Zhonghua Xin Xue Guan Bing Za Zhi. 2009 Apr;37(4):347-51.
Effects of bone marrow mesenchymal stem cells transplantation on heart function and ventricular remodeling in rats with isoproterenol-induced congestive heart failure.
1Department of Cardiology, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
To explore the effects of transplanted BMSCs (bone marrow mesenchymal stem cells) on cardiac function and ventricular remodeling in rats with isoproterenol (ISO) induced heart failure.
Wistar rats (n=50) received ISO (170 mg x kg(-1) x d(-1) for 4 days) injection. Four weeks later, rats with left ventricular ejection fraction (LVEF < 70%, n=26) were randomly assigned to receive intramyocardially BMSCs (2 x 10(7)/ml, 150 microl) injection (n=13) or equal volume culture medium (n=13). Another 10 normal rats served as normal controls. Four weeks after transplantation, heart function was assessed again by echocardiography, left ventricular morphology was evaluated through H&E and Masson’s trichome staining. Transplanted cells were observed by fluorescent microscope. RT-PCR and Western blot were performed to examine the myocardial expressions of type I and type III collagens, as well as MMP-2 and MMP-9.
LVEF [(78.51 +/- 6. 78)% vs. (65.40 +/- 12. 33)%] and LVFS [fractional shortening, (42.09 +/- 6. 53)% vs. (32.38 +/- 10. 22)%, all P < 0. 05] were significantly increased and LVDs [left ventricular systolic diameter, (2.91 +/- 0. 54) mm vs. (3.83 +/- 0.69) mm, P < 0.05] was significant decreased in BMSCs treated rats compared with culture medium treated rats. Myocardial fibrosis was also significantly attenuated in BMSCs rats than that in culture medium treated rats. The myocardial expressions of type I and type III collagens, as well as MMP-2 and MMP-9 were significantly decreased in the BMSCs group compared with those in culture medium treated group.
BMSCs transplantation can significantly improve heart function and attenuate LV remodeling in rats with ISO-induced heart failure mediated by reducing myocardial fibrosis and downregulation of myocardial MMP-2 and MMP-9 expressions.
Cell therapy in congestive heart failure.
1Department of Cardiovascular Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
Congestive heart failure (CHF) has emerged as a major worldwide epidemic and its main causes seem to be the aging of the population and the survival of patients with post-myocardial infarction. Cardiomyocyte dropout (necrosis and apoptosis) plays a critical role in the progress of CHF; thus treatment of CHF by exogenous cell implantation will be a promising medical approach. In the acute phase of cardiac damage cardiac stem cells (CSCs) within the heart divide symmetrically and/or asymmetrically in response to the change of heart homeostasis, and at the same time homing of bone marrow stem cells (BMCs) to injured area is thought to occur, which not only reconstitutes CSC population to normal levels but also repairs the heart by differentiation into cardiac tissue. So far, basic studies by using potential sources such as BMCs and CSCs to treat animal CHF have shown improved ventricular remodelling and heart function. Recently, however, a few of randomized, double-blind, placebo-controlled clinical trials demonstrated mixed results in heart failure with BMC therapy during acute myocardial infarction.
Keywords: Congestive heart failure, Acute myocardial infarction, Myocardial regeneration, Cell therapy
Transfusion. 2015 Feb;55(2):441-51; quiz 440. doi: 10.1111/trf.12826. Epub 2014 Aug 22.
Cell-based therapies for cardiac disease: a cellular therapist’s perspective.
1Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Veterans Affairs, Nashville, Tennessee.
Cell-based therapy is an exciting, promising, and a developing new treatment for cardiac diseases. Stem cell-based therapies have the potential to fundamentally transform the treatment of ischemic cardiac injury and heart failure by achieving what would have been unthinkable only a few years ago-the Holy Grail of myocardial regeneration. Recent therapeutic approaches involve bone marrow (BM)-derived mononuclear cells and their subsets such as mesenchymal stem/stromal cells (MSCs), endothelial progenitor cells as well as adipose tissue-derived MSCs, cardiac tissue-derived stem cells, and cell combinations. Clinical trials employing these cells have demonstrated that cellular therapy is feasible and safe. Regarding delivery methods, the safety of catheter-based, transendocardial and -epicardial stem cell injection has been established. However, the results, while variable, suggest rather modest clinical efficacy overall in both heart failure and ischemic heart disease, such as in acute myocardial infarction. Future studies will focus on determining the most efficacious cell type(s) and/or cell combinations and the most reasonable indications and optimal timing of transplantation, as well as the mechanisms underlying their therapeutic effects. We will review and summarize the clinical trial results to date. In addition, we discuss challenges and operational issues in cell processing for cardiac applications.