Pia Todtenhaupt | 18-12-2024 | Unravelling the developmental origins of disease: the power of mesenchymal stromal cells and monochorionic twins
This thesis explores the mechanisms linking adverse intrauterine environments to long-term health risks. Therefore, the Twinlife study was established. This study includes monochorionic (MC) twins discordant for birthweight to investigate how prenatal nutrition affects growth, cardiovascular health, and neurodevelopment.
The study also examines the disease mechanisms by charting gene expression and epigenetic changes in umbilical cord mesenchymal stromal cells (hUC-MSCs). Chapter 2 details the study design, objectives, and future directions of Twinlife.
Chapter 3 reviews commonly used biological materials in developmental origins of disease research, emphasizing the advantages of hUC-MSCs. These cells enable multi-omics analysis, functional assays, and phenotypic studies to uncover mechanisms underlying disease risk.
Chapter 4 introduces a standardized method to isolate and expand hUC-MSCs, minimizing variability and enhancing the reliability of results both within and between twin pairs.
Chapter 5 compares DNA methylation and transcriptomic profiles of birthweight discordant twins, uncovering molecular insights into diseases linked to prenatal nutrient access.
Finally, Chapter 6 uses state-of-the-art approaches to study umbilical cord helices’ development in MC twins, underscoring the value of this natural experiment for innovative research into developmental origins of disease.