Yao, K. et al. Administration of intracoronary bone marrow mononuclear cells on chronic myocardial infarction improves diastolic function. Heart 94, 1147-1153

Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
Heart (British Cardiac Society) (Impact Factor: 5.6). 04/2008; 94(9):1147-53. DOI: 10.1136/hrt.2007.137919
Source: PubMed


Regeneration of the myocardium and improved ventricular function have been demonstrated in patients with acute myocardial infarction (MI) treated by intracoronary delivery of autologous bone marrow mononuclear cells (BMC) a few days after successful myocardial reperfusion by percutaneous coronary intervention (PCI); however, the effects of intracoronary cell infusion in chronic MI patients are still unknown.
To investigate whether intracoronary infusion of BMC into the infarct-related artery in patients with healed MI could lead to improvement in left ventricular (LV) function.
Among 47 patients with stable ischaemic heart disease due to a previous MI (13 (SD 8) months previously), 24 were randomised to intracoronary infusion of BMC (BMC group) and 23 to a saline infusion (control group) into the target vessel after successful PCI within 12 hours after chest pain occurred. LV systolic and diastolic function, infarct size and myocardial perfusion defect were assessed with the use of echocardiography, magnetic resonance imaging (MRI) or (201)Tl single-photon-emission computed tomography (SPECT) at baseline and repeated at the 6-month follow-up examination.
BMC treatment did not result in a significant increase in LV ejection fraction in any of the groups by any of the methods used, and the apparent tendency of an improvement was not statistically different between the two groups. The two groups also did not differ significantly in changes of LV end-diastolic and systolic volume, infarct size or myocardial perfusion. However, there was an overall effect of BMC transfer compared with the control group with respect to early/late (E/A) (p<0.001), early diastolic velocity/late diastolic (Aa) velocity (Ea/Aa) ratio (p = 0.002) and isovolumetric relaxation time (p = 0.038) after 6 months, as evaluated by tissue Doppler echocardiography. We noted no complications associated with BMS transfer.
Intracoronary transfer of autologous BMC in patients with healed MI did not lead to significant improvement of cardiac systolic function, infarct size or myocardial perfusion, but did lead to improvement in diastolic function.

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    • "In patients with chronic MI, several studies suggested a significant improvement in LV function after bone marrow cell transplantation.31–36 The IACT investigators reported that bone marrow cell injection was associated with an 8% increase in LVEF on LV angiography.31 "
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    ABSTRACT: Despite advances in the management of myocardial infarction, congestive heart failure following myocardial infarction continues to be a major worldwide medical problem. Mononuclear cells from bone marrow are currently being studied as potential candidates for cell-based therapy to repair and regenerate damaged myocardium, with mixed results. The success of this strategy requires structural repair through both cardiomyogenesis and angiogenesis but also functional repair. However, pre-clinical and clinical studies with the intracoronary administration of cells indicate limited cardiomyogenesis and cell survival, controversial functional benefit and suggest paracrine effects mediated by the administered cells. Further investigations for optimizing therapeutic benefit focus on the requirement for stable cell engraftment and the involvement of cytokines in this process. This includes a large and varied range of strategies including cell or heart pre-treatment, tissue engineering and protein therapy. Although cell-based therapy holds promise in the future treatment of myocardial infarction, its current use is significantly hampered by biological and technological challenges.
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    ABSTRACT: Myocardial infarction remains a major cause of death despite the continuous improvements in standard invasive and pharmacologic therapy. Cardiac regeneration by use of stem cells or progenitor cells has been proposed, and it has been carried into clinical trials based on initial success in experimental studies. However, recently reported results were inconsistent, and the clinical efficacy is still debated. Strategies to optimize cell delivery and engraftment are highly relevant for the future success of this therapeutic approach. Noninvasive imaging may play a key role in this optimization process. It has been used to monitor the efficacy of therapy through recovery of perfusion, metabolism, and functional parameters as essential surrogate end points of clinical outcome. Additionally, novel techniques for visualization and tracking of transplanted cells after therapeutic administration have been introduced. Ultimately, it is anticipated that existing and novel noninvasive imaging approaches will provide further insights into biology of cells, disease, and therapeutic mechanisms, and may thereby help to expedite the success of cell therapy.
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    ABSTRACT: Potential therapeutic applications of the cells require clinically compliant protocols for cell isolation and expansion. The therapeutic utility of MSCs has been evaluated and found to be useful in several pre-clinical animal models as well as in clinical trials. We review human trials studying the role of stem cell therapy in cardiomyogenesis and vasculogenesis in postinfarct myocardium, the type and number of transplanted cells, culture procedures that affect MSCs viability and quantity, time point and routes of MSCs delivery, and methods of detecting MSC engraftment. This chapter is an attempt to describe the scientific basis for MSCs therapy from the point of view of the clinician, focusing on problems that arise with beginning translation into the clinical setting. Although modern medical technology has greatly developed, ischemic injury and heart failure are still the primary reasons for human morbility and disability all over the world. Since cardiomyocytes lack the ability to regenerate, persistent cardiac ischemia and necrosis leads to a gradual loss of myocytes, ventricular remodeling and chronic heart failure. This is the main reason for hospital admissions among the elderly. It had been demonstrated from in vivo and in vitro studies that MSCs, which are easy to acquire and safer than other kinds of cells, can restore the injured myocardium and improve left ventricular remodeling by myogenesis and angiogenesis. The results have encouraged scientists to perform more investigations of bone marrow stem cells transplantation. The subsequent studies have been extended from a few small-scale observations to multicentred, randomized placebo-controlled clinical trials conducted with a more objective attitude. In recent years, an increasing amount of clinical trials relating to cell transplantation have been conducted around the world. Table 5.1 represents some famous clinical trials of cell therapy for treating patients with acute myocardial infarction (AMI) and chronic ischemic cardiomyopathy (ICM) (Roseniweig, 2006). Up to now, the REPAIR-AMT trial is the largest, clinical multi-centred and randomized, placebo-controlled study in which 204 patients with AMI (after 3 to 7 days reperfusion treatment) accepted intracoronary transplantation of autologous bone marrow mononuclear cells (BMCs) or placebo (Schächinger et al, 2006a). After treatment, left ventricular ejection fraction (LVEF) had significantly increased in four months and cardiovascular episodes including cardiac death, myocardial reinfarction, revascularization, etc., had been significantly reduced during one-year follow-up in patients with cell therapy compared to those in the control group.
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