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Controlled intramyocardial release of engineered chemokines by biodegradable hydrogels as a treatment approach of myocardial infarction.

Projahn D, Simsekyilmaz S, Singh S, Kanzler I, Kramp BK, Langer M, Burlacu A, Bernhagen J, Klee D, Zernecke A, Hackeng TM, Groll J, Weber C, Liehn EA, Koenen RR - J. Cell. Mol. Med. (2014)

Bottom Line: Two different biodegradable hydrogels were implemented, a fast degradable hydrogel (FDH) for delivering Met-CCL5 over 24 hrs and a slow degradable hydrogel (SDH) for a gradual release of protease-resistant CXCL12 (S4V) over 4 weeks.Thus, we were able to significantly preserve the cardiac function after MI.This study demonstrates that time-controlled, biopolymer-mediated delivery of chemokines represents a novel and feasible strategy to support the endogenous reparatory mechanisms after MI and may compliment cell-based therapies.

View Article: PubMed Central - PubMed

Affiliation: Institute for Molecular Cardiovascular Research (IMCAR), Medical Faculty, RWTH Aachen University, Aachen, Germany; Institute for Cardiovascular Prevention (IPEK), University Hospital of the LMU Munich, Munich, Germany.

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Assessment of neutrophil infiltration after experimental myocardial infarction (MI). Neutrophil infiltration in the myocardium 1 day after MI by esterase-staining (A) and quantification (B) and MPO-staining (C) and -quantification (D) of fast degradable hydrogel slow degradable hydrogel (FDH SDH), Met-CCL5-FDH, CXCL12 (S4V)-FDH and Met-CCL5-FDH+CXCL12 (S4V)-FDH-treated mice (n = 6–9 per group). Insets in (A) and (B) show negative control staining; scale bars: 50 μm. Depicted P values are based on non-parametric anova (n ≥ 6).
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fig03: Assessment of neutrophil infiltration after experimental myocardial infarction (MI). Neutrophil infiltration in the myocardium 1 day after MI by esterase-staining (A) and quantification (B) and MPO-staining (C) and -quantification (D) of fast degradable hydrogel slow degradable hydrogel (FDH SDH), Met-CCL5-FDH, CXCL12 (S4V)-FDH and Met-CCL5-FDH+CXCL12 (S4V)-FDH-treated mice (n = 6–9 per group). Insets in (A) and (B) show negative control staining; scale bars: 50 μm. Depicted P values are based on non-parametric anova (n ≥ 6).

Mentions: The same applied for neutrophil recruitment (Fig. 3) and neovascularization (Fig. 4). The immediate infiltration of MI-induced neutrophils in the infarcted area (1 day after MI) was reduced in both the Met-CCL5-FDH (272 ± 35.8 per mm2) and the Met-CCL5-FDH+CXCL12 (S4V)-SDH groups (299 ± 33.6 per mm2), but not in the CXCL12 (S4V)-SDH group (876 ± 235.9 per mm2), compared with the control groups that received only hydrogel (810 ± 51.3 per mm2) or PBS (760.7 ± 72.2 per mm2; Fig. 3A and B). Similar results were obtained by staining with anti-MPO antibody (Fig. 3C and D), confirming the specificity of the administration of the CCR1 and CCR5 antagonist Met-CCL5 for the prevention of neutrophil recruitment.


Controlled intramyocardial release of engineered chemokines by biodegradable hydrogels as a treatment approach of myocardial infarction.

Projahn D, Simsekyilmaz S, Singh S, Kanzler I, Kramp BK, Langer M, Burlacu A, Bernhagen J, Klee D, Zernecke A, Hackeng TM, Groll J, Weber C, Liehn EA, Koenen RR - J. Cell. Mol. Med. (2014)

Assessment of neutrophil infiltration after experimental myocardial infarction (MI). Neutrophil infiltration in the myocardium 1 day after MI by esterase-staining (A) and quantification (B) and MPO-staining (C) and -quantification (D) of fast degradable hydrogel slow degradable hydrogel (FDH SDH), Met-CCL5-FDH, CXCL12 (S4V)-FDH and Met-CCL5-FDH+CXCL12 (S4V)-FDH-treated mice (n = 6–9 per group). Insets in (A) and (B) show negative control staining; scale bars: 50 μm. Depicted P values are based on non-parametric anova (n ≥ 6).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4119385&req=5

fig03: Assessment of neutrophil infiltration after experimental myocardial infarction (MI). Neutrophil infiltration in the myocardium 1 day after MI by esterase-staining (A) and quantification (B) and MPO-staining (C) and -quantification (D) of fast degradable hydrogel slow degradable hydrogel (FDH SDH), Met-CCL5-FDH, CXCL12 (S4V)-FDH and Met-CCL5-FDH+CXCL12 (S4V)-FDH-treated mice (n = 6–9 per group). Insets in (A) and (B) show negative control staining; scale bars: 50 μm. Depicted P values are based on non-parametric anova (n ≥ 6).
Mentions: The same applied for neutrophil recruitment (Fig. 3) and neovascularization (Fig. 4). The immediate infiltration of MI-induced neutrophils in the infarcted area (1 day after MI) was reduced in both the Met-CCL5-FDH (272 ± 35.8 per mm2) and the Met-CCL5-FDH+CXCL12 (S4V)-SDH groups (299 ± 33.6 per mm2), but not in the CXCL12 (S4V)-SDH group (876 ± 235.9 per mm2), compared with the control groups that received only hydrogel (810 ± 51.3 per mm2) or PBS (760.7 ± 72.2 per mm2; Fig. 3A and B). Similar results were obtained by staining with anti-MPO antibody (Fig. 3C and D), confirming the specificity of the administration of the CCR1 and CCR5 antagonist Met-CCL5 for the prevention of neutrophil recruitment.

Bottom Line: Two different biodegradable hydrogels were implemented, a fast degradable hydrogel (FDH) for delivering Met-CCL5 over 24 hrs and a slow degradable hydrogel (SDH) for a gradual release of protease-resistant CXCL12 (S4V) over 4 weeks.Thus, we were able to significantly preserve the cardiac function after MI.This study demonstrates that time-controlled, biopolymer-mediated delivery of chemokines represents a novel and feasible strategy to support the endogenous reparatory mechanisms after MI and may compliment cell-based therapies.

View Article: PubMed Central - PubMed

Affiliation: Institute for Molecular Cardiovascular Research (IMCAR), Medical Faculty, RWTH Aachen University, Aachen, Germany; Institute for Cardiovascular Prevention (IPEK), University Hospital of the LMU Munich, Munich, Germany.

Show MeSH
Related in: MedlinePlus