Mitochondrial mutations may affect the use of stem cell therapy

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(Last Updated On: April 23, 2017)
mitochondrial mutation may stop the use of stem cell therapy

Mitochondria shown in yellow color are the powerhouse of the cell. Credit: BSIP/UIG/Getty

New Study published in Nature last Thursday reveals mitochondrial mutations may affect the use of stem cell therapies. Induced pluripotent stem cells that are derived from adult cells are getting closer to clinical trials to be used in mainline treatments but there are still some more works to do. As a patient gets old, the chance of getting genetically mutated induced pluripotent stem cells derived from them increases.

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As a patient gets old, the chance of getting genetically mutated induced pluripotent stem cells derived from them increases. These genetic mutations in the induced pluripotent stem cells affect their function. But the interesting fact is that these mutations are not in the genomic DNA but in the mitochondrial DNA. These mutations are mitochondrial mutations.

Therefore, to check on how the mitochondrial DNA mutations affect the induced pluripotent stem cells, a team of researchers collected skin and blood samples from a 72-year-old patient. The team of the researchers was led by a reproductive biologist Shoukhrat Mitalipov from Oregon Health and Science University of Portland.

The researchers sequenced the mitochondrial DNA from the samples and transformed the adult cells into stem cells by infecting those cells with viruses. After producing induced pluripotent stem cells, they again sequenced the mitochondrial DNA of the induced pluripotent stem cells.

The interesting fact is that they didn’t find a significant rate of mitochondrial mutations but when they examined the mitochondrial DNA from randomly selected individual cells they found a significant and wide variety of mitochondrial mutations.

Furthermore, they analyzed the skin and blood samples from 14 people with the age in between 24 to 72. This analysis revealed that as the person gets older the mitochondrial mutations becomes higher.

Researchers also found that few such mutations happen in the DNA that codes for the proteins which play an important role in the production of induced pluripotent stem cells and their function if transplanted into a patient.

Jeanne Loring, a stem-cell biologist at the Scripps Research Institute in La Jolla, California said that it is one of the things that most of us don’t think about. She is involved in the study of treatment of Parkinson’s disease by using different types of induced pluripotent stem cells in her lab. She is now planning to study the mitochondrial in her induced pluripotent stem cell lines.

Mitalipov said that it is better to isolate at least 10 cells and select one of them with best mitochondrial to create a cell line before using induced pluripotent stem cells in treatments. According to him, these results also support the use of somatic-cell nuclear transfer.

Somatic-cell nuclear transfer is a technique used to create embryonic stem cells in which nucleus of a patient’s cell is transferred to a healthy young egg cell of which the nucleus has been removed. Altered donor cell produced this way is used to produce a blastocyte that contains mitochondria from a healthy donor and nuclear DNA from the patient. But this technique is not so easy than creating induced pluripotent stem cells and there are only fewer laboratories that have skills to employ this technique.

Another researcher from the New York Stem Cell Foundation, Dieter Egli said that these findings provide an argument. According to him, these results favor the use of embryonic stem cells instead of induced pluripotent stem cells that is surely going to affect their trials.

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Therefore, screening the cell lines is extremely important if the researchers are using them in a clinical trial rather than just in the lab. He said that you can’t just assume it does work or not for therapy but it’s better to conduct clinical trial rather than working in the lab.

Egli added that researchers need to determine how significant the mitochondrial mutation is because there are many biological factors that can cause problems. Studying on how the induced pluripotent stem cells differ from the embryonic stem cells, researchers found that these two cell types have different chemical markers on their DNA that can affect the way genes are expressed in these two cell types.

Reference: Nature
Article doi: 10.1038/nature.2016.19752

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