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Study shows no increased risk of mutations with iPSCs

Colony of iPSCs
Image from Salk Institute

The use of induced pluripotent stem cells (iPSCs) in biomedical research and medicine has been slowed by concerns that these cells are prone to increased numbers of genetic mutations.

However, a new study suggests iPSCs do not develop more mutations than cells that are duplicated by subcloning, a technique where single cells are cultured individually and then grown into a cell line.

Subcloning is similar to the technique used to create iPSCs, except the subcloned cells are not treated with the reprogramming factors that have been thought to cause mutations in iPSCs.

“These findings suggest that the question of safety shouldn’t impede research using iPSCs,” said study author Paul Liu, MD, PhD, of the National Human Genome Research Institute, part of the National Institutes of Health, in Bethesda, Maryland.

Dr Liu and his colleagues reported the findings in PNAS.

For this study, the researchers examined 2 sets of donated cells. One set came from a healthy individual, and the second came from a person with familial platelet disorder.

Using fibroblasts from each of the donors, the researchers created genetically identical copies of the cells using both the iPSC and subcloning techniques.

The team then sequenced the DNA of the fibroblasts as well as the iPSCs and the subcloned cells and determined that mutations occurred at the same rate in cells that were reprogrammed and cells that were subcloned.

More than 90% of the genetic variants detected in the iPSCs and subclones were rare variants inherited from the parent cells.

This suggests that most mutations in iPSCs are not generated during the reprogramming or iPSC production phase and provides evidence that iPSCs are stable and safe to use for both basic and clinical research, Dr Liu said.

“Based on this data, we plan to start using iPSCs to gain a deeper understanding of how diseases start and progress,” said study author Erika Mijin Kwon, PhD, also of the National Human Genome Research Institute.

“We eventually hope to develop new therapies to treat patients with leukemia using their own iPSCs. We encourage other researchers to embrace the use of iPSCs.”

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Colony of iPSCs
Image from Salk Institute

The use of induced pluripotent stem cells (iPSCs) in biomedical research and medicine has been slowed by concerns that these cells are prone to increased numbers of genetic mutations.

However, a new study suggests iPSCs do not develop more mutations than cells that are duplicated by subcloning, a technique where single cells are cultured individually and then grown into a cell line.

Subcloning is similar to the technique used to create iPSCs, except the subcloned cells are not treated with the reprogramming factors that have been thought to cause mutations in iPSCs.

“These findings suggest that the question of safety shouldn’t impede research using iPSCs,” said study author Paul Liu, MD, PhD, of the National Human Genome Research Institute, part of the National Institutes of Health, in Bethesda, Maryland.

Dr Liu and his colleagues reported the findings in PNAS.

For this study, the researchers examined 2 sets of donated cells. One set came from a healthy individual, and the second came from a person with familial platelet disorder.

Using fibroblasts from each of the donors, the researchers created genetically identical copies of the cells using both the iPSC and subcloning techniques.

The team then sequenced the DNA of the fibroblasts as well as the iPSCs and the subcloned cells and determined that mutations occurred at the same rate in cells that were reprogrammed and cells that were subcloned.

More than 90% of the genetic variants detected in the iPSCs and subclones were rare variants inherited from the parent cells.

This suggests that most mutations in iPSCs are not generated during the reprogramming or iPSC production phase and provides evidence that iPSCs are stable and safe to use for both basic and clinical research, Dr Liu said.

“Based on this data, we plan to start using iPSCs to gain a deeper understanding of how diseases start and progress,” said study author Erika Mijin Kwon, PhD, also of the National Human Genome Research Institute.

“We eventually hope to develop new therapies to treat patients with leukemia using their own iPSCs. We encourage other researchers to embrace the use of iPSCs.”

Colony of iPSCs
Image from Salk Institute

The use of induced pluripotent stem cells (iPSCs) in biomedical research and medicine has been slowed by concerns that these cells are prone to increased numbers of genetic mutations.

However, a new study suggests iPSCs do not develop more mutations than cells that are duplicated by subcloning, a technique where single cells are cultured individually and then grown into a cell line.

Subcloning is similar to the technique used to create iPSCs, except the subcloned cells are not treated with the reprogramming factors that have been thought to cause mutations in iPSCs.

“These findings suggest that the question of safety shouldn’t impede research using iPSCs,” said study author Paul Liu, MD, PhD, of the National Human Genome Research Institute, part of the National Institutes of Health, in Bethesda, Maryland.

Dr Liu and his colleagues reported the findings in PNAS.

For this study, the researchers examined 2 sets of donated cells. One set came from a healthy individual, and the second came from a person with familial platelet disorder.

Using fibroblasts from each of the donors, the researchers created genetically identical copies of the cells using both the iPSC and subcloning techniques.

The team then sequenced the DNA of the fibroblasts as well as the iPSCs and the subcloned cells and determined that mutations occurred at the same rate in cells that were reprogrammed and cells that were subcloned.

More than 90% of the genetic variants detected in the iPSCs and subclones were rare variants inherited from the parent cells.

This suggests that most mutations in iPSCs are not generated during the reprogramming or iPSC production phase and provides evidence that iPSCs are stable and safe to use for both basic and clinical research, Dr Liu said.

“Based on this data, we plan to start using iPSCs to gain a deeper understanding of how diseases start and progress,” said study author Erika Mijin Kwon, PhD, also of the National Human Genome Research Institute.

“We eventually hope to develop new therapies to treat patients with leukemia using their own iPSCs. We encourage other researchers to embrace the use of iPSCs.”

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Study shows no increased risk of mutations with iPSCs
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