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.
    Stem Cells and Cloning: Advances and Applications 01/2009; 2:11-19.
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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.
    Current Cardiovascular Imaging Reports 06/2009; 2(3):205-212. DOI:10.1007/s12410-009-0025-6
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    ABSTRACT: Determining which time point is optimal for bone marrow-derived cell (BMC) transplantation for acute myocardial infarction (AMI) has attracted a great deal of attention. Studies have verified the interaction between cell treatment effect and transfer timing and have suggested that the optimal time frame for BMC therapy is day 4 to day 7 after AMI. However, the potential mechanism underlying the time-dependent therapeutic response remains unclear. Recently, a growing body of in vitro evidence has suggested that stem cells are able to feel and respond to the stiffness of their microenvironment to commit to a relevant lineage, indicating that soft matrices that mimic brain are neurogenic, stiffer matrices that mimic muscle are myogenic and comparatively rigid matrices that mimic collagenous bone prove osteogenic. Simultaneously, considering the fact that the myocardium post-infarction experiences a time-dependent stiffness change from flexible to rigid as a result of myocardial remodelling following tissue necrosis and massive extracellular matrix deposition, we presume that the myocardial stiffness within a certain time frame (possibly day 4-7) post-AMI might provide a more favourable physical microenvironment for the phenotypic plasticity and functional specification of engrafted BMCs committed to some cell lineages, such as endothelial cells, vascular smooth muscle cells or cardiomyocytes. The beneficial effect facilitates angiogenesis and myocardiogenesis in the infarcted heart, and subsequently leads to more amelioration of cardiac functions. If the present hypothesis were true, it would be of great help to understand the mechanism underlying the optimal timing for BMC transplantation and to establish a direction for the time selection of cell therapy.
    Journal of Cellular and Molecular Medicine 03/2009; 13(4):660-3. DOI:10.1111/j.1582-4934.2009.00710.x · 4.01 Impact Factor
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