Regeneration of cardiomyocytes using bone marrow derived stem cell transplantation and other factors involved in heart repair.
Review ArticleRegeneration of Cardiomyocytes by Using Bone Marrow Derived Stem CellTransplantation and Other Factors Involved in Heart RepairPablo GonzálezAbstract: The heart is a very important organ in our body because it is in charge of pumping theoxygenated blood through the veins and capillaries. One way it can be affected is by suffering aheart attack. A heart attack can affect the heart by lowering its ability to pump and not carryingthe needed amount of oxygen through the body. If the heart continues at that rate its cells will bedamaged from lack of oxygen and the individual will suffer from heart failure. There are still nocures for heart failure, although there are treatments. One very important treatment is BoneMarrow Cell transplantation which consists of transplanting derived stem cells from the bonemarrow and injecting them into the cardiomyocytes. Stem cells will differentiate into heart cells,taking the place of the destroyed ones. Transplantation therapy still needs more research, but ithas shown significant results in the regeneration of cardiomyocytes. Other types of heart therapyare Vascular Endothelial Growth Factor intravenous injection and Drug Combination therapy.The first one consists of injecting the myocardium with vascular endothelial growth factor whichwill have an angiogenic and therapeutic effect. The second treatment requires the administrationof drugs such as statins, after the infarction to improve the viability of bone marrow derived stemcell transplantation.Introduction: The heart, a muscle approximately the size of a fist, is a vital organ. It contains four cavities: two atria, and two ventricles, and 1
pumps oxygenated blood through all the The results of this treatment have shown toveins and capillaries in our body. The cells improve the cardiac function. However,that make up the heart are called myocytes many have postulated that the mechanism ofor cardiomyocytes. When these cells suffer action of BMC therapy is via the release ofthe consequences of a heart attack, it is very paracrine factors such as vasculardifficult for the heart to replenish or endothelial growth factor. Aside from this,regenerate them causing heart failure and research has shown that implanted cells havepossible death. not been shown to survive in myocardium for long periods (Yeghiazarians 2009). Currently there is not a cure for heartfailure, but there are still treatments such as Discussed in this review article are themedicines and a healthier lifestyle (National current experiments and views onHeart Lung and Blood Institute 2010). A transplantation of bone marrow derived stemhealthier life style includes doing exercise, cells on infracted hearts and the differenteating healthy, managing stress, ect. One factors that affect them.new and very important treatment is the What is heart failure?transplantation of bone marrow derived cells(BMCs). This treatment consists of When someone suffers a myocardialtransplanting stem cells derived from the infarction (heart attack), the heart maybone marrow to the heart. When become scarred and lose its ability to pumptransplanted, the cells begin to differentiate enough blood through the body. A heartinto heart cells (cardiomyocytes), filling the attack occurs when plaque builds up insideplace of the previously destroyed ones. the coronary arteries, cutting off the oxygen rich blood to the heart. This is called 2
coronary heart disease and it is the number Bone Marrow Derived Cells:one cause of heart attacks. If blood flow is To solve the problems previously statednot restored quickly, the section of heart scientists are experimenting with themuscle without oxygen begins to die. The injection or extract of the cells derived frompart of the heart that becomes damaged is the bone marrow into the damaged heart.known as the myocardium. This is the These specific types of cells are called stemmuscular middle layer of the wall of the cells, which are undifferentiated cells thatheart that stimulates the heart contractions to can develop into any type of cells in thepump blood. body. There are many types of stem cells in When the heart suffers a myocardial the body. Some of these are: adipose derivedinfarction, its pumping becomes weaker stem cells (ADSCs), cardiac stem cellsprogressively and this opens the pathway for (CSCs), peripheral blood derived cells,heart failure. Heart failure is a progressive embryonic stem cells (ES), and induceddisorder in which the heart can not pump pluripotent stem cells (iPS) (Mingliangenough blood to meet the body’s demand. It 2009). The problem with these other typesis estimated that yearly17 million of the of stem cells is that either they cause anpeople worldwide die of cardiovascular adverse effect on the heart, or that they candiseases, specifically heart attacks and not be used because of ethicalstrokes . Despite advances in medicine, there considerations. Bone marrow derived cellsare currently no approaches in clinical (BMC) are currently the most widely used inpractice that replace myocardial scar with clinical trials because they are not asfunctioning contractile tissue (Yeghizarians controversial and are the ones that exhibit2009). the desired effect (Mingliang 2009). 3
To prove that the BMC therapy would affected myocardium and that it attractsimprove the condition of the heart, scientists stem cells to that area to promotein a research laboratory often induce heart reconstruction of myocardial growthattacks on a mouse or rat model to study the network (Hoeben 2004). VGEF can increasetherapy. The way they do this is by placing a permeability of capillary wall, activateligature around a major blood vessel matrix metalloproteinase, and promoteconnected to the heart muscle. This deprives endothelial cell proliferation and migrationthe cardiomyocytes of their oxygen causing (Mingliang 2009). The therapy consists onthe heart attack. One of the findings of the injecting the myocardium with VEGF toscientists when they were using the mouse induce angiogenesis after intramyocardialmodel was that the mice that received the transplantation. Researchers show thattransplanted cells survived in greater VEGF increases angiogenesis, has a longernumbers than mice with heart attacks that duration, and is probably necessary for thedid not receive the mouse stem cells preservation of the myocardium and(National Institute of Health). limitation of cellular destruction when the cells are deprived of oxygen (Hoeben 2004).How is Vascular Endothelial Growth In other words, VGEF helps improveFactor (VGEF) Related to Cardiac myocardial ischemia because there is anRepair? important relationship between VGEF, VGEF is a molecule that has been found angiogenesis, and recovery for cardiac cellto be an inducer of Angiogenesis, which therapy (Payne 2007).indicates wound healing. Scientist believethat VGEF molecule is secreted aftermyocardial infarction in the region of the 4
What Are the Effects of Drug Discussion:Combination Therapy on Infarcted There seems to be many new ideasHearts? involving BMC therapy along with other This type of therapy consists on the factors on how to treat heart diseases such asadministration of drugs to a patient after myocardial infarctions, but some of themsuffering from myocardial infarction. There still need to be further tested forare many types of drugs that can be applied, consistency. Even though tests have shownan example would be statins. Statins lower their effectiveness on mouse models andplasma cholesterol by blocking the action of patients, it cannot be concluded that BMCa chemical in the liver that is necessary for transplantation will cure heart failure. Somethe production of cholesterol (Ramasubbu of these ideas include the combination of2008). The use of these types of drugs drugs right after the BMC transplantation, orlowers the risks of heart attacks and strokes. the intravenous delivery of VEGF-A, whichIn addition to inhibiting myocyte showed a significant improvement (Hoebenhypertrophy, statins affect myocardial 2004). VEGF-blocking therapy appearsfibrosis (Ramasubbu 2008). Yang et.al used promising in the treatment of cancer,simvastatin in the combination therapy and although, the clinical trials are still at anobtained very good curative effects. Other early stage, and combination therapy seemsscientists have used different drugs such as more effective because both endothelial cellangiotensin converting enzyme (ACE) and tumor cell are targeted.inhibitor after an infarction and have In conclusion, transplanting bone marrowobtained similar results on the regeneration stem cells to the damaged heart has beenof the myocardium. proven to give beneficial results, but is even 5
more effective when it is combined with Vascular Endothelial Growth Factor, Angiogenesis, and Cardiac Repair Aftervascular endothelial growth factor therapy Muscle Cell Transplantation into Ischemic Hearts.[Internet]Cited November 15, 2011.or drug combination therapy. It has opened - Sambasiva K. R. S., Ananda K., Sai K,the pathway for new myocardial infarction Berrocal Ruben, Rao K.S.April 3, 2011.treatments that will make an improvement Myocardial infarction and stem cells.[Internet]Cited October 7, 2011.on society. - Strauer Bodo et.al. Regeneration of Human Infarcted Heart Muscle byReferences: Intracoronary Autologous Bone Marrow Cell Transplantation in Chronic Coronary-Boyle Andrew. Et.al. September 12, Artery Disease.2005.Journal of the2011.Myocardial Production and Release of American College of Cardiology.ElsevierMCP-1 and SDF-1 Following Myocardial Inc.Vol. 46, No.9.Cited October 13, 2011.Infarction: Differences Between Mice and -Strauer Bodo, Yousef Muhammad,Man.[Internet]Cited November 14, 2011. Schannwell Christiana.April 16, 2010.The-Hoeben Ann, Landuyt Bart, Highley Accute and Long Term Effects ofMartin, Wildiers Hans, Oosterom Aallan, Intracoronary Stem Cell Transplantation inBruijn Ernest.2004. Vascular Endothellial 191 Patients With Chronic Heart Failure:Growth Factor and The STAR-Heart Study.European Journal ofAngiogenesis.Pharmacological Heart Failure[Internet]Cited Novenber 14,Reviews.Vol. 56, No.4.Cited November 14, 2011.2011. - Can Stem Cells Repair a Damaged Heart?- Mingliang Ren, Zhang Bo, Wang In Stem Cell Information [World Wide WebZhengguo.June 15,2011. Stem Cells for site]. Bethesda, MD: National Institutes ofCardiac Repair: Status, Mechanisms, and Health, U.S. Department of Health andNew Strategies[Internet]Cited October 6, Human Services, 2009. [Internet] Cited2011. November 26, 2011.-National Heart Lung and Blood - Yeghizarians Yerem. Et.al. Imjection ofInstitute.January 1, 2010.What is heart Bone Marrow Extract Into Infarcted HeartsFailure?.[Internet]Cited November 14, 2011. Results in Functional Improvement Comparable to Intact Cell Therapy. March-Payne Thomas, Oshima Hideki, Okada 25, 2009. [Internet] Cited November 15,Masaho, Momoi Nobuo, Tobita Kimimasa, 2011.Keller Bradley, Peng Hairong, HuardJohnny.2007.A Relationship Between - Ramasubbu Kumudha, Estep Jerry, White Donna, Deswall Anita, Mann Douglas. 6
Experimental and Clinical Basis for the Useof Statins in Patients With Ischemic and Noischemic Cardiomyopathy. January 24,2008. Journal of the American College ofCardiology. Vol. 51, issue 4. CitedNovember 30,2011. 7