Heart failure cell transplantation

Abbreviations AMI, acute myocardial infarction BM-MNC. bone marrow mononuclear cell BOOST, bone marrow transfer to enhance ST-elevation infarct regeneration CPC, circulating progenitor cells HF, heart failure LV, left ventricle LVED, left ventricular end-diastolic diameter LVEDV, left ventricular end-diastolic volume LVER left ventricular ejection fraction Ml. myocardial infarction TOPCARE-AMI, transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction. Source From Ref. 21. 

Perin EC, Dohmann HE, Borojevic R, et al. Transendo-cardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation. May 13 2003 107(18) 2294-2302. 

The anthracycline antibiotics, which include doxorubicin, daunorubicin, bleomycin, and mitomycin C, inhibit DNA and RNA synthesis. Doxorubicin also interfers with topoisomerase II (a DNA gyrase), the activity of which is markedly increased in proliferating cells. Structurally related to doxorubicin are epirubicin and mitozantrone. The cytotoxic antibiotics are used to treat leukaemias and lymphomas and also for solid tumours in the breast, lung, thyroid and ovary. Cardiotoxicity is the major dose-limiting factor, with arrhythmias and myocardial depression (Bacon and Nuzzo 1993). The chronic phase of cardiotoxicity is a dose-dependent cardiomyopathy that leads to congestive heart failure in 2-10% of patients. Myocardial injury is the result of oxygen free radical formation. Children are particularly sensitive to these cardiotoxic reactions and may require a heart transplant in their later years. Epirubicin is less cardiotoxic than doxorubicin. 

I 5 Ott HC, BrechtkenJ, Swingen C, et al. Robotic minimally invasive cell transplantation for heart failure, J Thorac Cardiothorac Surg 2006 132 170-173. 

The book is comprised of five sections with part I covering systemic and endoluminal therapy with an incisive overview of hemostasis and thrombosis part II covers local therapy with several chapters devoted to drug-eluting stents and restenosis therapies part III covers cell therapy and therapeutic angiogenesis and includes chapters on cell transplantation and clinical trials in cellular therapy part IV covers adjunctive pharmacotherapy with chapters devoted to various patient populations including those with heart failure, diabetes, atrial fibrillation, peripheral artery disease,... 

Fukuhara S,Tomita S,NakataniT, et al. Comparison of cell labeling procedures for bone marrow cell transplantation to treat heart failure long-term quantitative analysis. Transplant Proc 2002 34 2718-21. 

In six patients who developed heart failure after high-dose conditioning therapy before stem cell transplantation, cyclophosphamide was suspected, despite the possible involvement of four drugs (7). The authors suggested monitoring high-risk patients. 

Parenteral nutrition was used to support a patient requiring autologous blood stem-cell transplantation, but vitamins were excluded (the reason was not identified). After about 28 days, the patient suddenly developed severe metabolic acidosis, heart failure, and deep coma. Thiamine was immediately infused, with rapid improvement. 

Moreover, cardiac muscle cannot replicate and regenerate by itself after injury [131, 132], Heart transplantation is a treatment option for end-stage heart failure, but it has endured a slow and somewhat troubled evolution to transform itself into a more validated and useful therapy for patients, mainly because of the limited availability of donor organs and potential complications involved in its use [133]. Stem cell therapy and TE might solve the problem of how to treat thousands of patients who survive myocardial infarction and heart failure. 

A possible novel therapeutic strategy for heart failure following myocardial infarction may be to increase the number of functional myocytes within the diseased area by the implantation of exogenous myogenic cells. Early studies used neonatal rat cardiomyocytes for transplantation, as these cells have cardiac phenotype and still retain some proliferation capacity [2-4]. Fetal cardiomyocyte cell grafts showed the formation of cell-to-cell contacts, complete with gap junction proteins [4]. Moreover, cultured human fetal cardiomyocytes were shown to survive, and fetal rat cardiomyocytes were shown to be present in the infarcted rats hearts for up to 6 months after transplantation [5]. Further studies in animal models of myocardial infarction showed that grafting of cardiomyocytes from fetal and neonatal sources was asso-... 

It is estimated that, typically, hundred of milhons of cardiomyocytes are lost in a large myocardial infarction that results in the development of heart failure. Moreover, the transplantation of an even a greater number of cells may be required to replace this ceU loss because of the significant number of cardiomyocytes that die following ceU grafting. Therefore, a major barrier for the possible use of hES cells in cell transplantation strategies is the generation of sufficient numbers of cardiomyocytes. 

Etzion, S., Battler, A., Barbash, I.M., Cagnano, E., Zarin, P., Granot, Y, et al. Influence of embryonic cardiomyocyte transplantation on the progression of heart failure in a rat model of extensive myocardial infarction. J Mol Cell Cardiol 33, 1321-1330 (2001). 

Skeletal muscle is able to repair itself after injury because of the presence of resident satellite cells (myoblasts) that proliferate in response to injury, and fuse with damaged muscle fibers to regenerate functional skeletal muscle. The injection of skeletal myoblasts has been reported to improve myocardial stroke work, end-dia-stolic segment length, contractile function, and diastolic relaxation. The first report of skeletal myoblast transplantation for human heart failure required the injection of 8x10 cells into the myocardium of a single patient with revascularizable New York Heart Association class III heart failure at... 

Armenian SH, Ding Y, MiUs G, Sun C, Venkataraman K, Wong FL, et al. Genetic susceptibility to anthracydine-related congestive heart failure in survivors of haematopoietic cell transplantation. Br J Haematol 2013 163(2) 205-13. 

FIGURE 3.5 Adenovirus pneumonia in a heart transplant patient who developed ARDS and respiratory failure. Infected cells within necrotizing exudate show intranuclear reactivity with antibody to adenovirus antigen. Some cells show inclusions with a clear halo around them, making a differential diagnosis from CMV difficult on H E stain. (Immunoperoxidase staining with DAB and hematoxylin counterstain x400.)... 

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