Coronary artery disease   Dilated Cardiomyopathy   Congestive Heart Failure
Myocardial infarction        

Coronary Artery Disease

Coronary artery disease (CAD) is also called as coronary heart disease. This is a condition in which plaque builds up inside the arteries which supply oxygen-rich blood to heart muscle. Plaque is made up of substances like fat, cholesterol, calcium, and other substances found in the blood. The formation of plaque in the arteries, is called as atherosclerosis. Plaque narrows the arteries and reduces blood flow to heart muscle. It makes it more likely to form blood clots in arteries which can partially or completely block blood flow. The completely blocked blood flow to the heart muscle can cause heart attack, which can lead to serious problems and even death if quick treatment is not provided.
CAD can weaken the heart muscle as a result heart cannot able to pump enough blood throughout body. Arrhythmia is also another condition occurs as a result of CAD, which varies the speed or rhythmus of heartbeat.

CAD is the leading cause of death worldwide. The disease is the most common cause of sudden death, and is also the most common reason for death of men and women over 20 years of age.

Endothelial Progenitor Cells (EPCs) can enhance angiogenesis by releasing cytokines and chemokines. These cells are also able to induce migration and growth of c-Kit+ cardiac progenitor cells by secretion of cytokines such as VEGF, IGF-1, and SDF-1. The cytokines released locally within the myocardium by the progenitor cells may activate the regenerative reservoir of the heart and possibly contribute to the beneficial effects observed in infarcted hearts treated with this cell population. For instance, endothelial progenitor cells from patients with cardiovascular disease display varying degrees of functional impairment, and an inverse correlation has been reported between the number of circulating EPCs and the prevalence of risk factors for CAD.

Multiple studies have consistently reported an association between lipid metabolism and the biology of human EPCs. The numbers of EPC colony forming units are significantly reduced in relatively healthy subjects with elevated serum cholesterol levels. In CAD, low-density lipoprotein (LDL) cholesterol inversely correlates with the reduced number of circulating EPCs. In addition, the functional characteristics of isolated EPCs, such as proliferation, migration, adhesion, and in vitro vasculogenic capacity, are also impaired in CAD patients with high cholesterol level.

Several small-scale phase 1 trials of bone marrow EPC transplantation in treatment of severe CAD, providing preliminary evidence of feasibility and safety of EPC transplantation have been performed.

Eduard S, Timothy W, Gregory Y.H. Lip Endothelial Progenitor Cells in Cardiovascular Disorders J. Am. Coll. Cardiol. 2007;49;741-752
Bodo et al.Regeneration of Human Infarcted Heart Muscle by Intracoronary Autologous Bone Marrow

Cell Transplantation in Chronic Coronary Artery Disease The IACT Study 2005, Journal of the American College of Cardiology Vol. 46, No. 9,


Dilated Cardiomyopathy

Dilated (Congestive) cardiomyopathy is the most common type of the disease. It mostly occurs in adults aged 20 to 60. The disease often starts in the left ventricle, the main pumping chamber of heart.The heart muscle begins to dilate and due to this the inside of the chamber enlarge. When the chambers dilate, the heart muscle doesn't contract normally. Moreover, the heart can't pump blood very well. Over time, the heart becomes weaker and heart failure can occur. Dilated cardiomyopathy also leads to arrhythmias, heart valve problems, and blood clots in the heart. This type of cardiomyopathy occurs when the muscle mass of the left ventricle enlarges or hypertrophies.

Despite this thickening the ventricle size often remains normal.
The recent trials supports the theory of paracrine manner rather then stem cells regeneration process by dividing and renewing themselves in to required cells type and can thus replicate and proliferate to form the heart muscle. As per paracrine mechanism stem cells are believed to work by secreting various chemical/ substances that helps in activation of regeneration process.

Dilated cardiomyopathy can be the end-stage form and common denominator of several cardiac disorders of known cause such as hypertensive, ischemic, diabetic and Chagasic diseases. Regenerative treatment of dilated, non-ischaemic cardiomyopathy represents a significant unmet clinical need. Intracoronary administration of autologous bone marrow stem cells has demonstrated positive results in treatment of post-infarct and chronic ischaemic patients.

Cell therapy in dilated cardiomyopathy: from animal models to clinical trials, C. del Corsso and A.C. Campos de Carvalho, Braz J Med Biol Res Online Provisional Version
Intramyocardial administration of autologous bone marrow mononuclear cells in a critically ill child with dilated cardiomyopathy, Cardiology in the Young (2011), 21, 110–112.

Stem cell transplantation for ischemic cardiomyopathy: Hope or hype? Vivek Rao, J Thorac Cardiovasc Surg 2005;130:1492-1493


Conjuctive Cardiac (Heart) Failure (CCF)

Heart failure or conjuctive cardiac failure is a life threatening condition in which the heart is not able to receive enough blood and oxygen as a result cannot pump enough blood through the body for its routine function. The cause of this can be either thickened or weakened heart muscle, blocked coronary arteries, arrhythmias, damaged heart valves, pericardial disease or uncontrolled hypertension.

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According to World Health Organization (WHO) estimates, in 2003, number of deaths, including men, women and children due to CVD each year is 16.7 million people around the globe and this is over 29 percent of all deaths globally. By 2020, the number of fatalities projected to increase to more than 20 million a year and to more than 24 million a year by 2030 making heart disease  leading cause of  death around the world.

Heart failure is a progressive disorder in which damage to the heart causes weakening of the cardiovascular system. Endothelial dysfunction is thought to play a major role in the development and clinical complications of heart failure. Studies have revealed that enhancing the number and functional capacity of Endothelial Progenitor Cells (EPCs) with targeted interventions may elicit functional improvement in individuals with heart failure. EPCs are immature, bone-marrow derived cells with the capacity to transform into mature endothelial cells and promote postnatal angiogenesis and vasculogenesis. Thus, they contribute to the restoration of the endothelial lining and maintenance of vascular homeostasis. Apart from EPCs, clinical trials conducted with Mesenchymal Stem Cells derived from either adipose tissue or bone marrow and mixture of progenitor cells and stem cells,.

Potential role of endothelial progenitor cells in the pathophysiology of heart failure: Clinical implications and perspectives, I. Andreou et al. / Atherosclerosis 189 (2006) 247–254

Circulating Apoptotic Progenitor Cells in Patients with Congestive Heart Failure, PLoS ONE 2008 | Volume 3 | Issue 9 | e3238
Endothelial progenitor cells: what use for the cardiologist? Siddique et al. Journal of Angiogenesis Research 2010, 2:6


Myocardial Infarction

Myocardial infarction (MI) or acute myocardial infarction (AMI), commonly known as a heart attack, is the interruption of blood supply to a part of the heart, causing heart cells to die. This is most commonly due to blockage of a coronary artery.  The blockage is an unstable collection of lipids (fatty acids) and white blood cells in the wall of an artery and results in the restriction in blood supply and oxygen shortage. If left untreated for a sufficient period of time, can cause damage of heart muscle tissue (myocardium) and can prove fatal.

Important risk factors are previous cardiovascular disease, older age, tobacco smoking, high blood levels of certain lipids (triglycerides, low-density lipoprotein) and low levels of high density lipoprotein (HDL), diabetes, high blood pressure, obesity, chronic kidney disease, heart failure, excessive alcohol consumption, the abuse of certain drugs and chronic high stress levels.

Myocardial infarction is a common presentation of ischemic heart disease. The WHO estimated in 2002, that 12.6 percent of worldwide deaths were from ischemic heart disease. It is the leading cause of death in developed countries, and third to AIDS and lower respiratory infections in developing countries.

Stem cells are believed to work by two major mechanisms. Infusion of ex vivo cultivated Endothelial Progenitor Cells (EPCs) may boost capillary density, neovascularization of ischemic tissue, significantly improved blood flow, cardiac function and reduced left ventricular scarring. In addition, transplantation of ex vivo cultivated Endothelial Progenitor Cells (EPCs) can significantly improved coronary flow reserve and left ventricular function in patients with acute myocardial infarction. Thus administration of endothelial progenitor cells (EPCs) is a promising therapy for post-infarction cardiac repair. Regeneration in vessel has made endothelial progenitor cells a suitable candidate for therapeutic applications aiming at tissue revascularization


Stem-Cell Transplantation in Myocardial Infarction: A Status Report. Michael S. Lee, MD; and Raj R. Makkar, MD
Progenitor cell therapy in a porcine acute myocardial infarction model induces cardiac hypertrophy, mediated by paracrine secretion of cardiotrophic factors including TGFbeta1.  Doyle et. al  Stem Cells Dev. 2008 Oct;17(5):941-51

Current developments in the use of stem cell for therapeutic neovascularisation: is the future therapy “cell-free”?
Zijiang Yanga, Stefano Di Santob, Christoph Kalkac Review article: Swiss Med Wkly. 2010; 140:w13130

Stem cell therapy of cardiac disease: an update, Honold et. al. (2004), Nephrol Dial Transplant, 19: 1673-1677