Heart Muscles from Stem Cells Promise Precision Cardiac Care

Micro Heart Muscles from Stem Cells

A new method of deriving heart muscle cells from stem cells was identified by researchers from Gladstone Institute this year in the journal title Scientific Reports. Earlier scientists derived heart muscle cells from induced pluripotent stem cells but it was very difficult to get access to these stem cells and very difficult to make them grow into the desired specialized cell. Moreover, even when they grew, they resembled heart cells that were there in an embryo rather than the heart muscles that exist in an adult. This made it difficult to carry out drug testing using these cells as it still remained a mystery how the actual beating heart would react to the medication.

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The researchers first isolated heart muscle cells and connective tissue cells from the induced pluripotent stem cells. They were then arranged in the shape of a dog bone and allowed to grow. The heart muscle cells then grew like neuronal cells and began to 'behave' like adult muscle cells. The scientists tested to see if the heart muscle cells were indeed adult like by adding chemicals that were toxic to fetal heart cells but not to adult cells. The micro heart muscles were found to be functioning, indicating that they were like adult cells.

Dr. Bruce Conklin, MD, who is the senior author of the study said "The beauty of this technique is that it is very easy and robust, but it still allows you to create three-dimensional miniature tissues that function like normal tissues. Our research shows that you can create these complex tissues with a simple template that exploits the inherent properties of these cells to self-organize. We think that the micro heart muscle will provide a superior resource for conducting research and developing therapies for heart disease."

Testing Drugs on Heart Muscle Cells from Stem Cells

Scientists from Stanford University have said that the muscle cells from stem cells express the same genes as adult heart cells, which make them ideal for testing drugs that could lead to heart damage.

There are two essential benefits in using these muscle cells that have been derived from stem cells:

• Some drugs used for medical conditions other than for the heart could affect the heart, which makes it highly risky to use them. These drugs can be tested on the heart muscle cells to ensure that the drugs are safe to use.
• More precise cardiac medications can be designed as the effect of the drugs on the heart muscles can be determined.

Dr. Joseph Wu who is the Director of the Stanford's Cardiovascular Institute while also a professor of radiology and of cardiovascular medicine says "Thirty percent of drugs in clinical trials are eventually withdrawn due to safety concerns, which often involve adverse cardiac effects. This study shows that these cells serve as a functional readout to predict how a patient's heart might respond to particular drug treatments and identify those who should avoid certain treatments."

Testing the Expression Pattern

Dr. Wu and Dr. Elena Matsa along with their colleagues created cardiac muscle cells from induced pluripotent stem cells. They isolated the heart muscle cells from 7 different people who were not known to have any genetic risk associated with cardiac ailments. The level of expression of RNA by the heart muscle cells was determined and the quantity of protein that they expressed. The values were compared within the individual as well as among the seven individuals.

The researchers studied the effect of two drugs on the cardiomyocytes.

• Rosiglitazone - This drug is used to treat type 2 diabetes. This drug is no longer sold in the United States due to the cardiac effects it produces in certain people.
• Tacrolimus - Immunosuppressant used after organ transplantation.

Both these drugs illicit cardiac effects on certain people but it is difficult to ascertain who might be affected by these drugs.

When asked about the result of the study Dr. Matsa said "We found that the gene expression patterns of the iPS cell-derived cardiomyocytes from each individual patient correlated very well. But there was marked variability among the seven people, particularly in genes involved in metabolism and stress responses. In fact, one of our subjects exhibited a very abnormal expression of genes in a key metabolic pathway. This person's cells produced abnormal amounts of reactive oxygen species, were unable to regenerate their mitochondria and contracted much more weakly when exposed to rosiglitazone than cells derived from the other subjects."

Identifying the Error

The researchers identified the genetic mutation that leads to the abnormal pathway by comparing the pathway followed by the other six unaffected individuals' cells. They used a gene editing technique to correct the error which increased the expression of a gene with a return of normal function.

Cross Checking

The scientists were not sure if the heart muscle cells that were derived from the induced pluripotent stem cells could be compared entirely with the native cardiomyocytes. They derived three more cardiac muscle cells from the induced pluripotent stem cells of three cardiac patients and studied the expression levels. They found similarity, especially in metabolic processes that were important to good cardiac health.

The study by Standford researchers will aid in more precise medications being prescribed to patients, without worrying about adverse effects to the heart. It could soon herald in a tailor made treatment platform where the drugs for treatment could be chosen based on the individual response of the patient, promising better treatment, faster recovery and without adverse effects.

References :

1. Stem Cell Basics - (http://stemcells.nih.gov/info/basics/pages/basics1.aspx)
2. Types of Stem Cells - (http://www.closerlookatstemcells.org/learn-about-stem-cells/types-of-stem-cells)
3. Micro Heart Muscle Created from Stem Cells - (https://gladstone.org/about-us/press-releases/micro-heart-muscle-created-stem-cells)

Source: Medindia