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 language | English |
|---|---|
| Pages (from-to) | 231-239 |
| Number of pages | 9 |
| Journal | Journal of Molecular and Cellular Cardiology |
| Volume | 74 |
| DOIs | |
| Publication status | Published - 2014 |
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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 journal › Article
}
TY - JOUR
T1 - Enhanced potency of cell-based therapy for ischemic tissue repair using an injectable bioactive epitope presenting nanofiber support matrix
AU - Tongers, Jörn
AU - Webber, Matthew J.
AU - Vaughan, Erin E.
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
PY - 2014
Y1 - 2014
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.
AB - 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.
KW - Angiogenesis
KW - Biomaterials
KW - Cell therapy
KW - Microcirculation
KW - Nanomedicine
KW - Regenerative medicine
UR - http://www.scopus.com/inward/record.url?scp=84904726425&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84904726425&partnerID=8YFLogxK
U2 - 10.1016/j.yjmcc.2014.05.017
DO - 10.1016/j.yjmcc.2014.05.017
M3 - Article
C2 - 25009075
AN - SCOPUS:84904726425
VL - 74
SP - 231
EP - 239
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
SN - 0022-2828
ER -