In this essay, I will be discussing the different cellular/tissue engineering methods that could be implemented as a treatment strategy for the patient's many conditions, while explaining why using these treatment strategies will be beneficial to the patient.
One of the patient's conditions is hypertension (high blood pressure) caused when the pumping of blood around the body and the resistance measure of blood flow in blood vessels is affected with a blood pressure reading measured above 140/90 mmHg (High blood pressure (hypertension), 2019). The impact of having persistent blood pressure causes continuous stress on blood vessels impacting other organs such as the brain and kidneys and their function, increasing the risk of other health conditions such as heart attacks (myocardial infarctions) (High blood pressure (hypertension), 2019). The treatment of hypertension involves the use of various medications such as ACE inhibitors that help to reduce blood pressure through the relaxation of the blood vessels (High blood pressure (hypertension) - Treatment, 2019). Calcium channel blockers help to reduce blood pressure through the widening of blood vessels (High blood pressure (hypertension) - Treatment, 2019). Even with several different treatments available to treat hypertension, there are many side effects through prolonged use like headaches and dizziness and tiredness (High blood pressure (hypertension) - Treatment, 2019).
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Another of the patient’s condition was having two myocardial infarctions (heart attack) caused by a blockage preventing the supply of blood to the heart, causing severe damage to surrounding heart muscles (Heart attack, 2019). One potential complication of having a myocardial infarction is it can affect other areas of the body, with a reduced supply of blood, preventing the maintenance of other cellular functions (known as a cardiogenic shock) (Heart attack, 2019). Many other potential complications that can arise from having a myocardial infarction is both serious and potentially life-threatening; these complications include arrhythmia are abnormal heartbeats, in which the beating of the heart rapidly increases before stopping leading to cardiac arrest, another is the rupturing of the heart, in which all the muscles, wall and valves of the heart are torn apart (Heart attack, 2019). All these complications can rapidly occur and can often lead to the death of the patient (Heart attack, 2019).
After a myocardial infarction, the types of treatment used is dependent on the severity; medication used is to dissolve any blood clots present, with surgery used to restore blood flow to the heart (treatments for heart attack, 2019). One procedure used is a coronary artery bypass graft, which involves using a blood vessel from another area of the patient’s body such as an arm or leg and is then attached to the coronary artery, to direct blood flow around the arteries, improving blood flow and the amount of oxygen supplied to the heart (treatments for heart attack, 2019).
The final condition of the patient is non-insulin dependent diabetes (type II diabetes) in which glucose levels in the blood continuously builds up; insulin is a hormone produced by the pancreas and is released after eating, helping with transporting glucose from the blood into cells around the body to be used for energy (What You Need to Know About Type 2 Diabetes, 2019). In type II diabetes, the body begins to display resistance to insulin isn't efficiently used, causing stress on the pancreas as a higher level of insulin is required to help with the uptake of glucose; eventually leads to further damage to the cells of the pancreas, as an insufficient level of glucose can affect many cells and the maintenance of cellular functions (What You Need to Know About Type 2 Diabetes, 2019).
Some symptoms of type II diabetes commonly identified are constantly feeling hunger and a dry mouth, excessive thirst, a lack of energy and fatigue (What You Need to Know About Type 2 Diabetes, 2019).
Type II diabetes can be controlled through dietary changes by including foods with high fibre content and regular exercise to help maintain blood glucose levels (What You Need to Know About Type 2 Diabetes, 2019). If these changes aren’t sufficient, there are many medications used, to maintain blood glucose levels, metformin helps to lower the level of glucose helps to improve how the body can respond to insulin; another example is dipeptidyl peptidase-4 inhibitors are a type of medication used to help decrease blood glucose levels to ensure it is maintained at the optimal level (What You Need to Know About Type 2 Diabetes, 2019).
Regenerative medicine is scientific research, focusing on the construction of cellular sources or treatments for implementation in the repair or replacement of damaged tissues and organs caused by many diseases (Regenerative medicine - Tissue Regenix, 2020). Regenerative medicine focuses on addressing obstacles, such as an increasingly ageing population, by helping to reduce healthcare costs; and by providing better management of symptoms commonly present in many chronic diseases, or through the development of cures to replace current treatments used for many chronic diseases (What we do · UK Regenerative Medicine Platform, 2018).
For the patient’s many conditions, the use of regenerative therapies could prove to be beneficial, as it could help to relieve the patient of his symptoms and may help to restore normal function through the replacement of damaged tissues and organs; as the patient has suffered from myocardial infarctions and both hypertension and type II diabetes.
Regenerative therapies focusing on the treatment of hypertension is required to ensure an optimal blood pressure reading between 90/60 mmHg or 120/80 mmHg is measured, supporting both the pumping and resistance of blood flow around the body.
An example of current research involves the use of cell-derived exosomes focused on therapies for use in treating cardiovascular diseases such as hypertension (Chimenti and Frati, 2018). The patient suffers from hypertension is at risk of having a stroke or kidney disease. The current treatment used for the patient involves a combination of medication used to control blood pressure. In some patients, they are still unable to maintain optimal blood pressure levels (Chimenti and Frati, 2018).
This research has shown that the interaction between both immunity and inflammation plays a significant role in the development of hypertension (Chimenti and Frati, 2018). Angiotensin II is a factor found to be involved in regulating blood pressure and has also been identified in the initiation of inflammation in both blood vessels and the kidney, showing angiotensin II is the central mechanism involved in hypertension development (Chimenti and Frati, 2018).
Cardiosphere-derived cells are a type of cardiac progenitor cells (CPC) have been studied for many diseases including myocardial infarction and Duchenne muscular dystrophy, it has shown that using these cardiosphere-derived cells through the secretion of exosomes helps to enhance tissue repair by exhibiting antiapoptotic and antifibrotic factors through modulation of the inflammatory response, tested using a mouse model and inducing hypertension in these mice. As shown in figure 1, it demonstrates the effects of using these cardiosphere-derived cells on fibrosis reduction (Chimenti and Frati, 2018).
]Figure 1. A diagrammatic representation of the functioning of cardiac progenitor cell exosomes containing Y RNAs is present in many cell types; the function of extracellular Y-RNA fragments is still unknown (Chimenti and Frati, 2018). The presence of the Y4 RNA RV-FYF1 from the 56-nucleotide fragment, found within cardiac progenitor cell exosomes is significantly involved in the protection of cardiac cells along with controlling the expression and release of IL-10, having an effect on resident macrophages, leads to a reduction in the accumulation of fibrosis within organs such as the heart (Cambier et al., 2018).
The results showed that using these CDC exosomes have shown numerous effects when tested using a cardiac hypertrophy model induced by angiotensin II, as both inflammation and hypertension are interlinked, as enhanced secretion of IL-10 exerts many anti-inflammatory effects, helping to mitigate cardiac hypertrophy along with improved kidney function without altering blood pressure level (Cambier et al., 2018).
By using these exosomes, it showed a reduction in the expression of proinflammatory cytokines such as IL-1b and IL-6 from the heart; as inflammation is commonly identified in cardiac hypertrophy and myocardial infarction, using these CDC exosomes can help to initiate both cell proliferation and structural remodeling of cardiac cells without triggering hypertension by blocking the function of Angiotensin II (Cambier et al., 2018). The use of these exosomes helps to improve tissue repair and would be beneficial to the patient, as it could help to prevent both fibrosis in organs such as the heart without inducing hypertension and could help to relieve the patient of fatigue and shortness of breath.
Although the findings demonstrate that using these CDC exosomes would be beneficial in the treatment of many cardiovascular diseases such as hypertension, the transition from using an animal to human models would be difficult, as the effects shown in the animals may not be the same for when tested in humans. The use of exosomes exhibits many beneficial effects, but integration in human trials would be difficult, as you are unable to track the exosomes in the body. This shows the impact of regenerative therapy in the treatment of cardiovascular diseases isn't apparent and doesn't show if this therapy has long-term benefits for the patient.
Regenerative therapies focusing on the treatment of myocardial infarction is to ensure the functioning of the heart is similar to normal function; by preventing fibrosis and arrhythmia with focus on repairing damaged muscles and valves and the walls of the heart. By using regenerative therapies, it could be beneficial to the patient, as it could help to restore normal function through the replacement of damaged vessels, induced by myocardial infarction and hypertension using tissue-engineered vascular grafts.
For cardiovascular disease, one treatment is blood vessel bypass surgery using autologous blood vessels; an advantage of this treatment is long-term patency is achieved; some issues identified are further trauma caused by surgery to the patient and obtainment of these autologous vessels for treatment is often insufficient (Li, Li, Xu and Zhang, 2019). By replacing this with artificial blood vessels, it would help to prevent the use of multiple surgeries for the patient, limiting further trauma and helping to potentially restore normal function of tissues and blood flow following myocardial infarction (Li, Li, Xu and Zhang, 2019).
Figure 2. A diagrammatic representation of the three fabrication methods used to manufacture tissue-engineered grafts, which includes sheet tissue engineering using a 2D cell sheet around a cylindrical base forming a tube that is shaped and developed into a tissue-engineered graft; the second method involves the joining of microtissues into a cylindrical mould, which is shaped and developed into the tissue-engineered graft (Li, Li, Xu and Zhang, 2019). The third method is bioprinting involves incorporating cells and materials together, forming the tissue-engineered graft (Li, Li, Xu and Zhang, 2019). (Image from (Pashneh-Tala, MacNeil and Claeyssens, 2016)
In tissue engineering, the production of a decellularized matrix involves using detergents and solvents in the decellularization of tissues helps to remove cellular material, that would initiate an immune response when administered to the patient, as shown in figure 3.
Figure 3. A diagrammatic representation of the decellularized matrix used to manufacture tissue-engineered grafts, one type are autografts commonly used, in which both the tissue and extracellular matrix are decellularized (Pashneh-Tala, MacNeil and Claeyssens, 2016). Following this is the extraction of the patient’s cells, which is seeded with stem cells onto the scaffold forming the tissue-engineered graft (Pashneh-Tala, MacNeil and Claeyssens, 2016). (Image from Pashneh-Tala, MacNeil and Claeyssens, 2016).
A current treatment used for myocardial infarction is a surgical procedure called coronary artery bypass graft, which involves using a blood vessel from another area of the patient’s body such as an arm or leg and is then attached to the coronary artery, to direct blood flow around the arteries, improving blood flow and the amount of oxygen supplied to the heart (treatments for heart attack, 2019).
Although using coronary artery bypass has been shown to improve blood flow after myocardial infarction; for the patient using a regenerative therapy that incorporates the use of tissue-engineered grafts could potentially be more beneficial, as the patient has previously had two myocardial infarctions, there would be extensive damage caused to both the tissues and vessels of the heart affecting the function of other organs within the body due to limited blood supply; and could result in the further development of conditions or diseases impacting the patient’s everyday life, that could potentially result in the death of the patient.
By implementing tissue-engineered grafts in the treatment strategy for the patient, it would help to limit the need for multiple surgeries; while helping to restore normal function of blood vessels and the heart improving blood flow around the body, helping to prevent issues with the functioning of other organs. The tissue-engineered grafts may also help to treat the patient's hypertension, as the grafts maintain blood pressure, it improves blood flow around the body and could potentially help to alleviate the patient of his symptoms such as shortness of breath and fatigue.
For many regenerative therapies, such as tissue-engineered grafts, there are still issues that need to be addressed, which includes an incompatibility between the graft and the patient’s blood vessels could lead to rupturing of the grafted vessel, leading to the insufficient function of the graft making it unsuitable for long-term treatment (Li, Li, Xu and Zhang, 2019). If the issues are addressed, it could be an effective long-term treatment for the patient, as shown above.
Regenerative therapies focusing on the treatment of non-insulin dependent diabetes is to ensure both glucose and insulin levels are maintained at an optimum level to help maintain normal cellular function in the body.
An example of research involves the use of human mesenchymal stem cells for the production of insulin-producing cells for the treatment of non-insulin dependent diabetes.
Mesenchymal stem cells can self-renew and differentiate into various cell types like bone and muscle cells; these stem cells have shown to be effective in the treatment of many diseases like non-insulin dependent insulin, which for the patient is ineffectively treated using available treatments (Kim and Park, 2017).
Figure 3. A diagrammatic representation of manufacturing processes such as using stem cells, reprogramming damaged islet cells or generating new islet cells in the pancreas (Zhou and Melton, 2018).
The use of mesenchymal stem cells for the treatment of non-insulin dependent diabetes has many advantages, that could be beneficial in long-term treatment for the patient; as mesenchymal stem cells can be isolated easily and expanded (Kim and Park, 2017). The mesenchymal stem cells can be obtained from a donor if there are limited islet cells extracted from the patient. Although using stem cells could have many potential advantages, there are still some disadvantages from using this type of therapy, which includes limited replication of these cells, would require the patient to have multiple doses of stems cells for treatment to ensure the benefits of this regenerative therapy are maintained (Kim and Park, 2017).
Overall, there are many potential benefits of using regenerative therapy, that could be used in the patient’s treatment strategy, as shown in the given examples, these therapies could help the patient to manage symptoms such as shortness of breath and fatigue, as a result of non-insulin dependent diabetes. The use of regenerative therapy could also help to potentially cure or reverse some of the damage caused to tissues or organs, as a result of diseases/ conditions such as myocardial infarction.
References:
- Cambier, L., Giani, J., Liu, W., Ijichi, T., Echavez, A., Valle, J. and Marbán, E., 2018. Angiotensin II–Induced End-Organ Damage in Mice Is Attenuated by Human Exosomes and by an Exosomal Y RNA Fragment. Hypertension, [online] 72(2), pp.370-380. Available at: [Accessed 27 March 2020].
- Chimenti, I. and Frati, G., 2018. Cell-Derived Exosomes for Cardiovascular Therapies. Hypertension, [online] 72(2), pp.279-280. Available at: [Accessed 22 March 2020].
- Healthline. 2019. What You Need To Know About Type 2 Diabetes. [online] Available at: [Accessed 21 March 2020].
- Kim, H. and Park, J., 2017. Usage of Human Mesenchymal Stem Cells in Cell-based Therapy: Advantages and Disadvantages. Development & Reproduction, [online] 21(1), pp.1-10. Available at: [Accessed 29 March 2020].
- Li, Z., Li, X., Xu, T. and Zhang, L., 2019. Acellular Small-Diameter Tissue-Engineered Vascular Grafts. Applied Sciences, [online] 9(14), p.2864. Available at: [Accessed 28 March 2020].
- nhs.uk. 2019. Heart Attack. [online] Available at: [Accessed 20 March 2020].
- nhs.uk. 2019. High Blood Pressure (Hypertension) - Treatment. [online] Available at: [Accessed 20 March 2020].
- nhs.uk. 2019. High Blood Pressure (Hypertension). [online] Available at: [Accessed 26 March 2020].
- nhs.uk. 2019. Treatments For Heart Attack. [online] Available at: [Accessed 20 March 2020].
- Pashneh-Tala, S., MacNeil, S. and Claeyssens, F., 2016. The Tissue-Engineered Vascular Graft—Past, Present, and Future. Tissue Engineering Part B: Reviews, [online] 22(1), pp.68-100. Available at: [Accessed 29 March 2020].
- Tissueregenix.com. 2020. Regenerative Medicine - Tissue Regenix. [online] Available at: [Accessed 21 March 2020].
- UK Regenerative Medicine Platform. 2018. What We Do · UK Regenerative Medicine Platform. [online] Available at: [Accessed 22 March 2020].
- Zhou, Q. and Melton, D., 2018. Pancreas regeneration. Nature, [online] 557(7705), pp.351-358. Available at: [Accessed 29 March 2020].
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