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Exosomes in mesenchymal stem cells, a new therapeutic strategy for cardiovascular diseases?

Huang L, Ma W, Ma Y, Feng D, Chen H, Cai B - Int. J. Biol. Sci. (2015)

Bottom Line: Notably, recent studies uncovered that MSCs were able to secret cholesterol-rich, phospholipid exosomes which were enriched with microRNAs (miRNAs).The released exosomes from MSCs acted on hearts and vessels, and then exerted anti-apoptosis, cardiac regeneration, anti-cardiac remodeling, anti-inflammatory effects, neovascularization and anti-vascular remodeling, which are considered as novel molecular mechanisms of therapeutic potential of MSCs transplantation.Here we summarized recent advances about the role of exosomes in MSCs therapy for CVDs, and discussed exosomes as a novel approach in the treatment of CVDs in the future.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Harbin Medical University (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin 150081, China.

ABSTRACT
Cardiovascular diseases (CVDs) are still a major cause of people deaths worldwide, and mesenchymal stem cells (MSCs) transplantation holds great promise due to its capacity to differentiate into cardiovascular cells and secrete protective cytokines, which presents an important mechanism of MSCs therapy for CVDs. Although the capability of MSCs to differentiate into cardiomyocytes (CMCs), endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) has been well recognized in massive previous experiments both in vitro and in vivo, low survival rate of transplanted MSCs in recipient hearts suggests that therapeutic effects of MSCs transplantation might be also correlated with other underlying mechanisms. Notably, recent studies uncovered that MSCs were able to secret cholesterol-rich, phospholipid exosomes which were enriched with microRNAs (miRNAs). The released exosomes from MSCs acted on hearts and vessels, and then exerted anti-apoptosis, cardiac regeneration, anti-cardiac remodeling, anti-inflammatory effects, neovascularization and anti-vascular remodeling, which are considered as novel molecular mechanisms of therapeutic potential of MSCs transplantation. Here we summarized recent advances about the role of exosomes in MSCs therapy for CVDs, and discussed exosomes as a novel approach in the treatment of CVDs in the future.

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Exosomes mediates beneficial effects of MSCs on hearts. MSCs secret exosomes containing miR-22 and miR-221 to target Mecp2 and PUMA, and thus exert anti-apoptotic effects. Anti-inflammatory effect of MSCs is mediated by exosomes as well as MVs. Exosomes are also responsible for anti-cardiac remodeling of MSCs. Cardiac regeneration property of MSCs has been proved, but whether exosomes are involved in this process remains unclear.
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Figure 2: Exosomes mediates beneficial effects of MSCs on hearts. MSCs secret exosomes containing miR-22 and miR-221 to target Mecp2 and PUMA, and thus exert anti-apoptotic effects. Anti-inflammatory effect of MSCs is mediated by exosomes as well as MVs. Exosomes are also responsible for anti-cardiac remodeling of MSCs. Cardiac regeneration property of MSCs has been proved, but whether exosomes are involved in this process remains unclear.

Mentions: Recent study has reported that MSCs had ability to ameliorate ischemic CMCs injury by transferring miR-22 in exosomes targeting methyl CpG binding protein 2 (Mecp2) to reduce apoptosis 52 (Fig. 2). Moreover, delivery of miR-221 in exosomes mediated anti-apoptotic effect of MSCs by inhibiting p53-upregulated modulator of apoptosis (PUMA), a subclass of the Bcl-2 protein family 49. PUMA was shown to interplay with BCL-xL and p53 53, and activate pro-apoptotic proteins while restrain anti-apoptotic proteins, so inhibition of PUMA by miR-221 could give rise to CMCs survival 49. These findings suggest that miRNAs-bearing exosomes are involving in anti-apoptotic process.


Exosomes in mesenchymal stem cells, a new therapeutic strategy for cardiovascular diseases?

Huang L, Ma W, Ma Y, Feng D, Chen H, Cai B - Int. J. Biol. Sci. (2015)

Exosomes mediates beneficial effects of MSCs on hearts. MSCs secret exosomes containing miR-22 and miR-221 to target Mecp2 and PUMA, and thus exert anti-apoptotic effects. Anti-inflammatory effect of MSCs is mediated by exosomes as well as MVs. Exosomes are also responsible for anti-cardiac remodeling of MSCs. Cardiac regeneration property of MSCs has been proved, but whether exosomes are involved in this process remains unclear.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4308409&req=5

Figure 2: Exosomes mediates beneficial effects of MSCs on hearts. MSCs secret exosomes containing miR-22 and miR-221 to target Mecp2 and PUMA, and thus exert anti-apoptotic effects. Anti-inflammatory effect of MSCs is mediated by exosomes as well as MVs. Exosomes are also responsible for anti-cardiac remodeling of MSCs. Cardiac regeneration property of MSCs has been proved, but whether exosomes are involved in this process remains unclear.
Mentions: Recent study has reported that MSCs had ability to ameliorate ischemic CMCs injury by transferring miR-22 in exosomes targeting methyl CpG binding protein 2 (Mecp2) to reduce apoptosis 52 (Fig. 2). Moreover, delivery of miR-221 in exosomes mediated anti-apoptotic effect of MSCs by inhibiting p53-upregulated modulator of apoptosis (PUMA), a subclass of the Bcl-2 protein family 49. PUMA was shown to interplay with BCL-xL and p53 53, and activate pro-apoptotic proteins while restrain anti-apoptotic proteins, so inhibition of PUMA by miR-221 could give rise to CMCs survival 49. These findings suggest that miRNAs-bearing exosomes are involving in anti-apoptotic process.

Bottom Line: Notably, recent studies uncovered that MSCs were able to secret cholesterol-rich, phospholipid exosomes which were enriched with microRNAs (miRNAs).The released exosomes from MSCs acted on hearts and vessels, and then exerted anti-apoptosis, cardiac regeneration, anti-cardiac remodeling, anti-inflammatory effects, neovascularization and anti-vascular remodeling, which are considered as novel molecular mechanisms of therapeutic potential of MSCs transplantation.Here we summarized recent advances about the role of exosomes in MSCs therapy for CVDs, and discussed exosomes as a novel approach in the treatment of CVDs in the future.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Harbin Medical University (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin 150081, China.

ABSTRACT
Cardiovascular diseases (CVDs) are still a major cause of people deaths worldwide, and mesenchymal stem cells (MSCs) transplantation holds great promise due to its capacity to differentiate into cardiovascular cells and secrete protective cytokines, which presents an important mechanism of MSCs therapy for CVDs. Although the capability of MSCs to differentiate into cardiomyocytes (CMCs), endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) has been well recognized in massive previous experiments both in vitro and in vivo, low survival rate of transplanted MSCs in recipient hearts suggests that therapeutic effects of MSCs transplantation might be also correlated with other underlying mechanisms. Notably, recent studies uncovered that MSCs were able to secret cholesterol-rich, phospholipid exosomes which were enriched with microRNAs (miRNAs). The released exosomes from MSCs acted on hearts and vessels, and then exerted anti-apoptosis, cardiac regeneration, anti-cardiac remodeling, anti-inflammatory effects, neovascularization and anti-vascular remodeling, which are considered as novel molecular mechanisms of therapeutic potential of MSCs transplantation. Here we summarized recent advances about the role of exosomes in MSCs therapy for CVDs, and discussed exosomes as a novel approach in the treatment of CVDs in the future.

Show MeSH
Related in: MedlinePlus