Timing of bone marrow cell therapy is more important than repeated injections after myocardial infarction.

Division of Cardiology, Department of Medicine, University of California-San Francisco, CA 94143-0103, USA.
Cardiovascular pathology: the official journal of the Society for Cardiovascular Pathology (Impact Factor: 1.63). 07/2011; 20(4):204-12. DOI: 10.1016/j.carpath.2010.06.007
Source: PubMed

ABSTRACT Bone marrow cell treatment has been proposed as a therapy for myocardial infarction, but the optimal timing and number of injections remain unknown.
Myocardial infarction was induced in mice followed by ultrasound-guided injection of mouse bone marrow cells at different time points post myocardial infarction (Days 3, 7, and 14) as monotherapy and at Days 3+7 as "double" therapy and at Days 3+7+14 as "triple" therapy. Controls received saline injections at Day 3 and Days 3+7+14. Left ventricular ejection fraction was evaluated post myocardial infarction prior to any therapy and at Day 28. Hearts were analyzed at Day 28 for infarct size and survival of donor cells.
Left ventricular ejection fraction decreased from 55.3±0.9% to 37.6±0.6% (P<.001) 2 days post myocardial infarction in all groups. Injection of bone marrow cells at Day 3 post myocardial infarction resulted in smaller infarct size (17.8±3.6% vs. 36.6±7.1%; P=.05) and improved LV function (left ventricular ejection fraction 40.3±2.0% vs. 31.1±8.3%; P<.05) compared to control. However, delayed therapy at Day 7 or 14 did not. Multiple injections of bone marrow cells, either double therapy or triple therapy, did not result in reduction in infarct size, but led to improvements in left ventricular ejection fraction at Day 28 compared to control (39.9±3.6% and 38.8±5.5% vs. 34.8±5.3%; all P<.05). The number of donor cells surviving at Day 28 did not correlate with improvement in left ventricular ejection fraction.
Injection of bone marrow cells at Day 3 reduced infarct size and improved left ventricular function. Multiple injections of bone marrow cells had no additive effect. Delaying cell therapy post myocardial infarction resulted in no functional benefit at all. These results will help inform future clinical trials.

1 Bookmark
  • [Show abstract] [Hide abstract]
    ABSTRACT: The ability of human pluripotent stem cells (hPSC) to differentiate into any cell type of the three germ layers makes them a very promising cell source for multiple purposes, including regenerative medicine, drug discovery, and as a model to study disease mechanisms and progression. One of the first specialized cell types to be generated from hPSC was cardiomyocytes (CM), and differentiation protocols have evolved over the years and now allow for robust and large-scale production of hPSC-CM. Still, scientists are struggling to achieve the same, mainly ventricular, phenotype of the hPSC-CM in vitro as their adult counterpart in vivo. In vitro generated cardiomyocytes are generally described as fetal-like rather than adult. In this review, we compare the in vivo development of cardiomyocytes to the in vitro differentiation of hPSC into CM with focus on electrophysiology, structure and contractility. Furthermore, known epigenetic changes underlying the differences between adult human CM and CM differentiated from pluripotent stem cells are described. This should provide the reader with an extensive overview of the current status of human stem cell-derived cardiomyocyte phenotype and function. Additionally, the reader will gain insight into the underlying signaling pathways and mechanisms responsible for cardiomyocyte development.
    Journal of Molecular and Cellular Cardiology 12/2013; · 5.15 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We investigate the extended (2+1)-dimensional shallow water wave equation. The binary Bell polynomials are used to construct bilinear equation, bilinear Bäcklund transformation, Lax pair, and Darboux covariant Lax pair for this equation. Moreover, the infinite conservation laws of this equation are found by using its Lax pair. All conserved densities and fluxes are given with explicit recursion formulas. The N-soliton solutions are also presented by means of the Hirota bilinear method.
    Chinese Physics B 05/2013; 22(5):050509. · 1.39 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Aging is associated with higher incidence of heart failure and death following myocardial infarction (MI). The molecular and cellular changes that lead to these worse outcomes are not known. Young and aging mice underwent induction of MI by LAD ligation. There was a significant increase in mortality in the aging mice. Neither the young nor aging hearts after MI had inducible ventricular tachycardia. Cardiomyocyte apoptosis increases early after MI in young and aging mice, but to a much greater degree in the aging mice. Caspase inhibition with Ac-DEVD-CHO resulted in a 61% reduction in activated caspase-3 and an 84% reduction in apoptosis in cardiomyocytes in young mice (P < 0.05), but not in aging mice. Gene pathway profiling demonstrated activation of both the caspase and Map3k1/Mapk10 pathways in aging mice following MI, which may contribute to their resistance to caspase inhibition. Aging hearts activate distinct apoptotic pathways have more cardiomyocyte apoptosis and are resistant to antiapoptotic therapies following MI. Novel or combination approaches may be required to improve outcomes in aging patients following MI.
    Cardiovascular Therapeutics 12/2013; 31(6):e102-10. · 2.85 Impact Factor


Available from
Jun 4, 2014