{"id":6855,"date":"2015-11-29T09:38:57","date_gmt":"2015-11-29T09:38:57","guid":{"rendered":"http:\/\/revoscience.com\/en\/?p=6855"},"modified":"2015-11-29T09:38:57","modified_gmt":"2015-11-29T09:38:57","slug":"study-says-human-cell-cloning-method-dramatically-improved","status":"publish","type":"post","link":"https:\/\/www.revoscience.com\/en\/study-says-human-cell-cloning-method-dramatically-improved\/","title":{"rendered":"Study says, Human Cell Cloning Method Dramatically Improved"},"content":{"rendered":"
\"Embryonic<\/a>
Embryonic stem cells<\/figcaption><\/figure>\n

Upping the stakes in the enduring competition between pluripotent\/embryonic stem cells made via the iPSC method, and via cloning, a Harvard University group has reported\u00a0dramatically<\/span><\/a>\u00a0improving the efficiency of cloning.<\/span><\/p>\n

For the first time, quality blastocysts have been derived from a full 14 percent of adult cells via cloning (somatic cell nuclear transfer: SCNT), and embryonic stem (ES) cells were created from an unprecedented 50 percent of those.<\/span><\/p>\n

\u201cThis 50 percent success rate is as high as one can get even using in vitro fertilization (IVF) embryos,\u201d Harvard stem cell biologist Yi Zhang, Ph.D., senior author, told\u00a0Drug Discovery & Developmen<\/em>t.<\/span><\/p>\n

Robert Lanza, Ph.D., Ocata Therapeutics CSO, told\u00a0Drug Discovery & Development<\/em>: \u201cThis is an important discovery.\u00a0 Considering the extreme difficulty in obtaining human eggs, this study represents a major advance in the ability to use SCNT, not only for drug discovery, but for the potential treatment of human diseases, such as mitochondrial-related disorders.\u201d Lanza was uninvolved with the study.<\/span><\/p>\n

From mouse to man<\/span><\/p>\n

In cellular cloning (again, SCNT), the nucleus of an adult cell\u2014which contains all of our DNA except our mitochondrial DNA\u2014is placed in an enucleated egg cell. Once ignited by chemicals or a zap of electricity, the egg cell is tricked into thinking the new nucleus is sperm-related, and turns back the clock on the old DNA, returning it to an embryonic state.<\/span><\/p>\n

ES cells that are immunologically identical to their adult donor can then be culled.<\/span><\/p>\n

[pullquote]For the first time, quality blastocysts have been derived from a full 14 percent of adult cells via cloning (somatic cell nuclear transfer: SCNT), and embryonic stem (ES) cells were created from an unprecedented 50 percent of those.[\/pullquote]<\/p>\n

However, efficiency has been low.\u00a0Last year<\/span><\/a>, for a\u00a0Cell\u00a0<\/em>paper, Zhang’s crew compared epigenomic and transcriptomic data on SCNT and IVF mouse embryos, and decided the low efficiency rate may be due to epigenetic methylation, which was keeping the adult donor cells switched into an adult state. So they injected into cloned mouse cells RNA encoding a histone demethylase, or enzyme, that blocks the kind of methylation they identified as problematic.<\/span><\/p>\n

Specifically, they injected RNA encoded for the H3K9me3 demethylase, Kdm4d. The methylation tag was blocked, and efficiency greatly improved.<\/span><\/p>\n

Success rate better than normal IVF ES cells<\/span><\/p>\n

This year, the team tried it again, on human cells. It worked again. No SCNT embryos without the added RNA made it to the expanded blastocyst stage. With the treatment, there was a 14 percent success rate.<\/span><\/p>\n

\u201cThe quality of the expanded blastocyst affects the rate of ES cell derivation,\u201d Zhang told\u00a0Drug Discovery & Development<\/em>. Even during IVF, where normal ES cells are culled, \u201cnot all the expanded blastocysts generated can successfully generate ES cell lines. In our study, eight SCNT embryos reached the expanded blastocyst stage. From this, we successfully derived four lines of ES cells that survived a long time in culture.\u201d That success rate bests that of the rate achieved by stem cell scientists culling ES cells from spare IVF clinic embryos.<\/span><\/p>\n

Given that Zhang\u2019s ES cells, like all ES cells from cloning or SCNT, come from adult cells, this theoretically\u00a0 could make SCNT ES cells not just less controversial than normal ES cells, but more plentiful.<\/span><\/p>\n

Zhang believes his cells are more physiologic than pluripotent cells made from adult cells via the induced pluripotent stem cell (iPSC) method. In that method, four genes are tweaked to bring adult cells back to am embryonic state. But those embryonic cells are not totipotent, that is, able to create all cells of the body, including the placenta.<\/span><\/p>\n

\u201cFor the mouse work that we published last year in\u00a0Cell<\/em>, we demonstrated that SCNT reprogramming can generate both the embryos and placenta,\u201d he said. \u201cSince it is illegal to implant human SCNT embryos, we are not allowed to test whether the human SCNT embryos can also contribute to placenta. However, theoretically, people believe reprogramming through SCNT can generate totipotent cells.\u201d<\/span><\/p>\n

Another reason he believes SCNT ES cells are more physiologic than iPSC cells: \u201cIPSC reprogramming is totally artificial as it does not generate blastocysts from which the pluripotent ESCs are derived,\u201d Zhang said. \u201cSCNT reprogramming generates blastocysts, which are the source of real ES cells.\u201d<\/span><\/p>\n

Furthermore, Zhang said: \u201cMany studies indicate that iPSCs possess epigenetic memory of their donor somatic cells unless it cultured in vitro for a long time. Yet culture in vitro for a long time can be a source of mutation.\u201d<\/span><\/p>\n

Finally, he said, since mitochondria are passed to offspring via eggs, SCNT cells possess the mitochondria of the donor egg. So when the adult nucleus donor has a mitochondrial disease, generating stem cells using the adult\u2019s DNA and healthy eggs may mitigate the mitochondrial problems.\u00a0 This is not true of iPSC-derived pluripotent cells.<\/span><\/p>\n

\u201cPatient somatic cell-derived iPSCs cannot fix mitochondria DNA because problems in the iPSC mitochondria DNA will be the same as the patient mitochondria DNA,\u201d he said. \u201cOn the other hand, the mitochondria DNA of SCNT derived ESCs are derived from the healthy egg donor, not from the patient.\u201d<\/span><\/p>\n

Regarding whether SCNT ES cells are more \u201cphysiologic\u201d than iPSCs, Lanza told\u00a0Drug Discovery & Development<\/em>: \u201cThe evidence suggests they may be, but more work needs to be done to know for sure.\u201d<\/span><\/p>\n","protected":false},"excerpt":{"rendered":"

Upping the stakes in the enduring competition between pluripotent\/embryonic stem cells made via the iPSC method, and via cloning, a Harvard University group has reported dramatically improving the efficiency of cloning.<\/p>\n","protected":false},"author":6,"featured_media":6856,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[17],"tags":[],"class_list":["post-6855","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-research"],"featured_image_urls":{"full":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2015\/11\/Human_embryonic_stem_cells.jpg",238,448,false],"thumbnail":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2015\/11\/Human_embryonic_stem_cells-150x150.jpg",150,150,true],"medium":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2015\/11\/Human_embryonic_stem_cells-159x300.jpg",159,300,true],"medium_large":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2015\/11\/Human_embryonic_stem_cells.jpg",238,448,false],"large":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2015\/11\/Human_embryonic_stem_cells.jpg",238,448,false],"1536x1536":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2015\/11\/Human_embryonic_stem_cells.jpg",238,448,false],"2048x2048":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2015\/11\/Human_embryonic_stem_cells.jpg",238,448,false],"ultp_layout_landscape_large":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2015\/11\/Human_embryonic_stem_cells.jpg",238,448,false],"ultp_layout_landscape":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2015\/11\/Human_embryonic_stem_cells.jpg",238,448,false],"ultp_layout_portrait":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2015\/11\/Human_embryonic_stem_cells.jpg",238,448,false],"ultp_layout_square":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2015\/11\/Human_embryonic_stem_cells.jpg",238,448,false],"newspaper-x-single-post":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2015\/11\/Human_embryonic_stem_cells.jpg",238,448,false],"newspaper-x-recent-post-big":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2015\/11\/Human_embryonic_stem_cells.jpg",191,360,false],"newspaper-x-recent-post-list-image":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2015\/11\/Human_embryonic_stem_cells.jpg",35,65,false],"web-stories-poster-portrait":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2015\/11\/Human_embryonic_stem_cells.jpg",238,448,false],"web-stories-publisher-logo":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2015\/11\/Human_embryonic_stem_cells.jpg",51,96,false],"web-stories-thumbnail":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2015\/11\/Human_embryonic_stem_cells.jpg",150,282,false]},"author_info":{"info":["Amrita Tuladhar"]},"category_info":"Research<\/a>","tag_info":"Research","comment_count":"0","_links":{"self":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/posts\/6855","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/users\/6"}],"replies":[{"embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/comments?post=6855"}],"version-history":[{"count":0,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/posts\/6855\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/media\/6856"}],"wp:attachment":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/media?parent=6855"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/categories?post=6855"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/tags?post=6855"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}