The role of endothelial colony forming cells in the treatment of limb ischaemia: challenges in clinical translation

Endothelial colony forming cells (ECFCs) are emerging as a promising therapeutic option for treating various vascular and degenerative disorders. These cells, also known as endothelial progenitor cells, which play a crucial role in angiogenesis, may be a promising therapeutic in the management of chronic limb-threatening ischaemia (CLTI). CLTI requires the regeneration of surrounding niche cells through vascular repair, which is often compromised by oxygen and nutrient deprivation. ECFCs have been extensively studied for their unique endothelial properties and their capacity for vascular repair. Numerous preclinical studies have been initiated to explore the safety and efficacy of ECFCs in treating CLTI. However, translating ECFC based therapies into clinical practice faces significant challenges, and there has been very limited translation to therapeutic studies in humans. Chief among these challenges is the inherent heterogeneity within ECFC populations, shaped by factors such as donor characteristics, tissue origin, and underlying health conditions. Despite this challenge, in vivo studies in animal models have laid the groundwork for potential clinical translation of ECFCs. These studies underscore the successful application of ECFCs in vascular repair and regeneration, emphasizing the specific parameters used in in vivo studies that contribute to a broader understanding of ECFCs and paving the way for their future clinical use. This report will review the current status of preclinical studies of the use of ECFCs in limb ischaemia and the challenges associated with human translation.