#164 Cellule Souche Pluripotente Induite (Français)

Cellule Souche Pluripotente Induite

Les cellules souches pluripotentes induites (iPS) retient l’attention du monde entier comme ce recherche gagne le prix Nobel de médecine 2012.

Les cellules souches adultes ont la capacité limitée de se transformer en divers types de cellules et de tissus. Elles sont à l’origine des cellules sanguines, dans le tissue adipeux ou encore dans l’épiderme. Ces cellules sont plus difficiles de cultiver que les cellules souches embryonnaires. En fait, les cellules souches embryonnaires sont comparativement faciles à cultiver. Or, pendant l’obtention, il pourrait exister une destruction d’un embryon, en suscitant les problèmes déontologiques. Donc, les cellules souches pluripotentes induites sont révolutionnaires comme découvertes en vertu du fait selon lequel ce type de cellule souche pourrait compenser les inconvénients certes des cellules souches adultes et des cellules souches embryonnaires.

Alors qu’est-ce exactement le cellule souche pluripotente induite ?

IPS est modifié génétiquement pour réactiver les signaux d’immaturité et de prolifération caractéristiques d’une cellule pluripotente. Le Pr Yamanaka, colauréat du prix Nobel de médecine, explique que la production des iPS est assez simple : « Si vous savez cuisiner, vous pouvez préparer des cellules iPS. » Après extraction de cellules de la peau (fibroblastes) de rongeurs, ils ont activé à l’aide d’un rétrovirus quatre gènes clés : Oct-4, Sox2, c-Myc et Klf4. Trois à quatre semaines plus tard, ces cellules devenaient pluripotentes. Les vecteurs viraux avaient l’inconvénient majeur de s’intégrer dans le génome de la cellule hôte et il existe un risque de mutation et d’expression prolongée de ces gènes. Ces défauts sont désormais corrigés grâce à l’utilisation de nouveaux vecteurs non intégratifs comme des plasmides ou le virus de Sendaï.

Les cellules IPS ne posent pas de problème éthique et elles sont vraiment faciles d’accès. Maintenant, il est possible de faire le traitement qui pourrait éviter un rejet de greffe. Malheureusement, il existe quelques bémols. Il est également légitime de se demander si la reprogrammation elle-même n’induit pas de mutations ou de modifications génétiques pouvant par la suite altérer le fonctionnement de ces cellules iPS.

http://www.lemonde.fr/sciences/article/2012/10/08/shinya-yamanaka-pere-des-cellules-ips_1771807_1650684.html

https://www.inserm.fr/thematiques/biologie-cellulaire-developpement-et-evolution/dossiers-d-information/cellules-pluripotentes-induites-ips

http://www.futura-sciences.com/sante/definitions/medecine-cellule-souche-pluripotente-induite-6207/

KSJ

#163 CRISPR-Cas9: The Gene Editing Technology Striving for Perfection (English)

CRISPR-Cas9: The Gene Editing Technology Striving for Perfection

Recently, a research titled “Correction of a pathogenic gene mutation in human embryos” was published on Nature. This groundbreaking, phenomenal research discovery captures CRISPR-Cas9 as the most promising genome editing technology.

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas9 (CRISPR-associated genes) is a stable form of ribonucleoprotein complex which is composed of the Cas nuclease Cas9 and the specific guide RNA (gRNA).

MECHANISM OF CRISPR-CAS9

Primarily, the enzyme Cas9 acts as a pair of ‘molecular scissors’ that can cut the two strands of DNA at a specific location in the genome so that bits of DNA can then be added or removed. The gRNA, which consists of a small piece of pre-designed RNA sequence located within a longer RNA scaffold. The scaffold part binds to DNA and the pre-designed sequence ‘guides’ Cas9 to the right part of the genome, making sure that the Cas9 enzyme cuts at the right point in the genome. The gRNA finds and binds to a specific sequence in the DNA with the complementary bases. Then, as the Cas9 follows the guide RNA to the same location in the DNA sequence and makes a cut across both strands of the DNA. The cell during the checkpoint recognizes that the DNA is damaged and attempts to repair it.

UNINTENDED MUTATIONS

According to the Columbia University Medical Centre, CRISPR-Cas9 gene-editing technology may cause hundreds of unanticipated mutations into the genome. Although CRISPR is renowned for its preciseness, it could alter other parts of the genome. When CRISPR is performed in cells or tissues in a dish and under predictive algorithms, it demonstrates perfection; however, when it is deployed in living animals, the incomplete genome sequencing can cause off-target effects. In fact, the researchers identified that CRISPR had successfully corrected a gene that causes blindness, but it also caused more than 1,500 single nucleotide mutations and more than 100 larger deletions and insertions which were not predicted by computer algorithms. These striking side-effects may cause potentially crucial mutations.

ERASING HEART DISEASE DEFECT IN HUMAN EMBRYOS

The new results demonstrated a major advance compared with earlier researches. In the new researches, scientists succeeded in eliminating the off-target effects of CRISPR-Cas9. To eliminate the mosaic phenomenon, the CRISPR-Cas9 gene editing materials were inserted before the fertilization process. In other words, the sperm with the mutated MYBPC3 gene was inserted along with the CRISPR-Cas9 in the oocyte during the M-phase, realizing the germ-line editing. Consequently, this gene editing technology successfully and completely cancelled out the heart disease defect in the embryo, avoiding the formation of a mosaic embryo.

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature23305.html?foxtrotcallback=true

http://www.genscript.com/cas9-related-protein.html?src=google&gclid=EAIaIQobChMIgZCM3vDl1QIVh4J-Ch2d7wX2EAAYASAAEgJWJ_D_BwE

https://www.neb.com/tools-and-resources/feature-articles/crispr-cas9-and-targeted-genome-editing-a-new-era-in-molecular-biology

https://www.sciencedaily.com/releases/2017/05/170529111228.htm

https://www.livescience.com/59971-crispr-used-on-embryos-in-us.html

KSJ

#162 Dental Filling (English)

Dental Filling

Gold, Amalgam, Ceramic

Before introducing the various dental fillings, I would like to clarify the dental cavity formation process.

At first, the susceptible tooth surface is revealed to the ingested food bolus. This leads to the formation of biofilm and microbial deposits. The microbes during the food fermentation process produce acid and alters the pH by releasing it. The change of the pH causes the dynamic equilibrium of minerals to shift, triggering the dissolution of minerals. Eventually, the dental caries initiate.

To elucidate this process, I can simply define dental caries as a multifactorial microbial disease of the calcified tissues of the teeth, characterized by demineralization of the inorganic portion and destruction of the organic substance of the tooth, leading to cavitation.

Now I will be evaluating multiple dental fillings, identifying both their advantages and disadvantages.

Gold fillings last at least 10 to 15 years, as it doesn’t corrode. It can withstand the hard and tough chewing forces. The gold may be aesthetically attracting. Unfortunately, its cost is much more expensive than the silver and amalgam fillings. Also, if the gold filling placed immediately next to a silver amalgam filling can cause a galvanic shock; the interaction between the metals and saliva causes an electric current to occur.

Silver fillings, which are known as the amalgams, possess similar advantages as the gold fillings. However, it could potentially cause the destruction of more tooth structure. In other words, the healthy parts of the tooth must often be removed to make a larger space. Also, the amalgam fillings experience a wider degree of expansion and contraction, causing frequent cracks and fractures. Recently, there is an increasing number of research presenting that the presence of mercury in amalgam restorations can cause allergic reactions.

Ceramics are made most often of porcelain, and they are more resistant to staining than other filling materials. Ceramic onlays and inlays maximize the conservation of the natural tooth. Since This is made out of a material that can easily look like your original tooth, it blends in perfectly. Although it is durable, it is an irrefutable fact that is costs as much as the gold amalgam.

http://www.webmd.com/oral-health/guide/dental-health-fillings

http://www.stlawrencedentistry.com/tooth-fillings-pros-cons-different-types-filling-available/

KSJ