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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: 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.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

Histology evaluation of an ischemic heart.Notes: (A–E) H&E staining of the tissue sections obtained from the MI region among the (A) sham group, (B) control group, (C) IGF-1 release group, (D) BIO release group, and (E) BIO and IGF-1 co-delivery group. Scale bar, 100 µm.Abbreviations: BIO, 6-bromoindirubin-3-oxime; IGF-1, insulin-like growth factor 1; H&E, hematoxylin and eosin; MI, myocardial infarction.
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f4-ijn-10-4691: Histology evaluation of an ischemic heart.Notes: (A–E) H&E staining of the tissue sections obtained from the MI region among the (A) sham group, (B) control group, (C) IGF-1 release group, (D) BIO release group, and (E) BIO and IGF-1 co-delivery group. Scale bar, 100 µm.Abbreviations: BIO, 6-bromoindirubin-3-oxime; IGF-1, insulin-like growth factor 1; H&E, hematoxylin and eosin; MI, myocardial infarction.

Mentions: In order to study the mechanism underlying the advancement of cardiac function for the administration of BIO + IGF-1 in the MI rats, H&E staining was used perform a histology evaluation following injection with our hydrogel system. Cardiac remodeling was found in our experimental groups; however, when compared with the control group, more cardiomyocytes were found in the BIO + IGF-1 group (Figure 4), and the results were further confirmed by double staining with the anti-cardiac troponin-T (green; cardiomyocyte marker) and anti-PCNA (red; proliferation marker) assay. The number of proliferating cardiomyocytes in the BIO + IGF-1 group (35±5), was the most significant among all groups, and the number of proliferating cardiomyocytes in the BIO group (27±5) was also significantly higher than that of both the sham (5±2) and the control groups (15±5) (Figure 5). In the BIO delivery group, the enhanced proliferation of cardiomyocytes was observed. In the co-delivery of the BIO + IGF-1 group, both enhanced proliferation of the cardiomyocytes and function recovery were seen. Moreover, angiogenesis plays a crucial role in tissue repair and heart function after MI; therefore, the CD31 antibody-positive angiogenesis assay was detected among the different groups (Figure 6). In the BIO + IGF-1 group, the most capillaries (70±8/mm2) was observed. In addition, significant increase of blood vessels (60±7/mm2) in the IGF-1 group was also detected. However, no significant increase in blood vessel density was observed in the BIO group (43±8/mm2), which suggested that BIO could not promote angiogenesis. Enhanced angiogenesis was accompanied by functional recovery in the BIO and IGF-1 group; this indicates that angiogenesis may be an important factor in the recovery of function.


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)

Histology evaluation of an ischemic heart.Notes: (A–E) H&E staining of the tissue sections obtained from the MI region among the (A) sham group, (B) control group, (C) IGF-1 release group, (D) BIO release group, and (E) BIO and IGF-1 co-delivery group. Scale bar, 100 µm.Abbreviations: BIO, 6-bromoindirubin-3-oxime; IGF-1, insulin-like growth factor 1; H&E, hematoxylin and eosin; MI, myocardial infarction.
© Copyright Policy
Related In: Results  -  Collection

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

f4-ijn-10-4691: Histology evaluation of an ischemic heart.Notes: (A–E) H&E staining of the tissue sections obtained from the MI region among the (A) sham group, (B) control group, (C) IGF-1 release group, (D) BIO release group, and (E) BIO and IGF-1 co-delivery group. Scale bar, 100 µm.Abbreviations: BIO, 6-bromoindirubin-3-oxime; IGF-1, insulin-like growth factor 1; H&E, hematoxylin and eosin; MI, myocardial infarction.
Mentions: In order to study the mechanism underlying the advancement of cardiac function for the administration of BIO + IGF-1 in the MI rats, H&E staining was used perform a histology evaluation following injection with our hydrogel system. Cardiac remodeling was found in our experimental groups; however, when compared with the control group, more cardiomyocytes were found in the BIO + IGF-1 group (Figure 4), and the results were further confirmed by double staining with the anti-cardiac troponin-T (green; cardiomyocyte marker) and anti-PCNA (red; proliferation marker) assay. The number of proliferating cardiomyocytes in the BIO + IGF-1 group (35±5), was the most significant among all groups, and the number of proliferating cardiomyocytes in the BIO group (27±5) was also significantly higher than that of both the sham (5±2) and the control groups (15±5) (Figure 5). In the BIO delivery group, the enhanced proliferation of cardiomyocytes was observed. In the co-delivery of the BIO + IGF-1 group, both enhanced proliferation of the cardiomyocytes and function recovery were seen. Moreover, angiogenesis plays a crucial role in tissue repair and heart function after MI; therefore, the CD31 antibody-positive angiogenesis assay was detected among the different groups (Figure 6). In the BIO + IGF-1 group, the most capillaries (70±8/mm2) was observed. In addition, significant increase of blood vessels (60±7/mm2) in the IGF-1 group was also detected. However, no significant increase in blood vessel density was observed in the BIO group (43±8/mm2), which suggested that BIO could not promote angiogenesis. Enhanced angiogenesis was accompanied by functional recovery in the BIO and IGF-1 group; this indicates that angiogenesis may be an important factor in the recovery of function.

Bottom Line: 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.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