This webinar will explore how rapid transcriptional and signalling events occurring during the first hours of long-term haematopoietic stem cell (LT-HSC) culture drive loss of over 70% of functional LT-HSCs within 24 hours. We will discuss the kinetics of this functional loss, the stress-response pathways triggered during early culture adaptation, and how these rapid molecular changes reduce stemness independently of cell-cycle progression. Finally, we will explore how targeted interventions, such as JAK/STAT inhibition during this critical window, can preserve LT-HSC function ex vivo and guide the development of improved clinical ex vivo gene therapy protocols.

Blood, Adaptation to Ex Vivo Culture Reduces Human Hematopoietic Stem Cell Activity Independently of the Cell Cycle; DOI: https://doi.org/10.1182/blood.2023021426

Learning Objectives

1. Understand the key molecular and functional changes that occur when HSCs are cultured outside the body for clinical approaches (ex vivo).
2. Explore how early intervention approaches such as JAK/STAT inhibition through Ruxolitinib, can preserve HSC function ex vivo.
3. Recognize the challenges of scalability and cost in personalized ex vivo gene therapy approaches, and how optimizing HSC biology ex vivo can help overcome them.