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Embryonic Stem Cells Left in iPS Dust

, 05/23/2011

May 23, 2011 — A few years ago, scientists were clamoring for access to human embryos for stem cell research. Now, the discovery of induced pluripotent stem cells (iPS) from human skin and other adult tissues has sidetracked interest in embryonic stem cells. The momentum is clearly going with iPS. Is there any longer a need for embryonic stem cell research?

Skirting controversy: “Stem cell research courts both controversy and support in the community- depending on your viewpoint,” began an article on Medical Xpress. “Now, for the first time, scientists at Monash University’s Immunology and Stem Cell Laboratories (MISCL) have shown that they can make human stem cells from healthy adult kidneys without working on human embryos, circumventing ethical concerns around this research.” A side-by-side comparison showed the kidney cells were just as good as embryonic stem cells in producing various tissues.
Chemotherapy-resistant bone marrow: Another article on Medical Xpress reported work at the Fred Hutchinson Cancer Research Center that stem cells from bone marrow can be genetically modified to resist damage from chemotherapy, helping cancer patients endure the treatment without harmful effects.
Previously, chemotherapy treatments for gliablastoma, a brain cancer, have taken a harsh toll on patients’ bone marrow. “Our initial results are encouraging because our first patient is still alive and without evidence of disease progression almost two years after diagnosis,” a doctor said.
Parkinson’s disease: Researchers from South Korea and Harvard have identified a “protein-based” human iPS cell” that appears promising for reversing nerve cell loss in patients with Parkinson’s Disease. Their experiments “reversed disease when transplanted into the brain of rats modeling Parkinson disease.” Though the article mentioned embryonic stem cells as one of the two sources of stem cells, it did not produce any evidence that embryonic stem cells are effective – only the iPS cells.
Vision forum: Eye diseases such as “age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy and other retinal diseases” affect millions worldwide, an article on Medical Xpress said. Can iPS stem cells from human skin treat these devastating conditions? Apparently so; “Scientists from Schepens Eye Research Institute are the first to regenerate large areas of damaged retinas and improve visual function using iPS cells (induced pluripotent stem cells) derived from skin,” they said. A paragraph in the article shows that many vision researchers would prefer to avoid ethical controversies with embryonic stem cells:

While Tucker, Young and other scientists were beginning to tap the potential of embryonic and adult stem cells early in the decade, the discovery that skin cells could be transformed into “pluripotent” cells, nearly identical to embryonic cells, stirred excitement in the vision research community. Since 2006 when researchers in Japan first used a set of four “transcription factors” to signal skin cells to become iPSCs, vision scientists have been exploring ways to use this new technology. Like embryonic stem cells, iPSCs have the ability to become any other cell in the body, but are not fraught with the ethical, emotional and political issues associated with the use of tissue from human embryos.

So far the tests are being done on mice. “The two scientists say their next step will be to take this technology into large animal models of retinal degenerative disease and eventually toward human clinical trials.”
Amniotic fluid health potion: In a paper on PLoS One,1 Chinese researchers announced success deriving multipotent stem cells from amniotic fluid of pigs. They were able to get these stem cells to differentiate into nerve, fat, and heart tissues without producing teratomas (tumors). They said, “These optimal features of pAF-MSCs provide an excellent alternative stem cell resource for potential cell therapy in regenerative medicine and transgenic animals.”. Even in China these researchers were aware of the controversy. They said, “human amniotic fluid may be a new source of pluripotent stem cells without any ethical concerns associated with human embryonic stem cells (hES cells) research.”
Umbilical vein health potion: Another paper in PLoS One by the Salk Institute showed success at getting induced pluripotent stem cells from human umbilical vein endothelial cells.2 Their process was “rapid and highly efficient,” they reported, and produced stem cells that were “indistinguishable from human embryonic stem (ES) cells with regards to morphology, pluripotent marker expression, and their ability to generate all embryonic germ layers in vitro and in vivo.”
Progeria find-and-replace: An exciting discovery at Salk Institute shows the potential of adult stem cells to do “find and replace” operations on diseased genes, such as those with progeria, a degenerative disease that causes premature aging. PhysOrg explained the process:

The gene-targeting approach developed by Suzuki and his colleagues relies on the use of so-called helper-dependent adenoviral vector to deliver large mutation-free DNA molecules into cells. Once there, these replacement pieces initiate a process known as homologous recombination, which works a bit like the “find-and-replace” command in a word processor. If a piece of DNA is long enough, it will find and line up with the same sequence in the genome and swap places.
“The process was remarkably efficient and we couldn’t detect any undesired off-target effects such genomic instability or epigenetic abnormalities,” says Liu. “What’s more, it allowed us to show that we can correct multiple mutations spanning large genomic regions.”

The team used adult mesenchymal stem cells and iPS cells from progeria patients to test the genetic editing procedure. The article said that these cells have been shown to differentiate into a wide variety of tissues, including “adipocytes, osteoblasts, chondrocytes, cardiomyocytes, adipocytes, and, as described lately, beta-pancreatic islets cells.”
Regeneration takes a village of cells: Don’t expect to grow a new arm with stem cells. In an article on Science Daily, researchers at the Washington University School of Medicine in St. Louis found that, at least for zebrafish, multiple cell types are needed to regrow a lost fin.
Crop yields: Plants have stem cells, too – and not just in their stems. Researchers at Texas Agrilife Research are studying stem cells in Arabidopsis to learn how to make plants produce more fruit, seeds and leaves, according to PhysOrg.

Have embryonic stem cells made any headway toward cures? It’s sometimes hard to tell in news reports. Science Daily ran a story from Monash University about research on how stem cells in the embryo differentiate into muscle tissue, for the purpose of helping the elderly who suffer from age-related muscle wasting conditions, but did not indicate whether human embryos were involved in the research. It appears they studied chicken embryos to watch what happens as the stem cells develop into muscle, not for the purpose of injecting embryonic stem cells for treatment.
A paper in Nature about embryonic stem cell research appears limited to understanding transcription in normal animals,3 without any mention of potential applications for human health. Similarly, an article on Science Daily discussed how scientists at the University of Pennsylvania are trying to understand how embryonic stem cells differentiate in living organisms. While the press release stated that “Investigators want to make embryonic stem cells for liver or pancreatic beta cells for therapies and research,” there was no indication that the team has come anywhere close to that goal. “By better understanding how a cell is normally programmed we will eventually be able to properly reprogram other cells,” one of them said. Once again, embryonic stem cell therapy looks like a pipe dream.
Is there a “state of the stem cell” address? An overview of stem cell research was provided by Erika Check Hayden in Nature,4 who said, “The field of induced pluripotent stem cells has grown up fast. Now it is entering the difficult stage.” She focused on the promise of iPS cells which are changing the face of biology. “Like human embryonic stem cells, iPS cells could potentially be used as therapies, disease models or in drug screening,” she wrote. “And iPS cells have clear advantages: they can be made from adult cells, avoiding the contentious need for a human embryo, and they can be derived from people with diseases to create models or even therapies based on a person’s genetic make-up.”
From there, Hayden described some of the “growing pains” of iPS stem cell research, but never mentioned any case in which embryonic stem cells are clearly superior to the ethics-friendly iPS cells. The ease of reprogramming adult cells into pluripotent stem cells has led to a gold rush of research into promising therapies. In spite of the fact that (as often happens in biology), “things are not as simple as we thought,” it was noteworthy that the thrust of Hayden’s article was about the strong momentum in the iPS research community. The silent subtext is that embryonic research has apparently lost a lot of steam. 1. Chen, Lu, Cheng, Peng, and Wang, “Isolation and Characterization of Porcine Amniotic Fluid-Derived Multipotent Stem Cells,” PLoS One 6(5): e19964. doi:10.1371/journal.pone.0019964.
2. Panopoulos, Ruiz et al, “Rapid and Highly Efficient Generation of Induced Pluripotent Stem Cells from Human Umbilical Vein Endothelial Cells,” PLoS One 6(5): e19743. doi:10.1371/journal.pone.0019743.
3. Pastor, Pape, Huang et al, “Genome-wide mapping of 5-hydroxymethylcytosine in embryonic stem cells,” Nature, published online 08 May 2011, doi:10.1038/nature10102.
4. Erika Check Hayden, Stem cells: The growing pains of pluripotency,” Nature published online 18 May 2011; Nature 473, 272-274 (2011); doi:10.1038/473272a.

It has been very encouraging for people who value ethics to see adult stem cell research take off, leaving embryonic stem cell research in its rear-view mirror. But what if it had turned out the other way? What if embryonic stem cells were actively producing cures? Experimenting on human embryos would still be unethical. A basic principle of ethics is that ends do not justify the means (see commentary from the 09/03/2010 entry). The past decade of stem-cell research has shown that some scientists’ greed for fame and money outruns their interest in ethics. It takes a concerned public to keep science in check, because scientists are only human, prone to the same moral lapses as the rest of us.


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