Enhanced potency of cell-based therapy for ischemic tissue repair using an injectable bioactive epitope presenting nanofiber support matrix

Jörn Tongers, Matthew J. Webber, Erin E. Vaughan, Eduard Sleep, Marie Ange Renault, Jerome G. Roncalli, Ekaterina Klyachko, Tina Thorne, Yang Yu, Katja Theres Marquardt, Christine E. Kamide, Aiko Ito, Sol Misener, Meredith Millay, Ting Liu, Kentaro Jujo, Gangjian Qin, Douglas W. Losordo, Samuel I Stupp, Raj Kishore

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The translation of cell-based therapies for ischemic tissue repair remains limited by several factors, including poor cell survival and limited target site retention. Advances in nanotechnology enable the development of specifically designed delivery matrices to address these limitations and thereby improve the efficacy of cell-based therapies. Given the relevance of integrin signaling for cellular homeostasis, we developed an injectable, bioactive peptide-based nanofiber matrix that presents an integrin-binding epitope derived from fibronectin, and evaluated its feasibility as a supportive artificial matrix for bone marrow-derived pro-angiogenic cells (BMPACs) used as a therapy in ischemic tissue repair. Incubation of BMPACs with these peptide nanofibers in vitro significantly attenuated apoptosis while enhancing proliferation and adhesion. Pro-angiogenic function was enhanced, as cells readily formed tubes. These effects were, in part, mediated via p38, and p44/p42 MAP kinases, which are downstream pathways of focal adhesion kinase. In a murine model of hind limb ischemia, an intramuscular injection of BMPACs within this bioactive peptide nanofiber matrix resulted in greater retention of cells, enhanced capillary density, increased limb perfusion, reduced necrosis/amputation, and preserved function of the ischemic limb compared to treatment with cells alone. This self-assembling, bioactive peptide nanofiber matrix presenting an integrin-binding domain of fibronectin improves regenerative efficacy of cell-based strategies in ischemic tissue by enhancing cell survival, retention, and reparative functions.

Original languageEnglish
Pages (from-to)231-239
Number of pages9
JournalJournal of Molecular and Cellular Cardiology
Volume74
DOIs
Publication statusPublished - 2014

Fingerprint

Nanofibers
Cell- and Tissue-Based Therapy
Epitopes
Injections
Integrins
Peptides
Extremities
Bone Marrow
Fibronectins
Cell Survival
Focal Adhesion Protein-Tyrosine Kinases
Nanotechnology
Mitogen-Activated Protein Kinase 1
Intramuscular Injections
Amputation
Homeostasis
Necrosis
Ischemia
Perfusion
Apoptosis

Keywords

  • Angiogenesis
  • Biomaterials
  • Cell therapy
  • Microcirculation
  • Nanomedicine
  • Regenerative medicine

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine
  • Medicine(all)

Cite this

Enhanced potency of cell-based therapy for ischemic tissue repair using an injectable bioactive epitope presenting nanofiber support matrix. / Tongers, Jörn; Webber, Matthew J.; Vaughan, Erin E.; Sleep, Eduard; Renault, Marie Ange; Roncalli, Jerome G.; Klyachko, Ekaterina; Thorne, Tina; Yu, Yang; Marquardt, Katja Theres; Kamide, Christine E.; Ito, Aiko; Misener, Sol; Millay, Meredith; Liu, Ting; Jujo, Kentaro; Qin, Gangjian; Losordo, Douglas W.; Stupp, Samuel I; Kishore, Raj.

In: Journal of Molecular and Cellular Cardiology, Vol. 74, 2014, p. 231-239.

Research output: Contribution to journalArticle

Tongers, J, Webber, MJ, Vaughan, EE, Sleep, E, Renault, MA, Roncalli, JG, Klyachko, E, Thorne, T, Yu, Y, Marquardt, KT, Kamide, CE, Ito, A, Misener, S, Millay, M, Liu, T, Jujo, K, Qin, G, Losordo, DW, Stupp, SI & Kishore, R 2014, 'Enhanced potency of cell-based therapy for ischemic tissue repair using an injectable bioactive epitope presenting nanofiber support matrix', Journal of Molecular and Cellular Cardiology, vol. 74, pp. 231-239. https://doi.org/10.1016/j.yjmcc.2014.05.017
Tongers, Jörn ; Webber, Matthew J. ; Vaughan, Erin E. ; Sleep, Eduard ; Renault, Marie Ange ; Roncalli, Jerome G. ; Klyachko, Ekaterina ; Thorne, Tina ; Yu, Yang ; Marquardt, Katja Theres ; Kamide, Christine E. ; Ito, Aiko ; Misener, Sol ; Millay, Meredith ; Liu, Ting ; Jujo, Kentaro ; Qin, Gangjian ; Losordo, Douglas W. ; Stupp, Samuel I ; Kishore, Raj. / Enhanced potency of cell-based therapy for ischemic tissue repair using an injectable bioactive epitope presenting nanofiber support matrix. In: Journal of Molecular and Cellular Cardiology. 2014 ; Vol. 74. pp. 231-239.
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AU - Sleep, Eduard

AU - Renault, Marie Ange

AU - Roncalli, Jerome G.

AU - Klyachko, Ekaterina

AU - Thorne, Tina

AU - Yu, Yang

AU - Marquardt, Katja Theres

AU - Kamide, Christine E.

AU - Ito, Aiko

AU - Misener, Sol

AU - Millay, Meredith

AU - Liu, Ting

AU - Jujo, Kentaro

AU - Qin, Gangjian

AU - Losordo, Douglas W.

AU - Stupp, Samuel I

AU - Kishore, Raj

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N2 - The translation of cell-based therapies for ischemic tissue repair remains limited by several factors, including poor cell survival and limited target site retention. Advances in nanotechnology enable the development of specifically designed delivery matrices to address these limitations and thereby improve the efficacy of cell-based therapies. Given the relevance of integrin signaling for cellular homeostasis, we developed an injectable, bioactive peptide-based nanofiber matrix that presents an integrin-binding epitope derived from fibronectin, and evaluated its feasibility as a supportive artificial matrix for bone marrow-derived pro-angiogenic cells (BMPACs) used as a therapy in ischemic tissue repair. Incubation of BMPACs with these peptide nanofibers in vitro significantly attenuated apoptosis while enhancing proliferation and adhesion. Pro-angiogenic function was enhanced, as cells readily formed tubes. These effects were, in part, mediated via p38, and p44/p42 MAP kinases, which are downstream pathways of focal adhesion kinase. In a murine model of hind limb ischemia, an intramuscular injection of BMPACs within this bioactive peptide nanofiber matrix resulted in greater retention of cells, enhanced capillary density, increased limb perfusion, reduced necrosis/amputation, and preserved function of the ischemic limb compared to treatment with cells alone. This self-assembling, bioactive peptide nanofiber matrix presenting an integrin-binding domain of fibronectin improves regenerative efficacy of cell-based strategies in ischemic tissue by enhancing cell survival, retention, and reparative functions.

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