By: Bradley Fikes — April 4th, 2011
Finally, some good news for advocates of using induced pluripotent stem cells for human therapy.
Induced pluripotent stem cells corrected for a genetic defect do not acquire substantially more potentially carcinogenic mutations, according to research published online today in the Proceedings of the National Academy of Sciences.
The results are positive for the use of gene therapy with a patient’s own genetically modified cells, according to the research team that performed the study.
“This study showed that the process of gene correction is compatible with therapeutic use,” said primary study author Sara Howden in a press release from the University of Wisconsin-Madison. Four authors are from UCSD’s Department of Bioengineering: Athurva Gore, Zhe Li, Ho-Lim Fung and Kun Zhang.
IPS cells reprogrammed from a woman's skin. Blue shows nuclei. Green indicate a protein found in reprogrammed cells but not in skin cells (NANOG). The red dots show the inactivated X chromosomes in each cell. These cells can be matured into cells of the body, and used for studying models of disease. The image was taken in the laboratory of Kathrin Plath at the University of California, Los Angeles. Courtesy California Institute for Regenerative Medicine: www.cirm.ca.gov.
IPS cells reprogrammed from a woman's skin. Blue shows nuclei. Green indicate a protein found in reprogrammed cells but not in skin cells (NANOG). The red dots show the inactivated X chromosomes in each cell. These cells can be matured into cells of the body, and used for studying models of disease. The image was taken in the laboratory of Kathrin Plath at the University of California, Los Angeles. Courtesy California Institute for Regenerative Medicine: www.cirm.ca.gov.
IPS cells acquire a number of mutations of unknown significance, according to recent studies. The risk of these mutations must be studied before these cells can be tested in humans.
IPS cells are made from adult cells like skin cells by adding genes or chemicals that reprogram them back to resembling embryonic stem cells. If they can be made suitable for therapy, these cells would have two advantages over embryonic stem cells; they would not carry the ethical issues of embryonic stem cells, and they could be grown directly from a patient, greatly reducing the chance of rejection.
That’s where gene therapy comes in: IPS cells grown from a patient with a genetic defect would also carry that defect. But if they were given a working copy of the gene, the IPS cells might be grown into healthy tissue and transplanted into the patient. Salk Institute scientists Inder Verma and Juan Carlos Izpisúa Belmonte are working on gene therapy approaches to using IPS cells.
The PNAS study was performed on IPS cells from a patient with gyrate atrophy of the choriod and retina, a disease that causes progressive loss of sight leading to blindness. This disease is an attractive target, the study said, because the target “RPE” retinal cells have already been created from IPS cells, and animal studies have shown these cells have a protective effect.
The study found that while the IPS cells used already had “a fairly substantial mutational load,” the gene therapy added minimally to that load.
“These results suggest that the accumulation of mutations may not limit the clinical utility of gene targeting approaches, but that extensive genetic characterization of the initial IPS cell clones will be critical,” the study said.
Finally, some good news for advocates of using induced pluripotent stem cells for human therapy.
Induced pluripotent stem cells corrected for a genetic defect do not acquire substantially more potentially carcinogenic mutations, according to research published online today in the Proceedings of the National Academy of Sciences.
The results are positive for the use of gene therapy with a patient’s own genetically modified cells, according to the research team that performed the study.
“This study showed that the process of gene correction is compatible with therapeutic use,” said primary study author Sara Howden in a press release from the University of Wisconsin-Madison. Four authors are from UCSD’s Department of Bioengineering: Athurva Gore, Zhe Li, Ho-Lim Fung and Kun Zhang.
IPS cells reprogrammed from a woman's skin. Blue shows nuclei. Green indicate a protein found in reprogrammed cells but not in skin cells (NANOG). The red dots show the inactivated X chromosomes in each cell. These cells can be matured into cells of the body, and used for studying models of disease. The image was taken in the laboratory of Kathrin Plath at the University of California, Los Angeles. Courtesy California Institute for Regenerative Medicine: www.cirm.ca.gov.
IPS cells reprogrammed from a woman's skin. Blue shows nuclei. Green indicate a protein found in reprogrammed cells but not in skin cells (NANOG). The red dots show the inactivated X chromosomes in each cell. These cells can be matured into cells of the body, and used for studying models of disease. The image was taken in the laboratory of Kathrin Plath at the University of California, Los Angeles. Courtesy California Institute for Regenerative Medicine: www.cirm.ca.gov.
IPS cells acquire a number of mutations of unknown significance, according to recent studies. The risk of these mutations must be studied before these cells can be tested in humans.
IPS cells are made from adult cells like skin cells by adding genes or chemicals that reprogram them back to resembling embryonic stem cells. If they can be made suitable for therapy, these cells would have two advantages over embryonic stem cells; they would not carry the ethical issues of embryonic stem cells, and they could be grown directly from a patient, greatly reducing the chance of rejection.
That’s where gene therapy comes in: IPS cells grown from a patient with a genetic defect would also carry that defect. But if they were given a working copy of the gene, the IPS cells might be grown into healthy tissue and transplanted into the patient. Salk Institute scientists Inder Verma and Juan Carlos Izpisúa Belmonte are working on gene therapy approaches to using IPS cells.
The PNAS study was performed on IPS cells from a patient with gyrate atrophy of the choriod and retina, a disease that causes progressive loss of sight leading to blindness. This disease is an attractive target, the study said, because the target “RPE” retinal cells have already been created from IPS cells, and animal studies have shown these cells have a protective effect.
The study found that while the IPS cells used already had “a fairly substantial mutational load,” the gene therapy added minimally to that load.
“These results suggest that the accumulation of mutations may not limit the clinical utility of gene targeting approaches, but that extensive genetic characterization of the initial IPS cell clones will be critical,” the study said.