Hyaluronic Acid Facilitates Angiogenesis of Endothelial Colony Forming Cell Combining With Mesenchymal Stem Cell via CD44/ MicroRNA-139-5p Pathway

• Published in: Frontiers in bioengineering and biotechnology Vol. 10; p. 794037
• Main Authors: Luo, Yufang, Liang, Fang, Wan, Xinxing, Liu, Shengping, Fu, Lanfang, Mo, Jiake, Meng, Xubiao, Mo, Zhaohui
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 08.03.2022
• Subjects: angiogenesis; Bioengineering and Biotechnology; CD44; endothelial colony-forming cells; hyaluronic acid; mesenchymal stem cells; miR-139-5p; endothelial colony-forming cells; angiogenesis; mesenchymal stem cells; CD44; miR-139-5p; hyaluronic acid
• ISSN: 2296-4185; 2296-4185
• DOI: 10.3389/fbioe.2022.794037

Stem cells and progenitor cells have been identified as potential new therapeutic options for severe limb ischemia to induce angiogenesis, and hyaluronic acid (HA) is commonly applied as a biomaterial in tissue engineering. However, the efficiency of HA combined with human umbilical cord blood-derived endothelial colony forming cells (ECFCs) and human umbilical-derived mesenchymal stem cells (MSCs) on angiogenesis is unclear. In the present study, we showed that HA promoted angiogenesis induced by MSCs-ECFCs in Matrigel plugs and promoted blood perfusion of murine ischemic muscles. Laser confocal microscopy revealed that human-derived cells grew into the host vasculature and formed connections, as shown by mouse-specific CD31 /human-specific CD31 double staining. assays revealed that HA supported cell proliferation and migration, enhanced CD44 expression and reduced microRNA (miR)-139-5p expression. Further analysis revealed that miR-139-5p expression was negatively regulated by CD44 in ECFCs. Flow cytometry assays showed that HA increased CD31 positive cells proportion in MSC-ECFC and could be reversed by miR-139-5p mimics transfection. Moreover, the improvement of MSC-ECFC proliferation and migration induced by HA could be blocked by upregulation of miR-139-5p expression. In conclusion, HA facilitates angiogenesis of MSCs-ECFCs, and this positive effect be associated with activation of the CD44/miR-139-5p pathway, providing a promising strategy for improving severe limb ischemia.