Skip to comments.Big Stem Cell News
Posted on 06/06/2007 12:31:12 PM PDT by ZGuy
The coming weeks issue of the scientific journal Nature, made available online today, includes several extraordinary new studies on an alternative avenue to embryonic-like stem cells that does not require the destruction of embryos. In the most important paper, scientists at MIT have chemically reprogrammed regular adult cells (like skin cells) in mice to function and appear like embryonic stem cells. They express their results with simplicity and confidence: Our results establish that somatic cells [i.e. normal adult non-reproductive cells] can be reprogrammed to a pluripotent state that is similar, if not identical, to that of normal embryonic stem cells. They note further, our results show that the biological potency and epigenetic state of in-vitro-reprogrammed induced pluripotent stem cells are indistinguishable from those of embryonic stem cells. In other words, adult cells into embryonic-like cells without the need for embryos.
This is one of three studies published today showing similar results with this technique. Its all still in mice, and results like this always need to be confirmed and re-confirmed over time, but this is a very big deal, and anticipation of it has been generating huge buzz in the stem cell world for a while now. The quotes in this Nature news story give a sense of how scientists in the field are reacting. The usually stoic German stem cell scientist Hans Scholer (who was not involved in the study himself) tells Nature, It's unbelievable, just amazing, for me it's like Dolly [the first cloned mammal]. It's that type of accomplishment.
But unlike Dolly, of course, this advance could also help relieve the concerns of those of us who worry about the destruction of embryos for research. This adds a heavy dose of credibility to the notion that it could be possible to get everything scientists value about embryonic stem cells without the need to destroy or harm human embryos. In the long run (and it may not be all that long to judge by the pace of progress in the past two years), the big stem cell debate of the past few years may well be made obsolete by scientific advances that get around the ethical issues.
Of course, no one has bothered to tell Nancy Pelosi. House Democrats have scheduled a vote on a bill that would turn its back on exactly this kind of work...tomorrow. Good timing.
There are a lot of things that can be done with mouse cells that don't transfer to human cells. I'll withold judgement until they can demonstrate the transfer.
If it means they don’t have to destroy babies, the Dems won’t accept it.
This will mean nothing to the liberals. They will continue to cling to embryo destruction as a validation of their abortion views. This is an issue that will continue to cause rancor and debate, regardless of what science reveals. They will never let go.
How about demonstrating at least one beneficial medical therapy in humans...oh I forgot, that does make them just like embryonic stem cells...except embryonic stem cells have been shown to be very harmful to human patients. Are we sure these kinds of cells would be just as harmful in terms of cancer and rejection.
The real agenda was to give abortion a false aura of necessity.
If true, this is great news!
Let's start with the "cures" we have with embryonic stem cells ~ I'll let you start actually because I can't find one right off hand. Although I'm usually pretty good searching the net, this time it's sluggish and doesn't name anything.
Embryonic stem cells have nothing to do with fetuses or abortion. Embryonic stem cells are created in a petri dish, and harvested when the embryo is abou 4 days old.
I don’t support embryonic stem cell research, but I do believe that we should try to be accurate.
By the way, I believe this is excellent news, although I will wait until they gain human results before I get excited about it.
Any scientific discovery, if used properly, is good news.
But this won’t make a pin’s worth of difference, because the proponents of fetal stem cell research WANT and NEED to kill babies. That’s the whole point. That’s why they insist on fetal stem cells and only fetal stem cells.
Their reasons are obvious.
Hey guys -- Thanks for the simplicity. I'm sure glad you didn't go for the complicated description. :=)
Right! In fact, when I read the story, all I could think is that the only thing embryonic stem cells seem to do when experimented with "therapeutically" is cause teratomas. This seems a roundabout way to accomplish an undesirable end!
No mention in this article of the many therapeutic applications of adult stem cells -- and NR has in the past been good on that!
Differentiated cells can be reprogrammed to an embryonic-like state by transfer of nuclear contents into oocytes or by fusion with embryonic stem (ES) cells. Little is known about factors that induce this reprogramming. Here, we demonstrate induction of pluripotent stem cells from mouse embryonic or adult fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES cell culture conditions. Unexpectedly, Nanog was dispensable. These cells, which we designated iPS (induced pluripotent stem) cells, exhibit the morphology and growth properties of ES cells and express ES cell marker genes. Subcutaneous transplantation of iPS cells into nude mice resulted in tumors containing a variety of tissues from all three germ layers. Following injection into blastocysts, iPS cells contributed to mouse embryonic development. These data demonstrate that pluripotent stem cells can be directly generated from fibroblast cultures by the addition of only a few defined factors.
The cells are harvested from your own blood, reduced and refined to provide only stem cells. Then injected directly into the heart to rebuild it. I’ve seen several men who have and the procedure done overseas and it is amazing.
Current studies are underway with at the Cleveland Clinic and a heart institute in Houston. A government grant has been give the Cleveland Clinic to start research on qualified CHF patients in September of this year.
Thanks for the ping. Great post ZGuy. Thanks to all participants on this thread. Very interesting.
Nature advance online publication 6 June 2007 | doi:10.1038/nature05934; Received 6 February 2007; Accepted 22 May 2007; Published online 6 June 2007 We have previously shown that pluripotent stem cells can be induced from mouse fibroblasts by retroviral introduction of Oct3/4 (also called Pou5f1), Sox2, c-Myc and Klf4, and subsequent selection for Fbx15 (also called Fbxo15) expression. These induced pluripotent stem (iPS) cells (hereafter called Fbx15 iPS cells) are similar to embryonic stem (ES) cells in morphology, proliferation and teratoma formation; however, they are different with regards to gene expression and DNA methylation patterns, and fail to produce adult chimaeras. Here we show that selection for Nanog expression results in germline-competent iPS cells with increased ES-cell-like gene expression and DNA methylation patterns compared with Fbx15 iPS cells. The four transgenes (Oct3/4, Sox2, c-myc and Klf4) were strongly silenced in Nanog iPS cells. We obtained adult chimaeras from seven Nanog iPS cell clones, with one clone being transmitted through the germ line to the next generation. Approximately 20% of the offspring developed tumours attributable to reactivation of the c-myc transgene. Thus, iPS cells competent for germline chimaeras can be obtained from fibroblasts, but retroviral introduction of c-Myc should be avoided for clinical application.
Generation of germline-competent induced pluripotent stem cells
Keisuke Okita1, Tomoko Ichisaka1,2 & Shinya Yamanaka1,2
1. Department of Stem Cell Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan
2. CREST, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan
Correspondence to: Shinya Yamanaka1,2 Correspondence and requests for materials should be addressed to S.Y. (Email: email@example.com).
Although ES cells are promising donor sources in cell transplantation therapies1, they face immune rejection after transplantation and there are ethical issues regarding the usage of human embryos. These concerns may be overcome if pluripotent stem cells can be directly derived from patients' somatic cells2. We have previously shown that iPS cells can be generated from mouse fibroblasts by retrovirus-mediated introduction of four transcription factors (Oct3/4 (refs 3, 4), Sox2 (ref. 5), c-Myc (ref. 6) and Klf4 (ref. 7)) and by selection for Fbx15 expression8. Fbx15 iPS cells, however, have different gene expression and DNA methylation patterns compared with ES cells and do not contribute to adult chimaeras. We proposed that the incomplete reprogramming might be due to the selection for Fbx15 expression, and that by using better selection markers, we might be able to generate more ES-cell-like iPS cells. We decided to use Nanog as a candidate of such markers.
Although both Fbx15 and Nanog are targets of Oct3/4 and Sox2 (refs 911), Nanog is more tightly associated with pluripotency. In contrast to Fbx15-null mice and ES cells that barely show abnormal phenotypes9, disruption of Nanog in mice results in loss of the pluripotent epiblast12. Nanog-null ES cells can be established, but they tend to differentiate spontaneously12. Forced expression of Nanog renders ES cells independent of leukaemia inhibitory factor (LIF) for self-renewal12, 13 and confers increased reprogramming efficiency after fusion with somatic cells14. These results prompted us to propose that if we use Nanog as a selection marker, we might be able to obtain iPS cells displaying a greater similarity to ES cells.
We have previously shown that pluripotent stem cells can be induced from mouse fibroblasts by retroviral introduction of Oct3/4 (also called Pou5f1), Sox2, c-Myc and Klf4, and subsequent selection for Fbx15 (also called Fbxo15) expression. These induced pluripotent stem (iPS) cells (hereafter called Fbx15 iPS cells) are similar to embryonic stem (ES) cells in morphology, proliferation and teratoma formation; however, they are different with regards to gene expression and DNA methylation patterns, and fail to produce adult chimaeras. Here we show that selection for Nanog expression results in germline-competent iPS cells with increased ES-cell-like gene expression and DNA methylation patterns compared with Fbx15 iPS cells. The four transgenes (Oct3/4, Sox2, c-myc and Klf4) were strongly silenced in Nanog iPS cells. We obtained adult chimaeras from seven Nanog iPS cell clones, with one clone being transmitted through the germ line to the next generation. Approximately 20% of the offspring developed tumours attributable to reactivation of the c-myc transgene. Thus, iPS cells competent for germline chimaeras can be obtained from fibroblasts, but retroviral introduction of c-Myc should be avoided for clinical application.
Article Nature advance online publication 6 June 2007 | doi:10.1038/nature05944; Received 27 February 2007; Accepted 22 May 2007; Published online 6 June 2007
In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state
Marius Wernig1,6, Alexander Meissner1,6, Ruth Foreman1,2,6, Tobias Brambrink1,6, Manching Ku3,6, Konrad Hochedlinger1,7, Bradley E. Bernstein3,4,5 & Rudolf Jaenisch1,2
1. Whitehead Institute for Biomedical Research and,
2. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
3. Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
4. Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA
5. Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
6. These authors contributed equally to this work.
7. Present address: Center for Regenerative Medicine and Cancer Center, Massachusetts General Hospital, Harvard Medical School and Harvard Stem Cell Institute, Boston, Massachusetts 02414, USA.
Correspondence to: Rudolf Jaenisch1,2 Correspondence and requests for materials should be addressed to R.J. (Email: firstname.lastname@example.org).
Nuclear transplantation can reprogramme a somatic genome back into an embryonic epigenetic state, and the reprogrammed nucleus can create a cloned animal or produce pluripotent embryonic stem cells. One potential use of the nuclear cloning approach is the derivation of 'customized' embryonic stem (ES) cells for patient-specific cell treatment, but technical and ethical considerations impede the therapeutic application of this technology. Reprogramming of fibroblasts to a pluripotent state can be induced in vitro through ectopic expression of the four transcription factors Oct4 (also called Oct3/4 or Pou5f1), Sox2, c-Myc and Klf4. Here we show that DNA methylation, gene expression and chromatin state of such induced reprogrammed stem cells are similar to those of ES cells. Notably, the cellsderived from mouse fibroblastscan form viable chimaeras, can contribute to the germ line and can generate live late-term embryos when injected into tetraploid blastocysts. Our results show that the biological potency and epigenetic state of in-vitro-reprogrammed induced pluripotent stem cells are indistinguishable from those of ES cells.
Thanks for the abstracts and offer, but I’m only interested in legit freebies.
Cell Stem Cell is slated to launch in July, 2007.