PMID- 32194175
OWN - NLM
STAT- MEDLINE
DCOM- 20210617
LR  - 20210617
IS  - 1873-4995 (Electronic)
IS  - 0168-3659 (Linking)
VI  - 322
DP  - 2020 Jun 10
TI  - Local delivery of cardiac stem cells overexpressing HIF-1alpha promotes angiogenesis 
      and muscular tissue repair in a hind limb ischemia model.
PG  - 610-621
LID - S0168-3659(20)30169-3 [pii]
LID - 10.1016/j.jconrel.2020.03.017 [doi]
AB  - 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-1alpha) by using 
      electroporation method, specifically optimized for CSCs yielding 45.77% of 
      transfection efficiency and 89.75% of viability. HIF-1alpha 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-1alpha (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.
CI  - Copyright (c) 2020. Published by Elsevier B.V.
FAU - Pei, Xing
AU  - Pei X
AD  - Tianjin Key Laboratory on Technologies Enabling Development of Clinical 
      Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, 
      Tianjin 300070, PR China.
FAU - Kim, Heejung
AU  - Kim H
AD  - Department of Pharmacy, College of Pharmacy, Ewha Womans University, Seoul 13760, 
      Republic of Korea.
FAU - Lee, Minjoo
AU  - Lee M
AD  - Department of Pharmacy, College of Pharmacy, Ewha Womans University, Seoul 13760, 
      Republic of Korea.
FAU - Wang, Nana
AU  - Wang N
AD  - Tianjin Key Laboratory on Technologies Enabling Development of Clinical 
      Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, 
      Tianjin 300070, PR China.
FAU - Shin, Jiyoung
AU  - Shin J
AD  - Department of Pharmacy, College of Pharmacy, Ewha Womans University, Seoul 13760, 
      Republic of Korea.
FAU - Lee, Seungjin
AU  - Lee S
AD  - Department of Pharmacy, College of Pharmacy, Ewha Womans University, Seoul 13760, 
      Republic of Korea. Electronic address: sjlee@ewha.ac.kr.
FAU - Yoon, Miyun
AU  - Yoon M
AD  - Department of cosmetology, Dongam Health University, Gyeonggi-do 16328, Republic 
      of Korea.
FAU - Yang, Victor C
AU  - Yang VC
AD  - Tianjin Key Laboratory on Technologies Enabling Development of Clinical 
      Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, 
      Tianjin 300070, PR China; Department of Pharmaceutical Sciences, College of 
      Pharmacy, University of Michigan, Ann Arbor, MI 48109-1065, USA.
FAU - He, Huining
AU  - He H
AD  - Tianjin Key Laboratory on Technologies Enabling Development of Clinical 
      Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, 
      Tianjin 300070, PR China. Electronic address: hehuining@tmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200316
PL  - Netherlands
TA  - J Control Release
JT  - Journal of controlled release : official journal of the Controlled Release 
      Society
JID - 8607908
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics
MH  - Ischemia/therapy
MH  - *Mesenchymal Stem Cells
MH  - Mice
MH  - Neovascularization, Pathologic
MH  - Neovascularization, Physiologic
MH  - *Peripheral Arterial Disease/therapy
OTO - NOTNLM
OT  - Cardiac stem cells
OT  - Electroporation-mediated gene transfection
OT  - Hind limb ischemia
OT  - Hypoxia-inducible factor-1 alpha
OT  - Therapeutic angiogenesis
COIS- Declaration of Competing Interest The authors declared no conflicts of interest 
      in this article.
EDAT- 2020/03/21 06:00
MHDA- 2021/06/22 06:00
CRDT- 2020/03/21 06:00
PHST- 2019/12/03 00:00 [received]
PHST- 2020/02/23 00:00 [revised]
PHST- 2020/03/13 00:00 [accepted]
PHST- 2020/03/21 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/03/21 06:00 [entrez]
AID - S0168-3659(20)30169-3 [pii]
AID - 10.1016/j.jconrel.2020.03.017 [doi]
PST - ppublish
SO  - J Control Release. 2020 Jun 10;322:610-621. doi: 10.1016/j.jconrel.2020.03.017. 
      Epub 2020 Mar 16.