Our laboratory is dedicated to understanding the earliest stages of human hematopoietic stem cell (HSC) development, particularly how these powerful stem cells emerge from the haemogenic endothelium of a specific region of the human embryo. We have successfully modelled this developmental process in vitro using human induced pluripotent stem cells (iPSCs), generating CD34+ hematopoietic stem and progenitor cells (iHSCs) that closely resemble their in vivo counterparts. A major focus of our work is to understand the molecular pathways and environmental cues. To track and optimize these processes, we utilize reporter iPSC lines, allowing real-time visualization of HSC emergence and behaviour during differentiation.
Impact
The insights gained from our research have therapeutic implications for treating blood disorders such as leukaemia, bone marrow failure, and other hematologic diseases where blood production is compromised. By developing robust methods to generate transplantable, patient-specific iHSCs in vitro, we could form the basis of an autologous cell therapy to benefit patients with a range of haematologic diseases requiring HSC transplantation, who might lack an optimally matched donor. Our ability to produce functional HSCs that engraft and self-renew in vivo opens the door to innovative cell-based treatments, offering new hope for patients who lack suitable donors. Ultimately, this work brings us a step closer to transforming the treatment landscape for a wide range of blood diseases.
Image description
The rounded, defined balls shown are called swirler embryoid bodies (SwBs), created using a reporter cell line that expresses mCherry during endothelial development. Within these SwBs, the red and orange regions indicate areas where endothelium is beginning to emerge. The small surrounding cell clusters that’s broken off from the SwBs represent blood cells that have formed from this developing endothelium.
Credits
Hasindu Edirisinghe, Research Assistant, Ritika Saxena, Research Assistant, Elefanty and Ng lab, reNEW Melbourne.
