With the prospect of using regenerative stem cell therapies looming, a consortium of biomedical scientists recently reported that approximately 30% of the induced pluripotent stem cells they analyzed from 10 research institutions were genetically unstable and could not be safely used clinically.
In a study published on June 9 in the journal Stem Cell Reports, a multi-institutional research team, supported by funding from the National Heart, Lung, and Blood Research Institute, comprehensively described a large group of induced pluripotent stem cells (iPSCs). These specialized iPSCs are reprogrammed from adult skin or infant umbilical cord blood cells and can potentially become any cell type in the body, a condition known as pluripotency that mimics the function of human embryonic stem cells (hESCs).
As part of the Progenitor Cell Biology Consortium, scientists are working to confirm that this emerging field of medical research is based on safe and sound science. Although the technology to produce safe and effective iPSCs exists, researchers reported that they encountered an unexpected number of erratic cell production processes. This includes some cell lines that are contaminated with bacteria or carry cancer-related genes and mutations.
The researchers also announced the creation of an online portal and database: https://www.synapse.org/. It gives scientists open access to data from research to support their own research into iPSC-based stem cell therapies. This allows researchers to compare the quality and stability of iPSCs currently generated in their labs.
Different tools, different results
The researchers compared 58 different cell lines submitted by different institutions. The researchers used various methods to generate cells with various genes and origins, such as adult skin or infant umbilical cord blood cells. The researchers evaluated iPSCs for genetic stability, pluripotency and other scientific criteria.
Genetic stability is critical for the safety of iPSCs to avoid cancer or other medical problems triggered by experimental treatments. It is also critical that iPSC lines are constantly updated and expanded in a blank form without introducing genetic errors before being instructed to become a specific cell type. The researchers also compared the molecular and functional characteristics of iPSCs with those of human embryonic stem cells, which are rarely used as the gold standard to benchmark quality.
How well the 56 iPSC lines met quality standards depended on the origin of the reprogrammed cells (skin vs blood, male vs female) and the specific programming method. These different methods include the use of various recombinant genes, vectors (engineered viruses that deliver genetic material to cells), or plasmids (small DNA molecules that can deliver recombinant genes).
Teratoma test
Pluripotency means that iPSCs can generate the three basic germ cell lines that make up the body—endoderm (gut area), ectoderm (epidermis, nervous tissue, etc.), and mesoderm (muscles, blood cells, etc.). Pluripotency can be tested to determine whether the iPSC lines are capable of forming so-called teratomas—benign tumors composed of different cell types (teeth, bone, brain, etc.).
It was thought that poor-quality iPSC lines were not pluripotent, a theory that had not been carefully tested until the current study because of expense, Lutzko said. This prompted Lutzko and her colleagues to examine and explore whether all iPSC cell lines—high and low quality—could produce teratomas.
To this end, the researchers studied different iPSC cell lines to see whether tumors formed, and secondly, whether the tumors contained three different germ cell types. Tests showed that both genetically stable and unstable iPSC lines can form teratomas with all three germ cell layers.
According to the study’s authors, while genetically unstable iPSC lines exhibit pluripotency, the clinical context involved may also lead to cancer, thus once again emphasizing the need for safe reprogramming methods. (Original text: Integrated Genomic Analysis of Diverse Induced Pluripotent Stem Cell from the Progenitor Cell Biology Consortium)
In January 2014, the research group of Professor Tian Jianhui of China Agricultural University and the laboratory of Researcher Gao Shaorong of the Beijing Institute of Life Sciences jointly discovered a gene called Zrsr1. The methylation level of this gene will affect the quality of induced pluripotent stem cells (iPS cells) and can be used to identify the quality of iPS cells. This research will be of great value to iPS cells in regenerative medicine and drug development and utilization.
Source: Biotong