(W1123) A novel form of Angiopoietin 1 as a priming agent to enhance the therapeutic efficacy of mobilized human peripheral blood stem cells in treating ischemic cardiovascular disease

Abstract: Ischemic diseases lead to necrosis and dysfunction of the organ, while current treatment
options have limited efficacy to induce tissue regeneration. Autologous cell therapy has
shown potential to augment tissue recovery, but its therapeutic efficacy still needs further
improvement, and its safety should be guaranteed before clinical application. Here, we
evaluated the efficacy of using Angiopoietin-1 (Ang1)-primed human peripheral blood stem
cells (mobPBSC) for cell therapy in ischemic diseases. Also, we established a priming strategy
which can be applied to the clinic for patients diagnosed with myocardial infarction. First, we
developed a stable form of Ang1 by genetic engineering, named FVA3-Ang1. FVA3-Ang1
priming conditions were tested on human umbilical vein endothelial cells, showing that a 1-
hour priming at 400ng/mL could induce maximal angiogenesis potential. Genetic ontology
analysis of 1-hour primed FVA3-Ang1 mobPBSC revealed no significant change in gene
expression, while the CD31 and CXCR4 protein expression increased. This implied that 1-
hour priming did not modify the cell characteristics, however could augment the angiogenic
potential of FVA3-Ang1 primed mobPBSC. In a mouse hind-limb ischemia model and a
myocardial infarction model, injection of FVA3-Ang1 primed mobPBSC to the infarcted area
showed superior engraftment and tissue regeneration compared to non-primed mobPBSC
injection. As to evaluate the efficacy and safety of FVA3-Ang1 primed mobPBSC in human
patients diagnosed as acute myocardial infarction, we are conducting a clinical trial which
will treat those patients with FVA3-Ang1 primed mobPBSC injected into the culprit coronary
artery after standard care.

Funding Source: This research was supported by the Bio & Medical Technology Development Program of the NRF& funded by the Korean government (MSIT) (No. RS-2022-NR067329)

Clinical Trial ID number: MAGIC cell-6 trial, NCT06364150