are Important When Novel Technologies Encounter Law, Politics, and Ethics

2010 ◽  
Vol 38 (2) ◽  
pp. 204-211 ◽  
Author(s):  
Lawrence Goldstein
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
In Vitro Fertilization ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Advanced Technology ◽  
Human Embryos ◽  
Vitro Fertilization ◽  
Novel Technologies

Lost at times in the heat of debate about stem cell research, or any controversial advanced technology, is the need for precision in debate and discussion. The details matter a great deal, ranging from the need to use words that have precise definitions, to accurately quote colleagues and adversaries, and to cite scientific and medical results in a way that reflects the quality, rigor, and reliability of the work at issue. Regrettably, considerable inaccuracy has found its way into the debates about stem cells, on all sides, with consequent fogging of the issues.A key detail that is often overlooked in the debates about the uses of human embryonic stem cells in research comes from the nature of in vitro fertilization (IVF) treatment for infertility. Specifically, there are many frozen human embryos (more precisely called blastocysts) that are in excess of reproductive needs of the couple who generated them, and that must be either frozen indefinitely, donated to another couple, or destroyed.

In vitro induction of natural killer T cells from embryonic stem cells prepared using somatic cell nuclear transfer

2008 ◽  
Vol 22 (7) ◽  
pp. 2223-2231 ◽  
Author(s):  
Hiroshi Wakao ◽  
Rika Wakao ◽  
Sakura Sakata ◽  
Kazuya Iwabuchi ◽  
Atsushi Oda ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Embryonic Stem Cells ◽  
Somatic Cell Nuclear Transfer ◽  
Nuclear Transfer ◽  
Embryonic Stem ◽  
Natural Killer T Cells ◽  
Killer T Cells ◽  
In Vitro Induction

scholarly journals Compromised Chondrocyte Differentiation Capacity in TERC Knockout Mouse Embryonic Stem Cells Derived by Somatic Cell Nuclear Transfer

2019 ◽  
Vol 20 (5) ◽  
pp. 1236 ◽  
Author(s):  
Wei-Fang Chang ◽  
Yun-Hsin Wu ◽  
Jie Xu ◽  
Li-Ying Sung
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Somatic Cell ◽  
Somatic Cell Nuclear Transfer ◽  
Nuclear Transfer ◽  
Embryonic Stem ◽  
Population Doubling ◽  
Chondrocyte Differentiation ◽  
Wild Type

Mammalian telomere lengths are primarily regulated by telomerase, consisting of a reverse transcriptase protein (TERT) and an RNA subunit (TERC). We previously reported the generation of mouse Terc+/− and Terc−/− embryonic stem cells (ntESCs) by somatic cell nuclear transfer. In the present work, we investigated the germ layer development competence of Terc−/−, Terc+/− and wild-type (Terc+/+) ntESCs. The telomere lengths are longest in wild-type but shortest in Terc−/− ntESCs, and correlate reversely with the population doubling time. Interestingly, while in vitro embryoid body (EB) differentiation assay reveals EB size difference among ntESCs of different genotypes, the more stringent in vivo teratoma assay demonstrates that Terc−/− ntESCs are severely defective in differentiating into the mesodermal lineage cartilage. Consistently, in a directed in vitro chondrocyte differentiation assay, the Terc−/− cells failed in forming Collagen II expressing cells. These findings underscore the significance in maintaining proper telomere lengths in stem cells and their derivatives for regenerative medicine.

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