New Method for Testing Induced Pluripotent Stem Cells Differentiation Potential Could Lead to Safer and More Potent Treatments

Though the discovery of Induced Pluripotent Stem Cells (iPSCs) have great potential to help in the development of regenerative medicine therapies the attempts to discover how safe and potent use of iPSCs are in treatment of diseases has been inconclusive or contradictory. Atlas Regeneration Inc., working together with Insillico Medicine, has developed a method for using pathway activity analysis to test for differentiation potential that makes iPSCs effective much quicker than could be done previously.

BALTIMORE, MD (PRWEB) August 3rd, 2015

The discovery of human induced pluripotent stem cells (iPSCs) in 2006 completely revolutionized the field of stem cell biology, and IPSC lines become powerful tools which can be used to study human embryonic development, as model systems for human diseases, and as a renewable source for regenerative medicine where these cells are expected to play a key role in the development of many regenerative medicine therapies.

Clinical iPSCs applications require the selection and characterization of iPSC lines that reliably, efficiently, and stably differentiate into disease-relevant cell types. However, despite the fact that iPSCs theoretically have the full potential of embryonic stem (ES) cells, there are several studies showing evidence that induction of iPSCs can generate cell lines with genetic or epigenetic variability and abnormalities that could affect iPSC differentiation potential and clinical safety. Many attempts have been made to evaluate the safety and potency of human induced pluripotent stem cells (iPSCs) for clinical applications using transcriptome data, but results so far have been ambiguous or even contradictory. Which requires additional overhead (typically 2-3 weeks) of differentiation assays to screen iPSC lines before these lines are used for translational research and regenerative medicine. As a result there is an urgent need to develop new biomarkers or strategies to make iPSCs screening faster.

During recent collaboration, the two companies, Atlas Regeneration in partnership with Insilico Medicine, demonstrated the close resemblance of iPSCs with ESCs at the pathway level, and provided examples of how pathway activity analysis can be applied to identify iPSC line abnormalities or to predict in vitro differentiation potential. The results indicate that pathway activation profiling is a promising strategy for evaluating the safety and potency of iPSC lines in translational medicine applications allowing scientists to test differentiation abilities of many iPSC lines in silico while saving valuable time for patients waiting for treatment.

Evgeny Makarev, Ph.D, COO of Atlas Regeneration, Inc., the leader of the study, said, “Regeneration Intelligence is unique among pathway analysis platforms. Using our algorithm along with proprietary pathway database, we established for the first time pathway activation profiles of iPS. Reusing data from publically-available gene expression data sets and evaluated signaling and metabolic pathway activation profiles for 20 human embryonic stem cell (ESC) lines, 12 human iPSC lines, we identified PAS quality score lines as a novel prognostic biomarker which can identify impaired iPSC lines.”

Anthony Atala, MD., Director of Atlas Regeneration said, “Our Regeneration Intelligence platform has been used in many iPSC lines and is helping stem cells biologist to improve and speed up decision-making. Unfortunately, the entire process of verification and validation of differentiation abilities using in vitro differentiation assays typically takes 12 weeks and time is critical for definitive treatment, especially in urgent cases. With the help of Regeneration Intelligence, we may be able to significantly reduce the time and cost of the process.”

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