Local delivery of cardiac stem cells overexpressing HIF-1 alpha promotes angiogenesis and muscular tissue repair in a hind limb ischemia model
- 주제(키워드) Cardiac stem cells , Hypoxia-inducible factor-1 alpha , Electroporation-mediated gene transfection , Therapeutic angiogenesis , Hind limb ischemia
- 주제(기타) Chemistry, Multidisciplinary
- 주제(기타) Pharmacology & Pharmacy
- 설명문(일반) [Pei, Xing; Wang, Nana; Yang, Victor C.; He, Huining] Tianjin Med Univ, Sch Pharm, Tianjin Key Lab Technol Enabling Dev Clin Therape, Tianjin 300070, Peoples R China; [Kim, Heejung; Lee, Minjoo; Shin, Jiyoung; Lee, Seungjin] Ewha Womans Univ, Coll Pharm, Dept Pharm, Seoul 13760, South Korea; [Yoon, Miyun] Dongam Hlth Univ, Dept Cosmetol, Gyeonggi Do 16328, South Korea; [Yang, Victor C.] Univ Michigan, Coll Pharm, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USA
- 등재 SCIE, SCOPUS
- 발행기관 ELSEVIER
- 발행년도 2020
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000168880
- 본문언어 영어
- Published As https://dx.doi.org/10.1016/j.jconrel.2020.03.017
- PubMed https://pubmed.ncbi.nlm.nih.gov/32194175
초록/요약
Critical limb ischemia (CLI) is the most advanced stage of peripheral artery disease, associated with significant risk of limb loss, morbidity and mortality; however, there remains unmet therapeutic needs for arterial revascularization and ischemic tissue repair. Stem cell therapies have emerged as compelling candidates due to beneficial proangiogenic and immunosuppressive function. Nevertheless, in vivo efficacy was insufficient in proliferation, differentiation and survival/engraftment rate. Cardiac stem cells (CSCs) was firstly attempted for CLI as a novel therapeutic modality to provide superior angiogenic potency to bone marrow-derived stem cells (BMSCs). It was noted that CSCs demonstrated 3.2-fold in HGF, 2.9-fold in VEGF and 8.7-fold in PDGF-B higher gene expressions compared to BMSCs. To enhance the hypoxia-induced proangiogenic effect, CSCs were transfected with hypoxia-inducible factor-1 alpha (HIF-1 alpha) by using electroporation method, specifically optimized for CSCs yielding 45.77% of transfection efficiency and 89.75% of viability. HIF-1 alpha overexpression significantly increased CSC survival in hypoxia, proangiogenic factors production and endothelial differentiation. In mouse hind limb ischemia model, local intramuscular delivery of CSC overexpressing HIF-1 alpha (HIF-CSC) significantly improved the blood flow recovery. Histological analysis revealed that muscle degeneration and fibrosis in the ischemic limb were attenuated. Local delivery of HIF-CSC might be a promising option for ischemic tissue restoration.
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