Kai WANG, PhD | Peking University; Xi WANG, PhD; Weijing KONG, PhD candidate; Zihang PAN, PhD candidate
Competition Sponsor: Chinese Academy of Medical Sciences
Awardee Year: 2024
Ischemic diseases, caused by blood vessel occlusion or disrupted hemodynamics, result in tissue ischemia, hypoxia, and cell death. These conditions are a leading global cause of mortality, significantly affecting health, life expectancy, and healthcare systems. While coronary intervention and bypass surgeries offer treatment for ischemic heart disease, critical lower limb ischemia, especially diabetic foot ulcers, lacks effective therapies, necessitating advanced research. Recent advancements highlight the therapeutic potential of stem cell-derived endothelial cells, mesenchymal stem cells, and organoids. Organoids, as 3D multicellular assemblies, mimic organ structures and functions, offering promising avenues for disease modeling and regenerative treatments. Vascular organoids, in particular, show potential for ischemic disease treatment, though challenges like differentiation efficiency, immune rejection, and engraftment remain.
Our research focuses on refining differentiation protocols for vascular organoids to enhance angiogenesis and clinical applicability. Leveraging transcription factors ETV2 and NKX3.1, we have developed efficient methods to differentiate pluripotent stem cells into vascular endothelial and smooth muscle cells. Using small molecules and growth factors in a 3D bioreactor, we have successfully created vascular organoids capable of forming perfusable networks in vitro and in vivo. This project aims to optimize these organoids and apply them to treat acute myocardial ischemia and critical lower limb ischemia, paving the way for clinical translation and innovative ischemic disease therapies.