Abstract
Control over cell engraftment, survival, and function remains critical for heart repair. We have established a tissue engineering platform for the delivery of human mesenchymal progenitor cells (MPCs) by a fully biological composite scaffold. Specifically, we developed a method for complete decellularization of human myocardium that leaves intact most elements of the extracellular matrix, as well as the underlying mechanical properties. A cell-matrix composite was constructed by applying fibrin hydrogel with suspended cells onto decellularized sheets of human myocardium. We then implanted this composite onto the infarct bed in a nude rat model of cardiac infarction. We next characterized the myogenic and vasculogenic potential of immunoselected human MPCs and demonstrated that in vitro conditioning with a low concentration of TGF-β promoted an arteriogenic profile of gene expression. When implanted by composite scaffold, preconditioned MPCs greatly enhanced vascular network formation in the infarct bed by mechanisms involving the secretion of paracrine factors, such as SDF-1, and the migration of MPCs into ischemic myocardium, but not normal myocardium. Echocardiography demonstrated the recovery of baseline levels of left ventricular systolic dimensions and contractility when MPCs were delivered via composite scaffold. This adaptable platform could be readily extended to the delivery of other reparative cells of interest and used in quantitative studies of heart repair.
| Original language | English |
|---|---|
| Pages (from-to) | 7974-7979 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 108 |
| Issue number | 19 |
| DOIs | |
| State | Published - May 10 2011 |
| Externally published | Yes |
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Keywords
- Biomaterial
- Cardiac patch
- Cardiac repair
- Human stem cell
ASJC Scopus subject areas
- General
Cite this
Composite scaffold provides a cell delivery platform for cardiovascular repair. / Godier-Furnémont, Amandine F G; Martens, Timothy P.; Koeckert, Michael S.; Wan, Leo; Parks, Jonathan; Arai, Kotaro; Zhang, Geping; Hudson, Barry; Homma, Shunichi; Vunjak-Novakovic, Gordana.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 19, 10.05.2011, p. 7974-7979.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Composite scaffold provides a cell delivery platform for cardiovascular repair
AU - Godier-Furnémont, Amandine F G
AU - Martens, Timothy P.
AU - Koeckert, Michael S.
AU - Wan, Leo
AU - Parks, Jonathan
AU - Arai, Kotaro
AU - Zhang, Geping
AU - Hudson, Barry
AU - Homma, Shunichi
AU - Vunjak-Novakovic, Gordana
PY - 2011/5/10
Y1 - 2011/5/10
N2 - Control over cell engraftment, survival, and function remains critical for heart repair. We have established a tissue engineering platform for the delivery of human mesenchymal progenitor cells (MPCs) by a fully biological composite scaffold. Specifically, we developed a method for complete decellularization of human myocardium that leaves intact most elements of the extracellular matrix, as well as the underlying mechanical properties. A cell-matrix composite was constructed by applying fibrin hydrogel with suspended cells onto decellularized sheets of human myocardium. We then implanted this composite onto the infarct bed in a nude rat model of cardiac infarction. We next characterized the myogenic and vasculogenic potential of immunoselected human MPCs and demonstrated that in vitro conditioning with a low concentration of TGF-β promoted an arteriogenic profile of gene expression. When implanted by composite scaffold, preconditioned MPCs greatly enhanced vascular network formation in the infarct bed by mechanisms involving the secretion of paracrine factors, such as SDF-1, and the migration of MPCs into ischemic myocardium, but not normal myocardium. Echocardiography demonstrated the recovery of baseline levels of left ventricular systolic dimensions and contractility when MPCs were delivered via composite scaffold. This adaptable platform could be readily extended to the delivery of other reparative cells of interest and used in quantitative studies of heart repair.
AB - Control over cell engraftment, survival, and function remains critical for heart repair. We have established a tissue engineering platform for the delivery of human mesenchymal progenitor cells (MPCs) by a fully biological composite scaffold. Specifically, we developed a method for complete decellularization of human myocardium that leaves intact most elements of the extracellular matrix, as well as the underlying mechanical properties. A cell-matrix composite was constructed by applying fibrin hydrogel with suspended cells onto decellularized sheets of human myocardium. We then implanted this composite onto the infarct bed in a nude rat model of cardiac infarction. We next characterized the myogenic and vasculogenic potential of immunoselected human MPCs and demonstrated that in vitro conditioning with a low concentration of TGF-β promoted an arteriogenic profile of gene expression. When implanted by composite scaffold, preconditioned MPCs greatly enhanced vascular network formation in the infarct bed by mechanisms involving the secretion of paracrine factors, such as SDF-1, and the migration of MPCs into ischemic myocardium, but not normal myocardium. Echocardiography demonstrated the recovery of baseline levels of left ventricular systolic dimensions and contractility when MPCs were delivered via composite scaffold. This adaptable platform could be readily extended to the delivery of other reparative cells of interest and used in quantitative studies of heart repair.
KW - Biomaterial
KW - Cardiac patch
KW - Cardiac repair
KW - Human stem cell
UR - http://www.scopus.com/inward/record.url?scp=79956371111&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79956371111&partnerID=8YFLogxK
U2 - 10.1073/pnas.1104619108
DO - 10.1073/pnas.1104619108
M3 - Article
C2 - 21508321
AN - SCOPUS:79956371111
VL - 108
SP - 7974
EP - 7979
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 19
ER -