TY - JOUR
T1 - Human embryonic stem cell-derived microvascular grafts for cardiac tissue preservation after myocardial infarction
AU - Kraehenbuehl, Thomas P.
AU - Ferreira, Lino S.
AU - Hayward, Alison M.
AU - Nahrendorf, Matthias
AU - van der Vlies, André J.
AU - Vasile, Eliza
AU - Weissleder, Ralph
AU - Langer, Robert
AU - Hubbell, Jeffrey A.
N1 - Funding Information:
This work was supported in part by NIH (grant HL060435 ), the European Union’s 6th Framework Program Expertissues, and the European Union’s 7th Framework Program Angioscaff. TPK was supported by the Swiss National Science Foundation (grant numbers 120938 and PBELP3-127902 ) and a Rotary Ambassadorial Scholarship . LSF was supported by a Marie Curie-Reintegration Grant, MIT-Portugal program, FCT ( PTDC/SAU-BEB/098468/2008 ) and Crioestaminal.
PY - 2011/2
Y1 - 2011/2
N2 - We present use of a synthetic, injectable matrix metalloproteinase (MMP)- responsive, bioactive hydrogel as an in situ forming scaffold to deliver thymosin β4 (Tβ4), a pro-angiogenic and pro-survival factor, along with vascular cells derived from human embryonic stem cells (hESC) in ischemic injuries to the heart in a rat model. The gel was found to substitute the degrading extracellular matrix in the infarcted myocardium of rats and to promote structural organization of native endothelial cells, while some of the delivered hESC-derived vascular cells formed de novo capillaries in the infarct zone. Magnetic resonance imaging (MRI) revealed that the microvascular grafts effectively preserved contractile performance 3 d and 6 wk after myocardial infarction, attenuated left ventricular dilation, and decreased infarct size as compared to infarcted rats treated with PBS injection as a control (3 d ejection fraction, + ∼7%, P < 0.001; 6 wk ejection faction, + ∼12%, P < 0.001). Elevation in vessel density was observed in response to treatment, which may be due in part to elevations in human (donor)-derived cytokines EGF, VEGF and HGF (1 d). Thus, a clinically relevant matrix for dual delivery of vascular cells and drugs may be useful in engineering sustained tissue preservation and potentially regenerating ischemic cardiac tissue.
AB - We present use of a synthetic, injectable matrix metalloproteinase (MMP)- responsive, bioactive hydrogel as an in situ forming scaffold to deliver thymosin β4 (Tβ4), a pro-angiogenic and pro-survival factor, along with vascular cells derived from human embryonic stem cells (hESC) in ischemic injuries to the heart in a rat model. The gel was found to substitute the degrading extracellular matrix in the infarcted myocardium of rats and to promote structural organization of native endothelial cells, while some of the delivered hESC-derived vascular cells formed de novo capillaries in the infarct zone. Magnetic resonance imaging (MRI) revealed that the microvascular grafts effectively preserved contractile performance 3 d and 6 wk after myocardial infarction, attenuated left ventricular dilation, and decreased infarct size as compared to infarcted rats treated with PBS injection as a control (3 d ejection fraction, + ∼7%, P < 0.001; 6 wk ejection faction, + ∼12%, P < 0.001). Elevation in vessel density was observed in response to treatment, which may be due in part to elevations in human (donor)-derived cytokines EGF, VEGF and HGF (1 d). Thus, a clinically relevant matrix for dual delivery of vascular cells and drugs may be useful in engineering sustained tissue preservation and potentially regenerating ischemic cardiac tissue.
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U2 - 10.1016/j.biomaterials.2010.10.005
DO - 10.1016/j.biomaterials.2010.10.005
M3 - Article
C2 - 21035182
AN - SCOPUS:78649446021
SN - 0142-9612
VL - 32
SP - 1102
EP - 1109
JO - Biomaterials
JF - Biomaterials
IS - 4
ER -