Recent research from the Hebrew University has shown that a significant proportion (more than one-fifth) of human pluripotent stem cell samples, including IPS and embryonic stem cells, that can be used for regenerative medicine have cancer-related mutations, most of which were acquired during culture propagation.
These findings underscore the importance of regular evaluation of cell cultures, as these mutations not only affect the growth dominance of the culture, but may also affect the transformation of cell fate during differentiation. The study highlights the need for increased vigilance when using such stem cell derivatives in research and clinical applications to ensure that the conclusions are accurate and the treatment method is safe.
Source: Nessim Benvenisti
Human pluripotent stem cells are cells with two very important characteristics: the seemingly endless ability to proliferate and the amazing ability to produce any cell in our body. These properties make these cells an important tool for studying early human development, disease modeling, and drug discovery, and most importantly, they are also the source of cells for several current regenerative medicine clinical trials.
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While human pluripotent stem cells can multiply in culture medium for long periods of time, they are also known to acquire genetic aberrations, which give them a selective advantage under culture conditions. This advantage allows a single cell with distortion to take over the entire cell population.
The laboratory of Professor Nissim Benvenisti at the Azrieli Center for Stem Cell and Gene Research at the Hebrew University has been a pioneer in identifying cancer-associated genes with such mutations and developing bioinformatics algorithms.
Recently, the increasing popularity of pluripotent stem cells in differentiation studies and clinical trials has prompted graduate students Elyad Lezmi, Jonathan Jung, and Ben Venisti to attempt to elucidate the mutational abundance profile of these cells and their differentiation derivatives used in basic and clinical research.
Their research was recently published in the prestigious journal Nature Biotechnology. Using bioinformatics tools, the researchers analyzed more than 2,200 samples from more than 140 different human pluripotent stem cell lines in hopes of revealing the abundance and severity of these cancer-associated mutations acquired during culture.
The researchers showed that 22 percent of the samples analyzed had at least one cancer-associated mutation, and at least 70 percent of them were acquired during culture propagation. Mutations acquired during differentiation, although rare, can occur, so the final product of the differentiation protocol needs to be monitored.
The predominant gene in the analysis was P53, the best-known tumor suppressor gene in human cancer. In-depth analysis of the mutations revealed that the mutations acquired during the culture of the stem cells were similar to those found in the patient's tumor. These mutations lead to a delay in the withdrawal of stem cells from pluripotency and the time of differentiation into adult cells.
This has led researchers to believe that these acquired mutations not only confer advantages in culture, but also have an impact on cell fate transitions – a key point of concern due to the rise of differentiation studies in stem cell research and clinical applications.
"The mutations we found are not known to researchers who use cells and publish studies, so they can lead to misleading conclusions, especially when phenotypic effects have been shown to exist," said author Jonathan Jung. "
参考文献：High prevalence of acquired cancer-related mutations in 146 human pluripotent stem cell lines and their differentiated derivatives