Apr. 30, 2001 NEW YORK – Researchers are one step closer to being able to perform so-called therapeutic cloning in mice. The research, which will be published in the April 27 issue of Science, is a joint effort between investigators at Memorial Sloan-Kettering Cancer Center and The Rockefeller University.
Therapeutic cloning uses cloning techniques – transferring the nucleus from an adult cell of one mouse to the oocyte (egg) of another – with an eye not toward developing another mouse, but manufacturing therapeutic cells that have the same genetic makeup as the mouse from which the nucleus was extracted. The technique may ultimately yield cells that not only can replace cells lost due to injury or disease, but also that genetically match the mouse receiving them. This approach may avoid problems with immunity and rejection, which could develop when donor cells are not matched to their recipient. Scientists believe that this finding may have important implications for Parkinson’s disease research. The next step in the lab is to investigate whether the technique can be used to treat mice with Parkinson’s-like disease.
"This was the very first step in showing this kind of therapy might work," said Lorenz Studer, MD, Head of the Stem Cell and Tumor Biology Laboratory at the Sloan- Kettering Institute and senior co-author of the study.
In this experiment, researchers took cells from the tail of one mouse and transferred the nuclei from those cells to the oocytes of another mouse that had their nuclei removed. After the oocytes developed for a few days, the researchers removed the embryonic stem cells, which have the capacity to become any part of the body, including bone, skin, blood, and brain. Researchers were then able to simulate natural conditions in the laboratory in order to develop the stem cells into dopamine neurons, the cells that are lost in patients who have Parkinson's.
"In the past we have made dopamine neurons starting with fetal brain stem cells, but this is the first time they have been made via nuclear transfer from an easily accessible source of adult cells such as the mouse’s own tail,” said co-author Viviane Tabar, MD, of the Neurosurgery Service at Memorial Sloan-Kettering and a member of Dr. Studer’s lab. This research doesn't prove the therapy will work, but it proves that unlimited numbers of genetically matched dopamine cells can be generated and suggests that therapeutic cloning has entered the realm of possibilities, at least in mice, she adds.
"These are a very specialized cell type," said Dr. Studer. "Even within the fully developed brain, only about 1 in 100,000 cells are midbrain dopamine neurons, so it's quite a feat to be able to generate them."
Dr. Studer recently received a grant from the Michael J. Fox Foundation that will be used to take this research to the next step: using skin cells from mice who have Parkinson's to make genetically matched dopamine neurons and then transplanting the cells back into those mice to see if it treats their disease.
The paper’s lead author from The Rockefeller University is Teruhiko Wakayama, PhD, working in the laboratory of Peter Mombaerts, MD, PhD. The Rockefeller team also included Ivan Rodriguez, Ph.D., and Anthony C. F. Perry, Ph.D.
Drs. Studer and Tabar are members of the neuroscience program in the Neurosurgical Service at Memorial Sloan-Kettering Cancer Center, the world’s oldest and largest institution devoted to prevention, patient care, research and education in cancer. Our scientists and clinicians generate innovative approaches to better understand, diagnose and treat cancer. Our specialists are leaders in biomedical research and in translating the latest research to advance the standard of cancer care worldwide.
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