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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

Injected hMPs can be detected in recipient mouse hearts at 14 days post-MI.The surviving injected cells expressed human cardiac Troponin I (hTnI, A, B) and green fluorescence protein (GFP, C, D) in the peri-infarct zone (PZ, n = 4). Nuclei were stained with DAPI (A, B).
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pone.0131123.g004: Injected hMPs can be detected in recipient mouse hearts at 14 days post-MI.The surviving injected cells expressed human cardiac Troponin I (hTnI, A, B) and green fluorescence protein (GFP, C, D) in the peri-infarct zone (PZ, n = 4). Nuclei were stained with DAPI (A, B).

Mentions: Previous studies including ours[5] have shown very low engraftment rates for hESC-derived CMs. As such, we investigated the fate of implanted hMPs at early (14 days post-MI) and late (28 days post-MI) time points. Immunohistochemical evaluation of tissue sections both at the injection sites and throughout the recipient hearts showed few retained human cTnI+ (n = 4, Fig 4A and 4B) or GFP+ cells (n = 4, Fig 4C and 4D) at 14 days post-MI and none at 28 days (n = 4, data not shown).


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)

Injected hMPs can be detected in recipient mouse hearts at 14 days post-MI.The surviving injected cells expressed human cardiac Troponin I (hTnI, A, B) and green fluorescence protein (GFP, C, D) in the peri-infarct zone (PZ, n = 4). Nuclei were stained with DAPI (A, B).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131123.g004: Injected hMPs can be detected in recipient mouse hearts at 14 days post-MI.The surviving injected cells expressed human cardiac Troponin I (hTnI, A, B) and green fluorescence protein (GFP, C, D) in the peri-infarct zone (PZ, n = 4). Nuclei were stained with DAPI (A, B).
Mentions: Previous studies including ours[5] have shown very low engraftment rates for hESC-derived CMs. As such, we investigated the fate of implanted hMPs at early (14 days post-MI) and late (28 days post-MI) time points. Immunohistochemical evaluation of tissue sections both at the injection sites and throughout the recipient hearts showed few retained human cTnI+ (n = 4, Fig 4A and 4B) or GFP+ cells (n = 4, Fig 4C and 4D) at 14 days post-MI and none at 28 days (n = 4, data not shown).

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