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Engineered M13 Nanofiber Accelerates Ischemic Neovascularization by Enhancing Endothelial Progenitor Cells

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Tissue Engineering and Regenerative Medicine Aims and scope

A Correction to this article was published on 19 January 2018

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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 EPC-based 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 by mutilayering SDKP motifs, which are the key active sites for thymosin β4, on the major 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 the M13 nanofiber-based novel peptide delivery and priming strategy in promoting EPC bioactivity and neovessel regeneration. To our knowledge, this is first report on M13 nanofibers harboring dual functional motifs, the use of which might be a novel strategy for stem and progenitor cell therapy against cardiovascular ischemic diseases.

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  • 19 January 2018

    There is a minor spelling error in the last of name of the 9th author in the originally published article.

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Acknowledgements

This work was supported by a grant from the National Research Foundation (NRF-2015M3A9B4051053, NRF-2015R1A5A2009656, NRF-2014R1A1A2056907), Korean Health Technology R&D Project, Ministry of Health and Welfare (HI13C1256, HI14C1863) funded by the Korean government, and the [2015 Post-Doc. Development Program] of Pusan National University.

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Author notes

  1. Jun Hee Lee and Sung Wook Kim have contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacology and Toxicology, University of Alabama at Birmingham School of Medicine, Birmingham, AL, 35294, USA

    Jun Hee Lee

  2. Laboratory 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

    Sung Wook Kim, Seung Taek Ji, Yeon Ju Kim, Woong Bi Jang & Sang-Mo Kwon

  3. Department of Nanoenergy Engineering, Pusan National University, 2, Busandaehak-ro 63beon-gil, Geumjeong-gu, Busan, 46241, Republic of Korea

    Jin-Woo Oh

  4. Research Institute of Convergence Biomedical Science and Technology, Pusan National University School of Medicine, 49, Busandaehak-ro, Mulgeum-eup, Yangsan, 50612, Republic of Korea

    Jaeho Kim & Sang-Mo Kwon

  5. Immunoregulatory Therapeutics Group in Brain Busan 21 Project, Pusan National University, 49, Busandaehak-ro, Mulgeum-eup, Yangsan, 50612, Republic of Korea

    Sang-Mo Kwon

  6. BIO-IT Foundry Technology Institute, Pusan National University, 2, Busandaehak-ro 63beon-gil, Geumjeong-gu, Busan, 46241, Republic of Korea

    So Young Yoo

  7. Laboratory of Cardiovascular Disease, Division of Cardiology, School of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea

    Sang Hong Beak

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  1. Jun Hee Lee
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  2. Sung Wook Kim
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  8. So Young Yoo
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  9. Sang Hong Beak
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Correspondence to Sang Hong Beak or Sang-Mo Kwon.

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Ethical statement

This study including all surgical interventions and postoperative animal care was approved by the Institutional Review Board of the Pusan National University Yangsan Hospital, Republic of Korea (Approval No. PNUH-2012-19).

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A correction to this article is available online at https://doi.org/10.1007/s13770-017-0109-3.

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Lee, J.H., Kim, S.W., Ji, S.T. et al. Engineered M13 Nanofiber Accelerates Ischemic Neovascularization by Enhancing Endothelial Progenitor Cells. Tissue Eng Regen Med 14, 787–802 (2017). https://doi.org/10.1007/s13770-017-0074-x

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