Diversity and stem cell research: why, how and when?

Biomedical scientists are becoming increasingly aware of the importance of diversity in their research. However, guidance on how and when to incorporate diversity into human induced pluripotent stem cell (hiPSC) research remains limited. PREPARE and reSOLVE researchers from reNEW now present a practical framework in Stem Cell Reports to support stem cell scientists in making informed diversity-related decisions when designing experiments. By doing so, the framework aims to foster comparability and reliability of stem cell research across studies.

Since their discovery two decades ago, human induced pluripotent stem cells (hiPSCs) have transformed biomedical research. This technology offers unprecedented opportunities to model organ function, study disease mechanisms, and develop therapeutics in a human-relevant context.

The diversity gap
While the importance of biological diversity has gained considerable attention in fields such as genomics, the discussion has only recently reached the stem cell community. For many years, hiPSCs were derived from a relatively homogeneous group of donors, limiting the relevance of preclinical findings for broader populations. It is now increasingly clear that variation in, for instance, donor sex and ancestry can significantly influence cellular function, disease phenotypes, and responses to treatment.

A framework for diversity
“Several initiatives are underway to increase diversity in stem cell research, for example by generating and incorporating hiPSC lines from underrepresented populations,” says first author and PhD candidate at Leiden University Medical Center Jesse Weidema. “Despite these efforts and growing recognition of its importance, integrating diversity into experimental design remains challenging. In this paper, we develop a framework that we hope can help researchers navigate this process.”

Balancing considerations
The team built on earlier work in genomics to develop a framework tailored specifically to hiPSC research, taking into account the unique characteristics and challenges of the field.

Weidema noted, “Existing diversity frameworks, particularly those from genomics, are primarily designed for studies involving human participants. These cannot be directly applied to hiPSC-based research, where you’re constantly dealing with technical challenges, such as limited sample sizes or a lack of standardization. This makes decisions about inclusion genuinely difficult. There is always a trade-off between platform stability and diversity, and our framework is designed to make that trade-off explicit and help researchers navigate it.”

The researchers identify four key criteria in the paper that should be evaluated in making decisions about how to incorporate diversity in hiPSC research: experimental purpose, biological plausibility, platform readiness, and statistical power. The framework balances these criteria and proposes that it is essential to ensure that diversity-related design choices are implemented in a practical and reliable way. To demonstrate its utility, the team applied the framework to three case studies.

Clear, comparable, and reliable
“It is encouraging to see that stem cell researchers worldwide are increasingly recognizing the importance of diversity in preclinical research,” concludes Associate Professor Nienke de Graeff from reNEW’s PREPARE team. “We hope our framework will be widely adopted and support transparent and well-informed decision-making in this area.”

Ultimately, the framework is intended to enhance comparability and reliability of stem cell–based preclinical research worldwide.