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Image-guided stem cells with functionalized self-assembling peptide nanofibers for treatment of acute myocardial infarction in a mouse model

文献作者:Xiao Li, Ying-Ying Chen, Xiu-Mei Wang, Kai Gao, Yun-Zhou Gao, Jian Cao, Zhuo-Li Zhang, Jing Lei, Zheng-Yu Jin, and Yi-Ning Wang   《American Journal of Translational Research》


ABSTRACTS
Aim: To investigate the survival of bone marrow mesenchymal stem cells (BMSCs) and the therapeutic effect for acute myocardial infarction (AMI) after co-transplantation with the functionalized self-assembling peptide nanofiber RAD/PRG or RAD/KLT. Methods: AMI of balb/c mice was induced. Mice were randomly divided into four groups, and received treatment of phosphate buffered saline (PBS) (Group A), GFP/Fluc-BMSCs (Group B), GFP/Fluc-BMSCs + RAD/PRG (Group C), and GFP/Fluc-BMSCs + RAD/KLT (Group D), respectively. Bioluminescence imaging (BLI) was performed on day 1 (d-1), d-4, d-7, d-10, and d-13 after transplantation. Magnetic resonance imaging (MRI) was performed at baseline (d-4 before transplantation) and d-29 after treatment. Mice were euthanized on d-29 following treatment. Paraffin sections were obtained from the top, mid and bottom part of the infarcted region along the long-axis of the heart. Hematoxylin and eosin (HE) staining and immunohistochemical staining were performed. The infarct ratio micro-vascular density (MVD) was quantified. Results: There was a significant higher of BLI signal intensity of BMSCs in Group C than that in Group B (d-4, 9713±320 vs. 8164±378, P=0.0008; d-7, 6489±241 vs. 5417±361, P=0.0026; d-10, 3768±255 vs. 0, P < 0.0001). The left ventricular ejection fraction (LVEF) via MRI examination was significantly improved in both Group C and Group D. Infarct ratio and MVD were significantly improved in both Group C and Group D. Conclusion: Our data highlights BMSCs combining functionalized self-assembling peptide nanofibers RAD/PRG or RAD/KLT as promising therapy for AMI.
KEY WORDS
Stem cell therapy, functionalized self-assembling peptide nanofibers, molecular imaging, acute myocardial infarction
SCREENSHOT

RELATED PRODUCTS
The self-assembling peptide RADA16-I (Ac-(RADA) 4 -CONH 2 ), functionalized peptide PRG (Ac-(RADA) 4 GPRGDSGYRGDS-CONH 2 ) and KLT (Ac-(RADA) 4 G 4 KLTWQELYQLKYKGI- CONH 2 ) were synthesized by China Peptides (Shanghai, China).
CHAINING
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5575186/

The self-assembling peptide RADA16-I
Ac-(RADA)4-CONH2
Ac-RADARADARADARADA-NH2
Number of Residues:16
1-Letter Code:Ac-RADARADARADARADA-NH2
3-Letter Code:Ac-Arg-Ala-Asp-Ala-Arg-Ala-Asp-Ala-Arg-Ala-Asp-Ala-Arg-Ala-Asp-Ala-NH2

Molecular weight (Mr):1712.8 g/mol
Isoelectric point:6.2
Net charge at pH 7.0:0.0
Average hydrophilicity:1.3
Ratio of hydrophilic residues / total number of residues:50 %




functionalized peptide PRG
Ac-(RADA)4GPRGDSGYRGDS-CONH2
Ac-RADARADARADARADAGPRGDSGYRGDS-NH2
Number of Residues:28
1-Letter Code:Ac-RADARADARADARADAGPRGDSGYRGDS-NH2
3-Letter Code:Ac-Arg-Ala-Asp-Ala-Arg-Ala-Asp-Ala-Arg-Ala-Asp-Ala-Arg-Ala-Asp-Ala-Gly-Pro-Arg-Gly-Asp-Ser-Gly-Tyr-Arg-Gly-Asp-Ser-NH2

Molecular weight (Mr):2918.01 g/mol
Isoelectric point:6.2
Net charge at pH 7.0:0.0
Average hydrophilicity:1.1
Ratio of hydrophilic residues / total number of residues:50 %


KLT
Ac-(RADA)4G4KLTWQELYQLKYKGI-CONH2
Ac-RADARADARADARADAGGGGKLTWQELYQLKYKGI-NH2
Number of Residues:35
1-Letter Code:Ac-RADARADARADARADAGGGGKLTWQELYQLKYKGI-NH2
3-Letter Code:Ac-Arg-Ala-Asp-Ala-Arg-Ala-Asp-Ala-Arg-Ala-Asp-Ala-Arg-Ala-Asp-Ala-Gly-Gly-Gly-Gly-Lys-Leu-Thr-Trp-Gln-Glu-Leu-Tyr-Gln-Leu-Lys-Tyr-Lys-Gly-Ile-NH2

Molecular weight (Mr):3834.27 g/mol
Isoelectric point:10.2
Net charge at pH 7.0:2.0
Average hydrophilicity:0.5
Ratio of hydrophilic residues / total number of residues:40 %

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