By D.S. Toft
The world of embryonic stem cell research may be under evaluation for a revolution after two scientists reported the revamping of skin cells into those that resemble human embryonic stem cells.2 The discovery was published in the journals “Cell” and “Science” two weeks ago. Shinya Yamanaka of Kyoto University and James Thomson of the University of Wisconsin were able to successfully transform human epithelial cells-Yamanaka’s from a cheek and Thomson’s from a newborn’s foreskin-into human embryonic stem (ES) cells.3
The potential of this breakthrough may not only eliminate the need for ES cells, which have caused ethical controversy in destroying embryos, it may be used to create stem cells for a patient, made specifically for his or her body2 and it would only require a skin scraping.1 Because the cells would be genetic matches, these types of stem cells will be less likely than ES cells to be rejected by the patient’s immune system.2
These new stem cells are necessary for research, even with plenty of adult stem cells in supply, and without the cost of embryos. The difference? Adult stem cells are highly regenerative but come from fully developed adult tissues that can only divide into the cell types they have already become.1 The new stem cells, like ES cells, are much more versatile.1 Not only are they highly degenerative, they are also able to become any cell type needed and are therefore much more promising.1
The significance of stem cells in medicine is found in their totipotency, more popularly known as pluripotency.4 This is the potential for a cell to become antofty of the human’s 220 cell types and eventually any of the four primary tissue types: muscle, nerve, epithelial or connective, which includes blood and bone.8,9
These tissues may be implanted into a patient who has injured or diseased tissue. For example nerve tissue for someone with a spinal cord injury.1 Or retinal epithelia implanted into a patient with a damaged retina.1 These tissues may also be used for transplants in patients with diseased or damaged organs. Though this is far down the road, at least five to 10 years, hearts or livers may be grown using one’s own skin cells as replacement organs.1
Already researchers such as Deepak Srivastava, director of the Gladstone Institute of Cardiovascular Disease (UCSF)-the same institute where Yamanaka is an investigator-have been able to grow heart valves using progenitor cells, or partially developed ES cells that have not quite yet become adult stem cells, on biodegradable scaffolds.11
In an interview with northern California broadcasting company KQED Quest, Srivastava explained that these scaffolds are first structured like heart valves and then seeded with the progenitor stem cells, which become a covering layer.11 Once the structure is intact, the scaffold is dissolved, leaving only the heart valve that can be implanted into a patient.11 ES cells would require cloning for this type of tissue transplantation to be possible.2 And those of us that have seen Michael Bay’s “The Island” know this doesn’t turn out well.
The reason pluripotency is characteristically high in ES cells is because these cells have yet to specialize, or differentiate. Differentiation is the structural and functional specialization of a cell as it matures.4 Therefore, as a cell ages it becomes more specialized, for example into a nerve cell for the brain or muscle cell for the heart, and less pluripotent.
For students, this is kind of like your education. After you have chosen a major and narrowed-down your focus of study, possibly going to graduate school to specialize further, you have specialized. You give up the potential to do anything you want and chose one specific field. You see a limit before the sky. Of course there is always changing your mind and restarting with a clean slate-which is what Yamanaka and Thomson have done to these epithelial cells. They have reversed the specialization of mature cells to create pluripotent stem cells.
The reversal was done by the insertion of four genes into the cells, which incorporate themselves into the gene sequence of the host epithelium2. Specifically this was done with the transcription factors Oct3/4, Sox2, c-Myc and Klf4, which are naturally occurring in the human body, using viral vectors.2,10 These virions were used to transfer the genetic material into the cells.5 The resulting induced pluripotent stem (iPS) cells were indistinguishable from ES cells in their morphology, proliferation, gene expression and teratoma formation, a tumor composed of tissues not normally present at the site, according to Yamanaka’s research site at Gladstone.10
If all went well-never a given for a teratoma-forming stem cell implanted into a body-there would not be any danger with iPS cells. However, just like with ES cells, danger is possible with the iPS cells, and it lies in their strength. Because the virions integrate the four pluripotency-associated genes into the epithelial sequence randomly, the potential for mutation and cancer arises.1,7 After all, stem cells share the same major characteristic of a cancer, massive division of abnormal cells. ES cells, not unlike iPS cells, have the potential to turn into tumors that can produce body tissues in areas that would cause it damage.2 For example: teeth in the brain, said New York Times biotechnology reporter Andrew Pollock in an interview.1
To prevent happenings such as this, the iPS cells must be grown to the specific cell type desired before insertion.2 And the samples must be pure in order to prevent infection of any unintended agents, whether they are toxins or unwanted tissue masses.1
Research with these new iPS cells for the next many years will revolve around their direct use, being transplanted into patients as replacement tissue, as well as their indirect use, understanding the pathology of diseases.1 An article on the UCSF website about Yamanaka’s discovery quotes him as saying, “We are now finally in a position to make patient-specific stem cells for therapies without fear of immune-rejection and to make disease-specific stem cells that will reveal the underlying cause of many human diseases.”6 And because of his and Thomson’s discovery in November, this research and its funding will be supported by the government and conservatives alike.
Thomson who also directed the research team that first isolated ES cells in 1995 and human ES cells in 1998 said in a New York Times article that, “If human embryonic stem cell research does not make you at least a little bit uncomfortable, you have not thought about it enough.” He said, “I thought long and hard about whether I would do it.”7,8 Eventually Thomson went ahead and made his decision to go through with the research because he would be using embryos from fertility clinics, which would otherwise have been destroyed.8
Provided that these epithelial stem (Revo-ES) cells prove to function and interact with their environment in the same manner as embryonic stem cells, the latter may eventually become obsolete-the former taking its place. “Isn’t it great to start a field and then to end it,” Thomson said.8
References:
1. Pollock, Andrew. “Interview.” Science Times Podcast. Nov. 27, 2007.
2. Pollock, Andrew. “After Stem-Cell Breakthrough, the Work Begins.” Science Times. Nov. 27, 2007.
3. Donnelly, Erin. “The Future of Stem Cells.” Body Philosophy. Nov. 24, 2007.
4. Daniel, Peter. “Process of Development.” Powerpoint from Bio 12 Lecture. Spring 2007.
5. Dictionary Widget. Entry: vector.
6. Tucker, Valerie. “Shinya Yamanaka Reprograms Human Adult Cells into Embryonic-like Stem Cells.” University of California, San Francisco Today. Nov. 20, 2007.
7. “Bio of James Thomson.” University of Wisconsin-Madison. 2007.
8. Kolata, Gina. “Man Who Helped Start Stem Cell War May End It.” The New York Times. Nov. 22, 2007.
9. “Human body.” New World Encyclopedia. Sept. 3, 2007.10. Yamanaka, Shinya. Gladstone Institute of Cardiovascular Disease.
11. “Stem Cell Gold Rush.” KQED Quest: Science, Environment and Nature in northern California. iTunes Quest Production.