화학공학소재연구정보센터
홈 로그인 로그아웃 연락처 사이트맵
Journal of Industrial and Engineering Chemistry, Vol.105, 210-221, January, 2022
DOI10.1016/j.jiec.2021.09.020  Export Citation
Cardiac-derived stem cell engineered with constitutively active HIF-1α gene enhances blood perfusion of hindlimb ischemia
Xing Pei, Jiyoung Shin1, Heejung Kim1, Nana Wang, Chaewon Seo1, Miyun Yoon2, Xiongwen Chen, Jianqing Gao3, Victor C. Yang4, Huining He†, and Seungjin Lee1
  • Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China
  • 1Department of Pharmacy, College of Pharmacy, Ewha Womans University, Seoul 03760, Republic of Korea
  • 2Department of Cosmetology, Dongnam Health University, 16328, Republic of Korea
  • 3College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
  • 4Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor Michigan 48109-1065, USA
E-mail:
Stem cell-based therapeutic approach provides a possible treatment for critical limb ischemia (CLI) by inducing revascularization and regenerating ischemic tissue. However, the clinical benefit is modest due to low cell survival and limited efficacy after transplantation. Cardiac-derived stem cells (CSCs) might be a novel cell source for CLI treatment owing to their superb endothelial differentiation potential and angiogenic paracrine functions. In this study, the angiogenic ability of CSCs was maximized by genetic engineering with constitutively active form of hypoxia-inducible factor-1α (CA-HIF-1α), resistant to oxygen-dependent degradation. CSCs transfected with CA-HIF-1α (CA-HIF-CSCs) promoted supplementary expression of proangiogenic factors including VEGF, bFGF, Ang-1 and PDGF-B, along with enhanced angiogenic 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 delivery vehicle, improved blood perfusion and limb functional recovery with minimal incidence of foot necrosis and limb loss by promoting new vessel formation. Histological evidence further confirmed that CAHIF-CSC/gel treatment markedly alleviated muscle degeneration and fibrosis. CSCs genetically engineered with constitutively active HIF-1a provide a novel therapeutic modality in CLI combining stem cell and gene therapy.
Keywords:Cardiac-derived stem cell;Constitutively active hypoxia-inducible;factor-1 α;Stem cell therapy;Fibrin;Critical ischemia
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