Early dynamic changes in iPSC oxygen consumption rate predict future cardiomyocyte differentiation

• Published in: Biotechnology and bioengineering Vol. 120; no. 8; pp. 2357 - 2362
• Main Authors: Nikitina, Arina A., Roysam, Tanya, Kemp, Melissa L.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.08.2023
• Subjects: Bioreactors; Cardiomyocytes; Cardiovascular diseases; Cell differentiation; cell manufacturing; critical quality attributes; induced pluripotent stem cells; machine learning; Manufacturing; Oxygen; Oxygen consumption; oxygen consumption rate; Oxygen probes; Pluripotency; Quality management; Stem cells; time‐series analysis; cell manufacturing; induced pluripotent stem cells; critical quality attributes; machine learning; oxygen consumption rate; time-series analysis
• ISSN: 0006-3592; 1097-0290; 1097-0290
• DOI: 10.1002/bit.28489

Human induced pluripotent stem cells (iPSCs) hold great promise for reducing the mortality of cardiovascular disease by cellular replacement of infarcted cardiomyocytes (CMs). CM differentiation via iPSCs is a lengthy multiweek process and is highly subject to batch‐to‐batch variability, presenting challenges in current cell manufacturing contexts. Real‐time, label‐free control quality attributes (CQAs) are required to ensure efficient iPSC‐derived CM manufacturing. In this work, we report that live oxygen consumption rate measurements are highly predictive CQAs of CM differentiation outcome as early as the first 72 h of the differentiation protocol with an accuracy of 93%. Oxygen probes are already incorporated in commercial bioreactors, thus methods presented in this work are easily translatable to the manufacturing setting. Detecting deviations in the CM differentiation trajectory early in the protocol will save time and money for both manufacturers and patients, bringing iPSC‐derived CM one step closer to clinical use. Timeseries mining of noninvasive oxygen consumption rates yielded highly predictive critical quality attributes of cardiomyocyte outcomes within the first 72 h of a standard iPSC differentiation protocol.