Toward standardized iPSC testing: Insights from a multi-year international Quality Assessment Round.
Alice Hägg, Rachel Wood, Ayako L Mochizuki, Keren Abberton, Elsa Abranches, Belén Alvarez-Palomo, Ricardo Baptista, Raiana Andrade Quintanilha Barbosa, Jacqueline Barry, Adriana Bastos Carvalho, Annelise Bennaceur Griscelli, Antonio Carlos Campos de Carvalho, Diana Chaker, Hong Chang, Hye Young Choi, Margarita Codinach, Begoña Arán Corbella, Scott Cowan, Sarah Jane Dickerson, Ngaire Elwood, Xueling Fan, Maxime Feyeux, Maddy Forrester, Andrew Gaffney, Solenn M Guilbert, Hye-Yeong Ha, Adam J Hirst, Arwen L Hunter, Leanne G Jamieson, Robert N Judson, Yonehiro Kanemura, Tais Hanae Kasai-Brunswick, Jung-Hyun Kim, Howard Kim, Manisha Kintali, Siddharth Krishnan, Bernd Kuebler, Chui Yu Lau, Wilson Li, Amanda Mack, Michael R MacLeod, Marinna Madrid, Hiroaki Mamiya, Lucie Manache-Alberici, Dragoş Mărginean, Olivier Mentre, Stefanie L Morgan, Joanne Mountford, Humayun Munir, Siemon H S Ng, Haruna Ogawa, Steve Oh, Hidetaka Ohara, Keiko Oono, Niall Park, Lygia V Pereira, Izabella Pereira da Silva Bezerra, Alexandru Robert Podovei, Sergio Querol, Jainy Raje, Angel Raya, Satoko Sakamoto, Raquel Sarafian, Kathleen Schmit, Silvia Selvitella, Gurbind Singh, Matthew J K Smart, Jihwan Song, Glyn Stacey, Stephen Sullivan, Miho Sumida, Cecile Terrenoire, Pei Tian, Elias Uhlin, José M A Vaquero, Anna Veiga, Jar Wei Vicky Wang, Katherine Warre-Cornish, Jamie Wood, Atsuyo Yamamoto, Gaojun Zhang, Takafusa Hikichi, Marc Turner, Anna Falk
Abstract
Despite rapid clinical translation, induced pluripotent stem cell (iPSC)-derived therapies face limited global adoption. Harmonized quality control (QC) remains absent, with even fundamental parameters evaluated inconsistently across laboratories. To address this, we conducted two international Quality Assessment Rounds (QARs): QAR 2019 (18 sites, 11 countries) and QAR 2023 (23 sites, 12 countries), evaluating flow cytometry-based assessment of the undifferentiated state and qPCR-based genomic integrity testing. QAR 2019 showed high consistency in genomic integrity testing, while uncovering substantial variability in flow cytometry, prompting QAR 2023 to introduce standardized workflows. These improvements enabled systematic, cross-site evaluation of marker performance across cell states, identifying OCT3/4, TRA-1-60, and SSEA5 as consistently robust pluripotency-associated markers. This global benchmarking effort provides the first empirical multi-site evidence for reproducible iPSC QC and marker-level reliability. Together, these findings establish a foundation for harmonized QC supporting interoperable iPSC banks, regulatory alignment, and scalable manufacturing of globally accessible regenerative therapies.