7 replies to this topic

[solbanger]

From Newsweek. Latest research points out the weaknesses in induced pluripotent stem cells. Apparently they are more susceptible to higher death rates via apoptosis versus embryonic.

Biologist Robert Lanza is quoted, "There was a 1,000- to 5,000-fold difference" between the iPS cells' ability to keep growing and dividing and the true embryonic cells' ability, he says. "In terms of whether you can use the cells therapeutically or to study disease, that's the difference between getting the study to work and being dead in the water." Other scientists working with iPS cells have begun to see the same problems, Lanza says, suggesting that "this whole population of cells is screwed up."

http://www.newsweek.com/id/233454

[tunt01]

this is really an issue. the integrity of iPS is quite poor. they are best a temporary stop gap solution for an underlying problem.

under science can complete re-engineer a healthy cell with long telomeres that looks and behaves like an embryonic cell, i don't see how iPS is any sort of fountain of youth.

[skylined]

The underlying problem is this conservative nonsense in the US that is holding up research. I never felt induced pluripotent cells were going to be of much use for those exact reasons. It's not just telomeres either but also epigenetic factors, dna mutation and degeneration (both mitochondrial and nuclear), as well as the 'garbage' that accumulates in cells as they age (e.g. misfolded or old proteins, inactive or broken molecules, reactive oxygen species, etc). Not wanting to get into the whole debate all over again but I really fail to see how cells in a dish have rights, or why a cell's "rights" are seemingly held in higher priority than those of suffering, sick or disabled people. As far as I can tell iPCs are simply a dead end - for any useful therapy like tissue regeneration or in vitro clone organ construction you need the new, undamaged embryonic cells.

[Medical Time Travel]

I would like to post my question here: If I've not understood it wrongly there is no longer need for Somatic Cell Nuclear Transfer (SCNT) or more popularly referred to as Therapeutic Cloning after the breakthrough with iPS in 2008?

Or is it iPS that is or should make hESC redundant?

However, I've always also had a feeling about that iPS is not as efficient as hESC.

Can someone give me an answer? Thanks.

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Edited by Medical Time Travel, 16 March 2010 - 09:56 PM.

[tunt01]

new method of iPS could possibly improve integrity of adult stem cells


http://www.scienceda...00415110039.htm


Novel Strategy for Generating Induced Pluripotent Stem Cells for Clinical Use Is Safe and Efficient, Study Finds

ScienceDaily (Apr. 15, 2010) — A new technique for reprogramming human adult cells could greatly improve the safety and efficiency of producing patient-specific stem cells for use in a range of therapeutic applications to repair or replace damaged or diseased tissues, according to new research.

A description of this innovative strategy is published in the peer-reviewed journal Cellular Reprogramming, published by Mary Ann Liebert, Inc.

Stem cells offer great promise for use in cellular therapy to regenerate specific cell populations in the body. The ability to derive stem cells from a patient's own tissue eliminates the risk that they will stimulate an immune response and be rejected after transplantation. The process for transforming adult somatic cells into a form of stem cells called induced pluripotent stem (iPS) cells, which are capable of differentiating into all three major cell types, involves reprogramming the cell's genetic contents. This is usually achieved using a virus to introduce multiple (typically four) genetic factors, called transcription factors, into the cells; these would include an oncogene, which carries the risk of cancerous transformation.

This new method was applied successfully to reprogram cells from the human gut to form iPS cells, as described in the article. This novel technique required only three transcription factors and no oncogenes. The authors, Yang Li, Hongxi Zhao, Feng Lan, Andrew Lee, Liu Chen, Changsheng Lin, Yuanqing Yao, and Lingsong Li, from Peking University and the Fourth Military Medical University, Tangdu Hospital, in the People's Republic of China, and Stanford University School of Medicine, in Stanford, California, demonstrated the pluripotency of these gut-derived stem cells and their ability to form cell types of all three germ layers.

"These observations are very exciting because they demonstrate that a different cell type can be used when making iPS cells. In addition, Lingsong Li and his colleagues show that Nanog has a key role when reprogramming these cells, whereas it does not with other cell types. This difference provides us with an important new opportunity to study the mechanisms involved in reprogramming," says Professor Sir Ian Wilmut, OBE, FRS, FRSE, Editor-in-Chief of Cellular Reprogramming and director of the MRC Centre for Regenerative Medicine in Edinburgh

[Hedrock]

Interesting!

So what are the 3 transcription factors? Any details?

[philguard]

The underlying problem is this conservative nonsense in the US that is holding up research. I never felt induced pluripotent cells were going to be of much use for those exact reasons. It's not just telomeres either but also epigenetic factors, dna mutation and degeneration (both mitochondrial and nuclear), as well as the 'garbage' that accumulates in cells as they age (e.g. misfolded or old proteins, inactive or broken molecules, reactive oxygen species, etc). Not wanting to get into the whole debate all over again but I really fail to see how cells in a dish have rights, or why a cell's "rights" are seemingly held in higher priority than those of suffering, sick or disabled people. As far as I can tell iPCs are simply a dead end - for any useful therapy like tissue regeneration or in vitro clone organ construction you need the new, undamaged embryonic cells.

I read your stem cell wars little bit. in a whole host of diseases will eventually repair with embryonic. I had two strokes in 2001 and have aphasia now. I talked to you on my Mac speech dictation. I'm going to purchase these two books on my Amazon kindle. Hooyaa! for advancement! Digital, etc. philguard

[kmoody]

I'll take a stab at a few of these...

1) If I've not understood it wrongly there is no longer need for Somatic Cell Nuclear Transfer (SCNT) or more popularly referred to as Therapeutic Cloning after the breakthrough with iPS in 2008?


Yes and no. These are two different approaches which have their own advantages and disadvantages. SCNT cells require an egg to put the DNA into. The process is expensive and inefficient, but certainly possible. There are, however, residual concerns about immune rejection on account of the mitochondrial DNA (which would be provided by the egg, not the nucleus) being foreign to the host. The advantage of iPSCs is that they are easier to make and by default host compatible. Most protocols simply involve dumping a virus containing major pluripotency genes and culturing the cells on feeder cells or matrigel for a few weeks. However, iPSCs created this way can act sporadically. Some have telomere elongation while others do not (and still succumb to hayflick's limit). They also present a risk of mutagenesis since the viral DNA can integrate with the chromosomal DNA, though there are approaches which try to circumvent that now. Both approaches should probably be pursued further to identify their potential and discern which shortcomings are easier to overcome for therapeutic applications. Also bear in mind that the ease of generating iPSCs makes them more suitable for research purposes, while creating SCNT cells may be more complicated (though I do not have much experience with SCNTs so I cannot say this for sure).


2) [iPSCs don't work well]. It's not just telomeres either but also epigenetic factors, dna mutation and degeneration (both mitochondrial and nuclear).


Do keep in mind that culturing hESCs indefinitely can also introduce DNA mutation and degeneration. In fact, it would be quite interesting to study whether or not there are actual evolutionary pressures in culture which select for certain hESCs during routine processes. The largest epigenetic hurdle seems to be methylation of histones and genes, and I am under the impression that there is some progress being made about "de-programming" cells in that respect. Although I'm in favor of hESCs myself, I would not write off iPSCs just yet. Remember that hESCs have immune rejection to overcome before they can be used ubiquitously in the clinic. I don't know of anyone who can call whether overcoming hESC rejection will be easier or harder than overcoming iPSC complications.