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Artificial Organs
The scientific technology that I have chosen to research is artificial organs, the reason that I find this particular technology interesting is that I find it fascinating that scientific research and development has come so far that we are now able to replace our organs which are needed for the human body to survive, with artificial matter and it can still work perfectly.
Five important aspects of artificial organs are:
- They can be produced 2 ways – either grown in a lab or 3D bio-printed
- It helps with our health outcomes as it provides another possibility instead of having organ transplants
- Assists with organ donor shortages
- Real organs have the possibility of immunorejection, artificial organs eliminate this
- Economically efficient as it eliminates the cost of anti-rejection drugs which typically cost $17,000 each year at minimum
How they are produced
Artificial organs can be manufactured in two ways they can either be bio-artificially grown or 3D printed. To grow an organ bio-artificially there are four steps involved in this process The architectural predesign, preparation of materials and construction tools, homogeneous or heterogeneous cell assembling and post multi tissue maturation. In the architectural pre design stage factors taken into consideration are the materials used to make the organ, so whether they are stem cells or other types of cells used to produce the organ. Stem cells are cells of a multicellular organism that are capable of establishing several more cells of the same type, because of their capability to refabricate cells of the exact same anatomical make up, stem cells are commonly used in the artificial organ manufacturing process. Cells from the patient receiving the organ are preferred for use so as to eliminate the high risk of immunorejection. Immunorejection is the bodys natural defence system to fight and defend against a foreign object. When a transplant occurs the recipients, immune system rejects the transplanted tissue and destroys it.
During the third cell assembling stage using stem cells is a promising approach to effectively grow an organ as they provide reproductive properties to efficiently grow the necessary organ. MSCs have also become increasingly popular in the organ manufacturing field, particularly adipose derived stem cells, umbilical cord blood stem cells and bone marrow mesenchymal stem cells, as they are able to differentiate into many different cell types and therefore creating another way for scientists to develop artificial organs. MSC stands for mesenchymal stem cells they are multipotent which means they can produce more than one type of specialized cell in the human body, because of this they are valued and extremely necessary in the bio artificial organ manufacturing process. MSC cells can also develop into skeletal tissue, nerve cells, heart muscle cells, liver cells and endothelial cells which form the inner layer of blood vessels. Therefore the growth factors of the MSC cells are crucial for any convoluted organ construction that involves the incorporation of the vascular, neural or lymphatic network.
Lastly the fourth stage of organ manufacturing- the post multi tissue maturation stage, this is the final stage of artificial organ manufacturing and is the final step that binds everything together and makes it a fully functional organ. During this stage the fully assembled 3D constructs that consist of living cells need to be stable for implantation. During this stage, physical, chemical or biochemical cross linking of the supportive polymers takes place to immobilise the currently living cells, this process also improves the structural integrity of the organ. Within the 3D construct cell aggregation transpires to form homocellular and heterocellular tissues. Hence post multi tissue maturation is a self-sufficiently completing process in which homogenous and heterogenous cell populations are able to come into contact and amalgamate to create fully functional, coherent organ tissues. Only through this process with multi tissue formation and maturation can a bioartificial organ grow to the point where it has a full range of necessary physiological functions. For a major organ with more than three cell types such as the liver, heart or kidney considerable time and space factors need to be greatly considered.
During this stage stem cells can also be introduced to 3D printed organs into disparate cell and tissue types such as endothelial cells or tissues and adipose cells or tissues under the guidance of consecutive growth factors.
Providing another avenue instead of organ transplants
Artificial organs can eliminate the need for an organ transplant. Almost any organ you can think of is able to be bio artificially grown or 3D printed. In any instance where an organ transplant is not an available option an artificial organ can be the way to go. Although a negative to this is that if it is a life or death situation and an immediate organ transplant is necessary the time may not be in our favour for an artificial organ to be grown as it takes several months to grow an efficient organ.
As of currently there are no other alternatives to a real human organ transplant apart from bio-artificially manufactured organs or 3D printed organs, because of this, the development of bio-artificial or 3D printed organs has become a crucial technology in organ transplants, to assist in the lives of those who desperately need a transplant. Although there are dialysis machines that are available, they are not a permanent solution.
Assisting with organ donor shortages
There is a worldwide organ donor shortage. In Australia alone currently 1400 patients are waitlisted for an organ transplant and there is a further 11,000 that are currently on dialysis who could benefit from a kidney transplant. In the United States of America a remarkable 122,000 people are on a waitlist for patients awaiting a transplant, the majority of these patients will be waiting months or even years to find a donor and unfortunately some never will. At the end of this day 22 people would have died in the united states alone awaiting an organ donor. See figure 3 for organ donor statistics
The dilemma is that there simply are not enough people willing to donate organs to reach the high demand of life saving donor organs. Many initiatives have been implemented to rise the amount of available organ donors, such as offering for people to sign up to become an official organ donor when they go for their drivers licence. Despite these efforts, according to the U.S department of health and human services the amount of organ donors has remained stagnant over the last decade, proving that this is a growing crisis worldwide, but particularly in the United states of America.
There is a strong push for living donors to sign up on the organ donor registry as last year 450 patients on the organ donor wait list died simply because families were unsure of their deceased relatives wishes on whether they want to donate or not.
As mentioned previously, stem cells also have the capability to grow and produce a healthy fully functioning body tissue, this can majorly assist in the growing epidemic of tissue donor shortages. Similar to organ donor shortages, there is also a colossal tissue donor shortage as well. Tissue is in high demand of those with severe diseases or illnesses, but it is not only those with severe illness that are in need of tissue. According to associate professor Justin Roe who has a medical practice in Sydney and receives tissue from Victoria, he is seeing a further increasing rate in major tissue injuries that require tissue transplants as there is an ever increasing intensity in sport, not only contact sport, but sports such as netball which cause severe rupture of the anterior cruciate ligament can require a tissue transplant in severe cases, see figure 4 for representation of increasing sport injuries and reconstruction rates. Not only is it the increasing intensity in sport but there are much higher participation rates which can further the injury rates of tissue and ligaments.
Making organs bioartificially available can dramatically assist in our worldwide organ donor shortages as we can create organs as we need them, introducing the possibility of artificial organs also limits the patients time on the wait list for an organ to come naturally as scientists can get to work straight away on developing the required organ.
Eliminating the risk of immunorejection
A transplant is the act of relocating cells, tissue or organs for the purpose of reconstructing or replacing a damaged or diseased tissue or organ. Although this is a marvellous medical breakthrough the bodys immune system creates a significant and difficult barrier to endure a completely successful organ transplant
When an organ transplant occurs, the patient is highly susceptible to immunorejection, a process in which the human body recognises an object as foreign or harmful . During this process the human body recognises the transplanted organ or tissue as foreign, which results in the destroying of the transplanted tissue or organ.
Foreign invaders in the human body are presented to our immune system as an antigen, a substance that when inside the human body triggers an immune response, this immune response activates lymphocytes which are white blood cells, they are also one of the bodys main types of immune cells. Lymphocytes are made in bone marrow and are a part of the lymphatic system, hence why they are also made in lymph tissue. From this point some of these cells travel to the thymus where they become what is known as T cells, others remain in the bone marrow where they are made, these become known as B cells. In the case of organ transplants B cells play a major role in the immunorejection. B cells are responsible for making antibodies, antibodies are proteins produced by the immune system to fight and defend against antigens. In this case, the transplanted organ is recognised as an antigen and destroyed. T cells recognise and destroy virus infected cells, one of the most common infected cells that T cells destroy are cancerous cells.
When a surgical transplant occurs and the transplanted tissue or organ is identified as a non self antigen, it triggers an immune response which uses specific antibodies to mark the transplant for destruction and assists in amplifying the immune response. The human leukocyte antigen (HLA) is a complex gene group that contains proteins that have the responsibly of identifying foreign matter. These proteins are found on all cells and acts as self markers, indicating to the immune system not to destroy that particular tissue or organ as it is not harmful. The complication in this circumstance is that due to the fact that each person has a unique and different genetic makeup each persons set of HLA is different and their immune system has learned not to react to their specific HLA gene, but when another organ or tissue enters the body with a different HLA gene it is immediately marked as non self and the immune system proceeds to destroy it.
The chances of immunorejection can be minimised but not fully eliminated by a few medical processes. First and foremost, the doctors check for a match in blood type between the recipient and the donor. If the blood group is not matched the transplant will be immediately rejected by the recipients immune system. Secondly a tissue match is searched for, another blood sample is taken from the person receiving the donor organ to identity the HLA agents present on their blood cells, the more alike the HLA agents are of the recipient and the donor the less likely the chances are of rejection. Although an identical match is not a possibility a similar match is. Family members are usually the best for finding a similar HLA match particularly siblings as they have genetic similarity. See figure 5 to view the development of HLA cells through the mother and father to the child and a visual representation of how they differ.
After these processes are complete a blood sample is taken from the donor and the recipient, these two bloods are mixed. If it is evident that the recipients antibodies are attacking the donor cells they are considered positive and a transplant will not be possible as there is an increase risk of hyper acute rejection.
Due to all these risks organ or tissue transplantation is a difficult and time consuming process to ensure that the chances of immunorejection are as allow as possible.
With bio artificially grown organs, the stem cells and MSCs can be taken from the recipient to ensure that immunorejection is as limited as possible. Due to the bio artificially grown organ having the same stem cells or MSCs as the recipient, as it is their cells used to grow the organ the chances of immunorejection are dramatically lowered as it is an exact HLA match. It would also limit the patients time on the wait list to receive a natural donor organ.
Eliminating the cost of anti-rejection drugs
Once an organ transplant has been completed the patient is immediately put onto immunosuppressants, these are drugs that lower the bodys alibility to reject the transplanted organ. These drugs, although assisting in the anti-rejection of the donor organ, in this process cause the weakening of the immune system. Anti rejection or immunosuppressant drugs need to be given as soon as the transplant is completed in a large dose and from here they are then taken as long as the transplanted organ remains in the human body. Over time your doctor may lessen your dosage of anti rejection drugs, this is because the chance of rejection lessens over time.
The combination of drugs and the amount taken can greatly vary depending on the type of transplant. Due to a number of factors such as the patient experiencing an acute rejection episode the drug is subject to change and an increased dosage is highly likely. Side effects and reactions to the chosen drug can also result in a change of prescription.
These drugs come with major limitations such as a severe immunodeficiency, the drugs taken to reduce the chance of rejection are non-specific, this means that instead of targeting a particular subject it reduces the immune system overall, this leaves patients susceptible to opportunistic infections. Furthermore many of these drugs are associated with adverse side effects, these include: increased blood pressure, impaired renal function, diabetes mellitus and an increased risk of cancer, this is because the immune system is weakened and the T cells are no longer as active, T cells are the cells responsible for destroying virus infected cells such as cancerous cells.
Taking these immunosuppressants every day for the rest of their life can have a major impact on someones health and lifestyle, a careful balance needs to be put in place with sufficiently suppressing the immune function to avoid rejection, avoiding drug toxicity and maintaining enough immune function to fight of any diseases that enter the body.
On an annual basis anti-rejection drugs cost roughly $17,000 each year at a minimum. Introducing the increased use of artificial organs, grown from the patients own stem cells can eliminate the need for anti rejection drugs as the organ has the same HLA as that that is already present in the patients body. Not only would artificial organs become a much more economically efficient option for organ transplant patients, but the patient would no longer need to take anti rejection drugs which need to pass through the kidneys and over a prolonged period of time could lead to kidney damage. See figure 6 for organ transplant medical costs from 2 years prior to 3 years post surgery
Importance of artificial organs in the future of society
As discussed previously artificial organs could pose a huge improvement in the future of society as they contain many health and economic benefits.
Artificial organs can make a dramatic improvement in organ donor shortages. As of currently there are thousands of people on the wait list for a donor organ which could be a life saving organ but unfortunately there is a colossal difference between the amount of people who desperately need a life saving donor organ and the amount of people that are actually willing to donate their organs. Artificial organ technology could help close the gap and hopefully one day, everyone in need of an organ will receive one, with the assistance of this technology.
Organ transplants require a significant amount of planning and testing prior to the actual transplant to ensure that it will not be rejected and destroyed by the bodys immune system. Through the technology of artificial organs, organs can be grown using the recipients own mesenchymal stem cells this means that they can produce a multitude of different cells, which in turn can be used to make an organ that wont be rejected by the recipients body as it has come from the same cell and therefore has the same HLA cells which dramatically reduces the chances of the organ being rejected.
Additionally, as the bio artificially produced organs have anti-rejection properties, this adequately reduces the cost and need for anti rejection drugs. This becomes extremely cost efficient for the patient, as anti rejection medication can cost a minimum of $17,000 each year. Not only is it more cost efficient than receiving a natural organ but it also aids the kidneys. The kidneys have to process a lifetimes worth of anti rejection drugs which can be extremely damaging, given that the majority of anti rejection drugs are also steroids this could also cause severe kidney damage after processing the high initial dose and then a lifetimes supply of them afterwards. Anti rejection medication can also make it difficult in leading our day to day lives as they need to be taken constantly and therefore possibly disrupting work or school patterns. If a dose of anti rejection medication is missed it can also cause a problem as the immune system quickly builds itself back up, if more than one dose is missed this can cause a severe issue and the organ may need to be removed.
Finally it is firmly believed that with a more prominent use of artificial organs in the transplant industry, there could be an improved quality of life after a transplant as well as providing the patient with tens of thousands of dollars saved each year on anti rejection drugs, not taking these drugs also keeps their immune system healthy and doesnt leave patients susceptible to illnesses due to a weakened immune system.
Artificial organs can also majorly assist in the international organ donor shortages and save thousands of lives in doing so, it would eliminate long wait lists and would end the death of a person simply waiting for an organ to save their lives and immediately provide them with their own specialized organ that doesnt trigger an immune response.
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