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1. What are induced pluripotent stem (iPS) cells?

Induced pluripotent cells (iPS cells) are adult non-pluripotent cells that were engineered (‘induced’) to become pluripotent, that is, able to form all cell types of the body. In other words, a cell with a specialized function (for example a skin cell) was ‘reprogrammed’ to an unspecialized state similar to that of an embryonic stem cell. While iPS cells and embryonic stem cells share many characteristics they are not identical.

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2. When was iPS discovered?

First developed in 2007, iPS cells were initially produced by inserting four genes into adult skin cells using viruses. However, the virus used to introduce the genetic stem cell factors sometimes causes cancers. To get around this problem, scientists are now using non-viral methods of delivery and adding permeable proteins directly to the adult cells.

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3. What are the benefits of using iPS cells?

Because no embryo is involved in the iPS process, the controversy associated with embryonic stem cell research could be avoided.

Also, because iPS cells can be expanded in culture like ESCs, there should be sufficient cells to work with.

In addition, because the iPS cells would be developed from adult cells from the patient, the technology used to generate iPS cells holds great promise for creating patient- and disease-specific cell lines for treatment that would not result in rejection.

In August 2008, Harvard researchers developed 10 disease-bearing iPS lines. The bits of skin tissue were taken from a range of patients representing different medical problems from a 3-month-old child with an extreme immune deficiency to a 57-year-old with Parkinson’s and an 80-year-old with Lou Gehrig’s disease (ALS). Studying the cells in a dish will allow researchers to watch how and when the various diseases develop and to test various treatments and drugs on the diseased tissue to see if it slows or stops the diseases.

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4. What problems need to be overcome?

Because the viruses used to introduce the genetic stem cell factors sometimes causes cancers, iPS cells cannot be used for treatment. Researchers are currently investigating non-viral delivery strategies. May 28, 2009, researchers at Harvard Medical School and Advanced Cell Technology indicated they successfully used four genetically engineered proteins without chemicals to develop iPS cells (“Patient-ready iPS cells?,” The Scientist Newsblog, 5-28-09 and “Generation of Human Induced Pluripotent Stem Cells by Direct Delivery of Reprogramming Proteins,” Cell Stem Cell, Volume4, Issue 6, May 28, 2009). In March 2009, Toronto researchers reported successfully introducing a gene into an adult cell without the use of viruses (“Stem Cell Coup for Toronto,” The Star.com, 3-2-09). In February 2009, German researchers reported being able to use just a single gene to get adult cells to revert to a pluripotent state (“Researchers Use Single Gene to Return Mature Stem Cells to Embryonic State,” JSOnline, 2-6-09).

However, a great deal of work remains before these methods can be used to generate stem cells suitable for safe and effective therapies.

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5. Can iPS replace embryonic stem cell research?

No. Although iPS cells open exciting new areas of stem cell research, this technology is at a very early stage and many fundamental questions remain. While iPS cells and embryonic stem cells share many characteristics they are not identical. The similarities and differences are still being explored.

Research on human embryonic stem cells, somatic cell nuclear transfer and ‘adult’ or tissue-specific stem cells needs to continue in parallel. All are part of a research effort that seeks to expand our knowledge of how cells function, what fails in the disease process, and how the first stages of human development occur. It is this combined knowledge that will ultimately generate safe and effective therapies.

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6. What is somatic cell nuclear transfer (SCNT) and how does it work?

Somatic cell nuclear transfer (SCNT), also referred to as therapeutic cloning, is a laboratory technique used to develop embryonic stem cell lines.

The nucleus (DNA) of a donated, unfertilized egg cell is removed and replaced with the DNA from a patient. Often the patient's nucleus is taken from a skin cell. Once the nucleus has been transferred, the egg becomes largely genetically identical to the patient. This egg can be tricked into dividing (despite never having been fertilized), eventually forming a blastocyst-like structure. The inner cell mass of the blastocyst is then removed to generate an embryonic stem cell line. This embryonic stem cell line is genetically identical to the patient whose skin cell was inserted as the nucleus. In theory, mature cells derived from the resultant stem cell line could then be transplanted into the patient without fear of immune rejection.

To date, this procedure has only been accomplished in animals, but not in humans.

Until recently, nuclear transfer or therapeutic cloning was the only way that scientists imagined it would be possible to develop patient-specific cell lines. But, since iPS has made it possible to derive patient-specific pluripotent lines by reprogramming adult human cells, and given that it has never been possible to do nuclear transfer successfully with human eggs, SCNT may no longer be relevant as a stem cell process.

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