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Sustained co-delivery of BIO and IGF-1 by a novel hybrid hydrogel system to stimulate endogenous cardiac repair in myocardial infarcted rat hearts.

Fang R, Qiao S, Liu Y, Meng Q, Chen X, Song B, Hou X, Tian W - Int J Nanomedicine (2015)

Bottom Line: However, their delivery for sustained release in MI-affected areas has proved to be challenging.The in vivo results indicated that the hybrid system could enhance the proliferation of cardiomyocytes in situ and could promote revascularization around the MI sites, allowing improved cardiac function.Taken together, we concluded that the hybrid hydrogel system can co-deliver BIO and IGF-1 to areas of MI and thus improve cardiac function by promoting the proliferation of cardiomyocytes and revascularization.

View Article: PubMed Central - PubMed

Affiliation: Bio-X Center, School of Life Science and Technology, Harbin Institute of Technology, Harbin, People's Republic of China ; Division of Biomedical Engineering, University of Saskatchewan, Saskatoon, SK, Canada.

ABSTRACT
Dedifferentiation and proliferation of endogenous cardiomyocytes in situ can effectively improve cardiac repair following myocardial infarction (MI). 6-Bromoindirubin-3-oxime (BIO) and insulin-like growth factor 1 (IGF-1) are two potent factors that promote cardiomyocyte survival and proliferation. However, their delivery for sustained release in MI-affected areas has proved to be challenging. In the current research, we present a study on the sustained co-delivery of BIO and IGF-1 in a hybrid hydrogel system to simulate endogenous cardiac repair in an MI rat model. Both BIO and IGF-1 were efficiently encapsulated in gelatin nanoparticles, which were later cross-linked with the oxidized alginate to form a novel hybrid hydrogel system. The in vivo results indicated that the hybrid system could enhance the proliferation of cardiomyocytes in situ and could promote revascularization around the MI sites, allowing improved cardiac function. Taken together, we concluded that the hybrid hydrogel system can co-deliver BIO and IGF-1 to areas of MI and thus improve cardiac function by promoting the proliferation of cardiomyocytes and revascularization.

No MeSH data available.


Related in: MedlinePlus

Effect of the hydrogen delivery system on the proliferation of 3D culture cardiomyocytes.Notes: Scheme showing the strategy used to detect the enhanced proliferation of 3D-cultured cardiomyocytes. Laser confocal images showing the PCNA-positive stained cells in the (A) BgNP group, (B) FgNP group, and (C) OgNP group. (D) Statistical analysis of the number of PCNA-positive cells (n=6). **P<0.01 versus the BgNP group.Abbreviations: BIO, 6-bromoindirubin-3-oxime; 3D, three dimensional; PCNA, proliferating cell nuclear antigen; NP, nanoparticle; BgNP, blank gelatin nanoparticle; OgNP, BIO-loaded gelatin nanoparticle; IGF-1, insulin-like growth factor 1; FgNP, IGF-1-loaded gelatin nanoparticle.
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f3-ijn-10-4691: Effect of the hydrogen delivery system on the proliferation of 3D culture cardiomyocytes.Notes: Scheme showing the strategy used to detect the enhanced proliferation of 3D-cultured cardiomyocytes. Laser confocal images showing the PCNA-positive stained cells in the (A) BgNP group, (B) FgNP group, and (C) OgNP group. (D) Statistical analysis of the number of PCNA-positive cells (n=6). **P<0.01 versus the BgNP group.Abbreviations: BIO, 6-bromoindirubin-3-oxime; 3D, three dimensional; PCNA, proliferating cell nuclear antigen; NP, nanoparticle; BgNP, blank gelatin nanoparticle; OgNP, BIO-loaded gelatin nanoparticle; IGF-1, insulin-like growth factor 1; FgNP, IGF-1-loaded gelatin nanoparticle.

Mentions: To mimic the in vivo effect of the drug delivery system among cardiac cells, a three-dimensional (3D) system was used to encapsulate the cardiomyocytes in hydrogel in the present study. The results showed that the percentage of proliferated cardiomyocytes in the BIO release system (15%±4%) was significantly higher than that in the control groups (7%±3%; P<0.05); however, no significant difference was observed in the IGF-1 release group (11%±2%), as shown by the laser confocal images (Figure 3A–C) and the statistical analyses (Figure 3D). Therefore, IGF-1 could not induce the proliferation of cardiomyocytes.


Sustained co-delivery of BIO and IGF-1 by a novel hybrid hydrogel system to stimulate endogenous cardiac repair in myocardial infarcted rat hearts.

Fang R, Qiao S, Liu Y, Meng Q, Chen X, Song B, Hou X, Tian W - Int J Nanomedicine (2015)

Effect of the hydrogen delivery system on the proliferation of 3D culture cardiomyocytes.Notes: Scheme showing the strategy used to detect the enhanced proliferation of 3D-cultured cardiomyocytes. Laser confocal images showing the PCNA-positive stained cells in the (A) BgNP group, (B) FgNP group, and (C) OgNP group. (D) Statistical analysis of the number of PCNA-positive cells (n=6). **P<0.01 versus the BgNP group.Abbreviations: BIO, 6-bromoindirubin-3-oxime; 3D, three dimensional; PCNA, proliferating cell nuclear antigen; NP, nanoparticle; BgNP, blank gelatin nanoparticle; OgNP, BIO-loaded gelatin nanoparticle; IGF-1, insulin-like growth factor 1; FgNP, IGF-1-loaded gelatin nanoparticle.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4524466&req=5

f3-ijn-10-4691: Effect of the hydrogen delivery system on the proliferation of 3D culture cardiomyocytes.Notes: Scheme showing the strategy used to detect the enhanced proliferation of 3D-cultured cardiomyocytes. Laser confocal images showing the PCNA-positive stained cells in the (A) BgNP group, (B) FgNP group, and (C) OgNP group. (D) Statistical analysis of the number of PCNA-positive cells (n=6). **P<0.01 versus the BgNP group.Abbreviations: BIO, 6-bromoindirubin-3-oxime; 3D, three dimensional; PCNA, proliferating cell nuclear antigen; NP, nanoparticle; BgNP, blank gelatin nanoparticle; OgNP, BIO-loaded gelatin nanoparticle; IGF-1, insulin-like growth factor 1; FgNP, IGF-1-loaded gelatin nanoparticle.
Mentions: To mimic the in vivo effect of the drug delivery system among cardiac cells, a three-dimensional (3D) system was used to encapsulate the cardiomyocytes in hydrogel in the present study. The results showed that the percentage of proliferated cardiomyocytes in the BIO release system (15%±4%) was significantly higher than that in the control groups (7%±3%; P<0.05); however, no significant difference was observed in the IGF-1 release group (11%±2%), as shown by the laser confocal images (Figure 3A–C) and the statistical analyses (Figure 3D). Therefore, IGF-1 could not induce the proliferation of cardiomyocytes.

Bottom Line: However, their delivery for sustained release in MI-affected areas has proved to be challenging.The in vivo results indicated that the hybrid system could enhance the proliferation of cardiomyocytes in situ and could promote revascularization around the MI sites, allowing improved cardiac function.Taken together, we concluded that the hybrid hydrogel system can co-deliver BIO and IGF-1 to areas of MI and thus improve cardiac function by promoting the proliferation of cardiomyocytes and revascularization.

View Article: PubMed Central - PubMed

Affiliation: Bio-X Center, School of Life Science and Technology, Harbin Institute of Technology, Harbin, People's Republic of China ; Division of Biomedical Engineering, University of Saskatchewan, Saskatoon, SK, Canada.

ABSTRACT
Dedifferentiation and proliferation of endogenous cardiomyocytes in situ can effectively improve cardiac repair following myocardial infarction (MI). 6-Bromoindirubin-3-oxime (BIO) and insulin-like growth factor 1 (IGF-1) are two potent factors that promote cardiomyocyte survival and proliferation. However, their delivery for sustained release in MI-affected areas has proved to be challenging. In the current research, we present a study on the sustained co-delivery of BIO and IGF-1 in a hybrid hydrogel system to simulate endogenous cardiac repair in an MI rat model. Both BIO and IGF-1 were efficiently encapsulated in gelatin nanoparticles, which were later cross-linked with the oxidized alginate to form a novel hybrid hydrogel system. The in vivo results indicated that the hybrid system could enhance the proliferation of cardiomyocytes in situ and could promote revascularization around the MI sites, allowing improved cardiac function. Taken together, we concluded that the hybrid hydrogel system can co-deliver BIO and IGF-1 to areas of MI and thus improve cardiac function by promoting the proliferation of cardiomyocytes and revascularization.

No MeSH data available.


Related in: MedlinePlus