Bringing dead myocardium back to life

by Megan Rajah

Myocardial Infarction (MI) refers to the irreversible death of cardiomyocytes (specialized cardiac muscle cells) secondary to ischaemia; which is usually caused by an atherosclerotic obstruction in one or many coronary arteries that supplies oxygen and nutrients to the heart muscle. The illness has found itself under the global spotlight for the last few decades as it has taken the wheel in driving morbidity and mortality in a significant proportion of the population in both developing and developed countries (1).

The clinical implication of a MI is an impairment in the cardiac contrac- tility that eventually culminates in cardiac failure. Currently, the only available treatment for cardiac failure is the use of a combination of commercially available drugs that control symptoms but fail to address or reverse the physical damage to the myocardium (1). This has sparked a generation of scientists to investigate the potential offered by Stem Cells and Biomaterials to regenerate the damaged myocardium (4)

A recent study by Kashiyama et al, has been accepted for publication in the Journal of Thoracic and Cardiovascular Surgery and shows promise in this area of research. The study investigated two different materials that have previously been described: Cell sheets and cardiac (scaffold) patches. What they did differently, however, was that they combined the two techniques and compared its efficacy to each method alone (4).

How did they do it? Adult stem cells were isolated from the adipose located in the Inguinal region of mice. After 10 days of standard stem cell culture, the cell aggregates were plated into wells and given 48 hours to form a cell sheet. For the cardiac patches, porcine hearts were decellularized and the extracellular matrix components were extracted and then electrosprayed onto a biodegradable polymer scaffold. The left anterior descending (LAD) coronary artery was surgically ligated in mice to induce MI. The mice were then treated with either (i) cell sheet (ii) cardiac patch (iii) cell sheet + cardiac patch and (iv) sham surgery (4).

An illustration summarizing the important steps taken to generate the therapeutic materials. Illustration created in BioRender.

What were their findings? After 8 weeks, mice treated with cardiac patches alone or in combination with cell sheets had a significantly smaller area of fibrosis in the damaged myocardium compared to the sham group and mice treated with cell sheets alone. A functional assessment by echocardiography (cardiac ultrasonographic investigation) showed that the three treatment groups had significantly im- proved their left ventricular ejection fraction (LVEF) compared to the sham group. Furthermore, of the three, the improvement was great- est in the arm treated with combination therapy (LVEF improved from roughly 30 to 50%). This group also demonstrated signs of better angiogenesis (and hence, reperfusion), therefore allowing for oxygen and nutrient supply to the repairing myocardium (4).

For science and medicine, this holds great promise. Both materials alone were capable of improving outcomes and when combined, those improvements were even more significant. As promising as this sounds, it is important to bear in mind that the long term benefits and risks have yet to be established. In the past, human trials involving cardiac regeneration have not always produced sustainable improvements and the immunogenicity of these materials has yet to be completely characterized.

The underlying mechanism of this therapy is also still up for debate. Potentially, myocardial regeneration occurs therefore replacing the damaged tissue or the constructs contain important molecular factors that save/protect the existing tissue from severe ischaemic damage. While it may take several years to understand and perfect the therapy, its likely to revolutionize the field and change patient lives while re- ducing drug costs and drug burdens. It certainly is exciting and I look forward to watching it progress!

References:

  1. Myocardial Infarction: Practice Essentials, Background, Definitions. Emedicine.medscape.com. 2020.
  2. Cardiovascular diseases. World Health Organisation. 2020.
  3. Cardiovascular Disease Statistics Reference Document. Heartfoundation.co.za. 2016.
  4. Kashiyama, N., Kormos, R., Matsumura, Y., D’Amore, A., Miyagawa, S., Sawa, Y., & Wagner, W. R. (2020). Adipose derived stem cell sheet under an elastic patch to improve cardiac function in rats after myocardial infarction. The Journal of Thoracic and Cardiovascular Surgery.

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