New study quantifies signaling pathway activation to monitor quality of induced pluripotent stem cells

Written by Elena Conroy

A collaborative study by Atlas Regeneration and Insilico Medicine demonstrates the promising strategy of pathway activation profiling in evaluating the safety and potency of iPSC lines in translational medicine applications

During a recent collaboration, two companies, Atlas Regeneration (NC, USA) and Insilico Medicine (MD, USA), demonstrated the close resemblance of human induced pluripotent stem cells (iPSCs) with embryonic stem cells 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 study was recently published in Oncotarget.

The discovery of iPSCs in 2006 completely revolutionized the field of stem cell biology and regenerative medicine. iPSC lines have become powerful tools that can be used to study human embryonic development, as model systems for human diseases. They are also helpful as a renewable source for regenerative medicine and are expected to play a key role in the development of many regenerative therapies.

The results of the study indicated that pathway activation profiling is a promising strategy for evaluating the safety and potency of iPSC lines in translational medicine applications. This would allow researchers to test differentiation abilities of many iPSC lines in silico while saving valuable time for patients waiting for treatment.

“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,” explained Evgeny Makarev, leader of the study and COO of Atlas Regeneration, Inc. “We reused data from publically available gene expression data sets and evaluated signaling and metabolic pathway activation profiles for 20 human embryonic stem cell lines, 12 human iPSC lines. Consequently, we identified PAS quality score lines as a novel prognostic biomarker that can identify impaired iPSC lines.”

“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,” concluded CEO of Atlas Regeneration Anthony Atala.

Sources: Makarev E, Fortney K, Litovchenko M, Braunewell KH, Zhavoronkov A, Atala A. Quantifying signaling pathway activation to monitor the quality of induced pluripotent stem cells. Oncotarget doi:10.18632/oncotarget.4673 (2015) (Epub ahead of print);