Limits...
Intravenous Cardiac Stem Cell-Derived Exosomes Ameliorate Cardiac Dysfunction in Doxorubicin Induced Dilated Cardiomyopathy.

Vandergriff AC, de Andrade JB, Tang J, Hensley MT, Piedrahita JA, Caranasos TG, Cheng K - Stem Cells Int (2015)

Bottom Line: CSC-derived exosomes (CSC-XOs) have been shown to be responsible for a large portion of the regenerative effects of CSCs.Mice receiving CSC-XOs showed improved heart function via echocardiography, as well as decreased apoptosis and fibrosis.The use of CSC-XOs holds promise for overcoming the limitations of stem cells and improving cardiac therapies.

View Article: PubMed Central - PubMed

Affiliation: Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27695, USA ; Joint Department of Biomedical Engineering, UNC-Chapel Hill and NC State University, Chapel Hill and Raleigh, NC, USA.

ABSTRACT
Despite the efficacy of cardiac stem cells (CSCs) for treatment of cardiomyopathies, there are many limitations to stem cell therapies. CSC-derived exosomes (CSC-XOs) have been shown to be responsible for a large portion of the regenerative effects of CSCs. Using a mouse model of doxorubicin induced dilated cardiomyopathy, we study the effects of systemic delivery of human CSC-XOs in mice. Mice receiving CSC-XOs showed improved heart function via echocardiography, as well as decreased apoptosis and fibrosis. In spite of using immunocompetent mice and human CSC-XOs, mice showed no adverse immune reaction. The use of CSC-XOs holds promise for overcoming the limitations of stem cells and improving cardiac therapies.

No MeSH data available.


Related in: MedlinePlus

Comparison of TUNEL staining of specimens receiving saline (a) or CSC-XO (b). Counting total amount of TUNELPos cells in each field of view indicates a significant drop in apoptotic cells (c).
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4553317&req=5

fig5: Comparison of TUNEL staining of specimens receiving saline (a) or CSC-XO (b). Counting total amount of TUNELPos cells in each field of view indicates a significant drop in apoptotic cells (c).

Mentions: In order to verify that disease-modifying changes were occurring at the cellular level, we performed histological analyses of the heart sections. hCSC-XOs have been shown to carry miRNAs (22, 24, 146, and 210) that decrease fibrosis by inhibiting TGF-β signaling pathways [15] and reduce apoptosis [16]. Detection of apoptosis was carried out with TUNEL, which showed a significant reduction in the CSC-XO treated hearts (Figure 5). Subsequently, we examined cellular proliferation through Ki67. In both groups there were numerous Ki67Pos cells (~23/HPF), yet there was no significant difference between the groups (Figure 6), indicating CSC-XO did not promote cardiomyocyte cycling. DCM does induce large amounts of fibrotic growth in the heart, which reduced contractility and function. Masson's Trichrome staining revealed that CSC-XO treatment decreases cardiac fibrosis (Figure 7). Previous studies have shown that CSC-XO is enriched with a variety of microRNAs which could have inhibited the apoptosis and fibrosis pathways in the post-MI heart.


Intravenous Cardiac Stem Cell-Derived Exosomes Ameliorate Cardiac Dysfunction in Doxorubicin Induced Dilated Cardiomyopathy.

Vandergriff AC, de Andrade JB, Tang J, Hensley MT, Piedrahita JA, Caranasos TG, Cheng K - Stem Cells Int (2015)

Comparison of TUNEL staining of specimens receiving saline (a) or CSC-XO (b). Counting total amount of TUNELPos cells in each field of view indicates a significant drop in apoptotic cells (c).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4553317&req=5

fig5: Comparison of TUNEL staining of specimens receiving saline (a) or CSC-XO (b). Counting total amount of TUNELPos cells in each field of view indicates a significant drop in apoptotic cells (c).
Mentions: In order to verify that disease-modifying changes were occurring at the cellular level, we performed histological analyses of the heart sections. hCSC-XOs have been shown to carry miRNAs (22, 24, 146, and 210) that decrease fibrosis by inhibiting TGF-β signaling pathways [15] and reduce apoptosis [16]. Detection of apoptosis was carried out with TUNEL, which showed a significant reduction in the CSC-XO treated hearts (Figure 5). Subsequently, we examined cellular proliferation through Ki67. In both groups there were numerous Ki67Pos cells (~23/HPF), yet there was no significant difference between the groups (Figure 6), indicating CSC-XO did not promote cardiomyocyte cycling. DCM does induce large amounts of fibrotic growth in the heart, which reduced contractility and function. Masson's Trichrome staining revealed that CSC-XO treatment decreases cardiac fibrosis (Figure 7). Previous studies have shown that CSC-XO is enriched with a variety of microRNAs which could have inhibited the apoptosis and fibrosis pathways in the post-MI heart.

Bottom Line: CSC-derived exosomes (CSC-XOs) have been shown to be responsible for a large portion of the regenerative effects of CSCs.Mice receiving CSC-XOs showed improved heart function via echocardiography, as well as decreased apoptosis and fibrosis.The use of CSC-XOs holds promise for overcoming the limitations of stem cells and improving cardiac therapies.

View Article: PubMed Central - PubMed

Affiliation: Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27695, USA ; Joint Department of Biomedical Engineering, UNC-Chapel Hill and NC State University, Chapel Hill and Raleigh, NC, USA.

ABSTRACT
Despite the efficacy of cardiac stem cells (CSCs) for treatment of cardiomyopathies, there are many limitations to stem cell therapies. CSC-derived exosomes (CSC-XOs) have been shown to be responsible for a large portion of the regenerative effects of CSCs. Using a mouse model of doxorubicin induced dilated cardiomyopathy, we study the effects of systemic delivery of human CSC-XOs in mice. Mice receiving CSC-XOs showed improved heart function via echocardiography, as well as decreased apoptosis and fibrosis. In spite of using immunocompetent mice and human CSC-XOs, mice showed no adverse immune reaction. The use of CSC-XOs holds promise for overcoming the limitations of stem cells and improving cardiac therapies.

No MeSH data available.


Related in: MedlinePlus