Hadasit Health Innovation
Creating synergies between academia, industry, and medicine

A novel pluripotent stem cell system for the study of sex-dependent differences


There is an unmet need for a preclinical model to analyze gender differences and their role in health and disease. The same medical condition may have markedly different incidence, symptoms, or prognosis in a sex-dependent manner, for example myocardial infarction, autoimmune diseases, and variety of mental disorders. Moreover, drugs may cause different rates of adverse effects in men and women. Nevertheless, women remain underrepresented in clinical studies, and cell and animal research studies are often biased, with female animals and cell lines being a minority. Even when using male-derived and female-derived cells for preclinical tests, a clear conclusion as to the gender-based differences cannot be deduced due to masking by the variability of the genetic background of these cells.

Our solution

Recently, researchers led by Prof. Benjamin Reubinoff, a world-renowned expert in stem cell technology, were able to develop a matched pair of human induced pluripotent stem cells (iPSCs) that bear identical chromosomes, except for the sex chromosomes, XX and XY. These are male and female stem cells with the same genetic code from the same person, which only differ in sex chromosomes. Using a unique and rare case of a mosaic Klinefelter syndrome patient, Prof. Reubinoff and his team reprogrammed the cells into iPSCs. This is the first time that cells with a different sex chromosome complement that are otherwise isogenic were developed. The XX and XY cells are pluripotent and can thus differentiate into any cell type. They allow the analysis of whether gender differences arise from the influence of sex chromosomes or hormones.


The autosomal-identical iPSCs (AI-iPSCs) with different sex chromosomes complement, the first human model for sex-dependent differences, will enable studies of sex-dependent differences in all human cells and tissues, including for the following applications:

  • Cell function and metabolism
  • Drug development – sex-dependent differences in effectivity, adverse effects, toxicity. In vitro pharmacokinetics (PK) and pharmacodynamics (PD) studies
  • Disease modelling – phenotypes and pathogenesis
  • Effects of sex chromosomes versus hormones
  • X-inactivation studies


Market size

Given the ability of the cells to differentiate to various cell types, this technology can support early-stage drug development for multiple diseases. The assessment of sex-different in vitro ADME-Tox profiles, and guiding patient stratification in clinical trials are examples of utilizing the technology in drug development. Given the high costs of drug development (median costs are over $5 billion), the technology can mitigate risks related to hitherto unknown sex-based differences in response to potential drugs.

Development Status

Cell lines are available for scaling production.

Intellectual Property

Patents granted in the US and Israel. Patent pending in Europe.


Waldhorn I, Turetsky T, Steiner D, Gil Y, Benyamini H, Gropp M, Reubinoff BE. Modeling sex differences in humans using isogenic induced pluripotent stem cells. Stem Cell Reports. 2022 Dec 13;17(12):2732-2744.


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