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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

(a) Outline of the in vivo portion of the study. Heart function analysis showing both the (b) shortening fraction and (c) ejection fraction. Both measurements of heart function showed improvement in the CSC-XO treated groups 7 days following CSC-XO injection.
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Related In: Results  -  Collection


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fig4: (a) Outline of the in vivo portion of the study. Heart function analysis showing both the (b) shortening fraction and (c) ejection fraction. Both measurements of heart function showed improvement in the CSC-XO treated groups 7 days following CSC-XO injection.

Mentions: An acute model of doxorubicin induced DCM was used for the animal study (Figure 4(a)). Seven days after injecting mice with doxorubicin, heart function decreased significantly from the baseline measurements. The animals receiving CSC-XO treatment showed a recovery of heart function (Figures 4(b) and 4(c)) whereas the animals receiving saline injections continued with cardiac functional deterioration. In a previous study by Aminzadeh et al. [17], a similar study was carried out but with several key differences. IM transplantation of CDCs was tested in Gαq mice, which spontaneously develop DCM. Their results showed a steady albeit decreased heart function as opposed to the current study which showed a recovery of heart function to the baseline levels. In addition, IM injection is quite invasive because open-chest procedures are normally needed and thus would be difficult for clinical translation.


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)

(a) Outline of the in vivo portion of the study. Heart function analysis showing both the (b) shortening fraction and (c) ejection fraction. Both measurements of heart function showed improvement in the CSC-XO treated groups 7 days following CSC-XO injection.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: (a) Outline of the in vivo portion of the study. Heart function analysis showing both the (b) shortening fraction and (c) ejection fraction. Both measurements of heart function showed improvement in the CSC-XO treated groups 7 days following CSC-XO injection.
Mentions: An acute model of doxorubicin induced DCM was used for the animal study (Figure 4(a)). Seven days after injecting mice with doxorubicin, heart function decreased significantly from the baseline measurements. The animals receiving CSC-XO treatment showed a recovery of heart function (Figures 4(b) and 4(c)) whereas the animals receiving saline injections continued with cardiac functional deterioration. In a previous study by Aminzadeh et al. [17], a similar study was carried out but with several key differences. IM transplantation of CDCs was tested in Gαq mice, which spontaneously develop DCM. Their results showed a steady albeit decreased heart function as opposed to the current study which showed a recovery of heart function to the baseline levels. In addition, IM injection is quite invasive because open-chest procedures are normally needed and thus would be difficult for clinical translation.

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