Cardiac-derived stem cell engineered with constitutively active HIF-1a gene enhances blood perfusion of hindlimb ischemia

• Published in: Journal of industrial and engineering chemistry (Seoul, Korea) pp. 210 - 221
• Main Authors: Xing Pei, Jiyoung Shin, 김희정, Nana Wang, Chaewon Seo, Miyun Yoon, Xiongwen Chen, Jianqing Gao, Victor C. Yang, Huining He, Seungjin Lee
• Format: Journal Article
• Language: English
• Published: 한국공업화학회 01.01.2022
• Subjects: 화학공학
• ISSN: 1226-086X; 1876-794X

Stem cell-based therapeutic approach provides a possible treatment for critical limb ischemia (CLI) byinducing revascularization and regenerating ischemic tissue. However, the clinical benefit is modestdue to low cell survival and limited efficacy after transplantation. Cardiac-derived stem cells (CSCs) mightbe a novel cell source for CLI treatment owing to their superb endothelial differentiation potential andangiogenic paracrine functions. In this study, the angiogenic ability of CSCs was maximized by geneticengineering with constitutively active form of hypoxia-inducible factor-1a (CA-HIF-1a), resistant tooxygen-dependent degradation. CSCs transfected with CA-HIF-1a (CA-HIF-CSCs) promoted supplementaryexpression of proangiogenic factors including VEGF, bFGF, Ang-1 and PDGF-B, along with enhancedangiogenic function including migratory effect, tube formation and endothelial differentiation potential. In the mouse CLI model, CA-HIF-CSCs transplanted into the ischemic region using fibrin gel as cell deliveryvehicle, improved blood perfusion and limb functional recovery with minimal incidence of foot necrosisand limb loss by promoting new vessel formation. Histological evidence further confirmed that CAHIF-CSC/gel treatment markedly alleviated muscle degeneration and fibrosis. CSCs genetically engineeredwith constitutively active HIF-1a provide a novel therapeutic modality in CLI combining stem cell andgene therapy. KCI Citation Count: 0