Diversity-in-a-dish: A practical framework for hiPSC model development

Stem Cell Reports, vol. 21, pp. 102858

Abstract

Human induced pluripotent stem cell (hiPSC) models inherit genetic and phenotypic variation from their donors that can influence differentiation, function, and disease phenotypes, with implications for model validity and generalizability. While diversity is widely discussed in biomedical research and extensively theorized in fields like genomics, comparable guidance remains limited in hiPSC research. Effectively, diversity-related decisions are often made implicitly without clear criteria for when inclusion is methodologically warranted. We address this by (1) analyzing how diversity is defined and operationalized in (pre)clinical research, (2) extending genomics frameworks to outline stem cell-specific recommendations for describing and reporting diversity, and (3) introducing a decision framework based on four criteria (experimental purpose, biological plausibility, platform readiness, and statistical power) to determine when and how diversity should be incorporated. The overall goal is to establish a shared basis for transparent and reproducible diversity-related design and reporting.

Authors 6

1. Jesse Weidema corresponding Aachen Department of Medical Ethics and Health Law

   Leiden University Medical Center

   Affiliation as printed

   Department of Medical Ethics and Health Law, Leiden University Medical Center, Leiden, the Netherlands. Electronic address: j.j.weidema@lumc.nl

2. Hanna Lammertse Aachen

   Leiden University Medical Center

   Affiliation as printed

   Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, the Netherlands; hDMT, Institute for Human Organ and Disease Model Technologies, Leiden, the Netherlands

3. Martine Charlotte de Vries Aachen Department of Medical Ethics and Health Law

   Leiden University Medical Center

   Affiliation as printed

   Department of Medical Ethics and Health Law, Leiden University Medical Center, Leiden, the Netherlands

4. Christine L. Mummery Aachen Department of Anatomy and Embryology

   Leiden University Medical Center

   Affiliation as printed

   Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, the Netherlands

5. Megan Munsie

   The University of Melbourne · Murdoch Children's Research Institute

   Affiliation as printed

   Stem Cell Medicine, Murdoch Children's Research Institute, Parkville, VIC, Australia; Melbourne Medical School, University of Melbourne, Parkville, VIC, Australia

6. Nienke de Graeff Aachen Department of Medical Ethics and Health Law

   Leiden University Medical Center

   Affiliation as printed

   Department of Medical Ethics and Health Law, Leiden University Medical Center, Leiden, the Netherlands