Cloning the heart

Existing methods of treatment are not quite effective in repairing damaged heart muscle in end-stage cardiovascular diseases. New research suggests that stem cells can regenerate into heart cells. Nandini Patwardhan traces the significance of stem cells in the cardiovascular segment

It is nothing short of a miracle that a cell, a combination of ova and a sperm, duplicates into a human body in nine months. That is the power of stem cells. This hypothesis has inspired stem cell research in cardiology in India.

Simply put, stem cells are the most basic cells in the human body. They are those unspecialised cells that can regenerate into a specific specialised cell. Stem cell therapy involves replacing diseased or degenerated cells with healthy, functioning ones. “These new techniques are being applied to a wide range of human diseases, including many types of cancer, neurological diseases such as Parkinson's and spinal cord, multiple sclerosis, diabetes, myocardial infarction,” explains Dr Satish Totey, Director, Manipal Acunova.

Heart matters

The field of cardiology has attracted significant attention in the world of stem cell research. Since current treatments, involving pharmacological management or interventional management (through the use of stents) have not been able to repair the damaged myocardium (heart muscle) in end-stage heart diseases.

“If you scratch your skin or if you get injured, it regenerates and you get back your normal skin. How does this happen? It is because stem cells have the capacity to regenerate and replenish,” explains V K Shah, Interventional Cardiologist and Principal Investigator at the Mumbai-based Hurkisondas Hospital. Unfortunately, heart and brain are supposed to be non-mytotic organs and once the cells are damaged, they don't have the power to multiply. Hence, we need an exogenous source to help the muscle revive.

Dr Ashok Seth Chairman & Chief Cardiologist Max Heart & Vascular Institute

Stem cells can be used for any kind of myocardial infarction (heart attack) like acute myocardial infarction, chronic myocardial infarction and congestive heart failure. However, it is advisable to treat patients with myocardial infraction at the earliest, preferably within 20-25 days of heart attack. “Stem cells help reduce cardiac infarction and improve ejection fraction,” reveals Totey. Also, stem cells can be injected in patients with cardiac myopathy. “Cardiac myopathy is a condition, in which, the heart muscle gets inefficient. And therefore, the pumping efficiency of the heart or ejection fraction as it is called, decreases to the extent that the patient starts to feel breathless and unable to function and heart failure occurs,” explains Dr Ashok Seth, Chairman and Chief Cardiologist, Max Heart & Vascular Institute, Delhi.

After a person gets a heart attack, the cardiomyocites can die within 20 minutes due to the occlusion of the artery. Once dead, the heart starts remodelling itself to maintain the normal cardiac output and to meet the demands of the body. Stem cells, if injected at the appropriate time, help in regenerating the damaged muscles and healing the scarred tissue, thereby, bringing the cardiac functions to almost normal without causing remodelling.

The process

Studies undertaken in small and big animals have proved that when injected with stem cells, they have the ability to home in on the diseased muscles and then change lineage. But the question that arises is, how do these cells multiply into the desired muscle cells?

“For instance, when we inject stem cells into the heart, they know exactly where they have to home in, based on the chemo attraction. The dead muscle gives out certain chemocytes, which attract stem cells to go there and convert into that lineage,” states Shah. “Before we ventured on to humans, we have seen this being proved through various experiments on small and big animals,” he adds. Unfortunately, there is no way to control multiplying stem cells into different non-desirable tissues. “However, there is not a single report which shows that stem cells, after injection into particular organ, have developed into undesirable tissue or cells. That shows that stem cells injection are quite safe,” reveals Totey.

The process of injecting stem cells is not a very long drawn process. “We inject stem cells by the intra-coronary method. This means, we inject them into the coronary artery—the culprit artery of the patient. The muscle which is subtended by this artery, which has been blocked, is our area of interest,” discloses Shah.

A guiding catheter is put into the coronary artery. Then a wire is sent over it into the culprit artery. A balloon is sent on the wire. Once inside the artery, the balloon is inflated to stop the blood supply for a couple of minutes. A lumen is inserted, through which a million stem cells, cultivated from the bone marrow of the patient, are injected in the artery. The stem cells reach the target area, where they have to home in. The balloon is inflated till the stem cells are injected so that blood does not flow during the process. “We keep the balloon inflated for two to three minutes, inject the stem cells and deflate the balloon. Again after three to four minutes, we repeat the procedure till all the stem cells are injected,” explains Shah. “On an average we inject 100 million stem cells. However, we are doing it arbitrarily right now,” he adds.

Research on the way

The results of various animal studies with respect to efficacy of stem cells in regenerating heart muscles have been encouraging. However, in human beings, things are not as simple. “As far as humans are concerned, the extent of repair by the stem cells is not proven so far,” states Totey. Further studies are going on in various institutions in order to understand the efficacy of stem cell treatment.

For instance, Hurkisondas hospital, under the guidance of Shah has treated seven to eight patients with stemcells so far, and studies are on to understand the benefits of this therapy. “Four patients have been re-studied after a period of six months and we have found that their cardiac indices have improved. We will be studying them again after six months to understand their progress,” reveals Shah.

The patients who have been recruited for the study have been made aware of it and the entire treatment is free of cost. However, they and two of their relatives are required to sign the consent form available. Once their consent is given, all the tests including echocardiogram, angiography, angioplasty and installing a stent followed by MRI scan is done free of cost. An echocardiogram is repeated, stem cells from the patients bone marrow are harvested and injected into them. They are called for a follow up, every 15 days for six months, after which the procedure (without stem cell injection) is repeated free of cost. “We get many patients who tell us on their own that they want to be a part of the study. However, we select patients with anterior myocardial infarction and without any other disorders,” states Shah.

“Stem Cell Research centre located at Manipal Hospital is actively involved in stem cell research and currently focussing on both adult and embryonic stem cells. Currently, Phase I clinical trial for safety and efficacy studies of bone marrow derived mesenchymal stem cells is going on myocardial infarction,” declares Totey. For the project titled 'Stem cell therapy for the treatment of damaged myocardium: safety and efficacy study', the institute is in process of recruiting patients. The purpose of the study is to ascertain whether bone marrow derived adult stem cells (AC133) and mesenchymal stem cells are safe and possibly effective in the treatment of acute myocardial infarction.

Seth informs that Max Healthcare is looking at undertaking studies in this area. A committee has been set up, which is going to look at which areas of stem cell research. “Our committee consists of neurologists, cardiologists to look at the use of stem cells in cases like, heart failure, Parkinsons disease, spinal cord disease and other immunological disorders. We are finalising the research that we will then submit to the ethical committee,” he says. Max Healthcare will be adopting the guidelines put forward by ICMR in this area. He also explains that they will have a systematic approach to the project. “We don't want to start research at random. We need to really look at and hone down on which is the most promising way of going about it, rather than just get into random research, because there are no-option patients,” he adds. AIIMS too has conducted a study on 35 cardiac patients, who have been injected with stem cells and have been monitored at six, 12 and 18 month intervals. According to the information available on the public domain, all the patients were brought in at a stage where they were beyond bypass surgery.

The results of the study have been very encouraging. Six months later, 56 percent of the dead muscle area injected with these cells had shown improvement. After eighteen months, this went up to 64 percent.

Unanswered questions

However, even today there are many unanswered questions about stem cell treatment in cardiology like—“Which is the best stem cell? Which is the right way of injecting them into the heart? Should it be injected directly through an operation into the heart muscle or into the arteries of the heart?

Thirdly, if it is given into the arteries of the heart, will it act by increasing the heart muscle cells or is it going to act by proliferating the blood vessels. “And even if it is being injected into the arteries, should it be allowed to stagnate in the arteries for three minutes or should it be allowed to flush out as the arteries are flowing. So the whole realm of this is still uncertain,” declares Seth. However, taking stock of the results of research activities in this area and a slew of guidelines that will be soon issued by the ICMR, stem cells might be the right cure for the broken heart.

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