An Alternative Source of Pluripotent Stem Cells
The earliest uses of stem cells in regenerative medicine occurred in the 1960s with the advent of bone-marrow derived stem cell transplants. Since that time, stem cell research has advanced to the forefront of science. Because stem cells hold the remarkable capacity of self-renewal and differentiation into more specialized cell lineages, they constitute a promising resource for the generation of a variety of cell types that can be useful in medical applications, including as potential source of rejection-free transplant tissues for a wide variety of diseases. Recent research has been focused on finding new sources of these powerful cells.
In mammals, there are two broad types of stem cells: embryonic stem cells, which are obtained from the inner cell mass of blastocysts, and adult stem cells, which are typically obtained from bone marrow, adipose, or blood. Due to the embryo destruction involved in retrieving embryonic stem cells, stem cell research has been highly politicized and become the subject of intense scrutiny.
Ever since a team of scientists from the University of Wisconsin first isolated embryonic stem cells grown from a human embryo in 1998, researchers have persisted in trying to find ways to create embryonic stem cells that would be an exact genetic match to a patient. These cloning techniques, which essentially insert a new set of genes into a recipient egg and initiate division to create an embryo, achieved notoriety with the cloning of "Dolly the Sheep".
With the advent of “induced” stem cells, the research focus shifted away from the hotly contested embryonic stem cells and towards efforts to create clones through reprogramming of the adult stem cells already available. Induced pluripotent stem cells, first created in 2007, are derived using gene alterations to revert adult cells back to an embryonic state capable of becoming any cell type that is needed. In 2012, Yamanaka and Gurdon were awarded the Nobel Prize in Physiology or Medicine for their innovative research on reprogramming cell fates. Recently, Japanese researchers have recently received permission to initiate a clinical study with induced pluripotent stem cells derived from the patient for treatment of age-related macular degeneration.
Growing cell lines from cloned embryos continued to experience failures, which were highlighted in 2006 by a notable case of academic fraud by a South Korean researcher. However, when a team lead by Shoukhrat Mitalipov of Oregon Health & Science University in Beaverton achieved a scientific first by producing embryonic stem cells from cloned embryos, attention shifted to reproductive cloning once again, along with the criticisms of the research and controversies surrounding the subject.
Dr. Mitalipov compared his team’s process to winning the lottery, in that “all the numbers have to line up the right way to win." According to the published paper in Cell, the lab implanted eggs donated by women volunteers that had been successfully integrated with chromosomes taken from skin cells of three other people into non-human primates. The result was embryos with cells that were genetic copies, or clones, of the cells of three different people.
With both cloned embryonic stem cells and induced stem cells a real possibility, the scientific question of which technique can most safely used in regenerative medicine and for possible tissue regeneration must be addressed. As preclinical and regulatory toxicologists at Charles River we are most interested in this debate of safety. Some, including Mitalipov, believe that the genetic abnormalities observed in induced stem cells are absent from embryonic ones. Others stress the potential risk of the embryonic cells for uncontrolled cell growth or unwanted tissue formation. Mitalipov also believes that the clinical trials already approved for embryonic-derived cells set an easier regulatory path for them to be tested on patients. He believes this may mean that cloned embryonic cells might prove more useful to patients and the field of regenerative medicine than the induced stem cells.
More work will be needed to test these theories and truly determine the best path forward to the clinic. But one thing is for sure: the Mitalipov results have re-ignited the debate over human cloning and the buzz concerning stem cells and the public.