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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 culture process going from heart biopsy, explants, cardiospheres, and finally CSCs. (b) Phase contrast images of cells at various stages of the culture process. Scale = 100 μm.
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fig1: (a) Outline of the culture process going from heart biopsy, explants, cardiospheres, and finally CSCs. (b) Phase contrast images of cells at various stages of the culture process. Scale = 100 μm.

Mentions: Microscopic analysis (Figure 1(a)) and flow cytometry (Figure 1(b)) confirmed the morphology and phenotype of cardiosphere-derived CSCs [2, 23, 24]. In order to confirm that the isolated particles were exosomes and not other cellular secretions such as microvesicles or apoptotic bodies, we examined both the size and expression of constitutive exosomal markers. The isolated particles expressed exosomal marker CD63 (Figure 2(a)). The size observed under the microscope appears larger than expected; this can be attributed to exosome clumping or due to the size of exosomes being less than the lateral resolution of the microscope. NTA confirmed the size of exosomes (less than 200 nm) (Figures 2(b) and 2(c)), confirming that they are indeed exosomes. Due to the ultrafiltration method used for exosome purification, there may be contamination with proteins over 100 kDa in size, though even other methods of isolation such as ultracentrifugation or polymer precipitation result in protein contamination as well [25]. When DiI-labeled exosomes were added to media for NRCMs, they were readily absorbed by the cells (Figure 3). The uptake of CSC-XO by cardiomyocytes warrants the potential to use them for therapeutic regeneration in DCM.


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 culture process going from heart biopsy, explants, cardiospheres, and finally CSCs. (b) Phase contrast images of cells at various stages of the culture process. Scale = 100 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: (a) Outline of the culture process going from heart biopsy, explants, cardiospheres, and finally CSCs. (b) Phase contrast images of cells at various stages of the culture process. Scale = 100 μm.
Mentions: Microscopic analysis (Figure 1(a)) and flow cytometry (Figure 1(b)) confirmed the morphology and phenotype of cardiosphere-derived CSCs [2, 23, 24]. In order to confirm that the isolated particles were exosomes and not other cellular secretions such as microvesicles or apoptotic bodies, we examined both the size and expression of constitutive exosomal markers. The isolated particles expressed exosomal marker CD63 (Figure 2(a)). The size observed under the microscope appears larger than expected; this can be attributed to exosome clumping or due to the size of exosomes being less than the lateral resolution of the microscope. NTA confirmed the size of exosomes (less than 200 nm) (Figures 2(b) and 2(c)), confirming that they are indeed exosomes. Due to the ultrafiltration method used for exosome purification, there may be contamination with proteins over 100 kDa in size, though even other methods of isolation such as ultracentrifugation or polymer precipitation result in protein contamination as well [25]. When DiI-labeled exosomes were added to media for NRCMs, they were readily absorbed by the cells (Figure 3). The uptake of CSC-XO by cardiomyocytes warrants the potential to use them for therapeutic regeneration in DCM.

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