Potential of Umbilical Cord Stem Cells to Repair Damaged Cardiac Tissue in Vascular Disease Patients: Analytical Essay

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Research report

Claim: Stems cells have the potential to improve life.

Research question: Does umbilical cord stem cells or 3D printed mini heart have the most potential to repair or replace damaged cardiac tissue in vascular disease patients?

Rationale

Cristy Lytal from the Keck School of Medicine of USC claimed that ‘if you lose a limb, it’s lost for life. If you damage a kidney, you won’t grow a new one. And if you have a heart attack, the scars are there to stay’. ‘But regenerative medicine is poised to change all of this. Building new tissue is within sight’. The article discussed how much potential stems cells have in regenerative medicine and how they could be used to grow or repair new organs. The article talked about various potential stem cell treatments, including ‘healing hearts’ and how they stem cells are still in the very early stages of research. (Growing hope: New organs? Not yet, but stem cell research is getting closer, 2020).

Consequently, a broad research question of “which potential stem cell treatment has the most potential to improve the heart” was created based on the research claim. This was further refined to detail two specific stem cell treatments and was limited to “damaged cardiac tissue in vascular disease patients”.

This report investigates which future treatment either using umbilical cord stem cells, or 3D printed mini hearts has the most potential to repair or replace damaged cardiac tissue in vascular disease patients. It explains both treatment options in detail and evaluates which is the more effective option to potentially repair or replace damaged cardiac tissue. It was found in this report that the 3D mini heart has the most potential then the Intravenous infusions with umbilical cord-derived stem cells. A potential problem with the research of this report was that the treatment of the heart using stem cells is still young does not have a large amount of clinical trials involving repairing or replacing damaged cardiac tissue. Conducting this investigation again when there is further research and clinical trials around stem cells plus the treatment of damaged cardiac tissue would fix this problem.

Diagram 1: coronary artery disease

Background

Cardiovascular disease refers to conditions such as heart attacks, chest pain, strokes, congenital heart disease (which a person is born with), coronary artery disease, among others. Cardiovascular disease can affect the body and heart in many different ways depending on the condition.

The following effects can be caused by heart disease: less blood flow which means that the heart doesn’t get the oxygen it needs which causes chest pain, affecting how well your heart pumps making the rest of the body short on oxygen which means your cells don’t work as well as they should causing shortness of breath or feeling tired. Having swollen legs, feet, ankles, or stomach because your body cannot get blood back to your heart. The heart muscle can become thick, stiff, or larger than normal which over time makes the heart get weaker which makes it harder for it to pump blood and keep its regular rhythm. If Heart muscle thickens then blood flow is limited, so the patient is short on oxygen which can cause problems like dizziness, fainting, and shortness of breath. Heart defects often make your heart work harder, which can cause heart failure. Some of these effects can be seen in diagram 1 (shown above).https://www.verywellhealth.com/coronary-artery-disease-symptoms-1745924

Cardiovascular disease is the leading cause of death in Australia. According to the Australian Bureau of Statistics in 2017 ‘there were 160,909 deaths in Australia (82,858 males and 78,051 females) …18,590 of those deaths were due to heart disease’. (3303.0 – Causes of Death, Australia, 2017, 2020). In 2017-2018 ‘An estimated 1.2 million (6%) Australian adults aged 18 years and over had 1 or more conditions related to heart or vascular disease, including stroke, in 2017–18’. (Cardiovascular disease, How many Australians have cardiovascular disease? – Australian Institute of Health and Welfare, 2020). Because cardiovascular disease is not yet treatable, affects 6% of the Australian population and, is the leading cause of death in Australia a potential treatment needs to be found.

Analysis

Intravenous infusion of umbilical cord mesenchymal stem cells:

As there is no cure or treatment for heart disease there have been many different trials investigating whether various stem cells could improve or replace damaged heart cells. A clinical trial using umbilical cord mesenchymal stem cells conducted by Circulation Research (Safety and Efficacy of the Intravenous Infusion of Umbilical Cord Mesenchymal Stem Cells in Patients With Heart Failure, 2020) ‘showed promise’ as a heart failure treatment. This trial involved giving 30 patients aged 18-75 with HFrEF (appendix A1) intravenous infusions (appendix A2) with either umbilical cord-derived stem cells or placebo. The patients treated with umbilical cord mesenchymal stem cells (UC-MSC) presented no adverse events related to the cell infusion and there were no alloantibodies (appendix A6) present at 0, 15 and 90 days. This means that the UC-MSC treatment is safe for any future clinical trials. (Umbilical cord stem cells show promise as heart failure treatment, 2020)

The trial also showed that at 3, 6 and 12 months the UC-MSC treated patients showed improvements in left ventricular ejection fraction (appendix A4 and A5) as seen in the table below, whereas the placebo treated group did not.

As shown by the table above this treatment improves left ventricular ejection fraction (LVEF) of UC-MSC treated patients but not the placebo treated patients. Therefore, this means that the amount of blood being pumped out of the left ventricle of the heart, the main pumping chamber is increased, thus helping to counteract HF-rEF (a lower than normal ejection fraction, Appendix A1).

US-MSC patients also answered multiple quality of life questionaries at flow-up points to assess their perception of the effects of heart failure on: physical, socioeconomic, psychological aspects of their life, physical limitation, symptoms, quality of life, social limitation, symptom stability, and self-efficacy. As shown in the table below, in the ‘Minnesota Living with Heart Failure Questionnaire’, the UC-MSC treated group showed a higher baseline and efficacy outcomes. Therefor this means that the UC-MSC treated patients’ quality of life improved due to the treatment whereas the placebo treated group did not. (Safety and Efficacy of the Intravenous Infusion of Umbilical Cord Mesenchymal Stem Cells in Patients With Heart Failure, 2020)

3D printed mini heart

Researchers from Aviv University have printed a 3D heart using a patient’s own cells. ‘Although the heart is about 2.5 centimetres and is too small for humans’ researchers say that it has great potential and could be used to patch diseased hearts and in full transplants. The heart is printed with blood vessels, ventricles and chambers using the cells from the patient’s own biological materials (Dr. Edith Bracho-Sanchez, 2020). This means that the heart is completely biocompatible and matches the patient, reducing the risk of rejection inside the body, and removing the need for the patient to take medication to prevent rejection. It is also believed that instead of printing full 3D hearts perhaps patches can be printed which can improve or remove the diseased areas of the heart and replace them with something that works. (Arnold, 2020)

The process of printing the mini heart is comprised of millions of cells and takes about three hours to print. The process works by taking fatty tissue from a patient, then separating it into cellular and non-cellular components. After this the cells are reprogrammed to become stem cells which are turned into heart cells. Finally, the cells mature for a month or so after being printed to allow them to beat and contract.

Although the mini heart has the potential to replace damaged hearts, they are not ready for humans and there is no set schedule for when they will be ready for clinical trials or even to be tested on animals. It is also unclear whether a 3D printer can produce hearts superior to human ones or not.

Conclusion

It was found in this report that both the 3D mini heart and the Intravenous infusions with umbilical cord-derived stem cells both have potential to repair or replace damaged cardiac tissue in vascular patients. However, the 3D mini heart has the most potential to replace and improve damaged cardiac tissue in vascular disease patients. Although the 3D mini heart is has not yet made it to clinical trials and is still in the initial stage or testing/research it is likely to be the effective option to go with as it has a higher chance of working. This is based on the proposed potential positive effects it could have on patients with vascular diseases in the future. As cardiovascular disease is the leading cause of death in Australia the mini heart could potentially save the lives of those inflicted with heart disease. If the mini heart is printed at the actual size of a human heart, then the research could lead to being able to 3D print any part of the body which could cure many other diseases or slow them down.

The Intravenous infusions with umbilical cord-derived stem cells has potential but does not have as much potential as the 3D mini heart to repair or replace damaged cardiac tissue in vascular disease patients. This treatment did show significant improvements in left ventricular ejection fraction and quality of life, but it cannot replace or repair the heart like the 3D printed mini heart has the potential to.

Overall it was found in this investigation that stems cells have the potential to improve life as the 3D mini heart (which is made from stem cells) has the potential to repair and replace damaged cardiac tissue in vascular patients, thus ‘improving life’.

Evaluate

All of the sources used in this investigation can be considered reliable and trustworthy. This is because all of the sites were fully referenced and sourced from a published study or trial. However, there are also issues associated with the sources. Ahajournals.org. 2020. Safety And Efficacy Of The Intravenous Infusion Of Umbilical Cord Mesenchymal Stem Cells In Patients With Heart Failure was the only source of information found that had conducted a trial on the heart using Intravenous infusion of umbilical cord mesenchymal stem cells. Another issue with the evidence is that there were no clinical trials for the 3D mini heart as it is still in the initial stages of research and not yet ready to be tested.

Suggestions, improvements, and extensions to the investigation

The 3D printed heart is still in the early stages of research/testing so if more research was conducted. For example testing the mini heart on an animal to see if the heart could actually work then if it does work moving onto the next stage – figuring out how to successfully print the 3D heart to the size of a human heart. After figuring out how to print a human sized heart a clinical trial should be conducted. The results of this clinical trial would allow for a more detailed research investigation to take place, providing more information on the heart and if it could actually repair or replace damaged heart or cardiac tissue.

An extension to this investigation would be adding more stem cell treatments. In this investigation only two stem cell treatments were researched, thus not all of the options were researched, so a better stem cell treatment could be out there. A larger range of stem cell treatments with clinical trials for each new option would allow for a better decision to be made on what stem cell treatment option has the most potential to repair or replace damaged cardiac tissue. A potential treatment that could be added is embryonic stem cells in cardiac repair and regeneration (appendix A3).

Appendix

Source 1 (code A1) – HfrEF definition

‘Reduced ejection fraction (HFrEF) – also referred to as systolic heart failure. The heart muscle does not contract effectively, and therefore less oxygen-rich blood is pumped out to the body’

Cleveland Clinic. 2020. Heart Failure: Types, Symptoms, Causes & Treatments. [online] Available at: [Accessed 4 June 2020].

Source 2 (code A2) – Intravenous infusion

Intravenous infusion is the ‘administration of fluids into a vein by means of a steel needle or plastic catheter.

TheFreeDictionary.com. 2020. Intravenous Infusion.. [online] Available at: [Accessed 4 June 2020].

Source 3 (code A3) – Embryonic stem cells in cardiac repair and regeneration

Clinical trial for embryonic stem cells in cardiac repair and regeneration. For more information visit the link below.

www.ncbi.nlm.nih.gov. 2020. Embryonic stem cells in cardiac repair and regeneration. [online] Available at: [Accessed 4 June 2020].

Source 4 (code A4) – EF

‘EF that is below normal can be a sign of heart failure. If you have heart failure and a lower-than-normal (reduced) EF (HF-rEF), your EF helps your doctor know how severe your condition is’.

www.heart.org. 2020. Ejection Fraction Heart Failure Measurement. [online] Available at: [Accessed 4 June 2020].

Source 5 (code A5) – Left ventricular ejection fraction (LVEF)

‘Left ventricular ejection fraction (LVEF) is the measurement of how much blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction’.

Cleveland Clinic. 2020. Ejection Fraction. [online] Available at: [Accessed 4 June 2020].

Source 6 (code A6) – Alloantibodies

‘Alloantibodies are immune antibodies that are only produced following exposure to foreign red blood cell antigens. Produced by exposure to foreign red cell antigens which are non-self antigens but are of the same species. They react only with allogenic cells. Exposure occurs through pregnancy or transfusion’.

Labce.com. 2020. Alloantibodies Vs. Autoantibodies – Labce.Com, Laboratory Continuing Education. [online] Available at: [Accessed 4 June 2020].

References

Ahajournals.org. 2020. Safety And Efficacy Of The Intravenous Infusion Of Umbilical Cord Mesenchymal Stem Cells In Patients With Heart Failure | Circulation Research. [online] Available at: [Accessed 23 May 2020].
Australian Institute of Health and Welfare. 2020. Cardiovascular Disease, How Many Australians Have Cardiovascular Disease? – Australian Institute Of Health And Welfare. [online] Available at: [Accessed 25 May 2020].
Abs.gov.au. 2020. 3303.0 – Causes Of Death, Australia, 2017. [online] Available at:

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