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Treatment with hESC-Derived Myocardial Precursors Improves Cardiac Function after a Myocardial Infarction.

Ye J, Gaur M, Zhang Y, Sievers RE, Woods BJ, Aurigui J, Bernstein HS, Yeghiazarians Y - PLoS ONE (2015)

Bottom Line: The GFP+/αMHC+ cells derived from this cell line behave as multipotent, human myocardial precursors (hMPs) in vitro.Infarct size, angiogenesis, apoptosis, cell fate, and teratoma formation were analyzed by immunohistochemical staining.Intramyocardial injection of hMPs improved cardiac function post-MI.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, 94143, United States of America.

ABSTRACT

Background: We previously reported the generation of a reporter line of human embryonic stem cells (hESCs) with enhanced green fluorescent protein (eGFP) expression driven by the α-myosin heavy chain (αMHC) promoter. The GFP+/αMHC+ cells derived from this cell line behave as multipotent, human myocardial precursors (hMPs) in vitro. In this study, we evaluated the therapeutic effects of GFP+/αMHC+ cells isolated from the reporter line in a mouse model of myocardial infarction (MI).

Methods: MI was generated in immunodeficient mice. hMPs were injected into murine infarcted hearts under ultrasound guidance at 3 days post-MI. Human fetal skin fibroblasts (hFFs) were injected as control. Cardiac function was evaluated by echocardiography. Infarct size, angiogenesis, apoptosis, cell fate, and teratoma formation were analyzed by immunohistochemical staining.

Results: Compared with control, hMPs resulted in improvement of cardiac function post-MI with smaller infarct size, induced endogenous angiogenesis, and reduced apoptosis of host cardiomyocytes at the peri-infarct zone at 28 days post-MI.

Conclusion: Intramyocardial injection of hMPs improved cardiac function post-MI. The engraftment rate of these cells in the myocardium post-MI was low, suggesting that the majority of effect occurs via paracrine mechanisms.

No MeSH data available.


Related in: MedlinePlus

Schematic representation of experiment design.MI: myocardial infarction; Echo: echocardiography; Histo: histological.
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pone.0131123.g001: Schematic representation of experiment design.MI: myocardial infarction; Echo: echocardiography; Histo: histological.

Mentions: LVEF was uniformly and significantly reduced from about 50.7% in both groups before MI to 35.9% (hMPs group) and 36.2% (hFFs group) at 2 days post-MI (P<0.0001), with no significant differences between two groups (Figs 1 and 2A). At 28 days post-MI, LVEF was improved significantly with injection of hMPs (39.3±2.7%), while LVEF continued to decline with injection of hFFs (30.7±4.1%) and the resultant LVEF of hMPs-injected group was significantly higher than that of hFFs-injected group (P<0.0001, Figs 1 and 2A). At 28 days post-MI, there was also less LV dilatation in the hMP-injected group (ESV: 40.4±5.2 μl; EDV: 66.4±6.4 μl) compared with the hFF-injected group (ESV: 52.3±10.1 μl, P = 0.005; EDV: 74.9±10.6 μl, P = 0.05, Fig 2B and 2C). Furthermore, there was significantly less wall thinning of the LV PZ in the hMP-injected group (0.53±0.07mm) compared with the hFF-injected group (0.45±0.07mm, p = 0.03, Fig 2D). The hMP-injected hearts also showed significantly smaller infarct size (12.44±8.29% of LV) compared to the hearts injected with hFFs (27.82±3.96% of LV) at 28 days post-MI (P = 0.012; Figs 1 and 3).


Treatment with hESC-Derived Myocardial Precursors Improves Cardiac Function after a Myocardial Infarction.

Ye J, Gaur M, Zhang Y, Sievers RE, Woods BJ, Aurigui J, Bernstein HS, Yeghiazarians Y - PLoS ONE (2015)

Schematic representation of experiment design.MI: myocardial infarction; Echo: echocardiography; Histo: histological.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4521814&req=5

pone.0131123.g001: Schematic representation of experiment design.MI: myocardial infarction; Echo: echocardiography; Histo: histological.
Mentions: LVEF was uniformly and significantly reduced from about 50.7% in both groups before MI to 35.9% (hMPs group) and 36.2% (hFFs group) at 2 days post-MI (P<0.0001), with no significant differences between two groups (Figs 1 and 2A). At 28 days post-MI, LVEF was improved significantly with injection of hMPs (39.3±2.7%), while LVEF continued to decline with injection of hFFs (30.7±4.1%) and the resultant LVEF of hMPs-injected group was significantly higher than that of hFFs-injected group (P<0.0001, Figs 1 and 2A). At 28 days post-MI, there was also less LV dilatation in the hMP-injected group (ESV: 40.4±5.2 μl; EDV: 66.4±6.4 μl) compared with the hFF-injected group (ESV: 52.3±10.1 μl, P = 0.005; EDV: 74.9±10.6 μl, P = 0.05, Fig 2B and 2C). Furthermore, there was significantly less wall thinning of the LV PZ in the hMP-injected group (0.53±0.07mm) compared with the hFF-injected group (0.45±0.07mm, p = 0.03, Fig 2D). The hMP-injected hearts also showed significantly smaller infarct size (12.44±8.29% of LV) compared to the hearts injected with hFFs (27.82±3.96% of LV) at 28 days post-MI (P = 0.012; Figs 1 and 3).

Bottom Line: The GFP+/αMHC+ cells derived from this cell line behave as multipotent, human myocardial precursors (hMPs) in vitro.Infarct size, angiogenesis, apoptosis, cell fate, and teratoma formation were analyzed by immunohistochemical staining.Intramyocardial injection of hMPs improved cardiac function post-MI.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, 94143, United States of America.

ABSTRACT

Background: We previously reported the generation of a reporter line of human embryonic stem cells (hESCs) with enhanced green fluorescent protein (eGFP) expression driven by the α-myosin heavy chain (αMHC) promoter. The GFP+/αMHC+ cells derived from this cell line behave as multipotent, human myocardial precursors (hMPs) in vitro. In this study, we evaluated the therapeutic effects of GFP+/αMHC+ cells isolated from the reporter line in a mouse model of myocardial infarction (MI).

Methods: MI was generated in immunodeficient mice. hMPs were injected into murine infarcted hearts under ultrasound guidance at 3 days post-MI. Human fetal skin fibroblasts (hFFs) were injected as control. Cardiac function was evaluated by echocardiography. Infarct size, angiogenesis, apoptosis, cell fate, and teratoma formation were analyzed by immunohistochemical staining.

Results: Compared with control, hMPs resulted in improvement of cardiac function post-MI with smaller infarct size, induced endogenous angiogenesis, and reduced apoptosis of host cardiomyocytes at the peri-infarct zone at 28 days post-MI.

Conclusion: Intramyocardial injection of hMPs improved cardiac function post-MI. The engraftment rate of these cells in the myocardium post-MI was low, suggesting that the majority of effect occurs via paracrine mechanisms.

No MeSH data available.


Related in: MedlinePlus