Tissue Eng Regen Med.  2017 Dec;14(6):787-802. 10.1007/s13770-017-0074-x.

Engineered M13 Nanofiber Accelerates Ischemic Neovascularization by Enhancing Endothelial Progenitor Cells

Affiliations
  • 1Department of Pharmacology and Toxicology, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294, USA.
  • 2Laboratory for Vascular Medicine and Stem Cell Biology, Department of Physiology, School of Medicine, Medical Research Institute, Pusan National University, 49, Busandaehak-ro, Mulgeum-eup, Yangsan 50612, Republic of Korea. smkwon323@hotmail.com
  • 3Department of Nanoenergy Engineering, Pusan National University, 2, Busandaehak-ro 63beon-gil, Geumjeong-gu, Busan 46241, Republic of Korea.
  • 4Research Institute of Convergence Biomedical Science and Technology, Pusan National University School of Medicine, 49, Busandaehak-ro, Mulgeum-eup, Yangsan 50612, Republic of Korea.
  • 5Immunoregulatory Therapeutics Group in Brain Busan 21 Project, Pusan National University, 49, Busandaehak-ro, Mulgeum-eup, Yangsan 50612, Republic of Korea.
  • 6BIO-IT Foundry Technology Institute, Pusan National University, 2, Busandaehak-ro 63beon-gil, Geumjeong-gu, Busan 46241, Republic of Korea.
  • 7Laboratory of Cardiovascular Disease, Division of Cardiology, School of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea. whitesh@catholic.ac.kr

Abstract

Dysfunction or loss of blood vessel causes several ischemic diseases. Although endothelial progenitor cells (EPCs) are a promising source for cell-based therapy, ischemia-induced pathophysiological condition limits the recovery rate by causing drastic cell death. To overcome this issue, we attempted to develop a cell-targeted peptide delivery and priming system to enhance EPCbased neovascularization using an engineered M13 bacteriophage harboring nanofibrous tubes displaying ∼ 2700 multiple functional motifs. The M13 nanofiber was modified by displaying RGD, which is an integrin-docking peptide, on the minor coat protein, and bymutilayering SDKPmotifs,which are the key active sites for thymosin b4, on themajor coat protein. The engineered M13 nanofiber dramatically enhanced ischemic neovascularization by activating intracellular and extracellular processes such as proliferation, migration, and tube formation in the EPCs. Furthermore, transplantation of the primed EPCs with the M13 nanofiber harboring RGD and SDKP facilitated functional recovery and neovascularization in a murine hindlimb ischemia model. Overall, this study demonstrates the effectiveness of theM13 nanofiber-based novel peptide deliveryandprimingstrategy inpromotingEPC bioactivity and neovessel regeneration. To our knowledge, this is first report onM13 nanofibers harboring dual functional motifs, the use of which might be a novel strategy for stem and progenitor cell therapy against cardiovascular ischemic diseases.

Keyword

M13 bacteriophage; Endothelial progenitor cell; RGD; SDKP; Neovascularization

MeSH Terms

Animals
Bacteriophages
Blood Vessels
Catalytic Domain
Cell Death
Endothelial Progenitor Cells*
Hindlimb
Ischemia
Nanofibers*
Regeneration
Stem Cells
Thymosin
Thymosin
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